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>> WELCOME.

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I'M WIN ARIAS AT THE NATIONAL

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INSTITUTES OF HEALTH IN

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BETHESDA, MARYLAND.

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AND IT'S A PLEASURE TO WELCOME

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YOU TO ANOTHER EXCITING

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00:00:20,616 --> 00:00:22,652
PRESENTATION IN A COURSE IN

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BRIDGE BUILDING.

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00:00:23,085 --> 00:00:25,488
THE NAME OF THE COURSE IS

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00:00:25,488 --> 00:00:27,123
DEMYSTIFYING MEDICINE.

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00:00:27,123 --> 00:00:30,960
AND IT HAS BEEN IN EXISTENCE AT

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00:00:30,960 --> 00:00:32,995
THE NIH FOR APPROXIMATELY 22

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00:00:32,995 --> 00:00:36,866
YEARS.

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THE PURPOSE IS TO BRIDGE THE

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EXCITING DEVELOPMENTS IN

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BIOLOGY, ENGINEERING AND

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COMPUTER SCIENCES WITH MEDICINE

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00:00:46,642 --> 00:00:49,345
AND GLOBAL HEALTH.

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00:00:49,345 --> 00:00:51,614
AND THE BRIDGE, AS EXEMPLIFIED

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00:00:51,614 --> 00:00:53,049
IN THE UPPER RIGHT PORTION OF

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00:00:53,049 --> 00:00:56,652
THIS SLIDE, THE BROOKLYN BRIDGE,

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00:00:56,652 --> 00:00:59,388
EACH WEEK FEATURES SOMETIMES

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ONLY ONE BUT USUALLY TWO, AND

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00:01:02,892 --> 00:01:05,428
THOSE TWO ARE OFTEN JOINED BY A

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PATIENT ON THE CATWALK OF THE

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00:01:06,295 --> 00:01:09,565
BRIDGE.

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00:01:09,565 --> 00:01:12,101
CONNECTING THEIR KNOWLEDGE AND

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EXPERIENCE BOTH FROM A CLINICAL

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00:01:15,805 --> 00:01:17,873
PERSPECTIVE AND ALSO FROM A MORE

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BASIC SCIENCE PERSPECTIVE.

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00:01:19,642 --> 00:01:21,610
THE GOAL IS TO CONVERT WHAT ARE

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SILOS OF INFORMATION, NAMELY THE

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00:01:26,082 --> 00:01:28,484
IDEA THAT MUCH OF SCIENCE HAS

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BECOME SO SPECIALIZED THAT THERE

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ARE ALMOST LANGUAGES ASSOCIATED

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WITH EACH DISCIPLINE.

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00:01:34,657 --> 00:01:37,793
AND LITTLE COMMUNICATION.

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BUT PROGRESS IN HEALTH AND

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MEDICINE HAS CERTAINLY

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FACILITATED WHEN PEOPLE

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COMMUNICATE, SHARE IDEAS, AND

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00:01:47,203 --> 00:01:48,838
BRING TOGETHER TO FORM ALMOST

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LIKE NEW DISCIPLINES, AND NEW

44
00:01:52,441 --> 00:01:54,677
APPROACHES TO COMBAT AND

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UNDERSTAND HUMAN DISEASE.

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00:01:57,379 --> 00:01:59,348
SO DEMYSTIFYING MEDICINE MEETS

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EVERY TUESDAY FROM 3:00 TO 5:00.

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00:02:04,687 --> 00:02:05,454
EASTERN STANDARD TIME FROM

49
00:02:05,454 --> 00:02:08,190
JANUARY UNTIL THE END OF MAY.

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YOU'RE WATCHING IT ON THE

51
00:02:10,826 --> 00:02:15,531
VIDEOCAST FOR THE NIH.

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00:02:15,531 --> 00:02:18,701
AS SEEP IN  SEEN IN THE EARLIER,

53
00:02:18,701 --> 00:02:20,236
THERE ARE CME CREDITS FOR

54
00:02:20,236 --> 00:02:21,103
PHYSICIANS WHO SEEK THIS.

55
00:02:21,103 --> 00:02:23,839
THE CODE NUMBER FOR TODAY'S

56
00:02:23,839 --> 00:02:27,777
SESSION IS 58786.

57
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NOW, OF GREAT IMPORTANCE IS WE

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ENCOURAGE YOU TO PLEASE ASK

59
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QUESTIONS AND SUBMIT THEM VIA

60
00:02:37,720 --> 00:02:39,688
THE "SEND LIVE FEEDBACK," WHICH

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00:02:39,688 --> 00:02:42,525
IS ON YOUR VIDEOCAST DISPLAY.

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00:02:42,525 --> 00:02:47,263
AND THOSE QUESTIONS WILL BE

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SORTED AND AT THE END OF THE

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00:02:49,565 --> 00:02:51,200
PRESENTATIONS, THERE WILL BE

65
00:02:51,200 --> 00:02:54,470
ABUNDANT TIME FOR DISCUSSION,

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QUESTIONS, AND WE ENCOURAGE YOU

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TO PLEASE DO THIS EVEN DURING

68
00:02:58,107 --> 00:03:01,143
THE COURSE OF THE PRESENTATIONS.

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00:03:01,143 --> 00:03:02,511
NOW, ALL OF THE PREVIOUS

70
00:03:02,511 --> 00:03:04,513
SESSIONS FOR THE PAST 20-ODD

71
00:03:04,513 --> 00:03:08,918
YEARS ARE ARCHIVED, AND YOU CAN

72
00:03:08,918 --> 00:03:10,986
ACCESS THEM IN THE WEB SITE

73
00:03:10,986 --> 00:03:14,156
INDICATED ON THIS SLIDE, AND IF

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00:03:14,156 --> 00:03:17,660
YOU WANT ANY ADDITIONAL

75
00:03:17,660 --> 00:03:19,061
INFORMATION, YOU CAN GET IN

76
00:03:19,061 --> 00:03:24,099
TOUCH WITH US AT

77
00:03:24,099 --> 00:03:24,767
DEMYSTIFYINGMED@NIH.GOV.

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00:03:24,767 --> 00:03:30,873
NOW TODAY'S TOPIC, NEXT SLIDE,

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PLEASE, TODAY'S SESSION IS

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00:03:32,208 --> 00:03:37,880
REALLY ENTITLED SCRATCHING THE

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00:03:37,880 --> 00:03:39,615
HISTORICAL SURFACE OF PRURITIS,

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WHICH IS LATIN FOR ITCHING.

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00:03:44,220 --> 00:03:46,422
NOW, WE ALL KNOW THE ITCHING

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00:03:46,422 --> 00:03:50,259
THAT'S ASSOCIATED WITH A MINOR,

85
00:03:50,259 --> 00:03:52,761
SAY, MOSQUITO BITE, BUT THERE

86
00:03:52,761 --> 00:03:56,599
ARE A HUGE NUMBER OF CLINICAL

87
00:03:56,599 --> 00:03:58,000
ASPECTS OF PRURITIS, SOME OF

88
00:03:58,000 --> 00:04:00,636
WHICH ARE MILD, AND MANY OF

89
00:04:00,636 --> 00:04:03,806
WHICH ARE PROLONGED, COMPLEX AND

90
00:04:03,806 --> 00:04:06,742
CAUSE REALLY GRAVE SUFFERING,

91
00:04:06,742 --> 00:04:09,178
LARGELY IN THE FORM OF

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00:04:09,178 --> 00:04:12,014
UNCONTROLLABLE PRURITIS

93
00:04:12,014 --> 00:04:14,850
PERIODICALLY, DISTURBING SLEEP,

94
00:04:14,850 --> 00:04:17,253
CHANGING LIGHT PATTERNS, AND

95
00:04:17,253 --> 00:04:19,355
OFTEN ASSOCIATED WITH OTHER

96
00:04:19,355 --> 00:04:21,323
DISEASES, PARTICULARLY OF THE

97
00:04:21,323 --> 00:04:23,926
LIVER, THE KIDNEY, CANCER,

98
00:04:23,926 --> 00:04:24,360
DRUGS.

99
00:04:24,360 --> 00:04:28,964
IT'S A COMPLEX FIELD.

100
00:04:28,964 --> 00:04:30,599
IN LOOKING AROUND, I DISCOVERED

101
00:04:30,599 --> 00:04:33,002
THE FIRST REFERENCE THAT I CAME

102
00:04:33,002 --> 00:04:36,405
TO ITCHING IS ACTUALLY FROM THE

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00:04:36,405 --> 00:04:39,675
OLD TESTAMENT IN THE BOOK OF

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DEUTERONOMY, WHERE WHEN THE LORD

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00:04:42,645 --> 00:04:46,348
DISPENSED MANY PLAGUES, THE LAST

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ONE WAS THE ITCH.

107
00:04:47,349 --> 00:04:51,820
AND THE QUOTE IS "THE LORD WILL

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AFFLICT YOU WITH THE ITCH FROM

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WHICH YOU CANNOT RECOVER."

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NOW, HI HIPPOCRATES AND OTHERS

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DESCRIBED DIFFERENT FORMS OF

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00:05:02,965 --> 00:05:05,167
PRURITIS, GAVE IT ITS NAME LATER

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00:05:05,167 --> 00:05:09,138
ON, AND ALSO VARIOUS TREATMENTS

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WHICH WERE EMPIRIC.

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IN THE 17TH CENTURY, A GERMAN

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PHYSICIAN, HAFFENREFFER, OFTEN

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00:05:18,847 --> 00:05:20,249
BEGAN THE CLINICAL DESCRIPTION

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OF VARIOUS FORMS OF PRURITIS.

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AND OVER THE NEXT 200 YEARS, IT

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SEEMS AS IF MOST OF THE EMPHASIS

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WAS ON THE DESCRIPTION OF THE

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CLINICAL PHENOTYPES, AND NOT

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00:05:33,862 --> 00:05:37,333
MUCH WAS KNOWN OR DISCOVERED

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ABOUT ACTUALLY MECHANISMS.

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AND IN FACT, IN A 1994 REVIEW,

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THERE ARE ACTUALLY TWO EXTENSIVE

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00:05:47,176 --> 00:05:50,012
REVIEWS, AND THEY BOTH MAKE THE

128
00:05:50,012 --> 00:05:51,780
SAME CONCLUSION, THAT NO

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MECHANISMS ARE DEFINITIVELY

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KNOWN.

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THAT'S 1994.

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NOW, IN THE NEXT COUPLE OF

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DECADES, ADVANCES IN

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NEUROBIOLOGY, IMMUNOLOGY AND IN

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PARTICULAR THE RECEPTOR BIOLOGY,

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HAVE DOMINATED THE FIELD AND

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HAVE BROUGHT ABOUT THE

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OPPORTUNITY TO STUDY AND LEARN

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MORE ABOUT MECHANISMS WHICH

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UNDERLIE EVENTUALLY THE DESIGN

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OF EFFECTIVE TREATMENTS.

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SO THE CHALLENGE IS TO BRIDGE

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THESE GREAT ADVANCES IN

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BIOLOGICAL SCIENCE WITH THE

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CLINICAL DISEASE.

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AND WE'RE VERY FORTUNATE TO HAVE

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TWO OUTSTANDING SCIENTISTS HERE

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AT THE NATIONAL INSTITUTES OF

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HEALTH WHO WORK IN THIS LARGE

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AREA AND HAVE M HAVE MADE VERY

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SIGNIFICANT CONTRIBUTIONS.

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OUR FIRST SPEAKER IS MARK HOON,

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WHO'S A PRINCIPAL SENIOR

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INVESTIGATOR IN THE NATIONAL --

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SORRY, I'VE GOT THE WRONG THING

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HERE.

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HE'S IN THE CRANIO -- THE

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NATIONAL INSTITUTE --

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>> NICDR --

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>> CDR, RIGHT,
CRANIOFACIAL

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RESEARCH.

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>> DENTAL.

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>> RIGHT.

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MARK RECEIVED HIS PH.D. IN THE

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UNITED KINGDOM AT THE UNIVERSITY

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OF LEEDS, AND THEN WAS A

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POSTDOCTORAL NATO FELLOW AT THE

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UNIVERSITY OF FREIBURG.

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HE CAME TO THE UNITED STATES,

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WHERE HE SPENT SEVERAL YEARS,

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VERY IMPORTANT YEARS, IN THE

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LABORATORY OF CHARLES ZUCKER AT

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COLUMBIA, WHERE RECEPTORS WERE

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DISCOVERED FOR SWEAT, TASTE,

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TOUCH, AND HE WAS THERE AT THAT

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TIME AND MADE SIGNIFICANT

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CONTRIBUTIONS TO UNDERSTANDING

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THE NATURE AND MECHANISM

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INVOLVED IN THIS INCREASING

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FAMILY OF RECEPTORS.

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IN 2006, HE CAME TO THE NIH AS A

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PRINCIPAL INVESTIGATOR.

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MARK HAS RECEIVED MANY AWARDS

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AND VARIOUS INVITATIONS.

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HIS RESEARCH CONCERNS THE

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SOMATOSENSORY RECEPTORS, THEIR

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MECHANISMS, INCLUDING THEIR

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RELATIONSHIP TO PRURITIS.

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AND HIS WORK HAS REALLY OPENED

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UP THE DOOR TO A LOT OF VERY

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EXCITING CHALLENGES AND

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POSSIBILITIES TO BETTER

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UNDERSTAND THIS SERIOUS AND

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DIVERSE PHENOTYPE OF SEVERE

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ITCHING.

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NOW, OUR SECOND SPEAKER, IAN

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MYLES, GRADUATED FROM COLORADO

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STATE UNIVERSITY AND RECEIVED

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HIS MEDICAL DEGREE FROM THE

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00:08:55,898 --> 00:08:58,033
UNIVERSITY OF COLORADO.

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HE HAD A RESIDENCY AT OHIO

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00:09:01,103 --> 00:09:03,505
STATE, AND AN NIH FELLOWSHIP IN

203
00:09:03,505 --> 00:09:08,744
ALLERGY AND IMMUNOLOGY.

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00:09:08,744 --> 00:09:11,580
IN 2011, HE JOINED THE U.S.

205
00:09:11,580 --> 00:09:12,481
PUBLIC HEALTH SERVICE, WHERE HE

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00:09:12,481 --> 00:09:15,517
IS AN OFFICER, AND HE

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00:09:15,517 --> 00:09:18,253
PARTICIPATED EXTENSIVELY IN THE

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00:09:18,253 --> 00:09:21,323
EBOLA VACCINE STUDY, WHICH WAS

209
00:09:21,323 --> 00:09:25,360
CONDUCTED IN AFRICA DURING THE

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00:09:25,360 --> 00:09:30,299
BEAEBOLA OUTBREAK IN THAT DECAD.

211
00:09:30,299 --> 00:09:32,601
IN 2016, HE RECEIVED HIS MASTER

212
00:09:32,601 --> 00:09:34,670
OF PUBLIC HEALTH FROM GEORGE

213
00:09:34,670 --> 00:09:35,871
WASHINGTON UNIVERSITY, AND TWO

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00:09:35,871 --> 00:09:40,175
YEARS LATER, CAME TO THE NIH AS

215
00:09:40,175 --> 00:09:41,877
A LASKER CLINICAL RESEARCH

216
00:09:41,877 --> 00:09:43,645
SCHOLAR.

217
00:09:43,645 --> 00:09:46,481
HE HEADS THE UNIT ON

218
00:09:46,481 --> 00:09:48,550
EXPERIMENTAL THERAPEUTICS, IN

219
00:09:48,550 --> 00:09:49,751
THE NATIONAL INSTITUTE OF

220
00:09:49,751 --> 00:09:53,488
ALLERGY AND INFECTIOUS DISEASES.

221
00:09:53,488 --> 00:09:55,023
HIS RESEARCH ORIGINALLY

222
00:09:55,023 --> 00:09:57,426
CONCERNED THE MICROBIOME AND ITS

223
00:09:57,426 --> 00:09:59,294
RELATIONSHIP TO SKIN DISEASE,

224
00:09:59,294 --> 00:10:02,998
AND HE'S BECOME INCREASINGLY

225
00:10:02,998 --> 00:10:05,300
INTERESTED AND WORKED ON

226
00:10:05,300 --> 00:10:09,404
IMMUNOLOGIC MECHANISMS AND IS HS

227
00:10:09,404 --> 00:10:11,740
SET UP THIS NEW UNIT ON

228
00:10:11,740 --> 00:10:12,474
EPITHELIAL THERAPEUTICS.

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00:10:12,474 --> 00:10:14,376
SO WE WELCOME BOTH OF YOU, LOOK

230
00:10:14,376 --> 00:10:17,145
FORWARD TO YOUR TALKS.

231
00:10:17,145 --> 00:10:18,747
WE ENCOURAGE THE AUDIENCE TO

232
00:10:18,747 --> 00:10:20,782
PLEASE SUBMIT QUESTIONS AT ANY

233
00:10:20,782 --> 00:10:24,453
TIME DURING THE PRESENTATIONS.

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00:10:24,453 --> 00:10:26,288
AND SO OUR FIRST SPEAKER IS MARK

235
00:10:26,288 --> 00:10:26,622
HOON.

236
00:10:26,622 --> 00:10:32,995
SO MARK, CARRY ON.

237
00:10:32,995 --> 00:10:34,730
>> THANK YOU, WIN, WITH
THAT

238
00:10:34,730 --> 00:10:36,465
INTRODUCTION.

239
00:10:36,465 --> 00:10:38,333
SO WHAT I'M BASICALLY GOING TO

240
00:10:38,333 --> 00:10:43,238
TALK TO YOU TODAY ABOUT IS THE

241
00:10:43,238 --> 00:10:44,773
BASIC MECHANISMS, THE MECHANISMS

242
00:10:44,773 --> 00:10:49,211
PART OF THE TITLE TODAY, AND

243
00:10:49,211 --> 00:10:50,912
TELL YOU ABOUT HOW SIGNALS

244
00:10:50,912 --> 00:10:54,182
TRANSMITTED FROM THE SKIN TO THE

245
00:10:54,182 --> 00:10:56,385
BRAIN AND TO PRODUCE THE

246
00:10:56,385 --> 00:10:59,221
SENSATION THAT'S CALLED ITCH OR

247
00:10:59,221 --> 00:10:59,721
PRURITIS.

248
00:10:59,721 --> 00:11:00,989
AND WITH THAT, I HAVE TO FIRST

249
00:11:00,989 --> 00:11:03,492
OF ALL ACKNOWLEDGE THAT ALTHOUGH

250
00:11:03,492 --> 00:11:09,164
THE MAJORITY OF ITCH IS ON THIS

251
00:11:09,164 --> 00:11:10,299
MECHANISM FROM THE SKIN TO THE

252
00:11:10,299 --> 00:11:13,535
BRAIN, THERE ARE SOME TYPES OF

253
00:11:13,535 --> 00:11:15,504
ITCH AS WIN ALLUDED TO THAT

254
00:11:15,504 --> 00:11:18,140
DON'T INVOLVE EITHER THE SKIN --

255
00:11:18,140 --> 00:11:20,976
DON'T INVOLVE THE SKIN, SO FOR

256
00:11:20,976 --> 00:11:26,682
INSTANCE, KIDNEY DISEASES.

257
00:11:26,682 --> 00:11:28,216
BUT I'VE REALLY RESTRICTED MY

258
00:11:28,216 --> 00:11:30,285
TALK TO THIS ONE PATHWAY, AND

259
00:11:30,285 --> 00:11:34,656
THAT'S FOR THE SAKE OF TIME.

260
00:11:34,656 --> 00:11:34,990
OKAY.

261
00:11:34,990 --> 00:11:37,626
SO I ALSO WANT TO POINT OUT THAT

262
00:11:37,626 --> 00:11:41,863
I'VE TRIED TO BREAK MY

263
00:11:41,863 --> 00:11:42,864
PRESENTATION INTO TWO DIFFERENT

264
00:11:42,864 --> 00:11:43,498
PARTS.

265
00:11:43,498 --> 00:11:46,468
THE FIRST PART IS MAINLY

266
00:11:46,468 --> 00:11:49,971
CONCERNING THE MECHANISMS

267
00:11:49,971 --> 00:11:51,873
INVOLVED IN ACUTE ITCH, SO THE

268
00:11:51,873 --> 00:11:53,241
SORT OF ITCH THAT WILL HAPPEN,

269
00:11:53,241 --> 00:11:54,776
FOR INSTANCE, WHEN YOU HAVE AN

270
00:11:54,776 --> 00:11:56,311
INSECT BITE.

271
00:11:56,311 --> 00:11:59,047
THE SECOND PART OF THE TALK, I'M

272
00:11:59,047 --> 00:12:01,116
GOING TO TALK ABOUT CHRONIC

273
00:12:01,116 --> 00:12:02,551
ITCH, AND THIS IS THE TYPE OF

274
00:12:02,551 --> 00:12:08,023
ITCH THAT'S ACTUALLY CLINICALLY

275
00:12:08,023 --> 00:12:08,357
IMPORTANT.

276
00:12:08,357 --> 00:12:10,859
THE DISEASES LIKE ATOPIC

277
00:12:10,859 --> 00:12:20,068
DERMATITIS, VIE C PSORIASIS ANDS

278
00:12:20,068 --> 00:12:22,671
WHICH LEAD TO ITCH.

279
00:12:22,671 --> 00:12:24,106
THE LAST IS I'M GOING TO --

280
00:12:24,106 --> 00:12:26,174
WHILE GIVING THIS TALK, GIVE AN

281
00:12:26,174 --> 00:12:27,209
OVERVIEW, BUT WHAT I'VE TRIED TO

282
00:12:27,209 --> 00:12:30,312
DO IS TO INTRODUCE SOME KEY

283
00:12:30,312 --> 00:12:33,782
EXPERIMENTS THAT WE PERFORMED

284
00:12:33,782 --> 00:12:35,784
AND OTHERS HAVE PERFORMED FROM

285
00:12:35,784 --> 00:12:37,552
OTHER GROUPS THAT ACTUALLY POINT

286
00:12:37,552 --> 00:12:39,388
TO THE EVIDENCE FOR THE PATHWAYS

287
00:12:39,388 --> 00:12:46,461
THAT I'M GOING TO BE DESCRIBING.

288
00:12:46,461 --> 00:12:47,662
WITH THAT, I'M GOING TO BEGIN

289
00:12:47,662 --> 00:12:48,964
WITH THE FIRST SLIDE HERE THAT I

290
00:12:48,964 --> 00:12:51,800
STARTED OUT WITH, WHICH IS AN

291
00:12:51,800 --> 00:12:54,002
IMAGE THROUGH THE SKIN OF A

292
00:12:54,002 --> 00:12:54,236
MOUSE --

293
00:12:54,236 --> 00:12:55,771
>> EXCUSE ME, DR. HOON,
YOU'RE

294
00:12:55,771 --> 00:12:57,172
NOT SHARING THE SCREEN JUST YET.

295
00:12:57,172 --> 00:12:58,373
>> OH, OKAY.

296
00:12:58,373 --> 00:13:08,483
I'M SORRY.

297
00:13:08,483 --> 00:13:18,827
LET ME TRY DO THAT.

298
00:13:21,997 --> 00:13:22,764
SO AM I SHARING NOW?

299
00:13:22,764 --> 00:13:23,865
>> YES, IT'S COMING UP.

300
00:13:23,865 --> 00:13:24,566
>> GREAT.

301
00:13:24,566 --> 00:13:25,734
SORRY ABOUT THAT.

302
00:13:25,734 --> 00:13:28,270
SO THIS FIRST IMAGE THAT YOU

303
00:13:28,270 --> 00:13:31,973
HOPEFULLY CAN SEE NOW IS A

304
00:13:31,973 --> 00:13:33,742
PICTURE THROUGH THE SKIN OF A

305
00:13:33,742 --> 00:13:35,710
MOUSE, AS I JUST TALKED TO YOU

306
00:13:35,710 --> 00:13:37,245
ABOUT, AND IN MAGENTA, YOU CAN

307
00:13:37,245 --> 00:13:38,447
SEE THE CELLS OF THE SKIN.

308
00:13:38,447 --> 00:13:42,717
AND YOU CAN SEE THAT IT'S A

309
00:13:42,717 --> 00:13:43,652
LAYERED STRUCTURE, SO DOWN AT

310
00:13:43,652 --> 00:13:44,953
THE VERY BOTTOM HERE IS THE

311
00:13:44,953 --> 00:13:49,257
DERMIS AND THE EP DEM EPIDERMISE

312
00:13:49,257 --> 00:13:51,126
TOP OF THIS IMAGE AND THIS IS

313
00:13:51,126 --> 00:13:51,693
THE OUTSIDE OF THE SKIN.

314
00:13:51,693 --> 00:13:54,429
WHAT YOU CAN SEE IN THIS IMAGE

315
00:13:54,429 --> 00:13:56,865
IS A GREEN FIBER THAT SNAKES ITS

316
00:13:56,865 --> 00:13:58,567
WAY UP TO THE VERY TOP PART OF

317
00:13:58,567 --> 00:14:01,736
THE SKIN.

318
00:14:01,736 --> 00:14:06,975
SO THIS IS THE STRUCTURE OF THE

319
00:14:06,975 --> 00:14:08,310
NERVE FIBER THAT'S ACTUALLY

320
00:14:08,310 --> 00:14:09,110
RECEIVING INFORMATION THAT'S THE

321
00:14:09,110 --> 00:14:14,216
FIRST PART OF THE ITCH PATHWAY.

322
00:14:14,216 --> 00:14:16,718
SO IF WE GO TO MY SECOND SLIDE,

323
00:14:16,718 --> 00:14:18,620
WE SEE A CARTOON OF THIS AT THE

324
00:14:18,620 --> 00:14:19,454
TOP HERE.

325
00:14:19,454 --> 00:14:22,123
AND YOU CAN SEE THAT I'VE GOT

326
00:14:22,123 --> 00:14:24,426
HERE A MOSQUITO THAT'S ABOUT TO

327
00:14:24,426 --> 00:14:28,964
BITE A FINGER, AND YOU CAN SEE

328
00:14:28,964 --> 00:14:30,832
THE NERVES GO FROM THE SKIN,

329
00:14:30,832 --> 00:14:32,801
THEY GO BACK, IT'S A VERY LONG

330
00:14:32,801 --> 00:14:34,402
AXON THAT THEN TERMINATES IN THE

331
00:14:34,402 --> 00:14:34,970
SPINAL CORD.

332
00:14:34,970 --> 00:14:37,939
BUT IMPORTANTLY, THE CELL BODIES

333
00:14:37,939 --> 00:14:41,676
OF THE NERVES THAT HAVE THESE

334
00:14:41,676 --> 00:14:42,644
FIBERS ARE PRESENT IN THIS

335
00:14:42,644 --> 00:14:44,513
STRUCTURE CALLED THE DORSAL ROOT

336
00:14:44,513 --> 00:14:47,115
GANGLION.

337
00:14:47,115 --> 00:14:48,917
AND THESE ARE FOUND CLOSE TO THE

338
00:14:48,917 --> 00:14:51,253
SPINAL CORD AND INNERVATES

339
00:14:51,253 --> 00:14:53,355
SPECIFIC AREAS OF THE SKIN.

340
00:14:53,355 --> 00:14:57,893
AND IN THE HEAD, THE GANGLION,

341
00:14:57,893 --> 00:15:00,028
IS CALLED THE TRIGEMINAL

342
00:15:00,028 --> 00:15:00,295
GANGLION.

343
00:15:00,295 --> 00:15:00,495
OKAY.

344
00:15:00,495 --> 00:15:02,564
YOU CAN ALSO SEE ON THIS SLIDE

345
00:15:02,564 --> 00:15:04,900
THAT I'VE ILLUSTRATED THAT

346
00:15:04,900 --> 00:15:08,003
THERE'S DIFFERENT TYPES OF

347
00:15:08,003 --> 00:15:09,237
SIGNAL THAT'S ACTUALLY COLLECTED

348
00:15:09,237 --> 00:15:11,907
BY THIS GROUP OF NEURONS, AND

349
00:15:11,907 --> 00:15:13,608
COLLECTIVELY THIS IS CALLED

350
00:15:13,608 --> 00:15:14,409
SOMATOSENSATION.

351
00:15:14,409 --> 00:15:16,545
SO SIGNALS FROM THE SKIN AND THE

352
00:15:16,545 --> 00:15:19,180
NERVES THAT INNERVATE IT

353
00:15:19,180 --> 00:15:20,715
COLLECTED FOR, FOR INSTANCE, HOT

354
00:15:20,715 --> 00:15:22,784
AND COLD, THE PAINFUL STIMULI,

355
00:15:22,784 --> 00:15:24,419
AND ALSO FOR ALL KINDS OF

356
00:15:24,419 --> 00:15:26,488
DIFFERENT TYPES OF TOUCH.

357
00:15:26,488 --> 00:15:28,790
AND IT'S GENERALLY NOW KNOWN

358
00:15:28,790 --> 00:15:32,527
THAT THESE ARE ACTUALLY DETECTED

359
00:15:32,527 --> 00:15:33,862
BY DIFFERENT CLASSES OF NEURONS,

360
00:15:33,862 --> 00:15:35,263
AND I'M GOING TO BE GOING INTO

361
00:15:35,263 --> 00:15:36,364
THIS A LITTLE BIT LATER.

362
00:15:36,364 --> 00:15:39,968
SO THESE ARE JUST COLOR-CODED

363
00:15:39,968 --> 00:15:41,269
HERE.

364
00:15:41,269 --> 00:15:42,671
SO WHAT DOES THIS ACTUALLY LOOK

365
00:15:42,671 --> 00:15:44,973
LIKE IN REAL LIFE?

366
00:15:44,973 --> 00:15:46,741
THIS NOW SLIDE I'M ACTUALLY

367
00:15:46,741 --> 00:15:48,043
ILLUSTRATING THIS IN A MOUSE

368
00:15:48,043 --> 00:15:52,414
TISSUE.

369
00:15:52,414 --> 00:15:53,615
SO OVER HERE YOU CAN SEE THE

370
00:15:53,615 --> 00:15:54,950
TISSUE FROM A MOUSE WHERE WE'VE

371
00:15:54,950 --> 00:15:57,252
INJECTED A VIRUS JUST INTO THE

372
00:15:57,252 --> 00:15:59,321
PORE OF THE MOUSE, AND THIS

373
00:15:59,321 --> 00:16:01,823
ILLUMINATES WITH A FLUORESCENT

374
00:16:01,823 --> 00:16:04,125
PROTEIN THE FIBERS THAT ARE

375
00:16:04,125 --> 00:16:07,195
COMING FROM THAT PAW, FROM THE

376
00:16:07,195 --> 00:16:07,729
HIND PAW.

377
00:16:07,729 --> 00:16:09,364
HERE ARE THE DORSAL ROOT

378
00:16:09,364 --> 00:16:11,333
GANGLION, THE CELL BODIES, AND

379
00:16:11,333 --> 00:16:12,767
THE FIBERS ARE GOING IN HERE

380
00:16:12,767 --> 00:16:18,340
INTO THE SPINAL CORD.

381
00:16:18,340 --> 00:16:19,975
I'VE ALSO SHOWN HERE ON THIS

382
00:16:19,975 --> 00:16:23,178
SLIDE AN IN SITU HYBRIDIZATION

383
00:16:23,178 --> 00:16:25,447
OF TWO GENES THAT IDENTIFY TWO

384
00:16:25,447 --> 00:16:26,982
DIFFERENT CLASSES OF SENSORY

385
00:16:26,982 --> 00:16:27,649
NEURONS.

386
00:16:27,649 --> 00:16:29,718
SO THIS ILLUSTRATES THAT THERE

387
00:16:29,718 --> 00:16:33,321
IS DIFFERENT CLASSES OF NEURONS,

388
00:16:33,321 --> 00:16:35,523
AND NOW THROUGH SEQUENCING

389
00:16:35,523 --> 00:16:37,392
INFORMATION, SINGLE CELL

390
00:16:37,392 --> 00:16:38,360
SEQUENCING INFORMATION, WE KNOW

391
00:16:38,360 --> 00:16:39,961
THERE'S AT LEAST 15 DIFFERENT

392
00:16:39,961 --> 00:16:41,763
DISTINCT CLASSES OF SENSORY

393
00:16:41,763 --> 00:16:42,130
NEURONS.

394
00:16:42,130 --> 00:16:43,498
AND SOME OF THOSE, IN FACT, A

395
00:16:43,498 --> 00:16:47,669
PAIR OF THOSE, TWO CLASSES, ARE

396
00:16:47,669 --> 00:16:49,838
DEDICATED FOR ITCH.

397
00:16:49,838 --> 00:16:53,541
SO THIS IS THE FUNDAMENTAL FIRST

398
00:16:53,541 --> 00:16:57,178
PART OF THE ITCH PATHWAY.

399
00:16:57,178 --> 00:16:58,613
THE NEXT PART OF THE PATHWAY

400
00:16:58,613 --> 00:16:59,914
TAKES PLACE BOTH IN THE SPINAL

401
00:16:59,914 --> 00:17:01,783
CORD AND THEN FURTHER IN THE

402
00:17:01,783 --> 00:17:02,250
CNS.

403
00:17:02,250 --> 00:17:03,752
I'M NOT GOING TO DESCRIBE THOSE

404
00:17:03,752 --> 00:17:05,387
TODAY BECAUSE, AGAIN, WE HAVE

405
00:17:05,387 --> 00:17:07,889
LIMITED TIME, AND I WANT TO

406
00:17:07,889 --> 00:17:08,990
REALLY CONCENTRATE ON WHAT'S

407
00:17:08,990 --> 00:17:10,525
REALLY HAPPENING AT THE VERY

408
00:17:10,525 --> 00:17:11,292
PERIPHERY.

409
00:17:11,292 --> 00:17:16,765
BUT THOSE ARE CLEARLY VERY

410
00:17:16,765 --> 00:17:18,066
IMPORTANT FOR THE SENSATION AND,

411
00:17:18,066 --> 00:17:23,872
IN FACT, THIS PART HERE IS

412
00:17:23,872 --> 00:17:25,173
CALLED PRERECEPTION FOR A GOOD

413
00:17:25,173 --> 00:17:29,511
IN FACT, IT'S NOT THE SPINAL SPL

414
00:17:29,511 --> 00:17:32,147
CORD THAT ACTUALLY TELLS YOU,

415
00:17:32,147 --> 00:17:33,682
THE ITCH IS IN YOUR BRAIN.

416
00:17:33,682 --> 00:17:34,883
I ALSO WANT TO ACKNOWLEDGE THAT

417
00:17:34,883 --> 00:17:36,317
ITCH ISN'T JUST THE SENSORY

418
00:17:36,317 --> 00:17:38,820
NERVES.

419
00:17:38,820 --> 00:17:41,356
WHAT THIS SLIDE HERE IS HERE TO

420
00:17:41,356 --> 00:17:45,927
TRY AND REMIND ME TO TELL YOU IS

421
00:17:45,927 --> 00:17:48,263
THAT AS WELL AS THE SENSORY

422
00:17:48,263 --> 00:17:49,330
NEURONS THAT ARE SHOWN OVER

423
00:17:49,330 --> 00:17:50,432
HERE, THE DIFFERENT CLASSES,

424
00:17:50,432 --> 00:17:51,866
THERE'S ALSO CLEARLY CELLS IN

425
00:17:51,866 --> 00:17:54,769
THE SKIN THAT WERE INVOLVED IN

426
00:17:54,769 --> 00:18:01,476
THE DEVELOPMENT OF ITCH.

427
00:18:01,476 --> 00:18:02,777
AND ALSO IMMUNE CELLS.

428
00:18:02,777 --> 00:18:04,913
I'LL BE COMING BACK TO THIS IN

429
00:18:04,913 --> 00:18:06,081
THE SECOND PART OF MY TALK WHERE

430
00:18:06,081 --> 00:18:07,382
I START TO TALK ABOUT CHRONIC

431
00:18:07,382 --> 00:18:07,882
ITCH.

432
00:18:07,882 --> 00:18:10,652
SO I WANT TO NOW GO BACK TO THE

433
00:18:10,652 --> 00:18:11,753
SENSORY NEURONS AND TELL YOU

434
00:18:11,753 --> 00:18:18,993
WHERE MY GROUP STARTED WORK ON

435
00:18:18,993 --> 00:18:19,327
PRERECEPTION.

436
00:18:19,327 --> 00:18:20,628
WE TRIED TO IDENTIFY SPECIFIC

437
00:18:20,628 --> 00:18:22,697
GENES NA WERE PRESENT IN

438
00:18:22,697 --> 00:18:24,466
DISTINCT POPULATION OF NEURONS

439
00:18:24,466 --> 00:18:25,633
IN THE HOPE THAT THIS WOULD

440
00:18:25,633 --> 00:18:28,436
ACTUALLY ALLOW US TO ACTUALLY

441
00:18:28,436 --> 00:18:31,940
START TO DISSECT THE MOLECULAR

442
00:18:31,940 --> 00:18:35,477
BASIS OF ITCH.

443
00:18:35,477 --> 00:18:37,011
THE KEY MOLECULE WE UNCOVERED IN

444
00:18:37,011 --> 00:18:38,880
THAT SEARCH WAS THIS ONE.

445
00:18:38,880 --> 00:18:40,081
IT'S NOT REALLY IMPORTANT, THE

446
00:18:40,081 --> 00:18:40,515
NAME.

447
00:18:40,515 --> 00:18:42,617
IT'S CALLED NPPB.

448
00:18:42,617 --> 00:18:45,220
WHAT'S IMPORTANT ABOUT THIS

449
00:18:45,220 --> 00:18:46,654
MOLECULE IS, FIRST OF ALL, YOU

450
00:18:46,654 --> 00:18:50,925
CAN SEE HERE IT'S EXPRESSED IN A

451
00:18:50,925 --> 00:18:52,761
VERY DISTINCT CLASS OF NEURONS.

452
00:18:52,761 --> 00:18:55,597
THESE ARE SMALL DIAMETER

453
00:18:55,597 --> 00:18:55,930
NEURONS.

454
00:18:55,930 --> 00:18:57,465
WE SEE THAT THEY'RE ALL ABOUT

455
00:18:57,465 --> 00:18:58,900
THE SAME SIZE, AND THIS IS

456
00:18:58,900 --> 00:19:00,368
DIFFERENT FROM OTHER CLASSES OF

457
00:19:00,368 --> 00:19:03,371
NEURONS.

458
00:19:03,371 --> 00:19:04,472
THE SECOND FEATURE OF THIS GENE

459
00:19:04,472 --> 00:19:06,775
IS THAT IT'S ACTUALLY A

460
00:19:06,775 --> 00:19:07,909
POLYPEPTIDE THAT'S RELEASED FROM

461
00:19:07,909 --> 00:19:11,479
THE NEURONS AND ACTS AS A

462
00:19:11,479 --> 00:19:11,780
TRANSMITTER.

463
00:19:11,780 --> 00:19:15,750
SO IN ORDER TO TRY TO UNDERSTAND

464
00:19:15,750 --> 00:19:16,985
WHAT THIS MOLECULE MIGHT BE

465
00:19:16,985 --> 00:19:20,221
DOING AND HOW THIS RELATES TO

466
00:19:20,221 --> 00:19:21,422
ITCH, WE OF COURSE -- AND THIS

467
00:19:21,422 --> 00:19:22,624
IS A VERY OLD SLIDE BECAUSE THIS

468
00:19:22,624 --> 00:19:23,992
IS WORK THAT WAS DONE MORE THAN

469
00:19:23,992 --> 00:19:27,128
10 YEARS AGO, WE MADE A

470
00:19:27,128 --> 00:19:27,562
KNOCKOUT.

471
00:19:27,562 --> 00:19:29,097
AGAIN I'M NOT GOING TO GO INTO

472
00:19:29,097 --> 00:19:31,065
ANY DETAIL ABOUT THAT, THIS IS

473
00:19:31,065 --> 00:19:32,267
REALLY OLD TECHNOLOGY.

474
00:19:32,267 --> 00:19:36,204
NOW WE MAKE KNOCKOUTS IN MUCH

475
00:19:36,204 --> 00:19:37,305
MORE SOPHISTICATED WAYS.

476
00:19:37,305 --> 00:19:40,141
WHAT'S IMPORTANT IS, IS WHAT

477
00:19:40,141 --> 00:19:43,745
THAT MOUSE TOLD US ABOUT THIS

478
00:19:43,745 --> 00:19:46,481
PARTICULAR MOLECULE, NPPB.

479
00:19:46,481 --> 00:19:49,551
AND WHAT IT TOLD US IS THAT

480
00:19:49,551 --> 00:19:52,253
COMPARED TO WHEN WE KNOCK IT

481
00:19:52,253 --> 00:19:54,255
OUT, IT DRAMATICALLY AFFECTS

482
00:19:54,255 --> 00:19:54,622
ITCH.

483
00:19:54,622 --> 00:19:56,891
AND SO I'M GOING TO GO THROUGH

484
00:19:56,891 --> 00:19:57,859
QUICKLY HERE THIS EXPERIMENT.

485
00:19:57,859 --> 00:19:59,360
WHAT WE DID IN THIS EXPERIMENT

486
00:19:59,360 --> 00:20:02,330
IS WE INJECTED INTO THE SKIN OF

487
00:20:02,330 --> 00:20:05,400
MICE DIFFERENT COMPOUNDS THAT

488
00:20:05,400 --> 00:20:06,701
CAUSE ITCH IN THOSE ANIMALS.

489
00:20:06,701 --> 00:20:08,036
THIS IS REFLECTED IN THE FACT

490
00:20:08,036 --> 00:20:10,104
THAT THE ANIMALS SCRATCH.

491
00:20:10,104 --> 00:20:13,174
AND AS YOU CAN SEE IN THE GREY

492
00:20:13,174 --> 00:20:15,243
BARS, THIS IS WHAT HAPPENS WHEN

493
00:20:15,243 --> 00:20:16,711
THESE COMPOUNDS ARE INJECTED,

494
00:20:16,711 --> 00:20:18,513
AND THERE'S A DRAMATIC DECREASE

495
00:20:18,513 --> 00:20:21,149
IN THE AMOUNT OF SCRATCHING THE

496
00:20:21,149 --> 00:20:23,651
ANIMALS THAT HAVE A KNOCKOUT OF

497
00:20:23,651 --> 00:20:24,452
NPPB DISPLAY.

498
00:20:24,452 --> 00:20:29,591
BUT IMPORTANTLY, THOSE SAME

499
00:20:29,591 --> 00:20:31,759
KNOCKOUT ANIMALS HAVE ALMOST

500
00:20:31,759 --> 00:20:35,263
NORMAL RESPONSES TO OTHER

501
00:20:35,263 --> 00:20:36,130
SOMATOSENSORY STIMULI.

502
00:20:36,130 --> 00:20:37,498
SO THIS IS A VERY SPECIFIC

503
00:20:37,498 --> 00:20:43,004
EFFECT ON THIS ONE TYPE OF

504
00:20:43,004 --> 00:20:45,073
MODALITY WITHIN SOMATOSENSATION,

505
00:20:45,073 --> 00:20:47,175
IT'S ONLY AFFECTING ITCH.

506
00:20:47,175 --> 00:20:54,415
AND THIS CAN BE NOW AS SHOWN

507
00:20:54,415 --> 00:20:56,684
HERE IN THIS SCHEMATIC, CAN SHOW

508
00:20:56,684 --> 00:21:00,455
YOU EXACTLY WHAT'S HAPPENING

509
00:21:00,455 --> 00:21:01,723
WITH THIS TRANSMITTER.

510
00:21:01,723 --> 00:21:05,460
WHAT'S HAPPENING IS, WHEN THESE

511
00:21:05,460 --> 00:21:08,730
NEURONS, THE PRIMARY ITCH

512
00:21:08,730 --> 00:21:12,233
NEURONS ARE ACTIVATED, THEY

513
00:21:12,233 --> 00:21:16,170
RELEASE THIS NEUROTRANSMITTER

514
00:21:16,170 --> 00:21:21,843
TOGETHER WITH -- THAT HAVE THE

515
00:21:21,843 --> 00:21:26,547
RECEPTOR FOR THIS PARTICULAR

516
00:21:26,547 --> 00:21:26,981
NEUROTRANSMITTER.

517
00:21:26,981 --> 00:21:29,284
AND IN TURN, THESE NEURONS THEN

518
00:21:29,284 --> 00:21:30,818
SIGNAL FURTHER IN THE SPINAL

519
00:21:30,818 --> 00:21:33,655
CORD AND EVENTUALLY SIGNALS GO

520
00:21:33,655 --> 00:21:35,290
ON TO HIGHER CENTERS IN THE

521
00:21:35,290 --> 00:21:37,392
BRAIN.

522
00:21:37,392 --> 00:21:37,825
OKAY.

523
00:21:37,825 --> 00:21:40,328
SO WHAT I'VE BEEN TELLING YOU SO

524
00:21:40,328 --> 00:21:41,663
FAR ARE EXPERIMENTS THAT WE

525
00:21:41,663 --> 00:21:43,631
PERFORMED IN THE LAB QUITE A FEW

526
00:21:43,631 --> 00:21:44,699
YEARS AGO.

527
00:21:44,699 --> 00:21:46,100
THESE ARE ALL EXPERIMENTS THAT

528
00:21:46,100 --> 00:21:48,202
WERE PERFORMED IN MICE.

529
00:21:48,202 --> 00:21:50,571
SO WE WERE VERY KEEN TO SEE

530
00:21:50,571 --> 00:21:52,273
WHETHER OR NOT IN WAS THE CASE

531
00:21:52,273 --> 00:21:55,977
ALSO IN HUMANS, AND SO MORE

532
00:21:55,977 --> 00:21:59,981
RECENTLY, WE EXAMINED THIS IN

533
00:21:59,981 --> 00:22:00,682
TWO DIFFERENT WAYS.

534
00:22:00,682 --> 00:22:04,519
WHAT I'M SHOWING YOU HERE AGAIN

535
00:22:04,519 --> 00:22:06,454
IS IMAGES THROUGH THE DORSAL

536
00:22:06,454 --> 00:22:07,455
ROOT GANGLIA WHICH I TOLD YOU

537
00:22:07,455 --> 00:22:08,756
ABOUT IN THE VERY BEGINNING,

538
00:22:08,756 --> 00:22:13,494
WHICH SHOW THAT NPPB IS

539
00:22:13,494 --> 00:22:16,664
EXPRESSED IN SENSORY NEURONS AND

540
00:22:16,664 --> 00:22:18,166
IS A VERY SPECIFIC CLASS AND IS

541
00:22:18,166 --> 00:22:20,368
EXPRESSED ALONG WITH OTHER

542
00:22:20,368 --> 00:22:22,570
TRANSCRIPTS THAT HAVE IMPORTED

543
00:22:22,570 --> 00:22:24,305
AND DEFINED SPECIFIC POPULATIONS

544
00:22:24,305 --> 00:22:25,673
OF NEURONS.

545
00:22:25,673 --> 00:22:31,512
THIS WE DID IN HUMAN NEURONS AND

546
00:22:31,512 --> 00:22:32,714
THEN OTHER GROUPS, THIS IS

547
00:22:32,714 --> 00:22:34,349
ACTUALLY DATA FROM A GROUP HERE

548
00:22:34,349 --> 00:22:39,620
AT THE NIH, THE RYBA GROUP IN MY

549
00:22:39,620 --> 00:22:41,356
INSTITUTE HAVE PERFORMED SINK EL

550
00:22:41,356 --> 00:22:44,325
CELL SEQUENCING OF HUMAN DRG

551
00:22:44,325 --> 00:22:44,659
NEURONS.

552
00:22:44,659 --> 00:22:46,294
WHAT YOU CAN SEE IS THERE'S

553
00:22:46,294 --> 00:22:48,262
ACTUALLY TWO CLASSES OF SENSORY

554
00:22:48,262 --> 00:22:50,331
NEURONS THAT ARE

555
00:22:50,331 --> 00:22:50,999
TRANSCRIPTIONALLY DISTINCT FROM

556
00:22:50,999 --> 00:22:54,836
EACH OTHER THAT EXPRESS NPPB.

557
00:22:54,836 --> 00:22:58,106
AND IF WE INTERROGATE THAT DATA

558
00:22:58,106 --> 00:23:02,377
EVEN FURTHER AND PERFORM OTHER

559
00:23:02,377 --> 00:23:03,811
LOCALIZATIONS, AGAIN, WHAT I'M

560
00:23:03,811 --> 00:23:06,647
SHOWING YOU HERE IS IN SITU

561
00:23:06,647 --> 00:23:09,917
HYBRIDIZATION DATA, AND BELOW

562
00:23:09,917 --> 00:23:11,319
HERE, THE SINGLE CELL SEQUENCING

563
00:23:11,319 --> 00:23:12,420
INFORMATION AND WHAT I'M SHOWING

564
00:23:12,420 --> 00:23:16,357
YOU HERE IS THAT THESE NEURONS

565
00:23:16,357 --> 00:23:18,993
EXPRESS NOW THE RECEPTORS THAT

566
00:23:18,993 --> 00:23:21,529
WOULD EXPECT FOR H NEURONS.

567
00:23:21,529 --> 00:23:25,433
IN PARTICULAR YOU CAN SEE A

568
00:23:25,433 --> 00:23:26,768
HISTAMINE RECEPTOR, AGAIN IN THE

569
00:23:26,768 --> 00:23:28,069
SINGLE CELL SEQUENCING

570
00:23:28,069 --> 00:23:29,570
INFORMATION, IT'S PRESENT IN

571
00:23:29,570 --> 00:23:33,307
THESE TWO POPULATIONS OF NPPB

572
00:23:33,307 --> 00:23:35,610
NEURONS, AND THEN ALSO ANOTHER

573
00:23:35,610 --> 00:23:38,579
RECEPTOR, THIS RECEPTOR WAS

574
00:23:38,579 --> 00:23:43,651
FIRST IDENTIFIED BY THE GROUP AT

575
00:23:43,651 --> 00:23:48,423
JOHNS HOPKINS, AND HE SHOWED --

576
00:23:48,423 --> 00:23:49,824
I THINK THIS IS PROBABLY THE

577
00:23:49,824 --> 00:23:51,259
REFERENCE THAT WIN TALKED ABOUT

578
00:23:51,259 --> 00:23:53,795
IN 2001, THAT THERE'S THIS LARGE

579
00:23:53,795 --> 00:23:59,200
FAMILY OF G PROTEIN COVERED

580
00:23:59,200 --> 00:24:04,405
REACCRECEPTORS, AND THEY SHOWED

581
00:24:04,405 --> 00:24:05,907
THEY'RE ACTUALLY ITCH RECEPTORS.

582
00:24:05,907 --> 00:24:10,945
SO I WANT TO NOTE FROM XINZHONG

583
00:24:10,945 --> 00:24:15,216
DONG'S GROUP THAT THESE CLASS OF

584
00:24:15,216 --> 00:24:18,820
RECEPTORS THAT ARE ACTIVATED BY

585
00:24:18,820 --> 00:24:26,327
QUITE DISTINCT PRURITOGENS THAT

586
00:24:26,327 --> 00:24:27,128
ARE ACTUALLY RELEASED PROBABLY

587
00:24:27,128 --> 00:24:28,663
WITHIN THE SKIN WHEN THE SKIN IS

588
00:24:28,663 --> 00:24:30,298
DAMAGED, IN MOUSE, AT LEAST,

589
00:24:30,298 --> 00:24:31,365
THIS IS A SEPARATE POPULATION

590
00:24:31,365 --> 00:24:34,035
FROM THE NEURONS THAT EXPRESS

591
00:24:34,035 --> 00:24:35,870
NPPB, AND THINGS ARE ACTUALLY A

592
00:24:35,870 --> 00:24:37,305
LITTLE BIT DIFFERENT BETWEEN THE

593
00:24:37,305 --> 00:24:44,312
MOUSE AND THE HUMAN IN THAT THE

594
00:24:44,312 --> 00:24:45,780
RECEPTORS ARE -- THE RECEPTOR

595
00:24:45,780 --> 00:24:50,318
FAMILY IS MUCH SMALLER AND THE

596
00:24:50,318 --> 00:24:52,954
RECEPTORS ARE FOUND IN BOTH

597
00:24:52,954 --> 00:24:54,489
POPULATIONS OF THE HUMAN ITCH

598
00:24:54,489 --> 00:24:56,991
NEURONS.

599
00:24:56,991 --> 00:24:58,192
OKAY.

600
00:24:58,192 --> 00:25:02,897
SO LE LET'S GO BACK TO THIS MAPF

601
00:25:02,897 --> 00:25:07,268
THE PATHWAY FOR ITCH.

602
00:25:07,268 --> 00:25:11,005
WHAT YOU'LL SEE HERE IS I'VE

603
00:25:11,005 --> 00:25:13,608
ADDED AN EXTRA DIMENSION OVER

604
00:25:13,608 --> 00:25:15,143
HERE, WHAT ARE THE AGENTS THAT

605
00:25:15,143 --> 00:25:17,111
ARE RELEASED POTENTIALLY IN THE

606
00:25:17,111 --> 00:25:21,516
SKIN THAT ACTIVATE THE NEURONS?

607
00:25:21,516 --> 00:25:26,087
SO WHAT ARE THE NPPB NEURONS

608
00:25:26,087 --> 00:25:27,622
DETECTORS FOR?

609
00:25:27,622 --> 00:25:33,094
AND SO IN ORDER TO DO THIS, MY

610
00:25:33,094 --> 00:25:34,495
GROUP HAS USED A VARIETY OF

611
00:25:34,495 --> 00:25:36,597
DIFFERENT METHODS TO TRY TO

612
00:25:36,597 --> 00:25:37,465
IDENTIFY RECEPTORS THAT ARE

613
00:25:37,465 --> 00:25:39,567
SPECIFIC TO THE NPPB NEURONS

614
00:25:39,567 --> 00:25:40,968
THAT MIGHT BE INVOLVED IN ITCH.

615
00:25:40,968 --> 00:25:43,771
AND WHAT WE IDENTIFIED WAS THREE

616
00:25:43,771 --> 00:25:45,339
DIFFERENT RECEPTORS.

617
00:25:45,339 --> 00:25:49,143
NAMES ARE NOT IMPORTANT AGAIN.

618
00:25:49,143 --> 00:25:51,012
HERE ARE THE THREE NAMES OF THE

619
00:25:51,012 --> 00:25:51,612
RECEPTORS.

620
00:25:51,612 --> 00:25:53,548
BUT WHAT I CAN TELL YOU IS THAT

621
00:25:53,548 --> 00:25:56,050
THIS RECEPTOR AND THIS RECEPTOR

622
00:25:56,050 --> 00:25:58,586
ARE RECEPTORS FOR SMALL LIPIDS,

623
00:25:58,586 --> 00:26:00,555
AND THIS IS THE RECEPTOR FOR

624
00:26:00,555 --> 00:26:02,690
SEROTONIN.

625
00:26:02,690 --> 00:26:04,258
IT'S A SPECIFIC SEROTONIN

626
00:26:04,258 --> 00:26:04,759
RECEPTOR.

627
00:26:04,759 --> 00:26:09,297
AND IN ORDER TO ACTUALLY

628
00:26:09,297 --> 00:26:10,298
DETERMINE WHETHER OR NOT THESE

629
00:26:10,298 --> 00:26:13,234
RECEPTORS AND THE AGONISTS THAT

630
00:26:13,234 --> 00:26:15,736
ACTIVATE THOSE RECEPTORS ARE

631
00:26:15,736 --> 00:26:18,706
ACTUALLY PRURITOGENS, WE MADE

632
00:26:18,706 --> 00:26:20,908
USE OF THIS BEHAVIORAL ASSAY IN

633
00:26:20,908 --> 00:26:22,076
MOUSE SO I'M GOING TO GO THROUGH

634
00:26:22,076 --> 00:26:23,177
THAT VERY QUICKLY.

635
00:26:23,177 --> 00:26:25,379
WHAT THIS ASSAY INVOLVES IS

636
00:26:25,379 --> 00:26:26,681
INJECTING DIFFERENT AGENTS INTO

637
00:26:26,681 --> 00:26:30,084
THE CHEEK OF MICE, AND WHEN

638
00:26:30,084 --> 00:26:32,253
SOMETHING THAT'S PAINFUL TO

639
00:26:32,253 --> 00:26:33,454
INJECT IT INTO THE CHEEK OF THE

640
00:26:33,454 --> 00:26:35,122
MICE, THEY HAVE THIS REACTION AS

641
00:26:35,122 --> 00:26:37,525
SHOWN HERE IN A AND B.

642
00:26:37,525 --> 00:26:45,066
THEY WIPE THEIR FACES.

643
00:26:45,066 --> 00:26:47,034
IN CONTRAST, IF AN AGENT THAT IS

644
00:26:47,034 --> 00:26:48,436
ITCHY IS INJECTED INTO THE

645
00:26:48,436 --> 00:26:49,203
CHEEK, THEY SCRATCH.

646
00:26:49,203 --> 00:26:53,040
AND SO WE TESTED THE LIGANDS FOR

647
00:26:53,040 --> 00:26:54,041
THESE THREE RECEPTORS IN THIS

648
00:26:54,041 --> 00:26:55,109
ASSAY.

649
00:26:55,109 --> 00:26:59,814
AND WHAT YOU'LL SEE IS THAT

650
00:26:59,814 --> 00:27:02,016
THESE THREE AGENTS DO NOT CAUSE

651
00:27:02,016 --> 00:27:02,350
WIPING.

652
00:27:02,350 --> 00:27:04,218
WHAT THEY DO IS THEY CAUSE

653
00:27:04,218 --> 00:27:07,989
SCRATCHING.

654
00:27:07,989 --> 00:27:08,356
OKAY.

655
00:27:08,356 --> 00:27:11,525
SO THIS IS ONE OF THE PIECES OF

656
00:27:11,525 --> 00:27:13,394
EVIDENCE THAT WE HAD TO SHOW

657
00:27:13,394 --> 00:27:17,665
THAT THE NPPB NEURONS ARE ITCH

658
00:27:17,665 --> 00:27:19,166
NEURONS, AND THAT THEY HAVE AS

659
00:27:19,166 --> 00:27:21,168
THIS SLIDE SUMMARIZES HAVE

660
00:27:21,168 --> 00:27:22,637
SELECT RECEPTORS.

661
00:27:22,637 --> 00:27:25,973
AND IT'S THE FACT THAT THERE'S

662
00:27:25,973 --> 00:27:27,375
INCREASED LEVELS OF THESE

663
00:27:27,375 --> 00:27:29,043
AGONISTS THAT LEADS TO THE

664
00:27:29,043 --> 00:27:31,312
SCRATCHING RESPONSE.

665
00:27:31,312 --> 00:27:33,180
AND IT'S NOT BY ACCIDENT THAT,

666
00:27:33,180 --> 00:27:37,118
IN FACT, THESE THREE COMPOUNDS

667
00:27:37,118 --> 00:27:38,753
ARE RULE TEULLY RELEASED FROM

668
00:27:38,753 --> 00:27:39,954
MAST CELLS.

669
00:27:39,954 --> 00:27:41,289
SO WHEN MAST CELLS ARE

670
00:27:41,289 --> 00:27:47,495
ACTIVATED, FOR INSTANCE, MANY

671
00:27:47,495 --> 00:27:52,233
DIFFERENT INSECTS, WHAT THEY

672
00:27:52,233 --> 00:27:54,935
INJECT INTO WILL CAUSE A

673
00:27:54,935 --> 00:28:01,509
DEGRAITDEGRADATION OF MAST CELLD

674
00:28:01,509 --> 00:28:02,710
THEY THEN RELEASE AND ACTIVATE

675
00:28:02,710 --> 00:28:04,011
SENSORY NEURONS AND IN TURN THIS

676
00:28:04,011 --> 00:28:05,346
CAUSES AN ITCH PATHWAY.

677
00:28:05,346 --> 00:28:07,415
SO THIS IS THE END OF THE PART

678
00:28:07,415 --> 00:28:11,752
OF MY TALK ABOUT ACUTE ITCH.

679
00:28:11,752 --> 00:28:13,220
I WANT TO NOW MOVE ON TO CHRONIC

680
00:28:13,220 --> 00:28:16,924
ITCH.

681
00:28:16,924 --> 00:28:22,730
ONE OF THE BIG CENTRAL CORE --

682
00:28:22,730 --> 00:28:24,899
OF CHRONIC ITCH IS WHAT'S CALLED

683
00:28:24,899 --> 00:28:27,802
THE ITCH-SCRATCH CYCLE.

684
00:28:27,802 --> 00:28:29,837
SO THE ITCH-SCRATCH CYCLE IS

685
00:28:29,837 --> 00:28:34,008
DEPICTED HERE IN THIS DIAGRAM

686
00:28:34,008 --> 00:28:38,045
THAT WHEN YOU FEEL VERY ITCHY,

687
00:28:38,045 --> 00:28:39,013
THIS LEADS TO YOU WANTING TO

688
00:28:39,013 --> 00:28:40,247
SCRATCH AND SCRATCHING.

689
00:28:40,247 --> 00:28:43,417
AND IN TURN, SCRATCHING CAUSES

690
00:28:43,417 --> 00:28:46,253
DISRUPTION OF THE SKIN.

691
00:28:46,253 --> 00:28:48,322
THE NOW DISTURBED, BROKEN SKIN,

692
00:28:48,322 --> 00:28:50,191
ALLOWS PENETRATION OF VARIOUS

693
00:28:50,191 --> 00:28:53,994
ALLERGENS AND IRRITANTS.

694
00:28:53,994 --> 00:28:55,896
THIS IN TURN CAUSES INPLA NATION

695
00:28:55,896 --> 00:29:00,134
INFLAMMATIONAND RECRUITMENT OF S

696
00:29:00,134 --> 00:29:02,870
TO THE SITE, AND IN FACT, THIS

697
00:29:02,870 --> 00:29:03,704
INFLAMMATION, THE IMMUNE CELLS

698
00:29:03,704 --> 00:29:04,739
AND THE COMPOUNDS THAT ARE

699
00:29:04,739 --> 00:29:07,441
RELEASED FROM THEM, CAUSES MORE

700
00:29:07,441 --> 00:29:11,379
ITCHING.

701
00:29:11,379 --> 00:29:13,581
WE ALL KNOW IF WE CAN STOP THAT

702
00:29:13,581 --> 00:29:14,682
SCRATCHING, VERY OFTEN, THE ITCH

703
00:29:14,682 --> 00:29:17,051
WILL GO AWAY, AND THE REASON FOR

704
00:29:17,051 --> 00:29:22,590
THIS IS THIS CYCLE.

705
00:29:22,590 --> 00:29:24,492
BUT IF YOU WERE TO TELL A

706
00:29:24,492 --> 00:29:25,393
PATIENT WHO HAS CHRONIC ITCH,

707
00:29:25,393 --> 00:29:27,261
OH, YOU SIMPLY NEED TO STOP

708
00:29:27,261 --> 00:29:29,096
SCRATCHING, THEY WILL PROBABLY

709
00:29:29,096 --> 00:29:33,167
GET PRETTY ANGRY WITH YOU,

710
00:29:33,167 --> 00:29:34,468
BECAUSE CHRONIC ITCH IS

711
00:29:34,468 --> 00:29:36,437
SOMETHING THAT YOU REALLY CAN'T

712
00:29:36,437 --> 00:29:40,274
STOP YOURSELF FROM SCRATCHING.

713
00:29:40,274 --> 00:29:41,475
SO BECAUSE OF THAT, WE NOW ARE

714
00:29:41,475 --> 00:29:46,280
STARTING TO HAVE SOME

715
00:29:46,280 --> 00:29:46,881
TREATMENTS.

716
00:29:46,881 --> 00:29:47,815
SO SOME OF THE TREATMENTS MIGHT

717
00:29:47,815 --> 00:29:52,286
BE TRYING TO REDUCE INFLAMMATION

718
00:29:52,286 --> 00:29:54,922
AND ONE OF THE VERY OLD

719
00:29:54,922 --> 00:29:58,159
TREATMENTS IS VARIOUS CORTISONES

720
00:29:58,159 --> 00:30:00,828
TO ACTUALLY TRY TO REDUCE THE

721
00:30:00,828 --> 00:30:04,732
INFLAMMATION, AND OFTEN THAT THE

722
00:30:04,732 --> 00:30:06,033
REASONABLY EFFECTIVE.

723
00:30:06,033 --> 00:30:08,235
BUT IF THEY COULD BE COMBINED

724
00:30:08,235 --> 00:30:10,171
WITH ACTUALLY STOPPING TWO PARTS

725
00:30:10,171 --> 00:30:16,243
OF THIS PATHWAY, AS INDICATED

726
00:30:16,243 --> 00:30:17,411
HERE, THEN THE NET EFFECT MIGHT

727
00:30:17,411 --> 00:30:18,045
BE EVEN GREATER.

728
00:30:18,045 --> 00:30:19,246
SO IF WE CAN ACTUALLY, FOR

729
00:30:19,246 --> 00:30:23,517
INSTANCE, STOP THIS -- WHAT'S

730
00:30:23,517 --> 00:30:24,885
RELEASED FROM THE IMMUNE CELLS

731
00:30:24,885 --> 00:30:26,454
FROM ACTIVATING THE NERVES THAT

732
00:30:26,454 --> 00:30:27,588
I TALKED ABOUT IN THE FIRST PART

733
00:30:27,588 --> 00:30:31,292
OF MY TALK, THEN PERHAPS YOU CAN

734
00:30:31,292 --> 00:30:33,427
ACTUALLY GET A BETTER CESSATION

735
00:30:33,427 --> 00:30:36,530
OF THIS ITCH-SCRATCH CYCLE.

736
00:30:36,530 --> 00:30:39,500
AND THE FIRST INDICATION OF WHAT

737
00:30:39,500 --> 00:30:43,704
MIGHT BE HAPPENING IN CHRONIC

738
00:30:43,704 --> 00:30:45,005
ITCH CAME FROM A NUMBER OF

739
00:30:45,005 --> 00:30:47,308
DIFFERENT GROUPS, NOT MY GROUP.

740
00:30:47,308 --> 00:30:52,346
THE FIRST IS A GROUP, MARTIN

741
00:30:52,346 --> 00:30:53,647
STEINHOF, THE SECOND, BRIAN KIM,

742
00:30:53,647 --> 00:30:54,949
WHERE THEY IDENTIFIED THAT, IN

743
00:30:54,949 --> 00:30:56,584
FACT, THE SENSORY NEURONS

744
00:30:56,584 --> 00:30:58,452
EXPRESS A DIFFERENT CLASS OF

745
00:30:58,452 --> 00:30:58,786
RECEPTOR.

746
00:30:58,786 --> 00:31:02,823
THESE ARE CYTOKINE RECEPTOR.

747
00:31:02,823 --> 00:31:05,226
SO ONE OF THE RECEPTORS IS A

748
00:31:05,226 --> 00:31:07,094
RECEPTOR FOR INTERLEUKIN 31, AND

749
00:31:07,094 --> 00:31:09,497
IN THIS PAPER, IT WAS SHOWN THAT

750
00:31:09,497 --> 00:31:10,598
INTERLEUKIN 4 RECEPTOR WAS

751
00:31:10,598 --> 00:31:13,534
IMPORTANT.

752
00:31:13,534 --> 00:31:16,170
THE FEATURE OF THE CYTOKINE

753
00:31:16,170 --> 00:31:17,705
RECEPTORS IS THEY WORK IN QUITE

754
00:31:17,705 --> 00:31:20,207
A DIFFERENT WAY FROM THE

755
00:31:20,207 --> 00:31:26,780
RECEPTORRINGS RECEPTORS I TALKEE

756
00:31:26,780 --> 00:31:28,215
ACUTE PART OF MY TALK.

757
00:31:28,215 --> 00:31:30,384
THOSE RECEPTORS CLASSICALLY LEAD

758
00:31:30,384 --> 00:31:33,454
TO INCREASE IN CALCIUM AND THEN

759
00:31:33,454 --> 00:31:35,322
DIRECT ACTION POTENTIAL FIRING.

760
00:31:35,322 --> 00:31:39,260
THESE RECEPTORS IS KNOWN TO

761
00:31:39,260 --> 00:31:43,297
OPERATE IN A VERY DIFFERENT WAY.

762
00:31:43,297 --> 00:31:43,964
CLASSICALLY, THEY WERE

763
00:31:43,964 --> 00:31:45,699
IDENTIFIED IN IMMUNE CELLS AND

764
00:31:45,699 --> 00:31:50,304
NOT IN NEURONS.

765
00:31:50,304 --> 00:31:53,240
AND THESE DISCOVERIES WERE SORT

766
00:31:53,240 --> 00:31:54,341
OF GROUNDBREAKING BECAUSE THEY

767
00:31:54,341 --> 00:31:58,178
ACTUALLY START TO EXPLAIN WHY A

768
00:31:58,178 --> 00:32:00,147
NUMBER OF BIOLOGICS WHICH ARE

769
00:32:00,147 --> 00:32:07,354
NOW VERY, VERY HOT AND BEING

770
00:32:07,354 --> 00:32:09,456
USED IN SEVERE SKIN CONDITIONS

771
00:32:09,456 --> 00:32:10,958
CAUSING CHRONIC ITCH.

772
00:32:10,958 --> 00:32:17,631
SO FIRST OF ALL, I WANT TO --

773
00:32:17,631 --> 00:32:25,172
AGAINST INTERLEUKIN 31,

774
00:32:25,172 --> 00:32:25,673
INTERLEUKIN 4 RECEPTOR.

775
00:32:25,673 --> 00:32:27,341
SO BOTH OF THOSE HAVE BEEN SHOWN

776
00:32:27,341 --> 00:32:29,009
TO BE CLINICALLY EXTREMELY

777
00:32:29,009 --> 00:32:30,210
EFFECTIVE TO REDUCING CHRONIC

778
00:32:30,210 --> 00:32:33,514
ITCH.

779
00:32:33,514 --> 00:32:37,117
SO OUR QUELL QUESTION A NUMBER F

780
00:32:37,117 --> 00:32:38,652
YEARS AGO WAS ARE THERE ANY

781
00:32:38,652 --> 00:32:40,187
OTHER CYTOKINE RECEPTORS BEYOND

782
00:32:40,187 --> 00:32:43,991
THE INTERLEUKIN 31 AND

783
00:32:43,991 --> 00:32:46,760
INTERLEUKIN 4 RECEPTORS.

784
00:32:46,760 --> 00:32:48,629
AND INDEED, THERE IS.

785
00:32:48,629 --> 00:32:50,364
AND THE RECEPTOR THAT WE

786
00:32:50,364 --> 00:32:51,999
IDENTIFIED IS SHOWN ON THIS NEXT

787
00:32:51,999 --> 00:32:52,433
SLIDE.

788
00:32:52,433 --> 00:32:56,604
THIS IS THE INTERLEUKIN -- THIS

789
00:32:56,604 --> 00:32:59,340
IS THE ONCOSTATIN M RECEPTOR,

790
00:32:59,340 --> 00:33:00,975
AND WHAT I'M SHOWING YOU HERE

791
00:33:00,975 --> 00:33:03,544
AGAIN IS IN SITU HYBRIDIZATION,

792
00:33:03,544 --> 00:33:07,014
AND BY NOW YOU S YOU SHOULD KNOT

793
00:33:07,014 --> 00:33:07,414
I'M SHOWING.

794
00:33:07,414 --> 00:33:10,150
THIS IS ONE OF THE RECEPTORS

795
00:33:10,150 --> 00:33:12,019
AGAINST NPPB, THE MOLECULE I

796
00:33:12,019 --> 00:33:12,753
TALKED ABOUT IN THE FIRST PART

797
00:33:12,753 --> 00:33:18,592
OF MY TALK, AND IF WE THEN LOOK

798
00:33:18,592 --> 00:33:22,730
AT WHAT'S PRESENT IN THE HUMAN,

799
00:33:22,730 --> 00:33:27,334
AGAIN, THE ONCOSTATIN M RECEPTOR

800
00:33:27,334 --> 00:33:30,170
IS FOUND IN HUMAN AND THE NPPB

801
00:33:30,170 --> 00:33:32,373
NEURONS AND THIS IS CONFIRMED BY

802
00:33:32,373 --> 00:33:33,240
SINGLE CELL SEQUENCING.

803
00:33:33,240 --> 00:33:36,944
SO THIS IS ANOTHER CYTOKINE

804
00:33:36,944 --> 00:33:37,845
RECEPTOR, DOESN'T MEAN IT'S

805
00:33:37,845 --> 00:33:38,479
INVOLVED IN ITCH.

806
00:33:38,479 --> 00:33:40,948
SO THE FIRST THING WE TURNED TO

807
00:33:40,948 --> 00:33:43,951
WAS TO ACTUALLY SEE IS

808
00:33:43,951 --> 00:33:46,020
ONCOSTATIN M, ARE ONCOSTATIN M

809
00:33:46,020 --> 00:33:48,122
LEVELS INCREASED IN CONDITIONS

810
00:33:48,122 --> 00:33:51,725
OF CHRONIC ITCH?

811
00:33:51,725 --> 00:33:53,360
SO WE TURNED TO SEQUENCING

812
00:33:53,360 --> 00:33:59,066
INFORMATION THAT'S FROM -- THAT

813
00:33:59,066 --> 00:34:00,701
ARE PUBLICLY AVAILABLE, AND AS

814
00:34:00,701 --> 00:34:02,770
YOU CAN SEE HERE IN PATIENTS

815
00:34:02,770 --> 00:34:04,605
WITH PSORIASIS, WHEN THEIR SKIN

816
00:34:04,605 --> 00:34:06,373
HAS BEEN SEQUENCED, THEY HAVE

817
00:34:06,373 --> 00:34:10,310
ELEVATED LEVELS OF ONCOSTATIN M.

818
00:34:10,310 --> 00:34:11,645
COMPARED TO NORMALS, SHOWN HERE

819
00:34:11,645 --> 00:34:15,482
IN BLACK.

820
00:34:15,482 --> 00:34:18,519
THIS IS ALSO THE CASE FOR OTHER

821
00:34:18,519 --> 00:34:21,255
SKIN CONDITIONS, FOR INSTANCE,

822
00:34:21,255 --> 00:34:22,589
ATOPIC DERMATITIS, ALSO ANOTHER

823
00:34:22,589 --> 00:34:24,858
CONDITION WHICH IS MUCH RARER,

824
00:34:24,858 --> 00:34:27,828
CUTANEOUS T-CELL LYMPHOMA.

825
00:34:27,828 --> 00:34:32,533
YOU CAN ALSO SEE THAT LEVELS OF

826
00:34:32,533 --> 00:34:34,601
IL4 AND 13 ARE ALSO ELEVATED IN

827
00:34:34,601 --> 00:34:38,305
ATOPIC DERMATITIS AND CTCL.

828
00:34:38,305 --> 00:34:41,909
BUT NOT IN PSORIASIS.

829
00:34:41,909 --> 00:34:44,645
AND IMPORTANTLY, FOR US, BECAUSE

830
00:34:44,645 --> 00:34:46,413
WE ARE A BASIC RESEARCH LAB, WE

831
00:34:46,413 --> 00:34:49,149
WANTED TO SEE WHETHER OR NOT THE

832
00:34:49,149 --> 00:34:51,218
MODELS THAT ARE COMMONLY USED

833
00:34:51,218 --> 00:34:53,420
FOR PSORIASIS AND ATOPIC

834
00:34:53,420 --> 00:34:56,156
DERMATITIS ALSO HAVE ELEVATED

835
00:34:56,156 --> 00:34:59,326
LEVELS OF ONCOSTATIN M, AND

836
00:34:59,326 --> 00:35:00,294
INDEED THAT'S THE CASE THAT YOU

837
00:35:00,294 --> 00:35:02,796
CAN SEE HERE IN THIS BOX,

838
00:35:02,796 --> 00:35:04,231
THERE'S ELEVATED ONCOSTATIN M IN

839
00:35:04,231 --> 00:35:09,570
A MODEL OF PSORIASIS, AND ALSO

840
00:35:09,570 --> 00:35:12,005
IN THE MODEL OF ATOPIC

841
00:35:12,005 --> 00:35:13,340
DERMATITIS.

842
00:35:13,340 --> 00:35:15,909
SO THESE ARE ALL INSILICO

843
00:35:15,909 --> 00:35:16,443
RESULTS.

844
00:35:16,443 --> 00:35:20,781
WE ALWAYS LIKE TO LOOK DIRECTLY

845
00:35:20,781 --> 00:35:23,751
IF THESE ARE SUPPORTED IN TISSUE

846
00:35:23,751 --> 00:35:27,454
SO WE TOOK TISSUE FROM THESE

847
00:35:27,454 --> 00:35:29,523
ANIMALS THAT HAVE A MODEL OF

848
00:35:29,523 --> 00:35:31,158
PSORIASIS, AND WE LOOKED AT --

849
00:35:31,158 --> 00:35:35,529
AGAIN, THIS IS IN SITU

850
00:35:35,529 --> 00:35:38,065
HYBRIDIZATION, THE ONCOSTATIN M

851
00:35:38,065 --> 00:35:38,499
IN THE TISSUE.

852
00:35:38,499 --> 00:35:39,767
YOU CAN SEE HERE THIS IS SKIN

853
00:35:39,767 --> 00:35:42,102
FROM THE EAR OF A MOUSE, AND

854
00:35:42,102 --> 00:35:44,271
THERE'S VERY LITTLE OF

855
00:35:44,271 --> 00:35:45,372
ONCOSTATIN M.

856
00:35:45,372 --> 00:35:48,108
THIS IS VERY MUCH INCREASED IN

857
00:35:48,108 --> 00:35:49,543
THIS MODEL, IN THIS MOUSE MODEL

858
00:35:49,543 --> 00:35:53,380
OF PSORIASIS.

859
00:35:53,380 --> 00:35:58,152
SO WE WANT TO, AGAIN, CHECK THIS

860
00:35:58,152 --> 00:35:59,386
IN THE HUMAN TISSUE, AND IN

861
00:35:59,386 --> 00:36:01,221
PARTICULAR, TO TRY TO UNDERSTAND

862
00:36:01,221 --> 00:36:03,657
WHAT ARE THE CELLS HERE IN THE

863
00:36:03,657 --> 00:36:07,694
SKIN THAT ARE ACTUALLY RELEASING

864
00:36:07,694 --> 00:36:08,796
THE ONCOSTATIN M.

865
00:36:08,796 --> 00:36:11,298
THE ANSWER IS SHOWN HERE.

866
00:36:11,298 --> 00:36:13,500
WHEN WE LOOK AT THE LEVEL OF

867
00:36:13,500 --> 00:36:16,570
ONCOSTATIN M, AND THIS IS NOW A

868
00:36:16,570 --> 00:36:18,639
PLOT OF THE DIFFERENT CELLS THAT

869
00:36:18,639 --> 00:36:22,142
ARE EXPRESSING ONCOSTATIN M, SO

870
00:36:22,142 --> 00:36:27,481
THE KERATINOCYTES, ENDOTHELIAL

871
00:36:27,481 --> 00:36:32,619
CELLS AND FIBROBLASTS DON'T

872
00:36:32,619 --> 00:36:36,256
EXPRESS ONCOSTATIN M, WHAT

873
00:36:36,256 --> 00:36:37,791
EXPRESSES -- THIS IS

874
00:36:37,791 --> 00:36:39,626
DRAMATICALLY INCREASED IN

875
00:36:39,626 --> 00:36:41,161
CUTANEOUS T-CELL LYMPHOMA, SO

876
00:36:41,161 --> 00:36:45,098
THIS IS ONE OF THE MOST PRURITIC

877
00:36:45,098 --> 00:36:46,533
CONDITIONS THAT IS KNOWN.

878
00:36:46,533 --> 00:36:49,036
AND YOU CAN SEE THAT THE

879
00:36:49,036 --> 00:36:51,939
ONCOSTATIN M IS EXPRESSED IN THE

880
00:36:51,939 --> 00:36:54,174
T CELLS, AND THIS IS ALSO THE

881
00:36:54,174 --> 00:36:57,144
CASE IN PSORIASIS, WHERE, IN

882
00:36:57,144 --> 00:37:01,849
FACT, THERE'S THIS ELEVATED

883
00:37:01,849 --> 00:37:03,050
ONCOSTATIN M IN BOTH THE T CELLS

884
00:37:03,050 --> 00:37:05,018
AND THE MACROPHAGES.

885
00:37:05,018 --> 00:37:05,886
OKAY.

886
00:37:05,886 --> 00:37:10,924
SO THIS IS ALL DESCRIPTIVE, IT'S

887
00:37:10,924 --> 00:37:12,226
TELLING US THAT THERE'S HIGH

888
00:37:12,226 --> 00:37:14,862
LEVELS OF ONCOSTATIN M IN THE

889
00:37:14,862 --> 00:37:16,496
SKIN FOR PATIENTS THAT HAVE

890
00:37:16,496 --> 00:37:20,100
THESE CHRONIC ITCH SKIN

891
00:37:20,100 --> 00:37:20,434
CONDITIONS.

892
00:37:20,434 --> 00:37:23,370
WE KNOW THE RECEPTORS ARE IN THE

893
00:37:23,370 --> 00:37:25,772
APPROPRIATE CELLS.

894
00:37:25,772 --> 00:37:30,143
SO WHAT MIGHT BE THE MECHANISMS

895
00:37:30,143 --> 00:37:33,113
BY WHICH ONCOSTATIN M MIGHT BE

896
00:37:33,113 --> 00:37:34,414
DOING SOMETHING IN THOSE

897
00:37:34,414 --> 00:37:37,150
NEURONS?

898
00:37:37,150 --> 00:37:41,655
SO THE TWO MECHANISMS THAT WE

899
00:37:41,655 --> 00:37:43,156
IDENTIFIED ARE THAT FIRST OF ALL

900
00:37:43,156 --> 00:37:45,792
IN AN ACUTE SETTING, THEY CAN

901
00:37:45,792 --> 00:37:47,561
POTENTIATE THE EFFECTS OF ITCH

902
00:37:47,561 --> 00:37:48,528
INDUCING AGENTS.

903
00:37:48,528 --> 00:37:51,164
SO IN OTHER WORDS, THEY ADD AN

904
00:37:51,164 --> 00:37:53,667
EXTRA BOOST TO THE EFFECTS OF

905
00:37:53,667 --> 00:37:56,403
THINGS LIKE SEROTONIN OR THOSE

906
00:37:56,403 --> 00:37:58,171
SMALL LIPIDS.

907
00:37:58,171 --> 00:38:01,875
AND THEN THE MORE INTERESTING

908
00:38:01,875 --> 00:38:04,077
EFFECT OF ONCOSTATIN M AND ALSO

909
00:38:04,077 --> 00:38:08,882
THE OTHER CYTOKINES WE ALSO

910
00:38:08,882 --> 00:38:10,884
STUDIED IS THAT THEY HAVE VERY

911
00:38:10,884 --> 00:38:12,519
MUCH LONG-TERM EFFECTS ON THE

912
00:38:12,519 --> 00:38:13,387
EXCITABILITY OF NEURONS.

913
00:38:13,387 --> 00:38:14,821
I WANT TO GO INTO SOME

914
00:38:14,821 --> 00:38:17,224
EXPERIMENTS WHERE WE ACTUALLY

915
00:38:17,224 --> 00:38:18,191
SHOW THIS.

916
00:38:18,191 --> 00:38:20,160
THE FIRST -- SO THEY BOTH MAKE

917
00:38:20,160 --> 00:38:22,029
USE OF ELECTROPHYSIOLOGY.

918
00:38:22,029 --> 00:38:23,330
SO FIRST OF ALL, I WANT TO SHOW

919
00:38:23,330 --> 00:38:24,865
YOU A PICTURE OF THESE NEURONS.

920
00:38:24,865 --> 00:38:26,600
THESE ARE THE NEURONS SHOWN HERE

921
00:38:26,600 --> 00:38:29,036
WITH THE FLUORESCENT MARKER, AND

922
00:38:29,036 --> 00:38:33,740
IN HERE IN THIS GHOST IS

923
00:38:33,740 --> 00:38:37,678
ACTUALLY AN ELECTRODE THAT'S

924
00:38:37,678 --> 00:38:40,380
BE -- WE CAN RECORD THE CURRENTS

925
00:38:40,380 --> 00:38:42,482
THAT ARE GOING INTO THAT NEURON.

926
00:38:42,482 --> 00:38:43,583
THE CURRENTS I WANT TO REMIND

927
00:38:43,583 --> 00:38:45,018
YOU ARE THE WAY IN WHICH NEURONS

928
00:38:45,018 --> 00:38:45,552
TALK.

929
00:38:45,552 --> 00:38:48,922
SO WHEN THERE'S AN INCREASED

930
00:38:48,922 --> 00:38:51,325
CURRENT, OR AN ACTION POTENTIAL

931
00:38:51,325 --> 00:38:52,526
FIRING, THIS IS THE WAY THAT

932
00:38:52,526 --> 00:38:55,062
NEURONS TALK AND RELEASE

933
00:38:55,062 --> 00:39:00,734
TRANSMITTERS DOWNSTREAM.

934
00:39:00,734 --> 00:39:03,603
SO WHAT HAPPENS WHEN WE RECORD

935
00:39:03,603 --> 00:39:07,975
FROM THESE NEURONS?

936
00:39:07,975 --> 00:39:11,144
SO IF WE GIVE A PREU RIT GENERAL

937
00:39:11,144 --> 00:39:15,449
LIKE HIS TA  HISTAMINE TO THESE,

938
00:39:15,449 --> 00:39:17,150
THEY HAVE A SMALL CURRENT.

939
00:39:17,150 --> 00:39:18,885
WHAT'S IMPORTANT IS, THOUGH, IF

940
00:39:18,885 --> 00:39:20,988
AFTER GIVING ONCOSTATIN M YOU

941
00:39:20,988 --> 00:39:27,494
GIVE THE STATE Y SAME STIMULUS,T

942
00:39:27,494 --> 00:39:28,795
CURRENT IS A LOT LARGER.

943
00:39:28,795 --> 00:39:30,497
AND FOR COMPARISON, THIS IS THE

944
00:39:30,497 --> 00:39:34,001
EFFECT IF YOU WERE TO GIVE TWO

945
00:39:34,001 --> 00:39:44,344
BOUTS OF HISTAMINE.

946
00:39:44,711 --> 00:39:47,848
THERE'S ACTUALLY REVERSAL OF THE

947
00:39:47,848 --> 00:39:48,682
DESENSITIZATION THAT OCCURS.

948
00:39:48,682 --> 00:39:50,117
SO AGAIN I WANT TO SHOW YOU DATA

949
00:39:50,117 --> 00:39:51,418
FROM WHAT HAPPENS ACTUALLY IN A

950
00:39:51,418 --> 00:39:57,491
MOUSE.

951
00:39:57,491 --> 00:39:59,559
AND IF YOU INJECT ONCOSTATIN M

952
00:39:59,559 --> 00:40:03,964
INTO A MOUSE ON ITS OWN, THE

953
00:40:03,964 --> 00:40:05,499
ANIMAL SCRATCHES BUT NOT A LOT

954
00:40:05,499 --> 00:40:09,436
MORE THAN IF YOU WERE TO INJECT

955
00:40:09,436 --> 00:40:14,808
SASALINE CONTROL.

956
00:40:14,808 --> 00:40:17,411
HOWEVER, IF YOU GO ONCOSTATIN M

957
00:40:17,411 --> 00:40:21,348
WITH A PRURITOGEN, THERE IS THIS

958
00:40:21,348 --> 00:40:22,649
BOOSTING OF THE EFFECTS OF

959
00:40:22,649 --> 00:40:23,750
HISTAMINE, AS I SAID.

960
00:40:23,750 --> 00:40:25,952
THIS IS A POTENTIATION THAT'S

961
00:40:25,952 --> 00:40:27,254
DERIVED FROM THE ONCOSTATIN M.

962
00:40:27,254 --> 00:40:31,958
SO I WANT TO GO ON TO THE SECOND

963
00:40:31,958 --> 00:40:33,960
EFFECT OF ONCOSTATIN M, AND TO

964
00:40:33,960 --> 00:40:40,367
DO THIS, I WANT TO TO A

965
00:40:40,367 --> 00:40:43,303
DIFFERENT TYPE OF

966
00:40:43,303 --> 00:40:43,970
ELECTROPHYSIOLOGY MEASUREMENT.

967
00:40:43,970 --> 00:40:45,038
WHAT WE'RE DOING IN THIS

968
00:40:45,038 --> 00:40:46,139
EXPERIMENT IS WE'RE EXCITING THE

969
00:40:46,139 --> 00:40:47,808
CELLS WITH DIFFERENT TYPES OF

970
00:40:47,808 --> 00:40:49,109
STIMULUS, THE STRONGEST ONE IS

971
00:40:49,109 --> 00:40:51,845
SHOWN HERE IN RED.

972
00:40:51,845 --> 00:40:53,146
AS YOU CAN SEE IN THE NORMAL

973
00:40:53,146 --> 00:40:54,481
CONDITION, THESE NEURONS NEED TO

974
00:40:54,481 --> 00:40:58,585
HAVE A LOT OF EXCITABILITY IN

975
00:40:58,585 --> 00:41:02,456
ORDER TO WHAT'S SHOWN HERE AS

976
00:41:02,456 --> 00:41:03,657
FIRE AND ACTION POTENTIAL.

977
00:41:03,657 --> 00:41:05,625
WHAT HAPPENS NOW IS IF YOU GIVE

978
00:41:05,625 --> 00:41:06,927
ONCOSTATIN M, THIS COMPLETELY

979
00:41:06,927 --> 00:41:08,395
CHANGES.

980
00:41:08,395 --> 00:41:13,934
SO NOW EVEN AT THE LOWEST

981
00:41:13,934 --> 00:41:16,236
EXCITABILITY, WE NOW GET ACTION

982
00:41:16,236 --> 00:41:17,003
POTENTIAL FIRING.

983
00:41:17,003 --> 00:41:19,339
SO THIS SHOWS THAT THERE'S A

984
00:41:19,339 --> 00:41:21,374
LONG TERM EFFECT THAT'S BOOSTING

985
00:41:21,374 --> 00:41:23,376
THE EFFECT ON THE NEURONS, AND

986
00:41:23,376 --> 00:41:26,780
THIS IS SOMETHING THAT OCCURS

987
00:41:26,780 --> 00:41:27,848
OVER TWO DAYS THAT YOU NEED

988
00:41:27,848 --> 00:41:29,616
THIS, BUT THIS DOESN'T GO AWAY

989
00:41:29,616 --> 00:41:32,752
QUICKLY.

990
00:41:32,752 --> 00:41:33,854
SO FOR THIS SECOND EFFECT,

991
00:41:33,854 --> 00:41:36,723
AGAIN, I WANT TO SHOW YOU DATA

992
00:41:36,723 --> 00:41:39,259
THAT IS CONFIRMATORY IN AN

993
00:41:39,259 --> 00:41:40,927
ANIMAL MODEL, AND FOR THIS

994
00:41:40,927 --> 00:41:44,831
EXPERIMENT, WHAT WE USE IS WE

995
00:41:44,831 --> 00:41:48,969
USED AN ANTAGONIST, A GP130, A

996
00:41:48,969 --> 00:41:51,171
BLOCKER, SO THIS IS THE

997
00:41:51,171 --> 00:41:54,474
RECEPTOR, ONCOSTA TIPSTATIN M, E

998
00:41:54,474 --> 00:41:56,443
NOT TOLD YOU THIS ACTUALLY FORMS

999
00:41:56,443 --> 00:41:57,878
A DIMER.

1000
00:41:57,878 --> 00:41:59,846
THERE ISN'T A BLOCKER FOR THE

1001
00:41:59,846 --> 00:42:02,015
ONCOSTATIN M BUT THERE IS FOR

1002
00:42:02,015 --> 00:42:04,651
ITS EXCLUSIVE PARTNER, GP130.

1003
00:42:04,651 --> 00:42:07,287
SO WHAT WE WANTED TO DO WAS TO

1004
00:42:07,287 --> 00:42:09,823
EXAMINE WHETHER OR NOT IF WE

1005
00:42:09,823 --> 00:42:13,193
BLOCKED THIS RECEPTOR, COULD WE

1006
00:42:13,193 --> 00:42:17,797
RELIEVE PSORIASIS AND IN A MOUSE

1007
00:42:17,797 --> 00:42:19,099
MODEL.

1008
00:42:19,099 --> 00:42:19,966
INDEED WE COULD.

1009
00:42:19,966 --> 00:42:28,275
SO THIS IS THE EFFECT OF JUST

1010
00:42:28,275 --> 00:42:29,409
VEHICLE CONTROL, THE ANIMALS

1011
00:42:29,409 --> 00:42:30,677
CONTINUE TO CARRY ON SCRATCHING

1012
00:42:30,677 --> 00:42:32,145
AND IF WE GIVE THE BLOCKER, WE

1013
00:42:32,145 --> 00:42:33,480
CAN ACTUALLY RELIEVE ALMOST

1014
00:42:33,480 --> 00:42:35,382
COMPLETELY THE SCRATCH RESPONSES

1015
00:42:35,382 --> 00:42:35,882
IN THE MOUSE.

1016
00:42:35,882 --> 00:42:37,851
SO THIS SHOWS THAT THE

1017
00:42:37,851 --> 00:42:43,323
ONCOSTATIN M RECEPTOR, NOT ONLY

1018
00:42:43,323 --> 00:42:44,457
IN ELECTROPHYSIOLOGICAL

1019
00:42:44,457 --> 00:42:45,392
EXPERIMENTS BUT ACTUALLY IN A

1020
00:42:45,392 --> 00:42:50,096
MOUSE, IF WE CAN BLOCK IT, WE

1021
00:42:50,096 --> 00:42:51,965
CAN PREVENT THIS MODEL.

1022
00:42:51,965 --> 00:42:53,600
IN THIS MODEL.

1023
00:42:53,600 --> 00:42:57,771
SO THIS IS SHOWN HERE, THIS PAIR

1024
00:42:57,771 --> 00:43:00,840
OF SCHEMATICS WHERE IN NORMAL

1025
00:43:00,840 --> 00:43:06,313
CONDITIONS, IF THERE'S A

1026
00:43:06,313 --> 00:43:07,981
PRURITOGEN, FOR INSTANCE, HIS TA

1027
00:43:07,981 --> 00:43:09,849
MEAN OR SOME OTHER MOLECULE THAT

1028
00:43:09,849 --> 00:43:12,352
GETS IN CONTACT WITH THOSE NERVE

1029
00:43:12,352 --> 00:43:14,421
FIBERS, THERE IS THIS CURRENT

1030
00:43:14,421 --> 00:43:16,223
AND THEN ACTION POTENTIAL FIRING

1031
00:43:16,223 --> 00:43:17,724
AND SIGNALING INTO THE SPINAL

1032
00:43:17,724 --> 00:43:20,794
CORD.

1033
00:43:20,794 --> 00:43:27,133
AND WHEN WE GO TO -- NOW WE HAVE

1034
00:43:27,133 --> 00:43:28,235
AN INFLAMMATORY CONDITIONS WHERE

1035
00:43:28,235 --> 00:43:31,071
THERE'S ELEVATED ONCOSTATIN M,

1036
00:43:31,071 --> 00:43:34,040
THE SAME PRURITOGEN CAUSES A

1037
00:43:34,040 --> 00:43:35,575
GREATER CURRENT, A MORE ACTION

1038
00:43:35,575 --> 00:43:37,110
POTENTIAL FIRING AND, HENCE,

1039
00:43:37,110 --> 00:43:47,053
MORE ITCH.

1040
00:43:47,053 --> 00:43:49,456
I WANT TO GO BACK TO A SLIDE I

1041
00:43:49,456 --> 00:43:50,991
HAD IN THE BEGINNING THAT

1042
00:43:50,991 --> 00:43:52,392
DESCRIBES THE FACT THAT THERE'S

1043
00:43:52,392 --> 00:43:53,159
THIS INTERACTION BETWEEN NOT

1044
00:43:53,159 --> 00:43:54,728
ONLY THE NEURONS BUT THE IMMUNE

1045
00:43:54,728 --> 00:43:55,795
CELLS, WHICH I'VE BEEN TALKING

1046
00:43:55,795 --> 00:43:58,465
ABOUT A LOT, THIS IS THE SOURCE

1047
00:43:58,465 --> 00:44:01,401
OF THE INTERLEUKINS INCLUDING

1048
00:44:01,401 --> 00:44:05,038
ONCOSTATIN M INTO INTERLEUKIN 3T

1049
00:44:05,038 --> 00:44:06,473
THERE'S ALSO CROSSTALK BACK FROM

1050
00:44:06,473 --> 00:44:10,543
THE NEURONS TO THE IMMUNE CELLS,

1051
00:44:10,543 --> 00:44:15,382
SO THIS IS MORE RECENT DATA

1052
00:44:15,382 --> 00:44:18,752
SHOWING THERE'S THIS NEUROIMMUNE

1053
00:44:18,752 --> 00:44:21,388
EPITHELIAL TRIAD THAT IS

1054
00:44:21,388 --> 00:44:23,690
INVOLVED IN SKIN HOMEOSTASIS.

1055
00:44:23,690 --> 00:44:29,396
NOT ONLY IS THERE INTERACTION

1056
00:44:29,396 --> 00:44:32,465
BETWEEN THE NERVES AND THE

1057
00:44:32,465 --> 00:44:33,767
IMMUNE CELLS AND IMMUNE CELLS

1058
00:44:33,767 --> 00:44:35,201
AND THE NERVES, BUT THIS IS ALSO

1059
00:44:35,201 --> 00:44:37,270
THE CASE WITH THE STROMAL CELLS

1060
00:44:37,270 --> 00:44:39,673
AND THE STROMAL CELLS INTERACT

1061
00:44:39,673 --> 00:44:40,907
WITH THE IMMUNE CELLS.

1062
00:44:40,907 --> 00:44:42,342
SO THIS IS A VERY COMPLICATED

1063
00:44:42,342 --> 00:44:44,644
SET OF INTERACTIONS, BUT AT ITS

1064
00:44:44,644 --> 00:44:48,181
CORE, YOU CAN SEE THERE'S

1065
00:44:48,181 --> 00:44:49,316
INTERLEUKINS THAT -- CYTOKINES

1066
00:44:49,316 --> 00:44:52,218
THAT ARE INVOLVED IN

1067
00:44:52,218 --> 00:44:53,853
POTENTIATING BOTH THIS

1068
00:44:53,853 --> 00:44:56,489
INTERACTION AND ALSO THIS

1069
00:44:56,489 --> 00:44:56,790
INTERACTION.

1070
00:44:56,790 --> 00:45:01,528
AND I WANT TO FINALLY NOTE,

1071
00:45:01,528 --> 00:45:02,629
ALTHOUGH I'VE TALKED ABOUT

1072
00:45:02,629 --> 00:45:05,165
HISTAMINE A GREAT DEAL IN THE

1073
00:45:05,165 --> 00:45:08,234
CASE OF THE CHRONIC ITCH WITH

1074
00:45:08,234 --> 00:45:17,110
THE EXCEPTION OF UTE C UTICARIA,

1075
00:45:17,110 --> 00:45:19,612
HISTAMINE IS NOT REQUIRED FOR

1076
00:45:19,612 --> 00:45:21,281
THE MAINTENANCE OF ITCH AND THIS

1077
00:45:21,281 --> 00:45:24,784
IS SOMETHING THAT -- THE ANSWER

1078
00:45:24,784 --> 00:45:26,753
TO THIS, THAT THE MAST CELLS ARE

1079
00:45:26,753 --> 00:45:27,787
PROBABLY NOT THAT IMPORTANT.

1080
00:45:27,787 --> 00:45:29,189
IN CHRONIC ITCH, IT'S ACTUALLY

1081
00:45:29,189 --> 00:45:30,657
THESE OTHER TYPES OF IMMUNE

1082
00:45:30,657 --> 00:45:32,359
KRELTS, THE T CELLS FOR INSTANCE

1083
00:45:32,359 --> 00:45:33,593
THAT ARE VERY IMPORTANT IN THAT.

1084
00:45:33,593 --> 00:45:35,462
AND MY LAST SLIDE, I'M GOING TO

1085
00:45:35,462 --> 00:45:37,430
COME UP HERE, PROBABLY MY MOST

1086
00:45:37,430 --> 00:45:38,531
IMPORTANT SLIDE, IS

1087
00:45:38,531 --> 00:45:39,733
ACKNOWLEDGING THE PEOPLE THAT

1088
00:45:39,733 --> 00:45:46,106
DID ALL THIS WORK.

1089
00:45:46,106 --> 00:45:50,243
SANTOSH, JUERGEN AND

1090
00:45:50,243 --> 00:45:51,578
HISPANIC-YEN, WHO HAVE ALL GONE

1091
00:45:51,578 --> 00:45:52,912
ON TO SUCCESSFUL CAREERS OUTSIDE

1092
00:45:52,912 --> 00:45:53,446
OF NIH.

1093
00:45:53,446 --> 00:45:55,281
AND WITH THAT, I'M GOING TO

1094
00:45:55,281 --> 00:45:55,515
FINISH.

1095
00:45:55,515 --> 00:45:59,018
>> THANK YOU VERY MUCH,
MARK.

1096
00:45:59,018 --> 00:46:00,453
SO IAN, WILL YOU CARRY ON,

1097
00:46:00,453 --> 00:46:10,597
PLEASE.

1098
00:46:18,371 --> 00:46:20,039
>> IT'S NOT LETTING ME
START MY

1099
00:46:20,039 --> 00:46:21,775
VIDEO.

1100
00:46:21,775 --> 00:46:25,645
IT SAID DISABLED.

1101
00:46:25,645 --> 00:46:27,046
>> WE SEE IT ON OUR SIDE.

1102
00:46:27,046 --> 00:46:28,381
>> OH, THERE WE GO.

1103
00:46:28,381 --> 00:46:29,048
OKAY.

1104
00:46:29,048 --> 00:46:32,085
ALL RIGHT.

1105
00:46:32,085 --> 00:46:36,022
SO I'M GOING TO I'M IAN MYLES, I

1106
00:46:36,022 --> 00:46:37,457
WORK WITH NIAID AND I'M GOING TO

1107
00:46:37,457 --> 00:46:38,992
TALK ABOUT SOME OF OUR WORK,

1108
00:46:38,992 --> 00:46:40,527
WHICH IS FOCUSED ON KIND OF

1109
00:46:40,527 --> 00:46:42,729
WHAT'S DRIVING THE DISEASE FROM

1110
00:46:42,729 --> 00:46:45,498
AN ENVIRONMENTAL STANDPOINT.

1111
00:46:45,498 --> 00:46:48,668
SO AS CONFLICT OF INTEREST,

1112
00:46:48,668 --> 00:46:51,604
NIAID DOES HAVE A DEAL WITH A

1113
00:46:51,604 --> 00:46:55,241
COMPANY CALLED SKINESA TO SELL

1114
00:46:55,241 --> 00:46:57,076
THE PROBIOTIC THAT I WILL

1115
00:46:57,076 --> 00:46:58,645
MENTION AND SPRAYING PEOPLE WITH

1116
00:46:58,645 --> 00:47:00,513
BACTERIA IS NOT FDA-APPROVED,

1117
00:47:00,513 --> 00:47:02,048
MAYBE ONE DAY BUT NOT TODAY.

1118
00:47:02,048 --> 00:47:03,716
JUST AS A BASELINE FOR A CASE

1119
00:47:03,716 --> 00:47:05,685
PRESENTATION, IN 2016 WHEN WE

1120
00:47:05,685 --> 00:47:07,320
OPENED THE BEGINNING OF THE

1121
00:47:07,320 --> 00:47:08,421
TRIAL, 19-YEAR-OLD MALE HAD COME

1122
00:47:08,421 --> 00:47:11,825
IN, HE SUFFERED WITH ATOPIC DERM

1123
00:47:11,825 --> 00:47:13,927
FOR MOST OF HIS LIFE, HE TRIED

1124
00:47:13,927 --> 00:47:14,894
STEROIDS AND SOME OF THE OTHER

1125
00:47:14,894 --> 00:47:16,229
TREATMENTS THAT WERE AVAILABLE

1126
00:47:16,229 --> 00:47:21,601
IN 2016 WHICH AD ADMITTEDLY WERE

1127
00:47:21,601 --> 00:47:22,569
FAR FEWER THAN TODAY.

1128
00:47:22,569 --> 00:47:29,809
HE WAS ON THE WAIT LIST FOR

1129
00:47:29,809 --> 00:47:32,111
DUPIXON, HE WASN'T ABLE TO GET

1130
00:47:32,111 --> 00:47:32,278
IT.

1131
00:47:32,278 --> 00:47:36,950
SO HE WENT -- AS SOON AS HE

1132
00:47:36,950 --> 00:47:37,917
CLICKED ENROLL, HE SAID HE

1133
00:47:37,917 --> 00:47:40,453
STARTED SEARCHING FOR

1134
00:47:40,453 --> 00:47:41,120
EXPERIMENTAL TREATMENTS AND KIND

1135
00:47:41,120 --> 00:47:45,492
OF CAME TO US.

1136
00:47:45,492 --> 00:47:47,026
SO I'LL COME BACK TO HIM.

1137
00:47:47,026 --> 00:47:48,561
HE'S CERTAINLY NOT ALONE IN

1138
00:47:48,561 --> 00:47:49,562
TODAY'S WORLD IN TERMS OF THE

1139
00:47:49,562 --> 00:47:55,368
RATES OF ATOPIC DERMATITIS.

1140
00:47:55,368 --> 00:47:59,639
DRTHE VERY FIRST DESCRIPTION OF

1141
00:47:59,639 --> 00:48:03,910
WHAT IS ALMOST CERTAINLY ATOPIC

1142
00:48:03,910 --> 00:48:11,384
DERM CAME OUT OF THE EBERS PA

1143
00:48:11,384 --> 00:48:12,385
PAPYRUS, THAT WAS DEFINITELY

1144
00:48:12,385 --> 00:48:14,053
ECZEMA LOOKING BACK.

1145
00:48:14,053 --> 00:48:14,854
HIPPOCRATES AS HE MENTIONED

1146
00:48:14,854 --> 00:48:20,493
SPOKE ABOUT IT FREQUENTLY,

1147
00:48:20,493 --> 00:48:22,362
AUGUSTUS WAS KNOWN TO HAVE THE

1148
00:48:22,362 --> 00:48:23,563
ALLERGIC TRIAD.

1149
00:48:23,563 --> 00:48:24,998
SO THESE DIAGNOSES HAVE BEEN

1150
00:48:24,998 --> 00:48:26,432
KNOWN FOR BASICALLY ALL OF

1151
00:48:26,432 --> 00:48:27,500
CIVILIZATIONS BUT THEIR RATES

1152
00:48:27,500 --> 00:48:28,501
HAVEN'T COME CLOSE TO WHAT WE

1153
00:48:28,501 --> 00:48:29,068
HAVE TODAY.

1154
00:48:29,068 --> 00:48:30,370
YOU SEE GRAPHED ON THIS

1155
00:48:30,370 --> 00:48:32,338
TIMELINE, THIS INSANE HOCKEY

1156
00:48:32,338 --> 00:48:33,907
STICK GRAPHED FORMAT THERE WITH

1157
00:48:33,907 --> 00:48:35,441
THE INFLECTION POINT OF THE

1158
00:48:35,441 --> 00:48:37,944
UNITED STATES BEING IN AND

1159
00:48:37,944 --> 00:48:39,145
AROUND 1970.

1160
00:48:39,145 --> 00:48:41,247
SO IN THE 50s OR SO, THE RATES

1161
00:48:41,247 --> 00:48:42,882
OF ATOPIC DERMATITIS WOULD HAVE

1162
00:48:42,882 --> 00:48:44,751
BEEN IN THE 1 OR 2%, AND TODAY

1163
00:48:44,751 --> 00:48:47,587
WE'RE LOOKING AT 15 TO 20% OVER

1164
00:48:47,587 --> 00:48:49,155
A VERY SHORT PERIOD OF TIME.

1165
00:48:49,155 --> 00:48:51,791
SO THERE HAS TO BE SOME KIND OF

1166
00:48:51,791 --> 00:48:53,326
ENVIRONMENTAL FACTOR THAT WAS

1167
00:48:53,326 --> 00:48:55,728
INTRODUCED IN THE 1970s TO

1168
00:48:55,728 --> 00:48:58,464
GENERATE ANYTHING CLOSE TO THAT.

1169
00:48:58,464 --> 00:49:00,433
AND YET YOU CAN PLAY THIS GAME

1170
00:49:00,433 --> 00:49:03,069
FOR YOURSELF IF YOU RESEARCH

1171
00:49:03,069 --> 00:49:06,573
ATOPIC DERM PATHOGENESIS OR

1172
00:49:06,573 --> 00:49:08,908
EX-PA PATHOGENESIS, ECZEMA

1173
00:49:08,908 --> 00:49:09,776
MECHANISM, WHATEVER WORDS YOU

1174
00:49:09,776 --> 00:49:10,743
WANT, YOU'RE GOING TO GET A

1175
00:49:10,743 --> 00:49:13,079
GRAPH THAT LOOKS SOMETHING LIKE

1176
00:49:13,079 --> 00:49:13,346
THIS.

1177
00:49:13,346 --> 00:49:14,380
THESE ARE VALUABLE INFORMATION

1178
00:49:14,380 --> 00:49:16,282
IN TERMS OF WHAT'S GOING ON

1179
00:49:16,282 --> 00:49:17,584
INSIDE THE SKIN BECAUSE OF THE

1180
00:49:17,584 --> 00:49:19,819
FACT THAT YOU CAN USE SOME OF

1181
00:49:19,819 --> 00:49:23,189
THESE MONOCLONAL ANTIBODIES AS

1182
00:49:23,189 --> 00:49:26,526
BLOCKERS IN PEOPLE WHO WERE

1183
00:49:26,526 --> 00:49:27,193
PREVIOUSLY SUFFERING FROM

1184
00:49:27,193 --> 00:49:28,494
DISEASE ARE SUFFERING A LOT LESS

1185
00:49:28,494 --> 00:49:29,829
BECAUSE OF THESE MEDICATIONS.

1186
00:49:29,829 --> 00:49:30,964
BUT YOU'LL NOTICE ALL OF THESE

1187
00:49:30,964 --> 00:49:32,265
HAVE ONE THING IN COMMON, WHICH

1188
00:49:32,265 --> 00:49:33,700
IS IT'S GOING TO START AT THE

1189
00:49:33,700 --> 00:49:34,100
SKIP.

1190
00:49:34,100 --> 00:49:36,769
AND IT'S SKIN.

1191
00:49:36,769 --> 00:49:38,071
IT'S GOING TO MAKE THIS

1192
00:49:38,071 --> 00:49:38,771
INSINUATION WHATEVER IS GOING ON

1193
00:49:38,771 --> 00:49:40,273
IN THE SKIN IS SOMEHOW BELOW THE

1194
00:49:40,273 --> 00:49:40,740
SURFACE OF THE SKIN.

1195
00:49:40,740 --> 00:49:41,874
THERE WILL BE SOME COMMENTS

1196
00:49:41,874 --> 00:49:43,576
ABOUT THE MICROBIOME OR SOME

1197
00:49:43,576 --> 00:49:44,777
IRRITANT BUT REALLY NOT MUCH

1198
00:49:44,777 --> 00:49:45,278
ELSE GOING ON.

1199
00:49:45,278 --> 00:49:47,814
SO WE KIND OF REALIZE FROM

1200
00:49:47,814 --> 00:49:48,448
EPIDEMIOLOGY THAT SOMETHING

1201
00:49:48,448 --> 00:49:50,416
OUTSIDE OF THE BODY HAS TO BE

1202
00:49:50,416 --> 00:49:53,386
THE INCITING EVENT, AND YET MOST

1203
00:49:53,386 --> 00:49:54,587
OF THE WORK IS ON EVERYTHING

1204
00:49:54,587 --> 00:49:57,890
THAT HAPPENS INSIDE OF THE BODY.

1205
00:49:57,890 --> 00:49:59,025
SO IF YOU GO THROUGH THE

1206
00:49:59,025 --> 00:50:00,126
LITERATURE AND ASK, ALL RIGHT,

1207
00:50:00,126 --> 00:50:04,430
WELL, WHAT HAVE PEOPLE ESTABL 

1208
00:50:04,430 --> 00:50:05,565
ESTABLISHED AS EXPOSURES THAT

1209
00:50:05,565 --> 00:50:07,567
PUT SOMEBODY AT RISK FOR ATOPIC

1210
00:50:07,567 --> 00:50:07,900
DERMATITIS?

1211
00:50:07,900 --> 00:50:10,103
I WOULD PUT THEM INTO FOUR BIG

1212
00:50:10,103 --> 00:50:10,803
CATEGORIES, THE FIRST OF WHICH

1213
00:50:10,803 --> 00:50:12,205
IS LIVING IN AN INDUSTRIAL

1214
00:50:12,205 --> 00:50:14,841
SOCIETY, SO PROCESSED FOODS,

1215
00:50:14,841 --> 00:50:16,709
PARTICULARLY HIGH CONSUMPTIONS

1216
00:50:16,709 --> 00:50:17,710
OF PROCESSED FOODS.

1217
00:50:17,710 --> 00:50:18,911
YOU SEE HERE THE DOTTED LINE

1218
00:50:18,911 --> 00:50:20,213
WOULD MEAN IT HAS NO EFFECT AT

1219
00:50:20,213 --> 00:50:22,448
ALL, SO THIS MEANS THAT THERE'S

1220
00:50:22,448 --> 00:50:24,017
A HIGHER RISK FOR PROCESSED

1221
00:50:24,017 --> 00:50:25,385
FOODS.

1222
00:50:25,385 --> 00:50:27,353
ANTIBIOTICS EXPOSURE, THERE'S

1223
00:50:27,353 --> 00:50:28,354
SOME RISK.

1224
00:50:28,354 --> 00:50:30,990
IF YOUR MOM HAS ALLERGIES, YOUR

1225
00:50:30,990 --> 00:50:33,192
CHANCES FOR ATOPIC DERM IS

1226
00:50:33,192 --> 00:50:34,093
HIGHER.

1227
00:50:34,093 --> 00:50:35,728
DAD DOESN'T SEEM TO BE RELEVANT

1228
00:50:35,728 --> 00:50:37,163
IN THIS PARTICULAR CALCULATION.

1229
00:50:37,163 --> 00:50:38,131
SIBLINGS ARE ACTUALLY

1230
00:50:38,131 --> 00:50:39,699
PROTECTIVE, WHICH IS INTRIGUING.

1231
00:50:39,699 --> 00:50:40,967
LIKE THE MORTGAGE OLDER SIBLINGS

1232
00:50:40,967 --> 00:50:49,042
MORE OLDER SIBLINGS YOUV THE LEG

1233
00:50:49,042 --> 00:50:50,710
TO HAVE ATOPIC D.

1234
00:50:50,710 --> 00:50:52,311
MOVING FROM A NON-INDUSTRIALIZED

1235
00:50:52,311 --> 00:50:53,546
COUNTRY TO THE UNITED STATES OR

1236
00:50:53,546 --> 00:50:55,748
EUROPE PRIOR TO TWO YEARS OF AGE

1237
00:50:55,748 --> 00:50:57,850
GREATLY INCREASES YOUR RISK AND

1238
00:50:57,850 --> 00:50:59,052
THEN THERE'S A COMPOUNDED RISK

1239
00:50:59,052 --> 00:51:01,888
ON TOP OF THAT IF YOU MOVE TO AN

1240
00:51:01,888 --> 00:51:02,722
URBAN ENVIRONMENT WITHIN THE

1241
00:51:02,722 --> 00:51:04,223
UNITED STATES.

1242
00:51:04,223 --> 00:51:05,324
AFTER SIX YEARS OF AGE YOU CAN

1243
00:51:05,324 --> 00:51:07,060
MOVE ANYWHERE YOU WANT IN THE

1244
00:51:07,060 --> 00:51:08,594
GLOBE AND YOUR RISK IS NOT GOING

1245
00:51:08,594 --> 00:51:09,729
TO CHANGE WHATSOEVER.

1246
00:51:09,729 --> 00:51:11,698
SO THAT KIND OF SPEAKS TO THE

1247
00:51:11,698 --> 00:51:12,999
CHANCE THAT THERE IS A

1248
00:51:12,999 --> 00:51:14,100
DEVELOPMENTAL WIN DOLE THAT IF

1249
00:51:14,100 --> 00:51:17,870
YOU EXPOSE SOMEBODY TO SOMETHING

1250
00:51:17,870 --> 00:51:20,373
THAT IS AMERICA OR EUROPE LEVEL

1251
00:51:20,373 --> 00:51:21,140
INDUSTRIALIZATION, THEY'RE GOING

1252
00:51:21,140 --> 00:51:23,009
TO BE AT RISK IF THEY GET PAST

1253
00:51:23,009 --> 00:51:24,010
THAT WINDOW, THEN IT DOESN'T

1254
00:51:24,010 --> 00:51:24,577
REALLY MATTER.

1255
00:51:24,577 --> 00:51:25,978
SO NORMALLY WHEN YOU TALK ABOUT

1256
00:51:25,978 --> 00:51:28,214
URBAN ENVIRONMENTS, WE TEND TO

1257
00:51:28,214 --> 00:51:29,315
ASSUME THAT'S FROM AUTOMOBILE

1258
00:51:29,315 --> 00:51:31,350
EXHAUST, WHICH WOULD BE THE

1259
00:51:31,350 --> 00:51:32,585
SECOND CATEGORY, BUT IF YOU LOOK

1260
00:51:32,585 --> 00:51:33,486
AT THE SPECIFIC COMPONENTS OF

1261
00:51:33,486 --> 00:51:34,053
AUTOMOBILE EXHAUST.

1262
00:51:34,053 --> 00:51:35,688
YOU CAN SEE SOME ARE RIGHT ON

1263
00:51:35,688 --> 00:51:37,390
THIS LINE OR NOT REALLY ALL THAT

1264
00:51:37,390 --> 00:51:38,324
RELEVANT AT ALL.

1265
00:51:38,324 --> 00:51:39,125
DESPIECT THE FACT THAT LIVING

1266
00:51:39,125 --> 00:51:40,326
NEAR A HIGHWAY PARTICULARLY

1267
00:51:40,326 --> 00:51:42,195
WHILE YOU ARE PREGNANT CAN HAVE

1268
00:51:42,195 --> 00:51:43,396
A PRETTY PROFOUND EFFECT.

1269
00:51:43,396 --> 00:51:44,731
SO THIS MEANS EITHER THESE

1270
00:51:44,731 --> 00:51:47,266
FACTORS FROM AN AUTOMOBILE ARE

1271
00:51:47,266 --> 00:51:48,568
SYNERGIZING WITH EACH OTHER OR

1272
00:51:48,568 --> 00:51:49,902
THAT THERE'S SOMETHING IN A CAR

1273
00:51:49,902 --> 00:51:51,003
EXHAUST THAT ISN'T BEING

1274
00:51:51,003 --> 00:51:54,273
MEASURED BY THE TRADITIONAL AIR

1275
00:51:54,273 --> 00:51:54,607
QUALITY INDEX.

1276
00:51:54,607 --> 00:51:56,409
SO WHEN YOU SEE THE AIR QUALITY

1277
00:51:56,409 --> 00:51:57,677
INDEX, THOSE ARE JUST SIX

1278
00:51:57,677 --> 00:51:58,578
CHEMICALS THAT TYPICALLY COME

1279
00:51:58,578 --> 00:52:00,012
OUT OF THE BACK OF AN

1280
00:52:00,012 --> 00:52:01,214
AUTOMOBILE, BUT THOSE SIX

1281
00:52:01,214 --> 00:52:03,449
CHEMICALS ARE NOT REALLY

1282
00:52:03,449 --> 00:52:04,951
ASSOCIATING WITH THE DISEASE

1283
00:52:04,951 --> 00:52:06,052
STRONGLY ON ANY INDIVIDUAL

1284
00:52:06,052 --> 00:52:07,253
LEVEL.

1285
00:52:07,253 --> 00:52:10,690
A NEW CATEGORY APPRECIATED IS

1286
00:52:10,690 --> 00:52:10,957
WILDFIRES.

1287
00:52:10,957 --> 00:52:15,394
IT REALLY BECAME PREVALENT AFTER

1288
00:52:15,394 --> 00:52:18,698
THE BIG FIRES IN AUSTRALIA WHICH

1289
00:52:18,698 --> 00:52:20,032
MADE THE NEWS, THEN THE MOST

1290
00:52:20,032 --> 00:52:20,900
RECENT ONES FROM CALIFORNIA,

1291
00:52:20,900 --> 00:52:25,838
MAYBE EACH  EVEN THE LAST ONES M

1292
00:52:25,838 --> 00:52:27,507
THE EASTERN PART OF CANADA

1293
00:52:27,507 --> 00:52:30,576
INCREASED RATES OF ATOPIC DERM,

1294
00:52:30,576 --> 00:52:36,415
INDUCING IMMEDIATE FLARES IN THE

1295
00:52:36,415 --> 00:52:37,950
PEOPLE AS THE PLUME GOES THROUGH

1296
00:52:37,950 --> 00:52:38,518
THEIR SOCIETY.

1297
00:52:38,518 --> 00:52:40,253
THEN THE LAST CATEGORY IS KIND

1298
00:52:40,253 --> 00:52:40,953
OF A HODGEPODGE.

1299
00:52:40,953 --> 00:52:42,021
IT WOULD BE THINGS THAT YOU

1300
00:52:42,021 --> 00:52:44,557
WOULD DO IN YOUR HOUSE, HOME

1301
00:52:44,557 --> 00:52:48,194
RENOVATION BEHAVIOR, WEARING

1302
00:52:48,194 --> 00:52:50,163
NYLON, SPANDEX OR POLYESTER CAN

1303
00:52:50,163 --> 00:52:54,200
INCREASE YOUR RISK OF DUST,

1304
00:52:54,200 --> 00:52:55,835
ENVIRONMENTAL TOBACCO --

1305
00:52:55,835 --> 00:52:57,203
SECONDHAND SMOKE.

1306
00:52:57,203 --> 00:52:58,938
ONLY IF YOU'RE UNDER 2, THAT

1307
00:52:58,938 --> 00:53:01,240
INCLUDES BY THE WAY IN THE WOMB,

1308
00:53:01,240 --> 00:53:03,776
SO IF YOU RENOVATE, THE RISK

1309
00:53:03,776 --> 00:53:05,211
GOES MUCH HIGHER.

1310
00:53:05,211 --> 00:53:06,078
AFTER FOUR YEARS, YOU CAN

1311
00:53:06,078 --> 00:53:06,946
BASICALLY DO WHATEVER YOU WANT

1312
00:53:06,946 --> 00:53:08,181
TO YOUR HOUSE AND IT'S NOT GOING

1313
00:53:08,181 --> 00:53:08,948
TO MAKE A DIFFERENCE.

1314
00:53:08,948 --> 00:53:10,817
SO THESE DON'T FEEL VERY WELL

1315
00:53:10,817 --> 00:53:12,018
CONNECTED AND IT WOULD BE HARD

1316
00:53:12,018 --> 00:53:14,220
TO FIND A THROUGH LINE, PER SE.

1317
00:53:14,220 --> 00:53:16,422
BUT WE THINK WE GOT A LITTLE BIT

1318
00:53:16,422 --> 00:53:20,359
SMARTER IN THE FIELD IN 2023, WE

1319
00:53:20,359 --> 00:53:22,128
HAD FOUR DIFFERENT STUDIES, ONE

1320
00:53:22,128 --> 00:53:23,362
OF WHICH WE'RE A COLLABORATOR

1321
00:53:23,362 --> 00:53:23,796
WITH.

1322
00:53:23,796 --> 00:53:25,198
THEY'RE IN FOUR DIFFERENT CAN

1323
00:53:25,198 --> 00:53:26,999
YCOUNTRIES.

1324
00:53:26,999 --> 00:53:28,534
ALL OF THEM TOOK SAMPLES OF

1325
00:53:28,534 --> 00:53:29,836
BABIES IN THE FIRST WEEK OF

1326
00:53:29,836 --> 00:53:31,204
LIFE, THEN THEY FOLLOWED THEM

1327
00:53:31,204 --> 00:53:33,372
FROM ANYWHERE FROM 1 TO 4 YEARS

1328
00:53:33,372 --> 00:53:35,675
TO SEE WHO WENT ON TO DEVELOP AN

1329
00:53:35,675 --> 00:53:37,143
ATOPIC DERMATITIS, AND NOW CAN

1330
00:53:37,143 --> 00:53:39,579
WE GO BACK TO OUR SAMPLES AND

1331
00:53:39,579 --> 00:53:41,314
SEE WHAT COULD HAVE PREDICTED

1332
00:53:41,314 --> 00:53:42,782
WHO WAS GOING TO GET ECZEMA AND

1333
00:53:42,782 --> 00:53:43,216
WHO WASN'T.

1334
00:53:43,216 --> 00:53:44,417
THEY USED THREE DIFFERENT

1335
00:53:44,417 --> 00:53:45,918
METHODS WHICH I DON'T NEED TO

1336
00:53:45,918 --> 00:53:48,721
DETAIL BECAUSE ALL OF THEM --

1337
00:53:48,721 --> 00:53:51,691
EACH METHOD HAD ITS OWN QUIRKY

1338
00:53:51,691 --> 00:53:52,859
FINDING BUT WHEN YOU ADD THEM

1339
00:53:52,859 --> 00:53:54,393
ALL TOGETHER, THERE WAS REALLY

1340
00:53:54,393 --> 00:53:55,328
ONLY ONE THROUGH LINE, THAT WAS

1341
00:53:55,328 --> 00:53:57,096
THESE CLASSES OF LIPIDS OR OILS,

1342
00:53:57,096 --> 00:54:00,032
WHATEVER YOU WANT TO CALL THEM

1343
00:54:00,032 --> 00:54:01,734
CALLED CERAMIDES, AS WELL AS

1344
00:54:01,734 --> 00:54:03,369
SINGLE LIPIDS AND PHOSPHOLIPIDS.

1345
00:54:03,369 --> 00:54:06,906
I GUARANTEE IF YOU GO TO YOUR

1346
00:54:06,906 --> 00:54:08,007
GROCERY STORE, YOUR DEPARTMENT

1347
00:54:08,007 --> 00:54:11,844
STORE, GO DOWN ONE OF THE --

1348
00:54:11,844 --> 00:54:13,579
THEY WILL BRAG ABOUT THE FACT

1349
00:54:13,579 --> 00:54:22,822
THAT IT HAS CERAMIDES, LIPIDS,

1350
00:54:22,822 --> 00:54:24,757
PHOSPHOLIPIDS AND IT WE WILL

1351
00:54:24,757 --> 00:54:26,626
COME BACK TO WHETHER THEIR

1352
00:54:26,626 --> 00:54:28,995
BRAGGING IS JUSTIFIABLE.

1353
00:54:28,995 --> 00:54:31,831
ATOPIC DERM IS AN EARLY LIFE

1354
00:54:31,831 --> 00:54:33,366
DEFICIENCY OF THESE SPECIFIC

1355
00:54:33,366 --> 00:54:33,866
LIPIDS.

1356
00:54:33,866 --> 00:54:34,934
SO SOMETHING IN THE ENVIRONMENT

1357
00:54:34,934 --> 00:54:36,903
MIGHT BE INFLUENCING THOSE.

1358
00:54:36,903 --> 00:54:39,438
AND THE GOOD NEWS IS FROM A

1359
00:54:39,438 --> 00:54:40,907
RESEARCH STANDPOINT, WE ARE NOT

1360
00:54:40,907 --> 00:54:44,076
THE ONLY CREATURES THAT SHARE

1361
00:54:44,076 --> 00:54:44,510
OUR ENVIRONMENT.

1362
00:54:44,510 --> 00:54:46,946
SO WE ALL HAVE MICROBIOME AND I

1363
00:54:46,946 --> 00:54:48,147
THINK THE GREATEST DEPICTION OF

1364
00:54:48,147 --> 00:54:50,049
WHAT YOU MIGHT THINK OF AS THE

1365
00:54:50,049 --> 00:54:57,456
MICROBIOME IS RICHARD SCARRY'S

1366
00:54:57,456 --> 00:54:58,057
BUSY TOWN.

1367
00:54:58,057 --> 00:55:00,459
THIS IS HOW THE MICROBIOME

1368
00:55:00,459 --> 00:55:01,594
RESEARCH KIND OF BUILT ON

1369
00:55:01,594 --> 00:55:02,261
ITSELF.

1370
00:55:02,261 --> 00:55:03,329
USUALLY IT WAS VERY BROAD

1371
00:55:03,329 --> 00:55:05,231
CLASSIFICATIONS LIKE MAMMALS

1372
00:55:05,231 --> 00:55:06,132
VERSUS WORMS AND YOU CAN GET

1373
00:55:06,132 --> 00:55:07,867
MORE AND MORE AND MORE DETAILED

1374
00:55:07,867 --> 00:55:09,502
ALL THE WAY DOWN TO WHAT WE

1375
00:55:09,502 --> 00:55:12,171
WOULD CALL STRAIN LEVEL

1376
00:55:12,171 --> 00:55:13,806
ANALYSIS, WHERE YOU CAN START TO

1377
00:55:13,806 --> 00:55:15,141
HAVE VERY SPECIFIC COMMENTS

1378
00:55:15,141 --> 00:55:16,876
ABOUT SPECIFIC ORGANISMS LIVING

1379
00:55:16,876 --> 00:55:18,044
ON THE SKIN.

1380
00:55:18,044 --> 00:55:20,880
BUT NOW WE HAVE A BETTER

1381
00:55:20,880 --> 00:55:21,881
APPRECIATION FOR THE FACT THAT

1382
00:55:21,881 --> 00:55:23,182
LIKE IN BUSY TOWN, THEY EACH

1383
00:55:23,182 --> 00:55:23,783
HAVE A ROLE.

1384
00:55:23,783 --> 00:55:25,184
THEY HAVE A JOB THAT THEY'RE

1385
00:55:25,184 --> 00:55:27,887
SUPPOSED TO PLAY.

1386
00:55:27,887 --> 00:55:29,422
WE CAN START TO CLASSIFY THEM BY

1387
00:55:29,422 --> 00:55:31,090
SAYING WHAT ARE THESE BACTERIA

1388
00:55:31,090 --> 00:55:32,725
SUPPOSED TO DO, BECAUSE THE SAME

1389
00:55:32,725 --> 00:55:34,827
EXACT SPECIES MIGHT END UP

1390
00:55:34,827 --> 00:55:36,529
PLAYING DIFFERENT ROLES BASED ON

1391
00:55:36,529 --> 00:55:42,101
THE SKIN VERSUS THE GUT, OR ONE

1392
00:55:42,101 --> 00:55:43,402
PERSON -- ONE PERSON MIGHT NOT

1393
00:55:43,402 --> 00:55:46,639
NEED VITAMIN K PRODUCTION,

1394
00:55:46,639 --> 00:55:47,273
SOMEBODY MIGHT USE SOMETHING

1395
00:55:47,273 --> 00:55:47,606
ELSE.

1396
00:55:47,606 --> 00:55:49,241
SO WE CAN REALLY START TO PIECE

1397
00:55:49,241 --> 00:55:50,509
TOGETHER WHAT THESE BACTERIA ARE

1398
00:55:50,509 --> 00:55:52,578
SUPPOSED TO BE DOING AND THESE

1399
00:55:52,578 --> 00:55:53,479
OTHER MICROORGANISMS ON THE

1400
00:55:53,479 --> 00:55:57,950
SKIN.

1401
00:55:57,950 --> 00:56:00,386
SO IN BECOMES INTRIGUING IF YOU

1402
00:56:00,386 --> 00:56:02,054
LOOK AT WHERE ON THE BODY YOU

1403
00:56:02,054 --> 00:56:03,789
EXPECT SOMEBODY WITH ATOPIC

1404
00:56:03,789 --> 00:56:05,024
DERMATITIS TO MANIFEST THEIR

1405
00:56:05,024 --> 00:56:05,291
RASH.

1406
00:56:05,291 --> 00:56:07,026
YOU CAN KIND OF SEE THIS IS MORE

1407
00:56:07,026 --> 00:56:08,461
OR LESS BASED ON AGE WHERE YOU

1408
00:56:08,461 --> 00:56:08,894
EXPECT IT.

1409
00:56:08,894 --> 00:56:13,966
OVER HERE IS A GRAPH FROM

1410
00:56:13,966 --> 00:56:16,435
DR. JULIE SEGRE AND DR. HEIDI

1411
00:56:16,435 --> 00:56:20,740
CONGRESS WHE HIGHKONG AND THEY L

1412
00:56:20,740 --> 00:56:22,541
OVER THE BODY WHERE DIFFERENT

1413
00:56:22,541 --> 00:56:23,042
ORGANISMS WERE LIVING.

1414
00:56:23,042 --> 00:56:24,910
AT THE TIME THEY WERE JUST DOING

1415
00:56:24,910 --> 00:56:26,746
SPECIES SO THEY ONLY KNEW WHICH

1416
00:56:26,746 --> 00:56:29,215
ANIMALS BUT NOT THEIR EXACT

1417
00:56:29,215 --> 00:56:29,482
FUNCTIONS.

1418
00:56:29,482 --> 00:56:31,851
I'VE COLORED IN ON TO THIS GRAPH

1419
00:56:31,851 --> 00:56:34,153
WHERE YOU WOULD EXPECT TO FIND

1420
00:56:34,153 --> 00:56:37,423
GRAM-NEGATIVE ORGANISMS, SO WHY

1421
00:56:37,423 --> 00:56:39,225
THAT WOULD BE IMPORTANT IS THAT

1422
00:56:39,225 --> 00:56:41,761
OF ALL THE ORGANISMS IN THE

1423
00:56:41,761 --> 00:56:43,195
MICROBIAL WORLD THAT ARE CAPABLE

1424
00:56:43,195 --> 00:56:46,065
OF MAKING CERAMIDES,

1425
00:56:46,065 --> 00:56:47,299
SPHINGOLIPIDS AND PHOSPHOLIPIDS,

1426
00:56:47,299 --> 00:56:48,801
THE THINGS WE SAID WILL PROTECT

1427
00:56:48,801 --> 00:56:50,069
THE KIDS AGAINST ATOPIC

1428
00:56:50,069 --> 00:56:50,336
DETERMINE.

1429
00:56:50,336 --> 00:56:51,937
ALMOST ALL OF THEM ARE

1430
00:56:51,937 --> 00:56:53,239
GRAM-NEGATIVE ORGANISMS AND THE

1431
00:56:53,239 --> 00:56:54,874
ONLY ONES THAT ARE GRAM

1432
00:56:54,874 --> 00:56:56,342
POSITIVES ARE ALSO RESIDENTS ON

1433
00:56:56,342 --> 00:56:56,876
THE SKIN.

1434
00:56:56,876 --> 00:56:58,444
SO MOST OF THE BACTERIA LIVING

1435
00:56:58,444 --> 00:57:00,446
ON YOUR SKIN ARE MAKING THE

1436
00:57:00,446 --> 00:57:03,282
CLASS OF LIPIDS THAT APPEAR TO

1437
00:57:03,282 --> 00:57:05,151
PROTECT YOU AGAINST ATOPIC

1438
00:57:05,151 --> 00:57:05,684
DERMATITIS.

1439
00:57:05,684 --> 00:57:08,187
THE FEW ORGANISMS THAT DON'T

1440
00:57:08,187 --> 00:57:09,989
ACTIVELY MAKE CERAMIDES FOR YOU

1441
00:57:09,989 --> 00:57:11,557
HELP YOU MAKE MORE CERAMIDES FOR

1442
00:57:11,557 --> 00:57:11,824
YOURSELF.

1443
00:57:11,824 --> 00:57:14,660
SO THIS IS OUT OF MIKE OTTO'S

1444
00:57:14,660 --> 00:57:16,162
GROUP HERE AT NIAID WHERE A

1445
00:57:16,162 --> 00:57:24,136
STRAIN OF STAPH -- IT SURE SEEMS

1446
00:57:24,136 --> 00:57:26,105
THAT ALL THE BACTERIAS FUNCTION

1447
00:57:26,105 --> 00:57:27,840
ON THE GUT SEEMS TO ALIGN WITH

1448
00:57:27,840 --> 00:57:29,008
MAKING THESE SPECIFIC LIPID

1449
00:57:29,008 --> 00:57:30,943
CLASSES TO PROTECT YOU AGAINST

1450
00:57:30,943 --> 00:57:32,144
ATOPIC DERMATITIS.

1451
00:57:32,144 --> 00:57:34,547
SO THIS KIND OF GENERATES TWO

1452
00:57:34,547 --> 00:57:35,648
QUESTIONS, THE FIRST OF WHICH

1453
00:57:35,648 --> 00:57:37,983
WAS ALL RIGHT, COULD WE PUT THE

1454
00:57:37,983 --> 00:57:39,185
BACTERIA BACK?

1455
00:57:39,185 --> 00:57:41,987
A PERSON WITH ATOPIC DERM LOST

1456
00:57:41,987 --> 00:57:44,457
THESE KIND OF BENEFICIAL

1457
00:57:44,457 --> 00:57:45,558
ORGANISMS, WHAT WOULD HAPPEN IF

1458
00:57:45,558 --> 00:57:47,326
WE PUT THOSE ORGANISMS BACK ON

1459
00:57:47,326 --> 00:57:48,994
THE SKIN, COULD WE USE THAT AS A

1460
00:57:48,994 --> 00:57:49,462
TREATMENT?

1461
00:57:49,462 --> 00:57:51,530
SO FIRST WE HAD TO LEARN HOW TO

1462
00:57:51,530 --> 00:57:53,632
GROW GRAM-NEGATIVES FROM THE

1463
00:57:53,632 --> 00:57:53,999
SKIN.

1464
00:57:53,999 --> 00:57:56,836
I'LL SPARE YOU THE MS. REOF THAT

1465
00:57:56,836 --> 00:58:04,410
MISERY OFTHAT ONE.

1466
00:58:04,410 --> 00:58:05,644
WE TOOK THIS ORGANISM FROM

1467
00:58:05,644 --> 00:58:07,480
PATIENTS WHO WERE HEALTHY --

1468
00:58:07,480 --> 00:58:09,315
EXCUSE ME -- VOLUNTEERS WHO WERE

1469
00:58:09,315 --> 00:58:11,150
HEALTHY VERSUS PATIENTS WHO HAVE

1470
00:58:11,150 --> 00:58:11,717
ATOPIC DETERMINE.

1471
00:58:11,717 --> 00:58:15,855
EVEN THOUGH THESE ORGANISMS ARE

1472
00:58:15,855 --> 00:58:20,092
REMARKABLY SIMILAR GENETICALLY,

1473
00:58:20,092 --> 00:58:21,827
JUST VISUALLY IT WAS OBVIOUS

1474
00:58:21,827 --> 00:58:22,795
THAT THESE BACTERIA WERE GOING

1475
00:58:22,795 --> 00:58:24,063
TO BE DIFFERENT, YOU COULD SEE

1476
00:58:24,063 --> 00:58:27,333
THIS KIND OF MUCOUSY, YOU KNOW,

1477
00:58:27,333 --> 00:58:28,434
LIPID-LIKE STRUCTURE VERSUS ONES

1478
00:58:28,434 --> 00:58:29,935
THAT ARE A LITTLE MORE

1479
00:58:29,935 --> 00:58:31,103
TRADITIONAL FOR BACTERIAL

1480
00:58:31,103 --> 00:58:31,570
GROWTH.

1481
00:58:31,570 --> 00:58:32,872
WE PUT THOSE INTO DIFFERENT

1482
00:58:32,872 --> 00:58:34,173
MODELS TO SEE WHAT WOULD HAPPEN,

1483
00:58:34,173 --> 00:58:35,975
AND THE SHORT VERSION IS THE

1484
00:58:35,975 --> 00:58:41,547
THEY WHEALTHY VERSION WAS GOOD T

1485
00:58:41,547 --> 00:58:42,648
IMPROVING DISEASE IN MICE AND

1486
00:58:42,648 --> 00:58:44,350
BARRIER FUNCTION IN MICE AS WELL

1487
00:58:44,350 --> 00:58:46,418
AS KILLING OFF SOME OF THE BAD

1488
00:58:46,418 --> 00:58:48,487
BACTERIA SO THIS LOOKED LIKE IT

1489
00:58:48,487 --> 00:58:50,189
HAD SOME OBVIOUS POTENTIAL

1490
00:58:50,189 --> 00:58:50,723
BENEFITS.

1491
00:58:50,723 --> 00:58:52,158
THE NEXT QUESTION, OF COURSE,

1492
00:58:52,158 --> 00:58:53,993
WAS, DO WE EVEN NEED A LIVE

1493
00:58:53,993 --> 00:58:55,494
BACTERIA IF WE'RE GOING TO START

1494
00:58:55,494 --> 00:58:56,896
SPRAYING PEOPLE WITH AN ORGANISM

1495
00:58:56,896 --> 00:58:58,364
THAT ISN'T REALLY WELL-KNOWN AT

1496
00:58:58,364 --> 00:58:59,665
THE TIME, WOULDN'T IT BE BETTER

1497
00:58:59,665 --> 00:59:02,635
TO USE SOME KIND OF EXTRACT OR A

1498
00:59:02,635 --> 00:59:03,536
DEAD BACTERIA.

1499
00:59:03,536 --> 00:59:04,937
AND THE SHORT VERSION IS WE DID

1500
00:59:04,937 --> 00:59:06,038
LOTS OF DIFFERENT WAYS AND

1501
00:59:06,038 --> 00:59:06,639
NOTHING WORKED.

1502
00:59:06,639 --> 00:59:08,507
THIS IS WHAT IT LOOK LIKE WHEN

1503
00:59:08,507 --> 00:59:09,975
YOU GIVE A MOUSE ECZEMA ON THE

1504
00:59:09,975 --> 00:59:10,276
EAR.

1505
00:59:10,276 --> 00:59:11,410
THIS IS WHAT IT LOOKS LIKE WHEN

1506
00:59:11,410 --> 00:59:13,179
YOU BASICALLY COMPLETELY TAKE IT

1507
00:59:13,179 --> 00:59:14,813
AWAY USING OUR LIVING BACTERIA,

1508
00:59:14,813 --> 00:59:16,849
BUT IF YOU KILL THE BACTERIA OR

1509
00:59:16,849 --> 00:59:18,250
EXTRACT, THE LIPIDS, DO

1510
00:59:18,250 --> 00:59:19,685
WHATEVER, IT DOESN'T CUT IT.

1511
00:59:19,685 --> 00:59:21,153
SO IT REALLY DOES SEEM THAT YOU

1512
00:59:21,153 --> 00:59:22,655
NEED A LIVING ORGANISM TO PULL

1513
00:59:22,655 --> 00:59:23,889
THIS OFF.

1514
00:59:23,889 --> 00:59:25,090
AND THEN OF COURSE WE WANT TO

1515
00:59:25,090 --> 00:59:26,425
ASK IS IT SAFE.

1516
00:59:26,425 --> 00:59:28,594
BECAUSE YOU ARE SPRAYING --

1517
00:59:28,594 --> 00:59:29,929
POTENTIALLY SPRAYING THIS ON

1518
00:59:29,929 --> 00:59:31,664
CHILDREN WHO HAVE DISRUPTED SKIN

1519
00:59:31,664 --> 00:59:31,931
FUNCTION.

1520
00:59:31,931 --> 00:59:33,499
SOME OF THAT BACTERIA MIGHT GET

1521
00:59:33,499 --> 00:59:34,633
INTO THEIR BLOODSTREAM AND COULD

1522
00:59:34,633 --> 00:59:35,601
THAT BE A PROBLEM.

1523
00:59:35,601 --> 00:59:36,735
SO WHAT YOU'RE LOOKING AT HERE

1524
00:59:36,735 --> 00:59:38,571
IS MOUSE DATA, WHERE WE INJECTED

1525
00:59:38,571 --> 00:59:39,905
THE MICE ON PURPOSE WITH LARGE

1526
00:59:39,905 --> 00:59:41,373
AMOUNTS OF VARIOUS DIFFERENT

1527
00:59:41,373 --> 00:59:42,374
KINDS OF ORGANISMS.

1528
00:59:42,374 --> 00:59:48,948
THIS IS THE ONE AT THE TIME WE

1529
00:59:48,948 --> 00:59:51,350
WERE PLANNING TO USE.

1530
00:59:51,350 --> 00:59:52,384
IT JUST DOESN'T HAVE THE

1531
00:59:52,384 --> 00:59:53,586
CAPACITY TO GENERATE AN

1532
00:59:53,586 --> 00:59:55,120
INFECTION IN A MOUSE.

1533
00:59:55,120 --> 00:59:57,623
YOU CAN COMPARE THAT TO OTHER

1534
00:59:57,623 --> 01:00:01,827
HEALTHY ORGANISMS O OF THE SKIN

1535
01:00:01,827 --> 01:00:03,028
AND THAT'S NOT TRUE.

1536
01:00:03,028 --> 01:00:04,330
BECAUSE THE BACTERIA IS NATURAL

1537
01:00:04,330 --> 01:00:06,265
OR NORMAL, THAT IT'S GOING TO

1538
01:00:06,265 --> 01:00:08,100
BE -- NOT GOING TO BE ABLE TO

1539
01:00:08,100 --> 01:00:09,969
CREATE AN INFECTION BECAUSE

1540
01:00:09,969 --> 01:00:11,870
YOU'RE USING IT AT SUCH NATURAL

1541
01:00:11,870 --> 01:00:14,607
DOSES THAT WOULD BE A NATURAL

1542
01:00:14,607 --> 01:00:15,107
EXPOSURE.

1543
01:00:15,107 --> 01:00:16,475
SO WITH ALL THAT, WE GO TO THE

1544
01:00:16,475 --> 01:00:18,410
FDA AND SAY WE'D LIKE TO DO OUR

1545
01:00:18,410 --> 01:00:19,178
CLINICAL TRIAL BECAUSE OF THE

1546
01:00:19,178 --> 01:00:20,913
MOUSE STUDIES, SO THIS IS A

1547
01:00:20,913 --> 01:00:22,548
RESULT FROM THE -- WHAT WE CALL

1548
01:00:22,548 --> 01:00:24,450
THE OPEN LABEL PHASE.

1549
01:00:24,450 --> 01:00:25,551
SO EVERYBODY IN THE STUDY GOT

1550
01:00:25,551 --> 01:00:27,186
THE REAL DRUG AND THEY KNEW THAT

1551
01:00:27,186 --> 01:00:28,354
THEY WERE GETTING THE REAL DRUG.

1552
01:00:28,354 --> 01:00:30,990
WE HAD TWO DIFFERENT DOSING

1553
01:00:30,990 --> 01:00:31,724
STRATEGIES.

1554
01:00:31,724 --> 01:00:32,725
IT DEPARTMENT SEEM TO MATTER.

1555
01:00:32,725 --> 01:00:36,495
PEOPLE USED IT TWICE A WEEK FOR

1556
01:00:36,495 --> 01:00:37,496
THREE MONTHS, AND THREE TIMES A

1557
01:00:37,496 --> 01:00:39,231
WEEK FOR THE FINAL MONTH.

1558
01:00:39,231 --> 01:00:44,169
AND ON AVERAGE, GOT ABOUT 57%

1559
01:00:44,169 --> 01:00:45,537
BETTER, BUT THE IMPORTANT PART

1560
01:00:45,537 --> 01:00:46,872
WAS YOU REALLY TALKED TO THE

1561
01:00:46,872 --> 01:00:47,940
PATIENTS AND YOU ASKED THEM WHAT

1562
01:00:47,940 --> 01:00:48,874
ARE YOU LOOKING FOR.

1563
01:00:48,874 --> 01:00:50,509
THEY'RE NOT LOOKING FOR ANOTHER

1564
01:00:50,509 --> 01:00:51,710
TOPICAL PRODUCT THAT THEY'RE

1565
01:00:51,710 --> 01:00:52,478
COMMITTED TO FOR THE REST OF

1566
01:00:52,478 --> 01:00:53,045
THEIR LIFE.

1567
01:00:53,045 --> 01:00:54,079
WHAT THEY REALLY WANT IS

1568
01:00:54,079 --> 01:00:55,814
SOMETHING THEY CAN USE AND STOP

1569
01:00:55,814 --> 01:00:57,483
AND GAIN BENEFIT THAT THEY DON'T

1570
01:00:57,483 --> 01:00:58,350
HAVE TO COMMIT TO.

1571
01:00:58,350 --> 01:01:02,021
SO WE HAD THIS EXTENDED WASHOUT

1572
01:01:02,021 --> 01:01:03,756
PERIOD, WE HAD STOPPED THE DRUG

1573
01:01:03,756 --> 01:01:05,291
AT 16 WEEKS BUT THEY WERE

1574
01:01:05,291 --> 01:01:06,925
FOLLOWED FOR ANOTHER THREE OR

1575
01:01:06,925 --> 01:01:08,093
FOUR MONTHS AND THEY CAME BACK

1576
01:01:08,093 --> 01:01:09,728
AND YOU COULD SEE THAT THE

1577
01:01:09,728 --> 01:01:13,198
TREATMENT PERSISTED UP TO 36

1578
01:01:13,198 --> 01:01:14,633
WEEKS OFFICIALLY, THAT WAS THE

1579
01:01:14,633 --> 01:01:16,702
FARTHEST THAT WE LOOKED OUT.

1580
01:01:16,702 --> 01:01:18,337
YOU CAN COLLECT BACTERIAL SWABS

1581
01:01:18,337 --> 01:01:20,706
AND USING GENETIC MARKERS ASK

1582
01:01:20,706 --> 01:01:22,007
WHETHER THE BACTERIA THAT WE

1583
01:01:22,007 --> 01:01:23,409
SPRAYED ON THEM IS PRESENT ON

1584
01:01:23,409 --> 01:01:23,876
THE SKIN.

1585
01:01:23,876 --> 01:01:27,313
AND THAT'S WHAT YOU'RE SEEING

1586
01:01:27,313 --> 01:01:29,081
HERE, THAT NO ONE CAME IN WITH

1587
01:01:29,081 --> 01:01:30,716
OUR SPECIFIC STRAINS OF BACTERIA

1588
01:01:30,716 --> 01:01:33,619
WHICH MAINGS SE MAKES SENSE BUTD

1589
01:01:33,619 --> 01:01:35,354
OF THE STUDY, EVERYBODY HAD SOME

1590
01:01:35,354 --> 01:01:36,021
BACTERIA ON THE SKIN.

1591
01:01:36,021 --> 01:01:36,922
THAT'S WHAT I WOULD ANTICIPATE

1592
01:01:36,922 --> 01:01:40,225
WOULD BE ABLE TO ALLOW THEM TO

1593
01:01:40,225 --> 01:01:41,894
HAVE THE LONG TERM BENEFIT,

1594
01:01:41,894 --> 01:01:43,262
BECAUSE THE BACTERIA ARE STILL

1595
01:01:43,262 --> 01:01:44,563
THERE DOING WHAT THEY NEED TO

1596
01:01:44,563 --> 01:01:50,469
DO, BUT YOU DON'T NEED TO USE

1597
01:01:50,469 --> 01:01:51,870
THE MEDICINE FOREVER MORE.

1598
01:01:51,870 --> 01:01:53,405
SO THE WAY THIS WORKS, THE NIH

1599
01:01:53,405 --> 01:01:55,040
LICENSED IT OUT TO THE PRIVATE

1600
01:01:55,040 --> 01:02:00,145
SECTOR, WHO RAN TO THEIR CREDIT

1601
01:02:00,145 --> 01:02:01,447
AN OUTPATIENT ECZEMA TRIAL

1602
01:02:01,447 --> 01:02:02,881
THROUGH THE HEART OF THE COVID

1603
01:02:02,881 --> 01:02:03,415
PANDEMIC.

1604
01:02:03,415 --> 01:02:04,550
BUT THERE WERE SOME THINGS THAT

1605
01:02:04,550 --> 01:02:06,885
COULD HAVE BEEN DONE BETTER IN

1606
01:02:06,885 --> 01:02:07,753
RETROSPECT.

1607
01:02:07,753 --> 01:02:08,387
THE FIRST THING IS THAT

1608
01:02:08,387 --> 01:02:09,988
EVERYBODY IN THE STUDY WAS

1609
01:02:09,988 --> 01:02:11,757
FORCED TO USE A LOTION THAT HAD

1610
01:02:11,757 --> 01:02:14,360
CERAMIDES IN IT, WHICH CREATES A

1611
01:02:14,360 --> 01:02:15,461
VEHICLE EFFECT, JUST TELLING

1612
01:02:15,461 --> 01:02:17,162
SOMEBODY TO USE A CERAMIDE

1613
01:02:17,162 --> 01:02:18,597
LOTION TWO OR THREE TIMES A DAY

1614
01:02:18,597 --> 01:02:19,998
SHOULD CREATE A BENEFIT ON ITS

1615
01:02:19,998 --> 01:02:21,400
OWN, AND THEY HAVE TO ADJUST FOR

1616
01:02:21,400 --> 01:02:22,701
THAT IN THE STUDY AND THEY DID

1617
01:02:22,701 --> 01:02:23,502
NOT.

1618
01:02:23,502 --> 01:02:26,839
BUT THE OTHER THING IS THAT

1619
01:02:26,839 --> 01:02:28,173
THERE WAS KIND OF THIS LONG

1620
01:02:28,173 --> 01:02:28,741
WASHOUT PERIOD.

1621
01:02:28,741 --> 01:02:31,310
THIS IS THE -- THEY STOPPED THE

1622
01:02:31,310 --> 01:02:32,311
MEDICINE AT FOUR MONTHS AND THEN

1623
01:02:32,311 --> 01:02:33,846
A MONTH LATER, WHICH IS AS FAR

1624
01:02:33,846 --> 01:02:35,547
AS THEY LOOKED, WE LOOKED AT 36

1625
01:02:35,547 --> 01:02:36,882
WEEKS, LIKE I SAID, THE PEOPLE

1626
01:02:36,882 --> 01:02:38,584
WHO WERE TREATED WITH THE REAL

1627
01:02:38,584 --> 01:02:40,018
DRUG, THE BENEFITS PERSISTED,

1628
01:02:40,018 --> 01:02:41,754
WHEREAS THE PLACEBO EFFECT

1629
01:02:41,754 --> 01:02:42,855
STARTED TO WEAR OFF, WHICH IS

1630
01:02:42,855 --> 01:02:44,556
WHAT YOU WOULD ANTICIPATE.

1631
01:02:44,556 --> 01:02:45,991
SO COULD HAVE BEEN BETTER, SO

1632
01:02:45,991 --> 01:02:48,927
WE'RE REDOING THIS TRIAL AND THE

1633
01:02:48,927 --> 01:02:50,996
TWO MAJOR CHANGES, NO ONE IS

1634
01:02:50,996 --> 01:02:52,164
BEING FORCED TO USE ANY

1635
01:02:52,164 --> 01:02:52,731
PARTICULAR LOTION AND WE'RE

1636
01:02:52,731 --> 01:02:54,266
GOING TO HAVE A MUCH LONGER

1637
01:02:54,266 --> 01:02:55,100
WASHOUT PERIOD UNDER THE

1638
01:02:55,100 --> 01:02:56,201
ANTICIPATION THAT EVEN IF YOU

1639
01:02:56,201 --> 01:02:57,736
HAVE PLACEBO RESPONSE, IT'S NOT

1640
01:02:57,736 --> 01:02:59,605
GOING TO STAY FOR THREE OR FOUR

1641
01:02:59,605 --> 01:03:00,806
MONTHS VERSUS THE TREATMENT

1642
01:03:00,806 --> 01:03:02,508
WHICH WE EXPECT TO HOLD TIGHT.

1643
01:03:02,508 --> 01:03:07,846
SO WE'RE STILL RUNNING THAT.

1644
01:03:07,846 --> 01:03:09,314
BUT BECAUSE IT SURE LOOKS LIKE

1645
01:03:09,314 --> 01:03:11,984
IT HAS SOME EVIDENCE FOR

1646
01:03:11,984 --> 01:03:14,052
EFFICACY AND THE SAFETY LOOKS

1647
01:03:14,052 --> 01:03:16,588
FANTASTIC, A FEW PEOPLE WHO --

1648
01:03:16,588 --> 01:03:17,823
IT FEELS A LITTLE WEIRD GOING ON

1649
01:03:17,823 --> 01:03:19,158
BECAUSE IT'S GOT SUGAR IN THERE

1650
01:03:19,158 --> 01:03:21,126
AS THE STABILIZER, BUT THIS IS

1651
01:03:21,126 --> 01:03:24,129
WHERE NIH MADE THE DEAL WITH

1652
01:03:24,129 --> 01:03:25,898
SKINESA TO SELL IT, SO SOME

1653
01:03:25,898 --> 01:03:27,966
PATIENTS ARE ALREADY USING THIS

1654
01:03:27,966 --> 01:03:28,801
OVER THE COUNTER AND THIS IS

1655
01:03:28,801 --> 01:03:31,537
AVAILABLE.

1656
01:03:31,537 --> 01:03:33,739
SO LIKE I SAID, OUR YOUNG MAN

1657
01:03:33,739 --> 01:03:35,040
CAME IN AND THIS IS WHAT HE

1658
01:03:35,040 --> 01:03:36,642
LOOKS LIKE, YOU KNOW, 8 WEEKS

1659
01:03:36,642 --> 01:03:37,843
LATER.

1660
01:03:37,843 --> 01:03:40,813
HE WAS ABLE TO SUSTAIN IT,

1661
01:03:40,813 --> 01:03:43,649
RETURNED TO CAMPUS, IT WAS

1662
01:03:43,649 --> 01:03:44,917
OVERALL DOING WELL AND THEN

1663
01:03:44,917 --> 01:03:47,553
NOTICED KIND OF SLIGHT WORSENING

1664
01:03:47,553 --> 01:03:51,590
IN HIS NEW DORM ROOM, NOTHING

1665
01:03:51,590 --> 01:03:52,925
BACK TO WHERE HE WAS BUT THEN IS

1666
01:03:52,925 --> 01:03:54,493
KIND OF ASKING THE QUESTION OF

1667
01:03:54,493 --> 01:03:56,028
LIKE, ALL RIGHT, IT WAS WORKING,

1668
01:03:56,028 --> 01:03:57,262
NOW IT'S NOT, WHAT DO YOU THINK

1669
01:03:57,262 --> 01:03:58,397
IS GOING ON?

1670
01:03:58,397 --> 01:04:00,466
AND AGAIN, THIS IS KIND OF THE

1671
01:04:00,466 --> 01:04:02,100
BROADER QUESTION NOT JUST WITHIN

1672
01:04:02,100 --> 01:04:06,138
AN INDIVIDUAL PATIENT, WHY AM I

1673
01:04:06,138 --> 01:04:08,874
FLARING TODAY WHEN I WAS FINE

1674
01:04:08,874 --> 01:04:09,975
TOMORROW?

1675
01:04:09,975 --> 01:04:11,176
BUT IT'S GREAT THAT THESE

1676
01:04:11,176 --> 01:04:12,478
BACTERIA CAN BE USED AS THERAPY,

1677
01:04:12,478 --> 01:04:13,645
BUT IT DOESN'T ANSWER IN ANY

1678
01:04:13,645 --> 01:04:15,280
WAY, SHAPE OR FORM WHY WE SHOULD

1679
01:04:15,280 --> 01:04:16,615
HAVE SUCH A PROBLEM SINCE THE

1680
01:04:16,615 --> 01:04:17,115
1970s.

1681
01:04:17,115 --> 01:04:18,417
SO TO GET AT THAT, WE STARTED

1682
01:04:18,417 --> 01:04:19,451
WITH TWO -- WE STARTED WITH THE

1683
01:04:19,451 --> 01:04:20,486
FIRST APPROACH ASKING THE

1684
01:04:20,486 --> 01:04:21,987
QUESTION OF LIKE ALL THE TOPICAL

1685
01:04:21,987 --> 01:04:23,188
SOAPS AND PRODUCTS AND STUFF

1686
01:04:23,188 --> 01:04:26,058
THAT WE USE NOWADAYS THAT HAVE A

1687
01:04:26,058 --> 01:04:26,859
THOUSAND INGREDIENTS IN THE

1688
01:04:26,859 --> 01:04:27,192
BACK.

1689
01:04:27,192 --> 01:04:28,594
LIKE I SAID, YOU CAN GO TO THE

1690
01:04:28,594 --> 01:04:30,896
STORE AND FIND ONE THAT BRAGS

1691
01:04:30,896 --> 01:04:32,631
THAT IT HAS CERAMIDES BUT THAT'S

1692
01:04:32,631 --> 01:04:33,832
NOT THE ONLY THING IT HAS IN

1693
01:04:33,832 --> 01:04:34,700
THAT BOTTLE.

1694
01:04:34,700 --> 01:04:36,034
SO ONE OF THE FIRST THINGS WE

1695
01:04:36,034 --> 01:04:37,736
LOOKED AT IS THE ABILITY OF

1696
01:04:37,736 --> 01:04:39,838
DIFFERENT WHAT THEY CALL

1697
01:04:39,838 --> 01:04:41,807
EMOLLIENTS OR MOISTURIZERS, THE

1698
01:04:41,807 --> 01:04:43,809
DIFFERENT CHEMICAL INGREDIENTS

1699
01:04:43,809 --> 01:04:45,277
TO KILL OFF THE GOOD BACTERIA

1700
01:04:45,277 --> 01:04:47,546
AND WE DO THIS -- THIS IS THE

1701
01:04:47,546 --> 01:04:51,617
SAME PLATE THAT YOU WOULD USE TO

1702
01:04:51,617 --> 01:04:54,086
TEST IF A BACTERIA IS RESISTANT

1703
01:04:54,086 --> 01:04:54,753
TO PENICILLIN.

1704
01:04:54,753 --> 01:05:00,058
SO THIS IS OUR GOOD KIND OF

1705
01:05:00,058 --> 01:05:00,325
ROSIMONAS.

1706
01:05:00,325 --> 01:05:03,595
YOU CAN SEE IT KILLS IT OFF AND

1707
01:05:03,595 --> 01:05:05,230
BLEACHES IT BEYOND THE INITIAL

1708
01:05:05,230 --> 01:05:07,833
CORE, AND THIS IS STAPH AUREUS

1709
01:05:07,833 --> 01:05:09,134
THAT FOR THE MOST PART SEEMS

1710
01:05:09,134 --> 01:05:10,335
PRETTY WELL ADJUSTED TO BEING

1711
01:05:10,335 --> 01:05:11,603
ABLE TO SURVIVE IN THE FACE OF

1712
01:05:11,603 --> 01:05:12,704
PAIR BINS.

1713
01:05:12,704 --> 01:05:13,772
SO WHAT THIS MEANS IS THAT SOME

1714
01:05:13,772 --> 01:05:16,041
OF THE PRODUCTS THAT YOU BUY

1715
01:05:16,041 --> 01:05:17,376
OVER THE STORE THAT YOU'RE

1716
01:05:17,376 --> 01:05:18,577
SLATHERING ON, THOSE

1717
01:05:18,577 --> 01:05:22,281
PRESERVATIVES THAT THEY USE IN

1718
01:05:22,281 --> 01:05:24,816
THERE ARE MEANT TO KEEP

1719
01:05:24,816 --> 01:05:26,184
MICROORGANISMS FROM GROWING AND

1720
01:05:26,184 --> 01:05:27,819
IF YOU SLATHER THOSE ON YOUR

1721
01:05:27,819 --> 01:05:29,021
SKIN, SOME OF THOSE WILL BE

1722
01:05:29,021 --> 01:05:30,355
REALLY GOOD AT KEEPING YOUR

1723
01:05:30,355 --> 01:05:31,423
COMMENSAL ORGANISMS FROM GROWING

1724
01:05:31,423 --> 01:05:33,258
AND WILL GIVE AN ADVANTAGE OR

1725
01:05:33,258 --> 01:05:34,459
DISADVANTAGE TO THE GOOD

1726
01:05:34,459 --> 01:05:36,161
BACTERIA OR BAD BACTERIA

1727
01:05:36,161 --> 01:05:37,496
DEPENDING ON THE SPECIFIC

1728
01:05:37,496 --> 01:05:37,796
INGREDIENTS.

1729
01:05:37,796 --> 01:05:38,463
THE OTHER PROBLEM IS THAT SOME

1730
01:05:38,463 --> 01:05:40,232
OF THESE MOISTURIZERS CAN

1731
01:05:40,232 --> 01:05:41,300
CONTAIN IRRITANTS THEMSELVES, SO

1732
01:05:41,300 --> 01:05:44,670
THIS IS FROM ONE STUDY THAT -- A

1733
01:05:44,670 --> 01:05:45,837
META-ANALYSIS THAT COLLECTED A

1734
01:05:45,837 --> 01:05:46,838
BUNCH OF DIFFERENT STUDIES AND

1735
01:05:46,838 --> 01:05:48,173
LOOKED AT WHAT ARE THE RATES OF

1736
01:05:48,173 --> 01:05:49,575
DIFFERENT TOPICAL PRODUCTS THAT

1737
01:05:49,575 --> 01:05:53,478
PEOPLE ARE STUDYING, HOW MANY OF

1738
01:05:53,478 --> 01:05:54,980
THEM HAVE A KNOWN IRRITANT OR

1739
01:05:54,980 --> 01:05:56,214
SOMETHING WE KNOW PEOPLE WILL

1740
01:05:56,214 --> 01:05:58,216
POTENTIALLY REACT TO.

1741
01:05:58,216 --> 01:06:03,589
ONLY 25% HAD NONE.

1742
01:06:03,589 --> 01:06:04,790
SO A LARGE PERCENTAGE OF

1743
01:06:04,790 --> 01:06:05,557
PRODUCTS ON THE SHELF WILL

1744
01:06:05,557 --> 01:06:06,558
EITHER HAVE SOMETHING THAT IS A

1745
01:06:06,558 --> 01:06:07,726
KNOWN IRRITANT OR IT WILL HAVE

1746
01:06:07,726 --> 01:06:09,595
SOMETHING THAT KILLS OFF YOUR

1747
01:06:09,595 --> 01:06:10,662
POTENTIALLY GOOD BACTERIA.

1748
01:06:10,662 --> 01:06:11,964
SO THAT BECOMES A LITTLE

1749
01:06:11,964 --> 01:06:16,568
PROBLEMATIC IN TERMS OF HOW ARE

1750
01:06:16,568 --> 01:06:17,869
PATIENTS SUPPOSED TO DEAL AND

1751
01:06:17,869 --> 01:06:19,838
PICK OUT THEIR BEST

1752
01:06:19,838 --> 01:06:20,505
MOISTURIZERS.

1753
01:06:20,505 --> 01:06:21,540
BUT WE DIDN'T START WITH THAT IN

1754
01:06:21,540 --> 01:06:22,541
THE 1970s.

1755
01:06:22,541 --> 01:06:23,408
THERE'S ABSOLUTELY NO WAY THAT

1756
01:06:23,408 --> 01:06:28,080
THAT COULD CREATE THIS KIND OF

1757
01:06:28,080 --> 01:06:29,081
IMPACT ON THE ENTIRETY OF

1758
01:06:29,081 --> 01:06:30,749
SOCIETY IN SUCH A SHORT PERIOD

1759
01:06:30,749 --> 01:06:32,351
OF TIME SO WE FIGURED IT HAD TO

1760
01:06:32,351 --> 01:06:33,018
BE SOMETHING DIFFERENT.

1761
01:06:33,018 --> 01:06:37,756
SO WHAT WE DID WAS, WE'RE

1762
01:06:37,756 --> 01:06:39,725
LOOKING FOR ECZEMA HOT SPOTS

1763
01:06:39,725 --> 01:06:41,059
THAT YOU'VE PROBABLY HEARD FOR

1764
01:06:41,059 --> 01:06:42,961
CANCER CLUSTERS OR THINGS THAT

1765
01:06:42,961 --> 01:06:43,862
ERIN BROCKOVICH MADE FAMOUS IN

1766
01:06:43,862 --> 01:06:45,063
THE MOVIE AND THE BOOK.

1767
01:06:45,063 --> 01:06:48,467
SO WHAT WE'RE DOING IS SAYING

1768
01:06:48,467 --> 01:06:51,370
WHICH TOWNS HAVE WAY MORE ATOPIC

1769
01:06:51,370 --> 01:06:52,904
DERM THAN WE EXPECT ON AVERAGE,

1770
01:06:52,904 --> 01:06:57,142
WHICH HAVE WAY LESS, BHU USING

1771
01:06:57,142 --> 01:06:58,877
EPA DATABASES, WHICH CHEMICALS

1772
01:06:58,877 --> 01:07:00,212
ARE OVERREPRESENTED IN EACH OF

1773
01:07:00,212 --> 01:07:01,179
THOSE DIFFERENT ZIP CODES.

1774
01:07:01,179 --> 01:07:04,750
TO CUT TO THE CHASE, THESE TWO

1775
01:07:04,750 --> 01:07:06,284
CHEMICALS ARE FAR AND AWAY THE

1776
01:07:06,284 --> 01:07:10,122
ONES WITH THE STRONGEST

1777
01:07:10,122 --> 01:07:11,623
ASSOCIATION WITH DISEASE ON A

1778
01:07:11,623 --> 01:07:12,057
POPULATION LEVEL.

1779
01:07:12,057 --> 01:07:14,026
WE THEN WANT TO GO BACK AND LOOK

1780
01:07:14,026 --> 01:07:15,661
AT THOSE DIFFERENT EPIDEMIOLOGIC

1781
01:07:15,661 --> 01:07:19,031
FACTORS THAT I TOLD YOU, LIVING

1782
01:07:19,031 --> 01:07:20,565
IN AN INDUSTRIALIZED

1783
01:07:20,565 --> 01:07:22,701
ENVIRONMENT, AUTOMOBILE EXHAUST,

1784
01:07:22,701 --> 01:07:24,269
AND WE START TO ASK THE

1785
01:07:24,269 --> 01:07:25,337
QUESTION, ARE THERE SIGNS THAT

1786
01:07:25,337 --> 01:07:29,708
THESE CHEMICALS ALIGN WITH THOSE

1787
01:07:29,708 --> 01:07:30,609
EXPOSURES?

1788
01:07:30,609 --> 01:07:33,612
SO TDI IS THE NUMBER ONE

1789
01:07:33,612 --> 01:07:37,883
ISOCYANATE, SO IN EARNEST ITS

1790
01:07:37,883 --> 01:07:41,386
MANUFACTURING BEGAN AROUND 1970.

1791
01:07:41,386 --> 01:07:44,656
XYLENE GAME -- MANUFACTURING FOR

1792
01:07:44,656 --> 01:07:46,425
IT ALSO KICKS OFF IN THE UNITED

1793
01:07:46,425 --> 01:07:48,160
STATES ON OR AROUND 1970 SO

1794
01:07:48,160 --> 01:07:49,361
THESE START TO SPRING UP RIGHT

1795
01:07:49,361 --> 01:07:50,829
AROUND THESE OUTBREAKS.

1796
01:07:50,829 --> 01:07:52,297
PRIOR TO 1970, NOT A SINGLE

1797
01:07:52,297 --> 01:07:53,565
AUTOMOBILE ON THE ROAD PRODUCED

1798
01:07:53,565 --> 01:07:55,300
EITHER ONE OF THESE CHEMICALS.

1799
01:07:55,300 --> 01:07:57,703
IN 1970, WE BEGAN TRANSITIONING

1800
01:07:57,703 --> 01:08:01,306
OFF OF LEADED GASOLINE AND ON TO

1801
01:08:01,306 --> 01:08:02,040
NON-LEADED GASOLINE.

1802
01:08:02,040 --> 01:08:05,343
I WOULD LIKE TO NOTE COMING OFF

1803
01:08:05,343 --> 01:08:08,180
LEADED GASOLINE HAS ITS OWN

1804
01:08:08,180 --> 01:08:12,417
MASSIVE BENEFITS BUT AN

1805
01:08:12,417 --> 01:08:13,952
UNFORTUNATE UNINTEND THE

1806
01:08:13,952 --> 01:08:15,120
CONSEQUENCE THAT AFTER THE

1807
01:08:15,120 --> 01:08:17,122
CATALYTIC CONVERTER WAS MANDATED

1808
01:08:17,122 --> 01:08:18,190
IN 1970 EVERY AUTOMOBILE BECAME

1809
01:08:18,190 --> 01:08:20,358
A PRODUCER OF XYLENE AND

1810
01:08:20,358 --> 01:08:21,460
ISOCYANATES, THUS POTENTIALLY

1811
01:08:21,460 --> 01:08:22,961
EXPLAINING THE CONNECTION WITH

1812
01:08:22,961 --> 01:08:23,762
HIGHWAYS.

1813
01:08:23,762 --> 01:08:25,130
THE ONLY NATURAL SOURCE OF BOTH

1814
01:08:25,130 --> 01:08:26,798
OF THESE CHEMICALS IS WILDFIRES

1815
01:08:26,798 --> 01:08:28,700
OR TIMBER WASTE.

1816
01:08:28,700 --> 01:08:31,636
SO THAT WAS CONCERNING.

1817
01:08:31,636 --> 01:08:32,871
THEN WHEN WE WENT THROUGH TO

1818
01:08:32,871 --> 01:08:34,973
START LOOKING, BECAUSE WHEN

1819
01:08:34,973 --> 01:08:37,209
THESE CAME UP, I HAD NEVER HEARD

1820
01:08:37,209 --> 01:08:38,310
OF THESE CHEMICALS IN OUR

1821
01:08:38,310 --> 01:08:38,877
ANALYSIS.

1822
01:08:38,877 --> 01:08:40,178
YOU START LOOKING IN WHAT THESE

1823
01:08:40,178 --> 01:08:43,548
THINGS ARE FOUND ON, THEY ARE IN

1824
01:08:43,548 --> 01:08:47,686
NEW FURNITURE, WALLPAPER GLUE,

1825
01:08:47,686 --> 01:08:50,522
SEALANTS AND PAINTS, ALL OF THE

1826
01:08:50,522 --> 01:08:52,791
THINGS THAT YOU WOULD USE TO

1827
01:08:52,791 --> 01:08:54,659
REMODEL A HOME ALMOST ALL

1828
01:08:54,659 --> 01:08:57,062
REQUIRE ONE IF NOT BOTH OF THESE

1829
01:08:57,062 --> 01:08:57,496
CHEMICALS.

1830
01:08:57,496 --> 01:08:58,663
LOOKING AT THE MECHANISM, I

1831
01:08:58,663 --> 01:08:59,564
WON'T BEAT THIS TO DEATH BUT THE

1832
01:08:59,564 --> 01:09:01,299
SHORT VERSION IS YOUR BACTERIA

1833
01:09:01,299 --> 01:09:02,300
BREATHED NITROGEN, AT LEAST THE

1834
01:09:02,300 --> 01:09:05,003
ONES ON THE SKIN, AND THESE

1835
01:09:05,003 --> 01:09:06,204
PARTICULAR CHEMICALS CHOKE OFF

1836
01:09:06,204 --> 01:09:07,639
THEIR ABILITY TO BREATHE

1837
01:09:07,639 --> 01:09:09,708
NITROGEN SO THE WAY THEY GET

1838
01:09:09,708 --> 01:09:11,243
AROUND THAT IS THEY STOP MAKING

1839
01:09:11,243 --> 01:09:12,744
THESE BENEFICIAL LIPIDS, THEY

1840
01:09:12,744 --> 01:09:14,613
TURN OFF THEIR CERAMIDE

1841
01:09:14,613 --> 01:09:16,648
PRODUCTION, AND THEY START

1842
01:09:16,648 --> 01:09:17,315
SHIFTING THEIR PHYSIOLOGY TO

1843
01:09:17,315 --> 01:09:18,517
SOMETHING THAT WILL PROTECT THEM

1844
01:09:18,517 --> 01:09:20,285
FROM THESE CHEMICALS BUT COME AT

1845
01:09:20,285 --> 01:09:20,819
OUR EXPENSE.

1846
01:09:20,819 --> 01:09:22,687
YOU CAN ACTUALLY WATCH THIS

1847
01:09:22,687 --> 01:09:24,756
HAPPEN ON THE DOSING, SO IN RED

1848
01:09:24,756 --> 01:09:26,958
IS THE AMOUNT OF CERAMIDES THAT

1849
01:09:26,958 --> 01:09:28,460
THESE BACTERIA ARE MAKING AND AS

1850
01:09:28,460 --> 01:09:30,562
A CRANK UP THE DOSE OF THESE

1851
01:09:30,562 --> 01:09:32,197
PARTICULAR CHEMICALS, THIS ONE

1852
01:09:32,197 --> 01:09:34,266
IS ISOCYANATE, I CAN TURN OFF

1853
01:09:34,266 --> 01:09:36,535
THE BA BACTERIA'S ABILITY TO MAE

1854
01:09:36,535 --> 01:09:38,203
THESE PARTICULAR LIPIDS, EVEN IN

1855
01:09:38,203 --> 01:09:40,472
LOWER CONCENTRATIONS WHERE THE

1856
01:09:40,472 --> 01:09:41,907
BACTERIAL GROWTH IS IMPROVED.

1857
01:09:41,907 --> 01:09:42,774
SO THESE BACTERIA HAVE THE

1858
01:09:42,774 --> 01:09:46,244
ABILITY TO EAT THESE TOXINS AND

1859
01:09:46,244 --> 01:09:48,280
GROW MORE, BUT THEY'RE DOING IT

1860
01:09:48,280 --> 01:09:50,515
AT THE EXPENSE OF OUR LIPID

1861
01:09:50,515 --> 01:09:54,553
PHYSIOLOGY AND SO TURNING OFF

1862
01:09:54,553 --> 01:09:57,823
THESE PARTICULAR PATHWAYS.

1863
01:09:57,823 --> 01:09:58,890
SO CONNECTING IT BACK TO THE

1864
01:09:58,890 --> 01:10:01,092
REAL WORLD TO SAY ALL RIGHT, IT

1865
01:10:01,092 --> 01:10:02,360
LOOKS LIKE THESE THINGS ARE

1866
01:10:02,360 --> 01:10:03,528
TURNING OFF THESE LIPIDS, IS

1867
01:10:03,528 --> 01:10:04,563
THERE ANYTHING IN THE REAL WORLD

1868
01:10:04,563 --> 01:10:05,430
THAT MIGHT BE CONCERNING?

1869
01:10:05,430 --> 01:10:06,832
I'LL SHOW YOU TWO THING HERE.

1870
01:10:06,832 --> 01:10:08,567
THE FIRST IS GOING BACK TO THAT

1871
01:10:08,567 --> 01:10:10,769
CLINICAL TRIAL, SO IF YOU GOT

1872
01:10:10,769 --> 01:10:11,870
TREATED, THAT'S THE ONE IN THE

1873
01:10:11,870 --> 01:10:13,271
PINK, WITH THE REAL TREATMENT

1874
01:10:13,271 --> 01:10:14,906
VERSUS THE BLACK WHICH IS THE

1875
01:10:14,906 --> 01:10:15,874
PLACEBO, YOU NOTICE ONCE AGAIN

1876
01:10:15,874 --> 01:10:17,843
LIKE I SHOWED YOU BEFORE, THE

1877
01:10:17,843 --> 01:10:19,377
PLACEBO WEARS OFF AND THE PINK

1878
01:10:19,377 --> 01:10:21,012
ONES HOLD TIGHT.

1879
01:10:21,012 --> 01:10:23,114
BUT IF YOU LIVE IN AN AREA WHERE

1880
01:10:23,114 --> 01:10:25,050
YOU HAVE MORE THAN AVERAGE

1881
01:10:25,050 --> 01:10:26,685
ISOCYANATE EXPOSURE, THE

1882
01:10:26,685 --> 01:10:27,786
BACTERIA ACTUALLY WORKED EVEN

1883
01:10:27,786 --> 01:10:28,920
BETTER FOR THOSE PEOPLE THAN

1884
01:10:28,920 --> 01:10:31,356
PEOPLE WHO LIVE IN BELOW AVERAGE

1885
01:10:31,356 --> 01:10:32,123
AREAS.

1886
01:10:32,123 --> 01:10:34,092
AND WE ARE FOLLOWING UP ON THIS

1887
01:10:34,092 --> 01:10:36,161
IN OUR SUBSEQUENT STUDY MORE

1888
01:10:36,161 --> 01:10:38,230
PURPOSEFULLY, BUT THE TAKE-HOME

1889
01:10:38,230 --> 01:10:39,598
FROM THIS IN OUR MIND IS THAT IF

1890
01:10:39,598 --> 01:10:41,399
YOU LIVE IN AN AREA WHERE YOUR

1891
01:10:41,399 --> 01:10:42,601
NATURAL BACTERIA ARE MORE LIKELY

1892
01:10:42,601 --> 01:10:45,303
TO BE POISONED OFF BY THESE

1893
01:10:45,303 --> 01:10:46,605
CHEMICALS, THEN REPLACING THEM

1894
01:10:46,605 --> 01:10:47,939
WITH BETTER BACTERIA IS GOING TO

1895
01:10:47,939 --> 01:10:49,341
BE MORE BENEFICIAL TO YOU THAN

1896
01:10:49,341 --> 01:10:50,642
IF YOU LIVE IN AN OTHERWISE

1897
01:10:50,642 --> 01:10:54,145
PRISTINE ENVIRONMENT.

1898
01:10:54,145 --> 01:10:55,680
THE LAST THING WE CAN DO IS TEST

1899
01:10:55,680 --> 01:10:57,315
THIS IN THE LAB, SO ALL OF THOSE

1900
01:10:57,315 --> 01:10:57,849
DIFFERENT THINGS THAT YOU

1901
01:10:57,849 --> 01:10:58,950
BROUGHT IN YOUR HOME, WE CAN

1902
01:10:58,950 --> 01:10:59,951
TEST THAT IN THE LAB.

1903
01:10:59,951 --> 01:11:02,787
SO HERE'S WHAT HAPPENS WHEN YOU

1904
01:11:02,787 --> 01:11:03,788
SPRAY STAPH AUREUS ON TO

1905
01:11:03,788 --> 01:11:05,390
DIFFERENT KINDS OF BED SHEETS

1906
01:11:05,390 --> 01:11:06,491
MADE OUT OF THESE DIFFERENT

1907
01:11:06,491 --> 01:11:08,126
MATERIALS, JUST LET THEM SIT AND

1908
01:11:08,126 --> 01:11:09,861
SEE HOW LONG THEY CAN SURVIVE ON

1909
01:11:09,861 --> 01:11:11,296
THE BED SHEETS BY THEMSELVES AND

1910
01:11:11,296 --> 01:11:11,730
LOOK AT THE GROWTH.

1911
01:11:11,730 --> 01:11:13,832
SO YOU CAN SEE COTTON AND BAMBOO

1912
01:11:13,832 --> 01:11:15,533
DO NOT SUPPORT THE GROWTH OF

1913
01:11:15,533 --> 01:11:16,768
STAPH AUREUS VERY LONG, EVEN

1914
01:11:16,768 --> 01:11:18,737
THOUGH THESE OTHER SYNTHETIC FAB

1915
01:11:18,737 --> 01:11:23,942
BRIFABRICS DO.

1916
01:11:23,942 --> 01:11:27,679
YOU MUTE L MIGHT LOOK AT OUR GOD

1917
01:11:27,679 --> 01:11:29,948
BACTERIA AND SAY THIS IS GOOD

1918
01:11:29,948 --> 01:11:31,249
NEWS, OF COURSE THE BAD NEWS IS

1919
01:11:31,249 --> 01:11:33,451
GROWING ON SPANDEX, NYLON OR

1920
01:11:33,451 --> 01:11:34,519
POLYESTER CAUSES THEM TO ONCE

1921
01:11:34,519 --> 01:11:35,620
AGAIN SHIFT THEIR PHYSIOLOGY.

1922
01:11:35,620 --> 01:11:37,689
SO THEY'LL GROW ON THOSE

1923
01:11:37,689 --> 01:11:39,991
FABRICS, BUT THEY WILL STOP

1924
01:11:39,991 --> 01:11:42,060
MAKING LIPIDS IN ORDER TO GROW

1925
01:11:42,060 --> 01:11:44,229
ON THOSE FABRICS.

1926
01:11:44,229 --> 01:11:46,331
AND SO FOR OUR PATIENT, WE KIND

1927
01:11:46,331 --> 01:11:48,600
OF GAVE HIM SOME GENERAL ADVICE,

1928
01:11:48,600 --> 01:11:50,068
SO IN HIS DORM, HE FOUND OUT HE

1929
01:11:50,068 --> 01:11:53,505
HAD A MEMORY FOAM MATTRESS SO HE

1930
01:11:53,505 --> 01:11:56,007
SWITCHED TO A LATEX FOAM

1931
01:11:56,007 --> 01:11:56,474
MATTRESS.

1932
01:11:56,474 --> 01:11:58,109
SHEETS WERE POLYESTER, HE

1933
01:11:58,109 --> 01:11:59,744
SWITCHED OVER TO COTTON.

1934
01:11:59,744 --> 01:12:01,346
I'M NOT -- I AM AWARE THAT THIS

1935
01:12:01,346 --> 01:12:03,748
IS NOT A 0-DOLLAR EVENT SO NOT

1936
01:12:03,748 --> 01:12:04,849
EVERYONE IS GOING TO BE ABLE TO

1937
01:12:04,849 --> 01:12:05,517
DO THAT.

1938
01:12:05,517 --> 01:12:07,052
HE GOT HIMSELF AN AIR FILTER.

1939
01:12:07,052 --> 01:12:08,987
WE CAN COME BACK TO THAT IF YOU

1940
01:12:08,987 --> 01:12:09,220
WANT.

1941
01:12:09,220 --> 01:12:10,622
IT'S HARD TO KNOW EXACTLY WHICH

1942
01:12:10,622 --> 01:12:12,490
ONE TO GET, BUT HE SEEMED TO

1943
01:12:12,490 --> 01:12:14,993
IMPROVE BACK TO HIS KIND OF

1944
01:12:14,993 --> 01:12:16,094
POST-TREATMENT LEVELS FOR WHAT

1945
01:12:16,094 --> 01:12:17,395
IT'S WORTH.

1946
01:12:17,395 --> 01:12:21,132
SO THESE TWO CHEMICALS ALIGN

1947
01:12:21,132 --> 01:12:23,868
WITH ISOCYANATES IN TIME IN

1948
01:12:23,868 --> 01:12:25,270
TERMS OF WHEN THEY HIT THE

1949
01:12:25,270 --> 01:12:26,137
MARKET SPACE IN TERMS OF WHERE

1950
01:12:26,137 --> 01:12:29,274
THEY ARE IN THE COUNTRY AND IN

1951
01:12:29,274 --> 01:12:29,641
YOUR HOME.

1952
01:12:29,641 --> 01:12:31,142
WE HAVE MECHANISMS THAT IMPLY

1953
01:12:31,142 --> 01:12:32,577
THAT BOTH THE INDIVIDUAL IS

1954
01:12:32,577 --> 01:12:34,546
HARMED AND THE MICROBIOME, SO

1955
01:12:34,546 --> 01:12:36,815
THE REALLY TAKE HOME POINTS FOR

1956
01:12:36,815 --> 01:12:38,249
THIS, THERE'S SOMETHING TO BE

1957
01:12:38,249 --> 01:12:39,684
HAD ABOUT GENUINE PREVENTION, IF

1958
01:12:39,684 --> 01:12:42,387
YOU REALLY WANT TO START TALKING

1959
01:12:42,387 --> 01:12:43,421
ABOUT PREVENTING THESE DISEASES

1960
01:12:43,421 --> 01:12:45,657
IN KIDS, YOU NEED TO START

1961
01:12:45,657 --> 01:12:47,192
PROTECTING THEM FROM THESE

1962
01:12:47,192 --> 01:12:48,259
EXPOSURES EARLY IN LIFE BECAUSE

1963
01:12:48,259 --> 01:12:49,461
A LOT OF TIMES PREVENTION

1964
01:12:49,461 --> 01:12:50,895
STUDIES TALK ABOUT SLATHERING

1965
01:12:50,895 --> 01:12:54,132
THEM IN SOME KIND OF MOISTURIZER

1966
01:12:54,132 --> 01:12:55,600
OR GIVING THEM A DRUG.

1967
01:12:55,600 --> 01:12:56,835
THAT'S NOT REALLY PREVENTION IN

1968
01:12:56,835 --> 01:12:57,769
THE WAY THAT WE WOULD THINK

1969
01:12:57,769 --> 01:12:59,070
ABOUT IT.

1970
01:12:59,070 --> 01:12:59,938
THERE'S IMPLICATIONS FOR

1971
01:12:59,938 --> 01:13:00,805
DISPARITIES IN TERMS OF THE

1972
01:13:00,805 --> 01:13:02,007
POPULATIONS THAT GET EXPOSED TO

1973
01:13:02,007 --> 01:13:03,074
THE MOST AMOUNT OF THESE

1974
01:13:03,074 --> 01:13:03,808
PARTICULAR DISORDERS ARE ALSO

1975
01:13:03,808 --> 01:13:06,177
THE ONES THAT HAVE THE HIGHEST

1976
01:13:06,177 --> 01:13:08,480
RATES OF ATOPIC DERM AND OTHER

1977
01:13:08,480 --> 01:13:09,347
ALLERGIC DISEASES SO THAT'S

1978
01:13:09,347 --> 01:13:10,015
SOMETHING THAT SHOULDING

1979
01:13:10,015 --> 01:13:10,882
FOLLOWED UP ON.

1980
01:13:10,882 --> 01:13:13,785
AND THERE'S SOMETHING TO BE HAD

1981
01:13:13,785 --> 01:13:14,486
ABOUT OTHER DISEASES.

1982
01:13:14,486 --> 01:13:16,221
WE MADE THE MODEL OF TRYING TO

1983
01:13:16,221 --> 01:13:17,655
FIND THE ECZEMA HOT SPOTS AND

1984
01:13:17,655 --> 01:13:20,458
THEN LOOKING FOR THE CHEMICALS

1985
01:13:20,458 --> 01:13:22,127
ASSOCIATED WITH THOSE ECZEMA HOT

1986
01:13:22,127 --> 01:13:22,761
SPOTS.

1987
01:13:22,761 --> 01:13:25,063
WE'VE SINCE EXPANDED TO MANY

1988
01:13:25,063 --> 01:13:25,930
OTHER DISEASES.

1989
01:13:25,930 --> 01:13:28,233
I AM JUST SHOWING YOU THE ONES

1990
01:13:28,233 --> 01:13:30,735
FOR WATER POLLUTION IN CHILDREN

1991
01:13:30,735 --> 01:13:32,704
6 TO 17, AND THIS IS UNPUBLISHED

1992
01:13:32,704 --> 01:13:34,105
BUT WE'RE WORKING TOWARDS THIS

1993
01:13:34,105 --> 01:13:36,207
AND I'M JUST GOING TO QUICKLY

1994
01:13:36,207 --> 01:13:38,043
HIGHLIGHT THE ONES IN YELLOW

1995
01:13:38,043 --> 01:13:40,211
HERE ARE BEHAVIORAL

1996
01:13:40,211 --> 01:13:42,080
NEURODEVELOPMENTAL DISORDERS.

1997
01:13:42,080 --> 01:13:45,050
SO WHEN WE'RE LOOKING AT WHICH

1998
01:13:45,050 --> 01:13:46,584
DISEASES HAVE THE STRONGEST

1999
01:13:46,584 --> 01:13:47,986
CHEMICAL SIGNAL, WHICH CHEMICALS

2000
01:13:47,986 --> 01:13:49,754
MIGHT BE DRIVING OTHER DISEASES

2001
01:13:49,754 --> 01:13:52,924
BEYOND ATOPIC DERM, THE

2002
01:13:52,924 --> 01:13:53,825
NEUROBEHAVIORAL DISORDERS ARE BY

2003
01:13:53,825 --> 01:13:55,326
FAR THE ONES THAT COME UP THE

2004
01:13:55,326 --> 01:13:56,628
MOST WITH SOME OF THESE

2005
01:13:56,628 --> 01:14:00,231
ENVIRONMENTAL TOXINS.

2006
01:14:00,231 --> 01:14:01,533
SO REALLY WHAT SHOULD WE BE

2007
01:14:01,533 --> 01:14:02,300
DOING ABOUT THIS?

2008
01:14:02,300 --> 01:14:03,468
THE FIRST THING IS TO KIND OF

2009
01:14:03,468 --> 01:14:04,803
RECOGNIZE THAT THE DISEASE CAN

2010
01:14:04,803 --> 01:14:06,271
BE TREATED BY DRUGS BUT IT

2011
01:14:06,271 --> 01:14:07,205
DOESN'T MEAN THE DISEASE IS

2012
01:14:07,205 --> 01:14:08,740
CAUSED BY A LACK OF THAT DRUG.

2013
01:14:08,740 --> 01:14:10,341
AND I THINK WE ALL INHERENTLY

2014
01:14:10,341 --> 01:14:11,776
KNOW THIS BUT IT'S EASY TO GET

2015
01:14:11,776 --> 01:14:14,746
VERY EXCITED ABOUT HOW YOU GIVE

2016
01:14:14,746 --> 01:14:16,281
A PATIENT A DRUG, THEY GET A LOT

2017
01:14:16,281 --> 01:14:17,782
BETTER AND YOU GET EXCITED TO

2018
01:14:17,782 --> 01:14:18,983
THINK IF I COULD JUST GIVE THIS

2019
01:14:18,983 --> 01:14:20,285
DRUG TO EVERYBODY, THEN WE COULD

2020
01:14:20,285 --> 01:14:21,619
MAKE A BIG IMPACT.

2021
01:14:21,619 --> 01:14:23,721
AND MAYBE.

2022
01:14:23,721 --> 01:14:25,990
BUT I STILL THINK PREVENTION

2023
01:14:25,990 --> 01:14:28,726
SHOULD REIGN IF WE HAVE THE

2024
01:14:28,726 --> 01:14:30,061
OPTION.

2025
01:14:30,061 --> 01:14:31,996
WE HEAR A LOT OH, I WORK ON

2026
01:14:31,996 --> 01:14:33,431
MECHANISM, AND I WOULD SAY THAT

2027
01:14:33,431 --> 01:14:34,199
MECHANISM DOESN'T START AT THE

2028
01:14:34,199 --> 01:14:36,367
SKIN, WE REALLY NEED TO FOCUS ON

2029
01:14:36,367 --> 01:14:37,702
THINGS ABOVE THE SKIN AND WE

2030
01:14:37,702 --> 01:14:40,004
NEED TO START DEMANDING

2031
01:14:40,004 --> 01:14:40,305
SPECIFICITY.

2032
01:14:40,305 --> 01:14:42,273
SO I HEAR THIS OH, WELL, INDIA

2033
01:14:42,273 --> 01:14:43,541
IS MORE POLLUTED THAN THE UNITED

2034
01:14:43,541 --> 01:14:44,776
STATES AND WHY DON'T THEY HAVE

2035
01:14:44,776 --> 01:14:45,543
HIGHER RATES?

2036
01:14:45,543 --> 01:14:47,078
MY RESPONSE TO THAT IS INDIA IS

2037
01:14:47,078 --> 01:14:47,912
DIFFERENT POLLUTED THAN THE

2038
01:14:47,912 --> 01:14:48,379
UNITED STATES.

2039
01:14:48,379 --> 01:14:49,914
WE CAN'T JUST USE POLLUTION AS A

2040
01:14:49,914 --> 01:14:51,015
BLANKET STATEMENT.

2041
01:14:51,015 --> 01:14:52,317
LOS ANGELES MAY HAVE MORE TOTAL

2042
01:14:52,317 --> 01:14:54,185
POLLUTANTS THAN, SAY, RURAL

2043
01:14:54,185 --> 01:14:55,253
KANSAS, BUT IF THE DISEASE

2044
01:14:55,253 --> 01:14:57,122
YOU'RE INTERESTED IN IS

2045
01:14:57,122 --> 01:14:58,556
AFFILIATED WITH HERBICIDES OR

2046
01:14:58,556 --> 01:14:59,524
PESTICIDES THAT ARE MORE LIKELY

2047
01:14:59,524 --> 01:15:01,259
TO BE SPRAYED ON FARMS, THEN

2048
01:15:01,259 --> 01:15:03,461
KANSAS IS MORE POLLUTED IN THAT

2049
01:15:03,461 --> 01:15:04,429
SPECIFIC CONTEXT THAN

2050
01:15:04,429 --> 01:15:05,330
LOS ANGELES.

2051
01:15:05,330 --> 01:15:06,865
SO ONE OF THE THINGS OUR LAB IS

2052
01:15:06,865 --> 01:15:08,700
TRYING TO DO IS COLLECT THIS

2053
01:15:08,700 --> 01:15:09,033
DIRECTLY.

2054
01:15:09,033 --> 01:15:13,204
SO THIS IS A PUMP THAT VACUUMS

2055
01:15:13,204 --> 01:15:14,739
IN AIR THROUGH THIS LITTLE

2056
01:15:14,739 --> 01:15:16,274
CASSETTE AND INSIDE THIS

2057
01:15:16,274 --> 01:15:17,909
CASSETTE ARE DIFFERENT FILTERS

2058
01:15:17,909 --> 01:15:19,444
THAT ARE BUILT TO CATCH

2059
01:15:19,444 --> 01:15:22,714
DIFFERENT TYPES OF CHEMICALS,

2060
01:15:22,714 --> 01:15:24,249
AND I'LL JUST SHOW YOU THE

2061
01:15:24,249 --> 01:15:25,683
TAKEHOME SO WE CAN BRING ONE OF

2062
01:15:25,683 --> 01:15:27,118
THESE INTO THE LAB AND DO IT IN

2063
01:15:27,118 --> 01:15:28,086
A CONTROLLED ENVIRONMENT WHERE

2064
01:15:28,086 --> 01:15:30,922
I'M ONLY RELEASING TWO SPECIFIC

2065
01:15:30,922 --> 01:15:36,461
CHEMICALS AND I CAN FIND SIGHLY

2066
01:15:36,461 --> 01:15:38,596
AND DIISOCYANATE, SO IN A

2067
01:15:38,596 --> 01:15:39,330
CONTROLLED ENVIRONMENT, I CAN

2068
01:15:39,330 --> 01:15:40,365
FIND EXACTLY WHAT I PUT.

2069
01:15:40,365 --> 01:15:41,599
THIS IS AFTER 24 HOURS.

2070
01:15:41,599 --> 01:15:42,901
THIS IS JUST POINTED AT THE

2071
01:15:42,901 --> 01:15:43,668
BELTWAY FOR FIVE HOURS.

2072
01:15:43,668 --> 01:15:44,769
AND THESE ARE ALL THE CHEMICALS

2073
01:15:44,769 --> 01:15:46,504
THAT I CAN START TO FIND AND IF

2074
01:15:46,504 --> 01:15:48,706
I GO LONGER, I BET I CAN PULL

2075
01:15:48,706 --> 01:15:49,474
OUT ISOCYANATE.

2076
01:15:49,474 --> 01:15:51,242
AND THEN I TOOK ONE OF THESE AND

2077
01:15:51,242 --> 01:15:53,678
PUT THEM ACTUALLY IN MY KITCHEN,

2078
01:15:53,678 --> 01:15:55,713
AND TIP OF THE HAT TO MY WINDOWS

2079
01:15:55,713 --> 01:15:57,382
AND DOORS, I GUESS, BECAUSE I'M

2080
01:15:57,382 --> 01:15:58,449
KEEPING OUT THE BELTWAY, BUT

2081
01:15:58,449 --> 01:15:59,951
THESE ARE ACTUALLY COOKING OILS

2082
01:15:59,951 --> 01:16:00,852
THAT I'M PICKING UP.

2083
01:16:00,852 --> 01:16:02,387
SO I KNOW I NEED TO BE A LITTLE

2084
01:16:02,387 --> 01:16:04,155
LIGHTER ON THE OILS WHEN I'M

2085
01:16:04,155 --> 01:16:04,389
COOKING.

2086
01:16:04,389 --> 01:16:07,458
BUT WE CAN START TO DO SPECIFIC

2087
01:16:07,458 --> 01:16:08,993
COMMENTS ABOUT THE EXACT

2088
01:16:08,993 --> 01:16:10,295
CHEMICALS IN A SPECIFIC

2089
01:16:10,295 --> 01:16:11,629
ENVIRONMENT AND HOW MUCH OF IT

2090
01:16:11,629 --> 01:16:12,897
AND MAYBE START USING THAT

2091
01:16:12,897 --> 01:16:14,666
RATHER THAN JUST KIND OF BLANKET

2092
01:16:14,666 --> 01:16:16,634
STATEMENTS ABOUT POLLUTION.

2093
01:16:16,634 --> 01:16:20,672
SO THE OTHER THING WE NEED TO DO

2094
01:16:20,672 --> 01:16:21,472
IS UNDERSTAND -- I'M SEEING THIS

2095
01:16:21,472 --> 01:16:23,741
MORE AND MORE NOW IN MICROBIOME

2096
01:16:23,741 --> 01:16:24,742
RESEARCH, SOMEBODY SAID OH,

2097
01:16:24,742 --> 01:16:27,245
THERE'S A MICROBIOME SIGNATURE

2098
01:16:27,245 --> 01:16:28,780
FOR THIS DISEASE OR THAT

2099
01:16:28,780 --> 01:16:30,114
DISEASE, AND THAT'S GREAT, BUT

2100
01:16:30,114 --> 01:16:31,416
WE'VE GOT TO UNDERSTAND THAT

2101
01:16:31,416 --> 01:16:33,718
THESE THINGS KIND OF RUN IN

2102
01:16:33,718 --> 01:16:34,919
FAMILIES AND THEY'RE GOING TO

2103
01:16:34,919 --> 01:16:35,453
CLUSTER IN THE SAME

2104
01:16:35,453 --> 01:16:36,120
ENVIRONMENTS.

2105
01:16:36,120 --> 01:16:37,188
SO THIS COMES UP MORE IN TERMS

2106
01:16:37,188 --> 01:16:38,957
OF THE PUSHBACK OF PEOPLE WHO

2107
01:16:38,957 --> 01:16:40,825
MIGHT SAY THAT OH, YOU KNOW,

2108
01:16:40,825 --> 01:16:41,793
ECZEMA IS GENETIC OR THIS

2109
01:16:41,793 --> 01:16:43,328
DISEASE IS GENETIC.

2110
01:16:43,328 --> 01:16:46,297
AND JUST FROM A MATERNAL

2111
01:16:46,297 --> 01:16:47,165
STANDPOINT, JUST FROM ASKING

2112
01:16:47,165 --> 01:16:49,634
ABOUT A MOM WHO'S GIVEN BIRTH TO

2113
01:16:49,634 --> 01:16:51,202
TWO CHILDREN, THESE ARE ALL THE

2114
01:16:51,202 --> 01:16:52,337
THINGS THAT COULD BE DIFFERENT

2115
01:16:52,337 --> 01:16:54,038
ABOUT THE HOME THAT YOU BRING

2116
01:16:54,038 --> 01:16:55,907
THOSE TWO CHILDREN INTO JUST

2117
01:16:55,907 --> 01:16:57,342
FROM -- THAT WOULD BE RELEVANT

2118
01:16:57,342 --> 01:16:59,410
TO ATOPIC DERM ALONE.

2119
01:16:59,410 --> 01:17:02,347
SO MAYBE MOM GOT ANTIBIOTICS

2120
01:17:02,347 --> 01:17:05,216
WITH THE FIRST ONE AND NOT THE

2121
01:17:05,216 --> 01:17:07,518
OTHER, OR MAYBE DIET WAS

2122
01:17:07,518 --> 01:17:09,187
DIFFERENT OR SMOKING EXPOSURE

2123
01:17:09,187 --> 01:17:09,587
WAS DIFFERENT.

2124
01:17:09,587 --> 01:17:10,888
SO THESE ARE ALL THINGS WE WOULD

2125
01:17:10,888 --> 01:17:12,223
NEED TO KNOW BEFORE WE WOULD

2126
01:17:12,223 --> 01:17:13,424
MAKE ASSUMPTIONS ABOUT THE

2127
01:17:13,424 --> 01:17:15,927
ENVIRONMENT CHILDREN GROW UP IN.

2128
01:17:15,927 --> 01:17:17,362
SO WHEN I HEAR PEOPLE SAY TWO

2129
01:17:17,362 --> 01:17:18,329
PEOPLE GROW UP IN THE SAME

2130
01:17:18,329 --> 01:17:19,864
ENVIRONMENT BUT ONLY ONE GOT THE

2131
01:17:19,864 --> 01:17:21,366
DISEASE SO WOULDN'T IT BE MORE

2132
01:17:21,366 --> 01:17:22,734
LIKELY TO BE SOMETHING GENETIC?

2133
01:17:22,734 --> 01:17:25,103
AND MY PUSHBACK WOULD BE WHAT DO

2134
01:17:25,103 --> 01:17:26,871
YOU MEAN BY THE SAME

2135
01:17:26,871 --> 01:17:27,505
ENVIRONMENT?

2136
01:17:27,505 --> 01:17:28,373
WHAT METRICS WOULD YOU USE?

2137
01:17:28,373 --> 01:17:32,110
ONCE YOU START GOING DOWN THAT

2138
01:17:32,110 --> 01:17:33,211
ROAD, YOU REALIZE VERY QUICKLY

2139
01:17:33,211 --> 01:17:35,813
THAT THE ENVIRONMENT IS FAR MORE

2140
01:17:35,813 --> 01:17:38,216
DYNAMIC THAN WE APPRECIATE.

2141
01:17:38,216 --> 01:17:39,550
SOME OF MY HYPOTHESIS HERE, I

2142
01:17:39,550 --> 01:17:41,286
DON'T HAVE DATA FOR IT YET, BUT

2143
01:17:41,286 --> 01:17:42,186
THE OLDER SIBLING IS THE ONE

2144
01:17:42,186 --> 01:17:43,788
THAT GETS THE NICE REMODELED

2145
01:17:43,788 --> 01:17:45,857
BEDROOM AND ALL THE OTHER FANCY

2146
01:17:45,857 --> 01:17:47,525
NEW EQUIPMENT, AND THE FOURTH

2147
01:17:47,525 --> 01:17:49,927
KID IS JUST GETTING WHATEVER THE

2148
01:17:49,927 --> 01:17:52,530
FIRST THREE DON'T DESTROY.

2149
01:17:52,530 --> 01:17:53,865
SO THEN THE LAST THING IS TO

2150
01:17:53,865 --> 01:17:57,802
KIND OF IMPROVE OUR FUTURE

2151
01:17:57,802 --> 01:17:59,003
PERFORMANCE SO WE REALLY NEED TO

2152
01:17:59,003 --> 01:18:00,338
START TEACHING ENVIRONMENTAL

2153
01:18:00,338 --> 01:18:01,072
ASSESSMENTS AND HAVING

2154
01:18:01,072 --> 01:18:01,839
CONVERSATIONS WITH OUR PATIENTS

2155
01:18:01,839 --> 01:18:03,174
ABOUT HOW TO DO THIS BECAUSE I

2156
01:18:03,174 --> 01:18:04,575
CAN ASSURE YOU THEY ARE VERY

2157
01:18:04,575 --> 01:18:05,777
INTERESTED IN THINGS THAT THEY

2158
01:18:05,777 --> 01:18:07,979
CAN DO EVEN IN ADDITION TO THEIR

2159
01:18:07,979 --> 01:18:08,413
MEDICATION.

2160
01:18:08,413 --> 01:18:10,481
THEY DON'T HAVE TO NECESSARILY

2161
01:18:10,481 --> 01:18:12,650
BE MEDICALLY AVERSE, BUT IN

2162
01:18:12,650 --> 01:18:15,753
ADDITION TO IT, WHAT CAN I DO.

2163
01:18:15,753 --> 01:18:19,924
SO NADIA SHOBNAM IS A FELLOW IN

2164
01:18:19,924 --> 01:18:21,893
THE LAB AND DEVELOPED THIS KIND

2165
01:18:21,893 --> 01:18:24,595
OF MNEMONIC, I'LL KIND OF SHOW

2166
01:18:24,595 --> 01:18:26,698
YOU ONE PART FOR THE AIR QUALITY

2167
01:18:26,698 --> 01:18:28,566
BECAUSE I THINK IT'S COUNTER

2168
01:18:28,566 --> 01:18:31,069
INTEU TI. YOCOUNTERINTUITIVE.

2169
01:18:31,069 --> 01:18:33,271
YOU MIGHT THINK IF THERE'S BAD

2170
01:18:33,271 --> 01:18:34,339
AIR OUTSIDE, I'LL LOCK THE

2171
01:18:34,339 --> 01:18:35,440
DOORS, CLOSE THE WINDOWS AND

2172
01:18:35,440 --> 01:18:36,207
I'LL BE PROTECTED.

2173
01:18:36,207 --> 01:18:38,609
THAT IS TRUE FROM LARGE

2174
01:18:38,609 --> 01:18:40,578
PARTICLES AND FROM POLL EN, BUT

2175
01:18:40,578 --> 01:18:42,213
IT IS NOT TRUE FROM GASES.

2176
01:18:42,213 --> 01:18:44,749
GASES ACTUALLY CONCENTRATE

2177
01:18:44,749 --> 01:18:47,251
INSIDE YOUR HOUSE IF YOU SEAL

2178
01:18:47,251 --> 01:18:48,019
EVERYTHING UP.

2179
01:18:48,019 --> 01:18:49,987
SO HERE WOULD JUST BE ONE THING

2180
01:18:49,987 --> 01:18:53,825
THAT PEOPLE COULD DO, CHEAP BOX

2181
01:18:53,825 --> 01:18:54,792
FANS, THE KIND OF STUFF YOU

2182
01:18:54,792 --> 01:18:56,427
WOULD FIND IN ANY DORM ROOM, YOU

2183
01:18:56,427 --> 01:19:01,065
CAN FIND ANY BASIC FILTER, MERV.

2184
01:19:01,065 --> 01:19:02,700
THE HIGHER THE NUMBER, THE

2185
01:19:02,700 --> 01:19:03,434
STRONGER THE FILTRATION.

2186
01:19:03,434 --> 01:19:04,802
YOU GO TOO HIGH, THE FAN MAY NOT

2187
01:19:04,802 --> 01:19:06,104
BE ABLE TO HANDLE IT.

2188
01:19:06,104 --> 01:19:07,972
BUT WHAT YOU DO IS YOU FIND

2189
01:19:07,972 --> 01:19:09,307
WHATEVER PART OF YOUR LIVING

2190
01:19:09,307 --> 01:19:10,375
ENVIRONMENT POINTS CLOSEST TO

2191
01:19:10,375 --> 01:19:11,676
THE BIGGEST ROAD AND YOU PUT A

2192
01:19:11,676 --> 01:19:13,678
FAN THERE AND YOU BLOW OUT.

2193
01:19:13,678 --> 01:19:14,979
AND THEN AS BEST YOU CAN ON THE

2194
01:19:14,979 --> 01:19:16,080
OTHER SIDE OF THE HOUSE, OTHER

2195
01:19:16,080 --> 01:19:17,582
SIDE OF THE APARTMENT OR SOME

2196
01:19:17,582 --> 01:19:19,584
OTHER PART OF THE LIVING SPACE,

2197
01:19:19,584 --> 01:19:21,419
YOU SET UP A WINDOW WHERE IT

2198
01:19:21,419 --> 01:19:23,421
DRAGGING AIR IN THROUGH THE

2199
01:19:23,421 --> 01:19:24,956
FILTER, SO THAT WAY YOU'RE NOT

2200
01:19:24,956 --> 01:19:26,791
PULLING IN THE SOOT OR THE POLL

2201
01:19:26,791 --> 01:19:28,993
ENINTO YOUR HOUSE, BUT YOU'RE

2202
01:19:28,993 --> 01:19:33,164
BRINGING IN FILTERED AIR AND

2203
01:19:33,164 --> 01:19:36,901
VENTILATING OUT CONTAMINATED

2204
01:19:36,901 --> 01:19:37,201
AIR.

2205
01:19:37,201 --> 01:19:38,102
JUST TO SHOW YOU SOME OF THE

2206
01:19:38,102 --> 01:19:39,737
RESULTS I HAD JUST FOR SETTING

2207
01:19:39,737 --> 01:19:41,172
THIS UP IN MY HOME, SO I COULD

2208
01:19:41,172 --> 01:19:42,907
TAKE THE TOTAL VOLATILE ORGANIC

2209
01:19:42,907 --> 01:19:46,310
COMPOUNDS FROM .041 TO .005,

2210
01:19:46,310 --> 01:19:49,714
THESE ARE THE ALDEHYDES DROP, I

2211
01:19:49,714 --> 01:19:51,349
CAN GET THE CO2 LEVELS TO DROP

2212
01:19:51,349 --> 01:19:53,451
BUT I DO GET A TRACE INCREASE IN

2213
01:19:53,451 --> 01:19:55,753
BOTH THE PARTICULATE MATTER

2214
01:19:55,753 --> 01:19:56,854
TELLING ME THAT MAYBE THIS

2215
01:19:56,854 --> 01:19:58,356
FILTER WASN'T QUITE GOOD ENOUGH

2216
01:19:58,356 --> 01:20:01,025
TO PREVENT EVERYTHING FROM GOING

2217
01:20:01,025 --> 01:20:03,861
THROUGH, BUT YOU GET THE IDEA.

2218
01:20:03,861 --> 01:20:08,766
WHAYOU WANT TO BRING IN FILTERED

2219
01:20:08,766 --> 01:20:11,836
AIR AND PUSH OUT THE BAD AIR,

2220
01:20:11,836 --> 01:20:13,171
NOT TO SEAL EVERYTHING UP AND

2221
01:20:13,171 --> 01:20:14,505
PREVENT AIR FROM COMING THROUGH.

2222
01:20:14,505 --> 01:20:18,209
SO WITH THAT, I'LL THANK MY

2223
01:20:18,209 --> 01:20:21,913
GROUP HERE FOR EVERYTHING, AND

2224
01:20:21,913 --> 01:20:23,147
AGAIN, NADIA AS WELL AS GRACE

2225
01:20:23,147 --> 01:20:24,048
HELPED CREATE THIS FIGURE.

2226
01:20:24,048 --> 01:20:25,349
IF YOU WANT MORE INFORMATION,

2227
01:20:25,349 --> 01:20:28,619
YOU CAN GO TO OUR -- THIS

2228
01:20:28,619 --> 01:20:29,587
PUBLICATION WHERE YOU CAN SEE

2229
01:20:29,587 --> 01:20:30,721
ALL THE DIFFERENT CHEMICALS,

2230
01:20:30,721 --> 01:20:32,123
WHAT THEY'RE DOING AND HOW TO

2231
01:20:32,123 --> 01:20:34,225
AVOID IT, AND I SHOWED YOU THE

2232
01:20:34,225 --> 01:20:35,660
CITATION FOR MITIGATION, AND

2233
01:20:35,660 --> 01:20:36,961
THIS IS OUR FLAG.

2234
01:20:36,961 --> 01:20:39,163
SO WITH THAT, I'LL STOP.

2235
01:20:39,163 --> 01:20:41,032
THANK YOU.

2236
01:20:41,032 --> 01:20:41,999
>> ALL RIGHT.

2237
01:20:41,999 --> 01:20:43,434
WELL, YOU KNOW, THIS HAS BEEN

2238
01:20:43,434 --> 01:20:47,839
REALLY A SPECTACULAR, EXCITING

2239
01:20:47,839 --> 01:20:52,543
PAIR OF PRESENTATIONS, WHICH

2240
01:20:52,543 --> 01:20:55,813
HAVE GREAT IMPORTANCE AND

2241
01:20:55,813 --> 01:20:58,015
LINKAGE.

2242
01:20:58,015 --> 01:21:00,218
AND I THINK WE'VE ALL ENJOYED

2243
01:21:00,218 --> 01:21:01,619
AND LEARNED A GREAT DEAL FROM

2244
01:21:01,619 --> 01:21:01,953
IT.

2245
01:21:01,953 --> 01:21:04,255
THERE ARE A WHOLE HOST OF

2246
01:21:04,255 --> 01:21:05,456
QUESTIONS HERE, AND SO I'M GOING

2247
01:21:05,456 --> 01:21:10,161
TO GO THROUGH MANY OF THEM,

2248
01:21:10,161 --> 01:21:14,866
PROBABLY NOT ALL.

2249
01:21:14,866 --> 01:21:16,167
SO LET'S BEGIN HERE.

2250
01:21:16,167 --> 01:21:18,035
SO IAN, DO CERAMIDE AND THE

2251
01:21:18,035 --> 01:21:28,513
OTHER LIPIDS RELEASED BY THE

2252
01:21:30,147 --> 01:21:32,049
ROSAMONA MUCOSA INTERACT WITH

2253
01:21:32,049 --> 01:21:32,683
ITCH RECEPTORS?

2254
01:21:32,683 --> 01:21:34,218
>> PROBABLY.

2255
01:21:34,218 --> 01:21:35,319
THE ONLY ITCH RECEPTOR THAT

2256
01:21:35,319 --> 01:21:37,088
WE'VE PLAYED AROUND WITH IS

2257
01:21:37,088 --> 01:21:39,824
CALLED TRIP RECEPTORS, SO TRIP

2258
01:21:39,824 --> 01:21:43,194
V1, TRPA1, THOSE ARE ITCH TRALT

2259
01:21:43,194 --> 01:21:44,962
AND PAIN, WHICH IS A LITTLE

2260
01:21:44,962 --> 01:21:46,063
DIFFERENT.

2261
01:21:46,063 --> 01:21:50,368
SO WE JOKE WITH DR. HOON, WE

2262
01:21:50,368 --> 01:21:51,969
HAVE NOT LOOKED AT THAT, BUT THE

2263
01:21:51,969 --> 01:21:54,705
TRIP RECEPTORS ARE LIKELY

2264
01:21:54,705 --> 01:21:56,240
INFLUENCED BY THESE LIPIDS, THE

2265
01:21:56,240 --> 01:21:59,210
SPECIFIC LIPID RESIDUES HAVE NOT

2266
01:21:59,210 --> 01:22:04,916
BEEN GENUINELY ASSESSED.

2267
01:22:04,916 --> 01:22:06,150
>> THERE WAS ALSO A
QUESTION

2268
01:22:06,150 --> 01:22:08,719
ABOUT THE ASSOCIATION WITH

2269
01:22:08,719 --> 01:22:15,293
WATER.

2270
01:22:15,293 --> 01:22:18,029
WHERE MUCH CONTAMINATION IN

2271
01:22:18,029 --> 01:22:19,697
WATER IS PARTICULARLY FROM THE

2272
01:22:19,697 --> 01:22:21,432
HORMONAL STANDPOINT IS

2273
01:22:21,432 --> 01:22:22,967
ASSOCIATED OR CLAIMED TO BE

2274
01:22:22,967 --> 01:22:28,673
ASSOCIATED WITH A WHOLE HOATS OF

2275
01:22:28,673 --> 01:22:34,478
DISORDERS, IS THERE AN

2276
01:22:34,478 --> 01:22:35,413
ASSOCIATION?

2277
01:22:35,413 --> 01:22:37,315
IS IT KNOWN WHETHER THE CHRONIC

2278
01:22:37,315 --> 01:22:41,385
ITCH DISORDERS HAVE ANY

2279
01:22:41,385 --> 01:22:47,725
EPIDEMIOLOGIC RELATIONSHIP TO

2280
01:22:47,725 --> 01:22:53,497
EXPOSURE TO WATER IN NATURE AND

2281
01:22:53,497 --> 01:22:55,700
DOES PURIFIED WATER OR THE

2282
01:22:55,700 --> 01:23:00,304
FILTERED WATER THAT'S SOLD IN A

2283
01:23:00,304 --> 01:23:06,344
SUPERMARKET, SHA DESUPERMARKET,F

2284
01:23:06,344 --> 01:23:07,945
THESE LIPID MOLECULES?

2285
01:23:07,945 --> 01:23:14,752
>> THERE HAVE BEEN A STUDY
OF --

2286
01:23:14,752 --> 01:23:16,954
THOSE ARE USELESS FOR ATOPIC

2287
01:23:16,954 --> 01:23:17,955
DERM, MAYBE THEY'RE GOOD FOR

2288
01:23:17,955 --> 01:23:21,459
SOMETHING ELSE, BUT THE

2289
01:23:21,459 --> 01:23:22,994
ASSOCIATIONS FOR PSORIASIS ARE A

2290
01:23:22,994 --> 01:23:24,528
LITTLE BIT DIFFERENT, AND

2291
01:23:24,528 --> 01:23:26,163
THEY'RE MORE AROUND BARIUM,

2292
01:23:26,163 --> 01:23:28,799
WHICH COULD SLIP THROUGH.

2293
01:23:28,799 --> 01:23:31,102
IN TERMS OF FILTERED WATER, A

2294
01:23:31,102 --> 01:23:31,969
LOT OF THE PROBLEM IS THE

2295
01:23:31,969 --> 01:23:33,404
FILTERED WATER COMES IN A BIG

2296
01:23:33,404 --> 01:23:35,373
PLASTIC JUG, AND YOU KNOW, ONE

2297
01:23:35,373 --> 01:23:37,908
OF OUR PH.D. STUDENTS WAS

2298
01:23:37,908 --> 01:23:40,077
LOOKING THROUGH FOR THE

2299
01:23:40,077 --> 01:23:41,846
MOLECULES CALLED PFAS, WHICH ARE

2300
01:23:41,846 --> 01:23:43,114
HORMONAL DISREGULATORS AND

2301
01:23:43,114 --> 01:23:44,582
THEY'RE KNOWN MORE FOR TEFLON

2302
01:23:44,582 --> 01:23:47,551
AND THE FOREVER CHEMICALS, AND

2303
01:23:47,551 --> 01:23:50,054
YOUR LAB WATER THAT YOU BUY TO

2304
01:23:50,054 --> 01:23:51,822
DO YOUR EXPERIMENTS AND HAS

2305
01:23:51,822 --> 01:23:53,457
PURIFIED WHAT TERL COMES IN A

2306
01:23:53,457 --> 01:23:56,093
PLASTIC JUG AND THAT PLASTIC HAS

2307
01:23:56,093 --> 01:23:58,295
DETECTABLE LEVELS OF PFAS.

2308
01:23:58,295 --> 01:24:01,465
SO IT IS HARD TO TRULY ELIMINATE

2309
01:24:01,465 --> 01:24:09,807
ALL EXPOSURE TO THESE.

2310
01:24:09,807 --> 01:24:12,309
>> YOU COMMENTED ABOUT THE
USE

2311
01:24:12,309 --> 01:24:13,611
OF FILTERS.

2312
01:24:13,611 --> 01:24:16,580
SO ONE OF OUR LISTENERS ASKED

2313
01:24:16,580 --> 01:24:18,315
ABOUT MEMORY FOAM.

2314
01:24:18,315 --> 01:24:20,117
I'M NOT FAMILIAR WITH MEMORY

2315
01:24:20,117 --> 01:24:21,852
FOAM, BUT MAYBE YOU CAN

2316
01:24:21,852 --> 01:24:22,953
ENLIGHTEN US.

2317
01:24:22,953 --> 01:24:25,289
>> SO THE TERM MEMORY FOAM
IS

2318
01:24:25,289 --> 01:24:26,357
USUALLY JUST USED FOR YOU PUT

2319
01:24:26,357 --> 01:24:27,992
YOUR HAND IN AND DOES IT, LIKE,

2320
01:24:27,992 --> 01:24:29,126
HOLD ITS SHAPE A LITTLE BIT.

2321
01:24:29,126 --> 01:24:33,264
SO THERE IS A LATEX-BASED MEMORY

2322
01:24:33,264 --> 01:24:36,133
FOAM WHICH DOES NOT HAVE

2323
01:24:36,133 --> 01:24:37,601
ISOCYANATES OR XYLENE OR ANY OF

2324
01:24:37,601 --> 01:24:40,871
THE CHEMICALS THAT WE ASSOCIATE

2325
01:24:40,871 --> 01:24:44,008
WITH ATOPIC DERM.

2326
01:24:44,008 --> 01:24:46,210
I CANNOT ATTEST TO ITS SAFETY

2327
01:24:46,210 --> 01:24:49,180
FOR EVERY OUT THERE BUT --

2328
01:24:49,180 --> 01:24:50,815
MEMORY FOAM, THE BRAND, AND THE

2329
01:24:50,815 --> 01:24:54,452
NAME OR WHATEVER, IF IT IS A

2330
01:24:54,452 --> 01:24:55,753
NON-LATEX FOAM MEMORY FOAM, IT

2331
01:24:55,753 --> 01:24:59,490
ALMOST CERTAINLY IS MADE OUT OF

2332
01:24:59,490 --> 01:25:02,126
THOSE PARTICULAR CHEMICALS, AND,

2333
01:25:02,126 --> 01:25:03,994
THEREFORE, GENERATE THESE RISKS

2334
01:25:03,994 --> 01:25:04,628
OF EXPOSURE.

2335
01:25:04,628 --> 01:25:06,363
SO WHEN YOU OFF-GAS A MATTRESS

2336
01:25:06,363 --> 01:25:08,899
AND YOU SEE THAT STINK WHEN YOU

2337
01:25:08,899 --> 01:25:11,102
UNSEAL IT, THIS IS PART OF IT.

2338
01:25:11,102 --> 01:25:12,369
AND WE DON'T REALLY KNOW HOW

2339
01:25:12,369 --> 01:25:13,838
LONG THAT LASTS AND WE'D LIKE TO

2340
01:25:13,838 --> 01:25:18,109
TEST THAT IN THE LAB TOO.

2341
01:25:18,109 --> 01:25:19,410
BUT LATEX FOAM IS DEVOID OF

2342
01:25:19,410 --> 01:25:21,112
THESE CHEMICALS.

2343
01:25:21,112 --> 01:25:22,980
NON-LATEX MEMORY FOAM IS MADE

2344
01:25:22,980 --> 01:25:25,616
OUT OF THEM.

2345
01:25:25,616 --> 01:25:29,420
>> COULD YOU EXPLAIN OR
MAYBE

2346
01:25:29,420 --> 01:25:31,522
MARK, IT SEEMS LIKE THE WORDS

2347
01:25:31,522 --> 01:25:35,359
ATOPIC DERMATITIS AND ECZEMA

2348
01:25:35,359 --> 01:25:38,295
SOMETIMES ARE ALMOST USED

2349
01:25:38,295 --> 01:25:38,662
INTERCHANGEABLY.

2350
01:25:38,662 --> 01:25:43,067
COULD YOU EXPLAIN THAT, PLEASE?

2351
01:25:43,067 --> 01:25:47,905
>> ATOPIC DETERMINE IS A
DERM IF

2352
01:25:47,905 --> 01:25:48,439
ECZEMA.

2353
01:25:48,439 --> 01:25:50,207
BUT IT'S OVERWHELMINGLY THE MOST

2354
01:25:50,207 --> 01:25:51,876
COMMON FORM OF ECZEMA, SO IF

2355
01:25:51,876 --> 01:25:52,743
YOU'RE TALKING TO A PATIENT,

2356
01:25:52,743 --> 01:25:55,479
THAT'S PROBABLY WHAT THEY MEAN.

2357
01:25:55,479 --> 01:26:00,084
BUT YOU KNOW, THERE'S NOMULAR

2358
01:26:00,084 --> 01:26:00,751
ECZEMA, THERE'S OTHER KINDS.

2359
01:26:00,751 --> 01:26:02,286
SO IT JUST DEPENDS ON THE

2360
01:26:02,286 --> 01:26:03,687
AUDIENCE, WHICH ONE YOU WANT TO

2361
01:26:03,687 --> 01:26:05,589
USE, BUT THEY OFTEN USE

2362
01:26:05,589 --> 01:26:06,457
INTERCHANGEABLY -- THE

2363
01:26:06,457 --> 01:26:08,092
DERMATOLOGISTS GET MORE UPSET

2364
01:26:08,092 --> 01:26:09,960
THAN THE ALLERGISTS DO WHEN YOU

2365
01:26:09,960 --> 01:26:11,395
USE THEM INTERCHANGEABLY, BUT

2366
01:26:11,395 --> 01:26:13,564
ATOPIC DERM IS A SUBTYPE OF

2367
01:26:13,564 --> 01:26:14,131
ECZEMA.

2368
01:26:14,131 --> 01:26:19,303
>> SO WHAT IS ECZEMA THEN?

2369
01:26:19,303 --> 01:26:20,704
>> THAT'S A DEEP QUESTION.

2370
01:26:20,704 --> 01:26:22,673
I GUESS IT DEPENDS ON WHICH

2371
01:26:22,673 --> 01:26:24,341
SPECIFIC SUBTYPE, I MEAN, I

2372
01:26:24,341 --> 01:26:26,410
WOULD SAY IT'S AN UMBRELLA TERM

2373
01:26:26,410 --> 01:26:28,045
FOR, YOU KNOW, REDNESS,

2374
01:26:28,045 --> 01:26:30,347
IRRITATION, THICK ENING OF THE

2375
01:26:30,347 --> 01:26:31,916
SKIN, AND IT JUST KIND OF

2376
01:26:31,916 --> 01:26:33,117
DEPENDS ON THE BREAKDOWN.

2377
01:26:33,117 --> 01:26:34,218
I'M SURE SOMEBODY HAS A BETTER

2378
01:26:34,218 --> 01:26:36,086
ANSWER, BUT I DON'T KNOW.

2379
01:26:36,086 --> 01:26:40,925
>> SO MARK, WHAT IS THE
ROLE OF

2380
01:26:40,925 --> 01:26:46,497
EOSEOSINOPHILIA IN ITCHING IN MY

2381
01:26:46,497 --> 01:26:49,934
OF THE PATHOLOGIC SPECIMENS FROM

2382
01:26:49,934 --> 01:26:53,871
PEOPLE WITH PARTICULARLY CHRONIC

2383
01:26:53,871 --> 01:26:58,375
ITCH, EOSINOPHILS ARE A

2384
01:26:58,375 --> 01:26:59,577
SIGNIFICANT POPULATION, AND EVEN

2385
01:26:59,577 --> 01:27:03,814
MANY OF THOSE PATIENTS HAVE

2386
01:27:03,814 --> 01:27:06,517
CIRCULATING EOSIN FEEL YA.

2387
01:27:06,517 --> 01:27:09,653
>> SO I DON'T KNOW
SPECIFICALLY,

2388
01:27:09,653 --> 01:27:14,792
BUT YEAH, I MEAN, IN THE END,

2389
01:27:14,792 --> 01:27:16,994
THEY'RE LIKELY TO BE RELEASING

2390
01:27:16,994 --> 01:27:20,931
THE TYPES OF MOLECULES THAT I

2391
01:27:20,931 --> 01:27:23,601
TALKED ABOUT THAT ACTIVATE THE

2392
01:27:23,601 --> 01:27:33,611
NPPB NEURONS, SO IN THE END,

2393
01:27:33,611 --> 01:27:35,179
EOSINOPHILS LIKE MAST CELLS HAVE

2394
01:27:35,179 --> 01:27:36,680
GRANULES THEY RELEASE AND

2395
01:27:36,680 --> 01:27:37,715
OFTEN -- THEY'RE NOT THE SAME,

2396
01:27:37,715 --> 01:27:44,722
BUT THEY'RE VERY SIMILAR.

2397
01:27:44,722 --> 01:27:46,891
 -- IN GENERAL WILL ACTIVATE

2398
01:27:46,891 --> 01:27:50,628
THESE NERVE ENDINGS.

2399
01:27:50,628 --> 01:27:58,168
SO HISTAMINE AND SEROTONIN ARE

2400
01:27:58,168 --> 01:28:00,137
BOTH MONO -- AN ASSORTMENT OF

2401
01:28:00,137 --> 01:28:04,008
OTHER LIPID MOLECULES WILL

2402
01:28:04,008 --> 01:28:04,541
ACTIVATE.

2403
01:28:04,541 --> 01:28:06,810
INCLUDING THEY RELEASED BY A

2404
01:28:06,810 --> 01:28:11,548
WHOLE SET OF DIFFERENT INNATE

2405
01:28:11,548 --> 01:28:12,549
IMMUNE CELLS.

2406
01:28:12,549 --> 01:28:16,053
>> YOU COMMENTED ABOUT THE

2407
01:28:16,053 --> 01:28:19,123
IMPORTANCE OF MAST CELLS IN THE

2408
01:28:19,123 --> 01:28:19,890
ACUTE REACTION.

2409
01:28:19,890 --> 01:28:22,960
DO THEY PARTICIPATE AT ALL IN

2410
01:28:22,960 --> 01:28:25,396
CHRONIC ITCH?

2411
01:28:25,396 --> 01:28:27,364
>> SO PEOPLE HAVE LOOKED
TIME

2412
01:28:27,364 --> 01:28:29,767
AND TIME AGAIN TO TRY TO SHOW A

2413
01:28:29,767 --> 01:28:32,069
CONNECTION, BUT TH THERE REALLY

2414
01:28:32,069 --> 01:28:33,837
ISN'T A CONNECTION.

2415
01:28:33,837 --> 01:28:39,543
THE ONLY EXCEPTION IS URTICARIA,

2416
01:28:39,543 --> 01:28:41,612
WHICH IS COMPLETELY DRIVEN BY

2417
01:28:41,612 --> 01:28:43,681
MAST CELLS.

2418
01:28:43,681 --> 01:28:47,718
BUT THAT'S QUITE A DIFFERENT

2419
01:28:47,718 --> 01:28:48,719
SKIN CONDITION.

2420
01:28:48,719 --> 01:28:54,992
IT'S CHARACTERIZED BY WHEELS, IT

2421
01:28:54,992 --> 01:28:56,760
TENDS TO BE PERIODIC SO IT COMES

2422
01:28:56,760 --> 01:29:01,231
AND GOES, SO THERE'S WAXES AND

2423
01:29:01,231 --> 01:29:02,733
WANES DEPENDING ON THE CONDITION

2424
01:29:02,733 --> 01:29:09,573
OF THE PATIENT.

2425
01:29:09,573 --> 01:29:10,541
AND FUNDAMENTALLY IT'S

2426
01:29:10,541 --> 01:29:12,076
DIFFERENT, IT'S THROUGH THE MAST

2427
01:29:12,076 --> 01:29:15,279
CELLS, SO FOR THOSE PATIENTS,

2428
01:29:15,279 --> 01:29:18,649
ANTIHISTAMINES WORK, ABSOLUTELY.

2429
01:29:18,649 --> 01:29:21,418
BUT FOR ATOPIC DERMATITIS

2430
01:29:21,418 --> 01:29:22,720
PATIENTS, MOSTLY THEY DON'T

2431
01:29:22,720 --> 01:29:25,689
WORK.

2432
01:29:25,689 --> 01:29:27,091
BUT IT'S VERY OFTEN THE FIRST

2433
01:29:27,091 --> 01:29:28,525
THING THAT A DERMATOLOGIST WILL

2434
01:29:28,525 --> 01:29:30,294
GIVE YOU.

2435
01:29:30,294 --> 01:29:31,495
BECAUSE IT'S THE EASIEST THING

2436
01:29:31,495 --> 01:29:37,001
TO GIVE YOU AND BASICALLY RULE

2437
01:29:37,001 --> 01:29:40,270
OUT THAT -- IT HELPS WITH THE

2438
01:29:40,270 --> 01:29:42,239
DIAGNOSIS I GUESS AND IT CHEAP

2439
01:29:42,239 --> 01:29:42,906
AND QUICK.

2440
01:29:42,906 --> 01:29:45,209
I SEE IAN SMILING BECAUSE HE'S

2441
01:29:45,209 --> 01:29:45,876
AGREEING WITH ME.

2442
01:29:45,876 --> 01:29:47,878
HE PROBABLY KNOWS BETTER THAN ME

2443
01:29:47,878 --> 01:29:50,781
SINCE HE'S THE PHYSICIAN HERE.

2444
01:29:50,781 --> 01:29:51,882
>> IAN, YOU WANT TO
COMMENT

2445
01:29:51,882 --> 01:29:52,516
ABOUT THAT?

2446
01:29:52,516 --> 01:29:53,417
>> I AGREE.

2447
01:29:53,417 --> 01:29:55,419
I MEAN, PEOPLE CHASE DOWN

2448
01:29:55,419 --> 01:29:58,255
HISTAMINE QUITE A BIT, AND IT

2449
01:29:58,255 --> 01:30:01,458
JUST IS COMPLETELY IRRELEVANT IN

2450
01:30:01,458 --> 01:30:02,993
THE DISORDER WHICH IS KIND OF

2451
01:30:02,993 --> 01:30:05,195
INTRIGUING FROM AN ALLERGY

2452
01:30:05,195 --> 01:30:06,730
STANDPOINT BECAUSE THE

2453
01:30:06,730 --> 01:30:08,399
HISTAMINES CAN HELP A LOT IN

2454
01:30:08,399 --> 01:30:10,801
ALLERGIC RHINITIS, BUT ARE

2455
01:30:10,801 --> 01:30:14,838
USELESS IN ATOPIC DERM.

2456
01:30:14,838 --> 01:30:18,142
LIKE YOU SAID.

2457
01:30:18,142 --> 01:30:21,111
>> WE HAD A QUESTION AS TO

2458
01:30:21,111 --> 01:30:24,915
WHETHER YOU THOUGHT BACTERIAL

2459
01:30:24,915 --> 01:30:30,087
TREATMENT AS A NASAL SPRAY COULD

2460
01:30:30,087 --> 01:30:33,357
HELP IN ALLERGIES.

2461
01:30:33,357 --> 01:30:37,895
>> YEAH, WE HAVEN'T --
WE'D WANT

2462
01:30:37,895 --> 01:30:39,963
TO KNOW WHAT WE THINK IS

2463
01:30:39,963 --> 01:30:42,299
DEFICIENT IN THE BACTERIA IN

2464
01:30:42,299 --> 01:30:44,735
NASAL SPRAYS, BUT WE DON'T YET

2465
01:30:44,735 --> 01:30:46,870
HAVE ANY REAL GOOD STUDIES WHERE

2466
01:30:46,870 --> 01:30:48,205
IT WOULD COLLECT THE BACTERIA IN

2467
01:30:48,205 --> 01:30:49,873
THE NOSE OF CHILDREN WHO DON'T

2468
01:30:49,873 --> 01:30:51,175
HAVE ALLERGIC DISEASE AND THEN

2469
01:30:51,175 --> 01:30:51,708
FOLLOW THEM.

2470
01:30:51,708 --> 01:30:53,210
THAT WOULD BE THE BEST STUDY TO

2471
01:30:53,210 --> 01:30:56,346
TELL YOU WHAT MIGHT BE MOST

2472
01:30:56,346 --> 01:30:57,214
PROMISING.

2473
01:30:57,214 --> 01:30:59,183
AND I'VE EVEN THOUGHT ABOUT, YOU

2474
01:30:59,183 --> 01:31:01,151
KNOW, COULD YOU USE -- COULD YOU

2475
01:31:01,151 --> 01:31:04,054
MA ANYBODY LATE THE GUT MICROBES

2476
01:31:04,054 --> 01:31:05,656
TO CREATE PROTECTION AGAINST

2477
01:31:05,656 --> 01:31:08,559
FOOD ALLERGY, HAVE A BENEFICIAL

2478
01:31:08,559 --> 01:31:09,860
ORGANISM THAT DRESSES UP LIKE A

2479
01:31:09,860 --> 01:31:11,095
PEANUT SO TO SPEAK IN A WAY

2480
01:31:11,095 --> 01:31:13,497
THAT'S A LITTLE MORE PEACE

2481
01:31:13,497 --> 01:31:14,698
OFFERING THAN THE PEANUT ITSELF.

2482
01:31:14,698 --> 01:31:17,901
SO YEAH, I THINK BACTERIAL

2483
01:31:17,901 --> 01:31:19,770
THERAPIES ARE PROMISING AND

2484
01:31:19,770 --> 01:31:20,671
THEY'LL EXPAND OVER THE YEARS.

2485
01:31:20,671 --> 01:31:25,676
>> SO DEALING WITH THE
QUESTION

2486
01:31:25,676 --> 01:31:31,081
OF THE VARIED AND SOMETIMES

2487
01:31:31,081 --> 01:31:36,553
SELECTIVE DISTRIBUTION, WE HAVE

2488
01:31:36,553 --> 01:31:38,188
A QUESTION AS TO WHETHER IT'S

2489
01:31:38,188 --> 01:31:40,624
POSSIBLE THAT THERE'S AN

2490
01:31:40,624 --> 01:31:43,227
ASSOCIATION BETWEEN THE

2491
01:31:43,227 --> 01:31:45,095
INTRAEPIDERMAL NERVE FIBER

2492
01:31:45,095 --> 01:31:46,830
DENSITY AND ANY PARTICULAR

2493
01:31:46,830 --> 01:31:48,065
REGION OF THE SKIN.

2494
01:31:48,065 --> 01:31:53,437
IS THAT A VARIABLE THAT COULD

2495
01:31:53,437 --> 01:31:55,639
AFFECT THE SOMEWHAT CURIOUS

2496
01:31:55,639 --> 01:31:56,940
DISTRIBUTION OF MANY OF THESE

2497
01:31:56,940 --> 01:32:07,117
DISORDERS?

2498
01:32:07,651 --> 01:32:09,086
>> CLEARLY THERE ARE SOME

2499
01:32:09,086 --> 01:32:10,521
DIFFERENCES IN INNOVATION, BUT I

2500
01:32:10,521 --> 01:32:13,157
THINK WHAT IAN WAS ALSO POINTING

2501
01:32:13,157 --> 01:32:15,025
TO IS THE EXPOSURE AS WELL.

2502
01:32:15,025 --> 01:32:18,328
I MEAN, CLEARLY YOUR BACK

2503
01:32:18,328 --> 01:32:21,064
DOESN'T GET EXPOSED TO MANY

2504
01:32:21,064 --> 01:32:23,901
DIFFERENT THINGS APART IN WHEN

2505
01:32:23,901 --> 01:32:25,802
YOU UNDRESS, WHEREAS YOUR HANDS

2506
01:32:25,802 --> 01:32:28,872
ARE FAR MORE LIKELY TO GET --

2507
01:32:28,872 --> 01:32:31,175
PERHAPS HAVE SYMPTOMS AND THEN

2508
01:32:31,175 --> 01:32:32,476
THEY'RE COMPLETELY EXPOSED ALL

2509
01:32:32,476 --> 01:32:34,044
THE TIME AND OFTEN BECOME

2510
01:32:34,044 --> 01:32:35,579
IMMERSED AND COVERED IN VARIOUS

2511
01:32:35,579 --> 01:32:38,415
DIFFERENT THINGS DURING THE DAY.

2512
01:32:38,415 --> 01:32:42,286
SO WITH THAT, THE THING IS, THE

2513
01:32:42,286 --> 01:32:43,253
INNOVATION IS DIFFERENT BUT ALSO

2514
01:32:43,253 --> 01:32:44,688
THE EXPOSURE IS DIFFERENT, SO I

2515
01:32:44,688 --> 01:32:47,491
THINK IT'S HARD TO REALLY SAY IF

2516
01:32:47,491 --> 01:32:50,160
ONE THING IS MORE IMPORTANT THAN

2517
01:32:50,160 --> 01:32:50,494
ANOTHER.

2518
01:32:50,494 --> 01:32:57,935
I MEAN, ONE THING IS FOR CERT 

2519
01:32:57,935 --> 01:33:02,573
CERTAIN, THE NERVES THAT I

2520
01:33:02,573 --> 01:33:03,540
TALKED ABOUT THAT ARE

2521
01:33:03,540 --> 01:33:06,076
INNERVATING THE SKIN, THEY ALSO

2522
01:33:06,076 --> 01:33:11,582
INNERVATE, FOR INSTANCE, THE --

2523
01:33:11,582 --> 01:33:12,683
CAVITY, OTHER PLACES IN THE

2524
01:33:12,683 --> 01:33:14,318
BODY, THEY MAY BE INVOLVED IN

2525
01:33:14,318 --> 01:33:15,819
DIFFERENT PROCESSES AND

2526
01:33:15,819 --> 01:33:19,489
DIFFERENT PLACES, AND CAUSE

2527
01:33:19,489 --> 01:33:22,960
DIFFERENT REACTIONS AS WELL.

2528
01:33:22,960 --> 01:33:26,430
SO I THINK THAT'S -- IT IS A

2529
01:33:26,430 --> 01:33:28,832
COMPLICATED THING AND ALSO THERE

2530
01:33:28,832 --> 01:33:33,971
ARE SOME STUDIES THAT HAVE

2531
01:33:33,971 --> 01:33:34,871
PROPOSED A REDUCTION IN THE

2532
01:33:34,871 --> 01:33:37,908
NUMBER OF FIBERS IS ASSOCIATED

2533
01:33:37,908 --> 01:33:43,680
ACTUALLY WITH INCREASED ITCH.

2534
01:33:43,680 --> 01:33:45,115
WHICH IS LARD TO REALLY

2535
01:33:45,115 --> 01:33:46,316
UNDERSTAND WHY THAT WOULD BE.

2536
01:33:46,316 --> 01:33:49,253
THE PROPOSAL IS THAT THIS IS THE

2537
01:33:49,253 --> 01:33:55,926
LEVEL OF THE SPINAL CORD, WHERE

2538
01:33:55,926 --> 01:33:57,127
THERE'S -- AND CLEARLY THERE'S A

2539
01:33:57,127 --> 01:33:59,896
LOT MORE TO BE UNDERSTOOD ABOUT

2540
01:33:59,896 --> 01:34:01,431
HOW THE DIFFERENT NERVES

2541
01:34:01,431 --> 01:34:02,666
ACTUALLY INTERACT WITH EACH

2542
01:34:02,666 --> 01:34:02,966
OTHER.

2543
01:34:02,966 --> 01:34:09,973
SO I MEAN, AS SOMEBODY WHO OFTEN

2544
01:34:09,973 --> 01:34:12,075
GETS OR HAS LARGE REACTIONS TO

2545
01:34:12,075 --> 01:34:13,610
MOSQUITOES, I KNOW THAT IF, FOR

2546
01:34:13,610 --> 01:34:18,215
INSTANCE, I PUT AN ICE CUBE ON

2547
01:34:18,215 --> 01:34:20,851
MY HAND AFTER A MOSQUITO BITE, I

2548
01:34:20,851 --> 01:34:22,286
DON'T SCRATCH, AND THAT'S A

2549
01:34:22,286 --> 01:34:24,021
REALLY EFFECTIVE WAY TO

2550
01:34:24,021 --> 01:34:25,589
BASICALLY COUNTER STIMULUS, SO

2551
01:34:25,589 --> 01:34:27,758
THE FACT THAT THERE MAY BE THIS

2552
01:34:27,758 --> 01:34:28,859
INTERACTION BETWEEN DIFFERENT

2553
01:34:28,859 --> 01:34:34,164
NERVE FIBERS IS NOT A WILD IDEA.

2554
01:34:34,164 --> 01:34:38,835
>> MARK, YOU MADE THE
STATEMENT

2555
01:34:38,835 --> 01:34:40,937
THAT ITCH IS FUNDAMENTALLY A

2556
01:34:40,937 --> 01:34:44,641
DISEASE OF THE BRAIN.

2557
01:34:44,641 --> 01:34:48,845
NOW, THE VARIOUS NEUROLOGIC

2558
01:34:48,845 --> 01:34:51,148
CONDITIONS AFFECTING THE BRAIN

2559
01:34:51,148 --> 01:34:56,286
OR THE SPINAL CORD INTERFERE OR

2560
01:34:56,286 --> 01:34:59,456
PREVENT THE PERCEPTION OF ITCH

2561
01:34:59,456 --> 01:35:01,458
BY A PATIENT?

2562
01:35:01,458 --> 01:35:07,597
DO PEOPLE WHO HAVE A VOAB ROW

2563
01:35:07,597 --> 01:35:09,199
VASCULAR ACCIDENT, HEMIPLEGIA?

2564
01:35:09,199 --> 01:35:10,567
>> SO I'M DOING THIS AT
THE

2565
01:35:10,567 --> 01:35:13,403
MOMENT, SCRATCHING MYSELF,

2566
01:35:13,403 --> 01:35:14,604
BECAUSE YOU'LL PROBABLY FIND

2567
01:35:14,604 --> 01:35:15,472
THERE'S SOME PEOPLE IN THE

2568
01:35:15,472 --> 01:35:16,840
AUDIENCE WHO WILL ACTUALLY BE

2569
01:35:16,840 --> 01:35:18,575
FOLLOWING ME.

2570
01:35:18,575 --> 01:35:19,576
 DOING THAT, AND IT

2571
01:35:19,576 --> 01:35:21,411
ACTUALLY BEEN STUDIED IN

2572
01:35:21,411 --> 01:35:23,580
MONKEYS, THAT IT'S ACTUALLY A

2573
01:35:23,580 --> 01:35:24,981
MIRROR BEHAVIOR.

2574
01:35:24,981 --> 01:35:30,120
SO IF YOU HAVE -- IF YOU SHOW A

2575
01:35:30,120 --> 01:35:31,254
VIDEO TO MONKEYS OF ANOTHER

2576
01:35:31,254 --> 01:35:33,757
MONKEY SCRATCHING, A VERY LARGE

2577
01:35:33,757 --> 01:35:34,858
NUMBER OF THEM WILL START

2578
01:35:34,858 --> 01:35:35,959
SCRATCHING.

2579
01:35:35,959 --> 01:35:42,332
SO THIS TELLS YOU THAT IT IS --

2580
01:35:42,332 --> 01:35:43,100
THE BRAIN.

2581
01:35:43,100 --> 01:35:44,101
BASICALLY IF YOU THINK OF

2582
01:35:44,101 --> 01:35:46,169
SOMETHING VERY ITCHY, IT'S

2583
01:35:46,169 --> 01:35:47,003
ACTUALLY PRETTY COMMON THAT YOU

2584
01:35:47,003 --> 01:35:50,640
WILL ACTUALLY START SCRATCHING.

2585
01:35:50,640 --> 01:35:57,748
SO CLEARLY THERE'S A GREAT DEAL

2586
01:35:57,748 --> 01:35:59,649
OF SUPPRESSION FOR ITCHING AND

2587
01:35:59,649 --> 01:36:00,417
FOR ALL KIND OF DIFFERENT

2588
01:36:00,417 --> 01:36:00,851
REASONS.

2589
01:36:00,851 --> 01:36:03,153
SO VERY OFTEN I WILL SCRATCH --

2590
01:36:03,153 --> 01:36:05,322
PERHAPS WHEN I'M NEWER VEST,

2591
01:36:05,322 --> 01:36:12,596
IT'S JUST SOMETHING THAT YOU DO.

2592
01:36:12,596 --> 01:36:14,097
SO FROM THAT EXAMPLE, WHAT I'M

2593
01:36:14,097 --> 01:36:16,533
SAYING IS THAT THERE MAY BE

2594
01:36:16,533 --> 01:36:21,471
CENTRAL ITCH, WHAT A

2595
01:36:21,471 --> 01:36:22,005
NEUROBIOLOGIST WOULD CALL

2596
01:36:22,005 --> 01:36:23,340
CENTRAL ITCH, AND THIS IS NOT

2597
01:36:23,340 --> 01:36:25,208
UNUSUAL TO THINK ABOUT,

2598
01:36:25,208 --> 01:36:27,644
BECAUSE -- AND BECAUSE FOR

2599
01:36:27,644 --> 01:36:31,581
INSTANCE, THERE'S NEUROGENIC

2600
01:36:31,581 --> 01:36:34,518
PAIN, SO YOU CAN HAVE PATIENTS

2601
01:36:34,518 --> 01:36:36,720
THAT HAVE NO SYMPTOM AT ALL,

2602
01:36:36,720 --> 01:36:37,954
THEY SEEM TO BE COMPLETELY

2603
01:36:37,954 --> 01:36:40,157
RECOVERED AFTER AN INJURY, BUT

2604
01:36:40,157 --> 01:36:45,829
THEY STILL HAVE PAIN.

2605
01:36:45,829 --> 01:36:48,465
SO IT'S THOUGHT THAT THIS COULD

2606
01:36:48,465 --> 01:36:52,235
ALSO OCCUR FOR ITCH AS WELL.

2607
01:36:52,235 --> 01:36:54,104
IT'S PROBABLY JUST A LOT LESS

2608
01:36:54,104 --> 01:36:57,240
COMMON.

2609
01:36:57,240 --> 01:37:00,544
SO ONE OF THE SYMPTOMS OF

2610
01:37:00,544 --> 01:37:04,314
SHINGLES, FOR INSTANCE, IS LESS

2611
01:37:04,314 --> 01:37:07,350
COMMON BUT SOME PEOPLE ACTUALLY

2612
01:37:07,350 --> 01:37:08,552
DEVELOP CHRONIC ITCH AFTER

2613
01:37:08,552 --> 01:37:09,119
SHINGLES.

2614
01:37:09,119 --> 01:37:12,289
SO THIS IS SOMETHING THAT

2615
01:37:12,289 --> 01:37:13,390
BECOMES PERMANENT AND THEY DON'T

2616
01:37:13,390 --> 01:37:14,958
GET RID OF IT.

2617
01:37:14,958 --> 01:37:18,428
AND THAT'S PURELY NEUROGENIC.

2618
01:37:18,428 --> 01:37:20,297
THERE'S NOTHING HAPPENING TO

2619
01:37:20,297 --> 01:37:22,399
THEIR SKIN.

2620
01:37:22,399 --> 01:37:24,267
THERE'S NO OTHER REASON THAT THE

2621
01:37:24,267 --> 01:37:27,003
NERVE FIBERS HAVE BEEN ACTIVATED

2622
01:37:27,003 --> 01:37:32,509
AND STAY ACTIVATED.

2623
01:37:32,509 --> 01:37:34,945
>> SO IF SOMEONE HAS A

2624
01:37:34,945 --> 01:37:39,950
HEMIPLEGIA AND ECZEMA OR ATOPIC

2625
01:37:39,950 --> 01:37:42,953
DERMATITIS, DO THEY ITCH IN THE

2626
01:37:42,953 --> 01:37:44,020
DEINNERVATED PORTION OF THEIR

2627
01:37:44,020 --> 01:37:50,494
BODY?

2628
01:37:50,494 --> 01:37:52,596
>> PROBABLY NOT.

2629
01:37:52,596 --> 01:37:54,798
I'VE NOT LOOKED INTO THAT, BUT I

2630
01:37:54,798 --> 01:37:56,433
WOULD BE SURPRISED IF THEY DID,

2631
01:37:56,433 --> 01:37:58,101
BECAUSE YOU NEED TO HAVE THE

2632
01:37:58,101 --> 01:37:59,736
CONNECTION.

2633
01:37:59,736 --> 01:38:09,179
AND ITCH IS LOCATION-SPECIFIC.

2634
01:38:09,179 --> 01:38:10,347
SO THERE'S THE CONNECTIONS INTO

2635
01:38:10,347 --> 01:38:12,249
THE CENTRAL NERVOUS SYSTEM ARE

2636
01:38:12,249 --> 01:38:14,584
DEFINED, I MEAN, THAT'S WHY YOU

2637
01:38:14,584 --> 01:38:17,420
KNOW YOU'VE BEEN -- A MOSQUITO'S

2638
01:38:17,420 --> 01:38:19,489
GOT YOUR LEFT HAND RATHER THAN

2639
01:38:19,489 --> 01:38:21,691
YOUR RIGHT HAND.

2640
01:38:21,691 --> 01:38:26,129
YOU KNOW WHERE THE CRITTERS GOT

2641
01:38:26,129 --> 01:38:26,296
YOU.

2642
01:38:26,296 --> 01:38:31,034
>> SO IAN, YOU'RE THE
CLINICIAN.

2643
01:38:31,034 --> 01:38:32,669
DO HEMIPLEGIC PATIENTS ITCH IF

2644
01:38:32,669 --> 01:38:35,739
THEY HAVE ATOPIC DERMATITIS?

2645
01:38:35,739 --> 01:38:37,307
>> I HAVEN'T STUDIED THAT

2646
01:38:37,307 --> 01:38:38,942
DIRECTLY, BUT I AGREE WITH MARK,

2647
01:38:38,942 --> 01:38:39,476
I'D SAY NO.

2648
01:38:39,476 --> 01:38:42,746
I MEAN, YOU HEAR ABOUT

2649
01:38:42,746 --> 01:38:44,247
NEUROPATHIC PAIN SYNDROMES, BUT

2650
01:38:44,247 --> 01:38:46,449
I'VE NEVER HEARD ANYBODY SAY

2651
01:38:46,449 --> 01:38:49,419
THAT THEY HAVE ITCH.

2652
01:38:49,419 --> 01:38:52,822
IF THEY'RE GENUINE, THEY DENER

2653
01:38:52,822 --> 01:38:54,891
SERRATED IN THAT AREA, THEY

2654
01:38:54,891 --> 01:38:56,293
DON'T HAVE ITCH EITHER.

2655
01:38:56,293 --> 01:39:02,933
>> SO MARK, ARE THERE WAYS
OF

2656
01:39:02,933 --> 01:39:08,204
DIRECTLY INHIBITING MPBB?

2657
01:39:08,204 --> 01:39:10,307
>> SO I DIDN'T GO INTO
THIS IN

2658
01:39:10,307 --> 01:39:13,476
MY TALK.

2659
01:39:13,476 --> 01:39:14,911
SO WE TOGETHER WITH

2660
01:39:14,911 --> 01:39:17,847
COLLABORATORS IN NCATS ACTUALLY

2661
01:39:17,847 --> 01:39:19,749
PERFORMED A HIGH-THROUGHPUT

2662
01:39:19,749 --> 01:39:25,121
SCREEN TO TRY AND IDENTIFY

2663
01:39:25,121 --> 01:39:27,424
ANTAGONISTS TO THE NPPB

2664
01:39:27,424 --> 01:39:29,626
RECEPTOR, THIS IS A RECEPTOR

2665
01:39:29,626 --> 01:39:33,463
CALLED N PB1, AND WE'VE

2666
01:39:33,463 --> 01:39:34,431
IDENTIFIED ANTAGONISTS AND AT

2667
01:39:34,431 --> 01:39:36,633
LEAST IN ANIMAL STUDIES, THEY

2668
01:39:36,633 --> 01:39:39,069
WORK.

2669
01:39:39,069 --> 01:39:41,237
THEY PREVENT THE ANIMAL

2670
01:39:41,237 --> 01:39:47,110
SCRATCHING TO PRURITOGENS.

2671
01:39:47,110 --> 01:39:48,311
SO IN THEORY, YES, THAT WOULD BE

2672
01:39:48,311 --> 01:39:52,449
A WAY THAT YOU COULD ACTUALLY

2673
01:39:52,449 --> 01:39:53,550
PREVENT ITCH.

2674
01:39:53,550 --> 01:39:56,019
I MEAN, ONE OF THE REASONS WHY

2675
01:39:56,019 --> 01:39:57,654
WE THOUGHT OF THAT AS A

2676
01:39:57,654 --> 01:39:59,923
POTENTIAL WAY IS THAT IT WOULD

2677
01:39:59,923 --> 01:40:02,993
CIRCUMVENT THE NEED TO DEVELOP

2678
01:40:02,993 --> 01:40:04,894
ANTAGONISTS TO INDIVIDUAL

2679
01:40:04,894 --> 01:40:09,733
CHEMICALS TO DIFFERENT

2680
01:40:09,733 --> 01:40:11,468
RECEPTORS, BECAUSE THIS

2681
01:40:11,468 --> 01:40:12,335
TRANSMITTER IS CENTRAL TO

2682
01:40:12,335 --> 01:40:15,672
TRANSMISSION OF ALL THE ITCH

2683
01:40:15,672 --> 01:40:16,439
SIGNALS.

2684
01:40:16,439 --> 01:40:18,341
SO THAT'S SOMETHING THAT'S STILL

2685
01:40:18,341 --> 01:40:20,710
UNDER DEVELOPMENT, BECAUSE THE

2686
01:40:20,710 --> 01:40:23,046
MOLECULES THAT WE IDENTIFIED,

2687
01:40:23,046 --> 01:40:27,417
FIRST OF ALL, ARE NOT HIGH

2688
01:40:27,417 --> 01:40:29,619
AFFINITY AND NOT ITCH SPECIFIC

2689
01:40:29,619 --> 01:40:31,354
SO WE KNOW THERE CAN BE SOME

2690
01:40:31,354 --> 01:40:36,126
EFFECTS ON OTHER RECEPTORS.

2691
01:40:36,126 --> 01:40:39,929
>> SO WHAT IS THE
PHYSIOLOGIC

2692
01:40:39,929 --> 01:40:41,564
PURPOSE IN HAVING ITCH

2693
01:40:41,564 --> 01:40:45,769
RECEPTORS?

2694
01:40:45,769 --> 01:40:48,405
>> SO YOU'RE ASKING ME TO

2695
01:40:48,405 --> 01:40:51,474
SPECULATE NOW, AND I'M HAPPY TO

2696
01:40:51,474 --> 01:40:53,243
SPECULATE, BUT SO THE AUDIENCE

2697
01:40:53,243 --> 01:40:55,011
UNDERSTANDS, THIS IS NOT KNOWN,

2698
01:40:55,011 --> 01:40:58,348
SO THIS IS JUST ME MAKING THINGS

2699
01:40:58,348 --> 01:40:58,515
UP.

2700
01:40:58,515 --> 01:41:02,619
I MEAN, CLEARLY, I WOULD SAY

2701
01:41:02,619 --> 01:41:09,392
ITCH CAN BE THOUGHT OF AS AN

2702
01:41:09,392 --> 01:41:10,160
ANTIPARASITIC DEFENSE.

2703
01:41:10,160 --> 01:41:12,095
IT'S NOT AN ACCIDENT THAT MOST

2704
01:41:12,095 --> 01:41:15,098
OF THE NATURAL PARASITES THAT

2705
01:41:15,098 --> 01:41:19,803
TRY TO PREY ON US MAKE US

2706
01:41:19,803 --> 01:41:22,005
SCRATCH, AND IF YOU THINK ABOUT

2707
01:41:22,005 --> 01:41:25,875
SCRATCHES, WE'RE REMOVING THE

2708
01:41:25,875 --> 01:41:26,843
VERY OUTER LAYERS OF THE SKIN,

2709
01:41:26,843 --> 01:41:28,978
SO THIS COULD BE QUITE AN

2710
01:41:28,978 --> 01:41:30,447
EFFECTIVE WAY TO POTENTIALLY --

2711
01:41:30,447 --> 01:41:32,248
FIRST OF ALL WE MOVE THE

2712
01:41:32,248 --> 01:41:36,753
PARASITE, BUT THEN WE MOVE

2713
01:41:36,753 --> 01:41:37,887
ANYTHING ELSE THAT MIGHT BE IN

2714
01:41:37,887 --> 01:41:38,855
THAT TOP LAYER OF THE SKIN.

2715
01:41:38,855 --> 01:41:40,290
THE OTHER THING THAT I'LL POINT

2716
01:41:40,290 --> 01:41:43,026
OUT IS THAT IT IS THAT VERY TOP

2717
01:41:43,026 --> 01:41:46,029
LAYER THAT THE ITCH NEURONS

2718
01:41:46,029 --> 01:41:47,230
ACTUALLY INNERVATE, THAT TOP

2719
01:41:47,230 --> 01:41:49,199
LAYER IS NOT INNERVATED BY THE

2720
01:41:49,199 --> 01:41:51,101
NEURONS THAT ARE INVOLVED IN

2721
01:41:51,101 --> 01:41:52,869
DETECTING PAINFUL STIMULI,

2722
01:41:52,869 --> 01:41:54,938
THEY'RE MUCH DEEPER, VERY MUCH

2723
01:41:54,938 --> 01:41:56,973
MUCH MORE IN THE DERMIS, AND WE

2724
01:41:56,973 --> 01:42:04,080
ALL KNOW THAT RECENT WHY WE

2725
01:42:04,080 --> 01:42:05,715
OFTEN SCRATCH AND THEN WE STOP

2726
01:42:05,715 --> 01:42:06,816
SCRATCHING IS WE'VE ACTUALLY GOT

2727
01:42:06,816 --> 01:42:07,951
DOWN TO THAT DEEPER LAYER AND

2728
01:42:07,951 --> 01:42:12,122
ITCH IS REPLACED BY PAIN.

2729
01:42:12,122 --> 01:42:14,624
AND PAIN EVOLUTIONARILY, WE

2730
01:42:14,624 --> 01:42:16,526
WOULD STOP SCRATCHING.

2731
01:42:16,526 --> 01:42:21,431
SO THIS COULD BE A MECHANISM FOR

2732
01:42:21,431 --> 01:42:29,239
REMOVAL OF EGG TO PARASITES.

2733
01:42:29,239 --> 01:42:31,841
>> THERE'S A QUESTION
ABOUT

2734
01:42:31,841 --> 01:42:36,913
WHETHER -- LET'S SEE.

2735
01:42:36,913 --> 01:42:38,381
AS SOMEONE WHO HAS ATOPIC

2736
01:42:38,381 --> 01:42:43,319
DERMATITIS AND IS CURRENTLY ON

2737
01:42:43,319 --> 01:42:48,124
DUPIXENT, IN MY EXPERIENCE, THE

2738
01:42:48,124 --> 01:42:50,326
ITCH IS REALLY FOCUSED ON WHERE

2739
01:42:50,326 --> 01:42:52,095
THE NERVES ARE.

2740
01:42:52,095 --> 01:42:54,097
ENDS ARE ALWAYS THE WORST, MOST

2741
01:42:54,097 --> 01:42:55,832
LIKELY DUE TO ALL THE NERVES IN

2742
01:42:55,832 --> 01:42:56,399
THE AREA.

2743
01:42:56,399 --> 01:42:58,301
I FIND THAT LOCATIONS WITH FEWER

2744
01:42:58,301 --> 01:43:01,037
NERVES ARE SIGNIFICANTLY LESS

2745
01:43:01,037 --> 01:43:03,106
ITCHY.

2746
01:43:03,106 --> 01:43:05,508
STOMACH, BACK, BUT STILL ITCHY

2747
01:43:05,508 --> 01:43:08,178
IF THERE'S AN ALLERGEN

2748
01:43:08,178 --> 01:43:10,713
TRIGGERING MY ECZEMA.

2749
01:43:10,713 --> 01:43:17,053
WHAT DO YOU THINK ABOUT THAT?

2750
01:43:17,053 --> 01:43:23,126
IS THAT A COMMON OBSERVATION?

2751
01:43:23,126 --> 01:43:24,627
>> I DON'T KNOW IF PEOPLE
PEGGED

2752
01:43:24,627 --> 01:43:27,063
TO THE NERVES, BUT CERTAINLY

2753
01:43:27,063 --> 01:43:31,568
HAND DISEASES MOST COMMON FOR

2754
01:43:31,568 --> 01:43:34,537
ADULTS, BUT THEN AS SHOWN IN THE

2755
01:43:34,537 --> 01:43:37,240
PICTURES, IT'S MORE EXTREMITIES

2756
01:43:37,240 --> 01:43:40,810
ARE GOING TO BE MORE AFFECTED

2757
01:43:40,810 --> 01:43:44,314
THAN YOUR CHEST AND BACK, SO I

2758
01:43:44,314 --> 01:43:46,182
DON'T KNOW HOW -- YOU CAN'T

2759
01:43:46,182 --> 01:43:48,751
NECESSARILY SORT THOSE APART

2760
01:43:48,751 --> 01:43:50,386
DIRECTLY, NERVE CONCENTRATION

2761
01:43:50,386 --> 01:43:51,487
VERSUS EXPOSURE OF THOSE

2762
01:43:51,487 --> 01:43:56,626
PARTICULAR AREAS, KIND OF LIKE

2763
01:43:56,626 --> 01:43:57,594
DR. WIN WAS ALREADY SAYING.

2764
01:43:57,594 --> 01:43:59,395
BUT YES, THAT'S A COMMON

2765
01:43:59,395 --> 01:44:02,232
PRESENTATION, PARTICULARLY FOR

2766
01:44:02,232 --> 01:44:05,235
ADULTS, IS THE HAPPENED.

2767
01:44:05,235 --> 01:44:05,902
 -- THE HAND.

2768
01:44:05,902 --> 01:44:07,537
>> AND I'LL ADD TO WHAT
IAN HAS

2769
01:44:07,537 --> 01:44:11,608
SAID THAT AS I POINTED OUT, THIS

2770
01:44:11,608 --> 01:44:13,943
IS AN ITCH-SCRATCH CYCLE, SO

2771
01:44:13,943 --> 01:44:17,547
CLEARLY, YOUR HANDS, YOU HAVE

2772
01:44:17,547 --> 01:44:18,848
ACCESS TO, TO SCRATCH.

2773
01:44:18,848 --> 01:44:21,885
IF YOU DON'T SCRATCH, IT WILL

2774
01:44:21,885 --> 01:44:24,287
PROBABLY CLEAR UP OR BE A LOT

2775
01:44:24,287 --> 01:44:27,257
LESS.

2776
01:44:27,257 --> 01:44:29,592
AND THAT'S NOT TO SAY THAT IT

2777
01:44:29,592 --> 01:44:33,096
EASY TO STOP SCRATCHING, BUT

2778
01:44:33,096 --> 01:44:34,964
CLEAR LIE YOU'RE NOT GOING TO BE

2779
01:44:34,964 --> 01:44:36,499
SCRATCHING YOUR BACK, ALSO

2780
01:44:36,499 --> 01:44:38,368
BECAUSE, SOCIALLY, THAT WOULD BE

2781
01:44:38,368 --> 01:44:41,237
SORT OF A STRANGE THING TO BE

2782
01:44:41,237 --> 01:44:43,006
DOING, WHEREAS SCRATCHING YOUR

2783
01:44:43,006 --> 01:44:46,242
HANDS, YEAH, YOU CAN DO IT UNDER

2784
01:44:46,242 --> 01:44:52,849
THE TABLE AND BE -- MAKE THE

2785
01:44:52,849 --> 01:44:55,218
ITCH WORSE, INCREASE THE

2786
01:44:55,218 --> 01:44:57,320
INFLAMMATION, AND AS I WAS

2787
01:44:57,320 --> 01:44:59,088
SAYING, IT'S THE ITCH-SCRATCH

2788
01:44:59,088 --> 01:45:00,290
CYCLE.

2789
01:45:00,290 --> 01:45:06,462
AND I'VE HEARD FROM SOME

2790
01:45:06,462 --> 01:45:07,864
PHYSICIANS, IN REALLY BAD CASES

2791
01:45:07,864 --> 01:45:11,467
OF PRURITIS, ONE TREATMENT IS

2792
01:45:11,467 --> 01:45:13,069
ACTUALLY TO BUNDLE THE PATIENT

2793
01:45:13,069 --> 01:45:15,905
IN BANDAGES, PREVENT THEM FROM

2794
01:45:15,905 --> 01:45:19,409
SCRATCHING, AND THIS ACTUALLY IS

2795
01:45:19,409 --> 01:45:23,579
VERY EFFECTIVE.

2796
01:45:23,579 --> 01:45:28,551
>> WHY NOT JUST WEAR
GLOVES OR

2797
01:45:28,551 --> 01:45:29,018
SOME SOFT --

2798
01:45:29,018 --> 01:45:33,289
>> SO THAT'S EXACTLY WHAT

2799
01:45:33,289 --> 01:45:36,326
KIDS -- I THINK -- I'VE HEARD

2800
01:45:36,326 --> 01:45:41,864
THAT AT LEAST YOU TRIM THE NAILS

2801
01:45:41,864 --> 01:45:44,033
AND YOU PUT SOME LITTLE GLOVES

2802
01:45:44,033 --> 01:45:45,902
ON, ON THE KIDS, AND THIS WILL

2803
01:45:45,902 --> 01:45:49,372
STOP THEM FROM SCRATCHING

2804
01:45:49,372 --> 01:45:52,742
EFFECTIVELY AND PREVENT -- I HAD

2805
01:45:52,742 --> 01:45:57,113
NO -- IN RESEARCH ANIMALS, OFTEN

2806
01:45:57,113 --> 01:45:58,281
THE VETERINARIAN WILL ACTUALLY

2807
01:45:58,281 --> 01:45:59,482
TRIM THE NAILS OF THE ANIMALS

2808
01:45:59,482 --> 01:46:01,451
AND THIS WILL ACTUALLY REDUCE

2809
01:46:01,451 --> 01:46:04,687
THE AMOUNT OF DAMAGE THAT THE

2810
01:46:04,687 --> 01:46:08,324
ANIMALS INFLICT TO THEMSELVES.

2811
01:46:08,324 --> 01:46:12,161
SO THIS IS A REAL THING THAT YOU

2812
01:46:12,161 --> 01:46:14,230
ACTUALLY STIMULATE MORE

2813
01:46:14,230 --> 01:46:14,964
INFLAMMATION IF YOU SCRATCH

2814
01:46:14,964 --> 01:46:16,466
MORE, AND THAT'S JUST GOING TO

2815
01:46:16,466 --> 01:46:20,770
CAUSE MORE ITCH.

2816
01:46:20,770 --> 01:46:23,172
>> IAN, THERE ARE STUDIES
ON THE

2817
01:46:23,172 --> 01:46:26,709
CHANGE IN THE MICROBIOME WITH

2818
01:46:26,709 --> 01:46:29,879
ADVANCING AGE, PARTICULARLY VERY

2819
01:46:29,879 --> 01:46:34,484
ADVANCED AGE.

2820
01:46:34,484 --> 01:46:36,719
AND DP ARE IS THERE ANY

2821
01:46:36,719 --> 01:46:37,487
RELATIONSHIP OR ANY INFORMATION

2822
01:46:37,487 --> 01:46:39,922
ON THE ROLE OF LET'S CALL IT

2823
01:46:39,922 --> 01:46:43,626
POLLUTION IN THESE OLDER

2824
01:46:43,626 --> 01:46:50,033
ADUME --PARTICULARLY IN LIGHT OE

2825
01:46:50,033 --> 01:46:53,903
CHANGING PLY MIE  MICROBIOME WI?

2826
01:46:53,903 --> 01:46:55,772
>> MOST OF THE MICROBIOME

2827
01:46:55,772 --> 01:46:57,173
STUDIES I'VE SEEN HAVE SUGGESTED

2828
01:46:57,173 --> 01:46:58,641
YOU GET A RAPID CHANGE FROM

2829
01:46:58,641 --> 01:47:01,611
BIRTH ALL THE WAY THROUGH AND A

2830
01:47:01,611 --> 01:47:06,382
STEADY CHANGE ALL THE WAY TO 26.

2831
01:47:06,382 --> 01:47:07,350
AND 26 AND FORWARD, IT TENDS TO

2832
01:47:07,350 --> 01:47:08,351
BE FAIRLY STABLE.

2833
01:47:08,351 --> 01:47:10,420
SO I HAVEN'T SEEN DRAMATIC

2834
01:47:10,420 --> 01:47:11,854
CHANGES WITH AGE.

2835
01:47:11,854 --> 01:47:15,558
THE BIGGEST PROBLEM IS MOST OF

2836
01:47:15,558 --> 01:47:17,160
THE GUT MICROBIOME STUDIES ARE

2837
01:47:17,160 --> 01:47:19,429
GOING TO BE ENTIRELY DEPENDENT

2838
01:47:19,429 --> 01:47:21,564
ON DIET, SO YOU START TO GET OF

2839
01:47:21,564 --> 01:47:27,136
THE AGE WHERE DIETARY STAGES --

2840
01:47:27,136 --> 01:47:28,438
EXPECT TO SEE MICROBIOME

2841
01:47:28,438 --> 01:47:28,771
CHANGES.

2842
01:47:28,771 --> 01:47:31,140
THERE HAS NOT BEEN VERY MUCH

2843
01:47:31,140 --> 01:47:32,442
EVALUATION OF MAYBE THE TERM

2844
01:47:32,442 --> 01:47:35,745
WOULD BE FOOD POLLUTION.

2845
01:47:35,745 --> 01:47:40,149
OF WHAT DOES -- WHAT DO

2846
01:47:40,149 --> 01:47:42,785
PROCESSED INGREDIENTS DO TO THE

2847
01:47:42,785 --> 01:47:44,320
MICROBIOME, WHAT CONTAMINANTS DO

2848
01:47:44,320 --> 01:47:51,294
TO THE MICRO  MICROBIOME.

2849
01:47:51,294 --> 01:47:53,096
 -- WILL KILL OFF GUT BACTERIA

2850
01:47:53,096 --> 01:47:54,330
TOO, IS SOMEWHAT THEY ARE BUILT

2851
01:47:54,330 --> 01:47:55,698
TO PREVENT ORGANISMS FROM

2852
01:47:55,698 --> 01:47:57,033
GROWING IN WHATEVER PRODUCT YOU

2853
01:47:57,033 --> 01:47:58,000
PUT THEM IN.

2854
01:47:58,000 --> 01:48:02,472
AND SO WHEN YOU START DRINKING

2855
01:48:02,472 --> 01:48:03,973
THESE THROUGH WATER

2856
01:48:03,973 --> 01:48:05,274
CONTAMINATION, BECAUSE NOT --

2857
01:48:05,274 --> 01:48:06,709
NOT EVERY MUNICIPALITY WILL

2858
01:48:06,709 --> 01:48:09,512
FILTER OUT EVERY SINGLE CON TAM

2859
01:48:09,512 --> 01:48:09,846
CONTAMINANT.

2860
01:48:09,846 --> 01:48:12,014
OR IF THEY'RE INTENTIONALLY PUT

2861
01:48:12,014 --> 01:48:15,518
INTO FOODS TO PREVENT MICROBIAL

2862
01:48:15,518 --> 01:48:17,320
OVERGROWTH, THEY WILL WIPE THAT

2863
01:48:17,320 --> 01:48:18,521
OUT AS WELL.

2864
01:48:18,521 --> 01:48:23,359
SO I HAVEN'T SEEN A STRONG

2865
01:48:23,359 --> 01:48:24,894
SIGNAL FOR MICROBIOME IN AGING.

2866
01:48:24,894 --> 01:48:26,896
IF THERE IS ONE, I WOULD BET THE

2867
01:48:26,896 --> 01:48:27,897
OVERWHELMING MAJORITY OF THAT

2868
01:48:27,897 --> 01:48:32,535
SIGNAL WILL BE IMMEDIATELY TIED

2869
01:48:32,535 --> 01:48:33,536
TO -- AND I DON'T SEE ANYWHERE

2870
01:48:33,536 --> 01:48:35,838
NEAR THE RESEARCH THAT WE NEED

2871
01:48:35,838 --> 01:48:37,807
FOR WHAT DO DIETARY FACTORS DO

2872
01:48:37,807 --> 01:48:39,275
TO THE MICROBIOME AND TO START

2873
01:48:39,275 --> 01:48:40,376
TO GET VERY SPECIFIC.

2874
01:48:40,376 --> 01:48:42,778
YOU CAN FIND ONES FOR LIKE OH,

2875
01:48:42,778 --> 01:48:45,014
PUT SOMEBODY ON AN

2876
01:48:45,014 --> 01:48:46,549
ULTRAPROCESSED DIET, KETO DIET

2877
01:48:46,549 --> 01:48:49,352
OR VEGAN DIET SO YOU SEE THESE

2878
01:48:49,352 --> 01:48:50,419
SWEEPING DIFFERENCES BUT I FEEL

2879
01:48:50,419 --> 01:48:51,654
LIKE THE NEXT PHASE IS GOING TO

2880
01:48:51,654 --> 01:48:53,923
BE SPECIFIC INGREDIENT AND

2881
01:48:53,923 --> 01:48:55,091
SPECIFIC EXPOSURES TO SEE WHAT

2882
01:48:55,091 --> 01:48:58,494
HAPPENS.

2883
01:48:58,494 --> 01:49:01,998
>> SO IAN, WHAT DO YOU
THINK IS

2884
01:49:01,998 --> 01:49:08,738
HAPPENING AT AGE 2, 3 OR 4, THAT

2885
01:49:08,738 --> 01:49:12,542
CHANGES THE PHENOTYPE WITH

2886
01:49:12,542 --> 01:49:19,248
RESPECT TO ATOPIC DERMATITIS?

2887
01:49:19,248 --> 01:49:21,517
>> I THINK COMBINING WHAT
MARK

2888
01:49:21,517 --> 01:49:24,120
IS TALKING ABOUT, MY BIGGEST

2889
01:49:24,120 --> 01:49:25,755
WORRY WOULD BE SOME SORT OF

2890
01:49:25,755 --> 01:49:26,489
NEUROLOGIC PRIMING.

2891
01:49:26,489 --> 01:49:28,124
THIS IS THE TIME FOR

2892
01:49:28,124 --> 01:49:30,660
NEURODEVELOPMENT, IMMUNE

2893
01:49:30,660 --> 01:49:34,697
DEVELOPMENT, AND YOU FORCE THE

2894
01:49:34,697 --> 01:49:36,299
CHILD TO APPROPRIATELY RESPOND

2895
01:49:36,299 --> 01:49:37,600
TO A VERY INAPPROPRIATE STIMULUS

2896
01:49:37,600 --> 01:49:39,035
OF THESE PARTICULAR TOXINS THAT

2897
01:49:39,035 --> 01:49:42,638
THEY'RE GETTING.

2898
01:49:42,638 --> 01:49:44,574
AND THAT WILL EVENTUALLY GET

2899
01:49:44,574 --> 01:49:47,510
BUILT INTO SYSTEMS OF

2900
01:49:47,510 --> 01:49:48,945
PARTICIPATING AND POTENTIALLY

2901
01:49:48,945 --> 01:49:49,378
OVERREACTING.

2902
01:49:49,378 --> 01:49:51,180
I THINK IT MORE CLEAR FOR ASTHMA

2903
01:49:51,180 --> 01:49:53,349
IN THE LUNGS, WHERE CHRONIC

2904
01:49:53,349 --> 01:49:54,684
EXPOSURE CREATE A LOT OF

2905
01:49:54,684 --> 01:49:55,651
NEUROGENIC RESPONSE IN THE LUNG

2906
01:49:55,651 --> 01:49:58,354
AND THE NEXT EXPOSURE WILL

2907
01:49:58,354 --> 01:49:59,589
TRIGGER A MORE ROBUST RESPONSE

2908
01:49:59,589 --> 01:50:01,557
FROM ANYBODY ELSE, BUT I THINK

2909
01:50:01,557 --> 01:50:02,992
YOU ARE TRAINING THE IMMUNE

2910
01:50:02,992 --> 01:50:04,560
SYSTEMS AND THE PRIF PAL NERVOUS

2911
01:50:04,560 --> 01:50:06,329
SYSTEM TO RESPOND TO THESE

2912
01:50:06,329 --> 01:50:07,430
CHEMICALS, AND I THINK THAT THAT

2913
01:50:07,430 --> 01:50:11,167
IS A HARD LESSON TO UNLEARN.

2914
01:50:11,167 --> 01:50:12,368
OVER THE COURSE.

2915
01:50:12,368 --> 01:50:13,836
NOW, ONE OF THE BIGGEST

2916
01:50:13,836 --> 01:50:15,504
MYSTERIES IN ECZEMA IS WHY IS IT

2917
01:50:15,504 --> 01:50:17,573
THAT IN EVERY SOCIETY ON THE

2918
01:50:17,573 --> 01:50:18,507
PLANET, THE VAST MAJORITY OF

2919
01:50:18,507 --> 01:50:19,942
CHILDREN WITH ECZEMA WILL

2920
01:50:19,942 --> 01:50:21,877
EVENTUALLY OUTGROW IT.

2921
01:50:21,877 --> 01:50:22,979
OUTGROWING IT BEING A VERY

2922
01:50:22,979 --> 01:50:24,480
POORLY USED TERM, BUT THE SKIN

2923
01:50:24,480 --> 01:50:26,115
WILL CLEAR UP AND THEY MIGHT BE

2924
01:50:26,115 --> 01:50:27,850
LEFT WITH ALLERGIES AND ASTHMA

2925
01:50:27,850 --> 01:50:30,353
AND SO FORTH.

2926
01:50:30,353 --> 01:50:32,221
THERE'S NOT REALLY WELL-KNOWN, I

2927
01:50:32,221 --> 01:50:35,057
WOULD START TO THEN QUESTION

2928
01:50:35,057 --> 01:50:36,559
ABOUT NEUROLOGIC -- WHERE WE

2929
01:50:36,559 --> 01:50:37,994
TALKED ABOUT BEFORE, RECEPTOR

2930
01:50:37,994 --> 01:50:38,728
CONCENTRATIONS IN DIFFERENT PART

2931
01:50:38,728 --> 01:50:40,730
OF THE BODY, WE HAVE ONE STUDY

2932
01:50:40,730 --> 01:50:42,031
WHERE WE'RE TRYING TO LOOK AT

2933
01:50:42,031 --> 01:50:43,966
THE DIFFERENT NEURORECEPTORS AS

2934
01:50:43,966 --> 01:50:45,701
A MOUSE AGES, YOU OBVIOUSLY

2935
01:50:45,701 --> 01:50:47,536
CAN'T DO THIS IN HUMANS, BUT

2936
01:50:47,536 --> 01:50:48,604
FROM BIRTH ALL THE WAY FORWARD

2937
01:50:48,604 --> 01:50:50,373
TO SAY LIKE IS THERE A POINT

2938
01:50:50,373 --> 01:50:53,709
WHERE YOU JUST -- YOUR NEWER

2939
01:50:53,709 --> 01:50:54,810
LOGIC PRESENTATION CHANGES AS

2940
01:50:54,810 --> 01:50:56,445
YOU AGE.

2941
01:50:56,445 --> 01:50:59,081
OTHER PEOPLE HAVE JUST

2942
01:50:59,081 --> 01:51:00,916
HYPOTHESIZED THE STIN SCIN JUST

2943
01:51:00,916 --> 01:51:03,185
GETS THICKER AS YOU GO FROM 2 TO

2944
01:51:03,185 --> 01:51:05,721
10 TO 25 AND SO FORTH.

2945
01:51:05,721 --> 01:51:09,625
BUT THAT WOULD BE, I THINK

2946
01:51:09,625 --> 01:51:12,561
IMMUNOLOGIC AND NEUROLOGIC

2947
01:51:12,561 --> 01:51:15,197
TRAINING.

2948
01:51:15,197 --> 01:51:21,203
>> WE HAVE THE QUESTION
ABOUT

2949
01:51:21,203 --> 01:51:27,743
RELATIONSHIP OF MITOCHONDRIA TO

2950
01:51:27,743 --> 01:51:28,611
THESE PROCESSES.

2951
01:51:28,611 --> 01:51:30,246
I REALIZE THAT'S A PRETTY BIG

2952
01:51:30,246 --> 01:51:32,415
TOPIC, BUT IS THERE ANY EVIDENCE

2953
01:51:32,415 --> 01:51:35,351
LINKING MITOCHONDRIAL DYNAMICS

2954
01:51:35,351 --> 01:51:41,123
OR METABOLISM TO ATOPIC

2955
01:51:41,123 --> 01:51:42,658
DETERMINE TIGHT OR IN

2956
01:51:42,658 --> 01:51:45,127
RELATIONSHIP TO THE NEURAL

2957
01:51:45,127 --> 01:51:51,500
PATHWAYS?

2958
01:51:51,500 --> 01:51:55,638
>> I CAN ANSWER FOR ATOPIC
DERM.

2959
01:51:55,638 --> 01:51:58,774
IT'S BEEN PRETTY EXHAUSTIVELY

2960
01:51:58,774 --> 01:52:00,943
EVALUATED -- WE HAVE TOPICAL

2961
01:52:00,943 --> 01:52:03,145
STEROID WITHDRAWAL THAT IS OFTEN

2962
01:52:03,145 --> 01:52:04,380
CONFUSED FOR ATOPIC DERMATITIS,

2963
01:52:04,380 --> 01:52:06,816
SO IT LOOKS A LOT LIKE ATOPIC

2964
01:52:06,816 --> 01:52:07,483
DERM.

2965
01:52:07,483 --> 01:52:09,518
AND THAT INVOLVES MITOCHONDRIAL

2966
01:52:09,518 --> 01:52:11,120
DEFECTS THAT RUN THROUGH THE

2967
01:52:11,120 --> 01:52:17,360
COAL NER JIG PCHOLINERGIC PATHW.

2968
01:52:17,360 --> 01:52:19,328
BUT FOR YOUR ROUTINE ATOPIC

2969
01:52:19,328 --> 01:52:20,296
DERMATITIS PATIENT WALKING

2970
01:52:20,296 --> 01:52:24,533
AROUND, THERE HAS NOT BEEN ANY

2971
01:52:24,533 --> 01:52:26,168
STRONG SIGNAL IMPLICATING

2972
01:52:26,168 --> 01:52:31,340
MITOCHONDRIA IN ANY WAY.

2973
01:52:31,340 --> 01:52:34,810
>> LET SEE.

2974
01:52:34,810 --> 01:52:38,814
>> LET'S SEE.

2975
01:52:38,814 --> 01:52:49,358
WE HAD ANOTHER INTERESTING -- SO

2976
01:52:49,825 --> 01:52:51,460
DO EITHER OF YOU SEE A WAY IN

2977
01:52:51,460 --> 01:52:55,297
WHICH THESE TWO TYPES OF

2978
01:52:55,297 --> 01:53:02,104
RESEARCH THAT EACH OF YOU ARE  

2979
01:53:02,104 --> 01:53:06,976
DOING CAN BRIDGE OR AFFECT YOUR

2980
01:53:06,976 --> 01:53:11,981
BLANS PLANS FOR FUTURE RESEARCHN

2981
01:53:11,981 --> 01:53:12,515
COLLABORATIVELY?

2982
01:53:12,515 --> 01:53:16,852
ARE THERE THREADS IN BOTH THAT

2983
01:53:16,852 --> 01:53:20,489
TEND TO MAYBE INTRODUCE NEW

2984
01:53:20,489 --> 01:53:22,124
IDEAS OR DO WE HAVE A WAYS TO GO

2985
01:53:22,124 --> 01:53:27,730
YET?

2986
01:53:27,730 --> 01:53:29,198
>> I THINK ONE OF THE
THINGS

2987
01:53:29,198 --> 01:53:33,135
THAT IAN TALKED ABOUT WAS -- AND

2988
01:53:33,135 --> 01:53:34,236
I THINK IT WAS BROUGHT UP IN A

2989
01:53:34,236 --> 01:53:36,739
QUESTION AS WELL, WAS THE -- SO

2990
01:53:36,739 --> 01:53:39,208
WHAT MIGHT BE THE RECEPTORS FOR

2991
01:53:39,208 --> 01:53:40,309
THE SETTING OF SOME OF THESE

2992
01:53:40,309 --> 01:53:45,247
THINGS UP.

2993
01:53:45,247 --> 01:53:50,319
AND CLEARLY NOW WE'RE TO SAY IN

2994
01:53:50,319 --> 01:53:51,654
THIS GENOMIC AGE THAT BASICALLY

2995
01:53:51,654 --> 01:53:53,189
A LOT OF THIS INFORMATION IS

2996
01:53:53,189 --> 01:53:55,357
PUBLICLY AVAILABLE.

2997
01:53:55,357 --> 01:53:57,560
SO BASICALLY IAN DOESN'T REALLY

2998
01:53:57,560 --> 01:54:00,362
NEED ME.

2999
01:54:00,362 --> 01:54:02,565
ALL HE NEEDS IS A COMPUTER AND

3000
01:54:02,565 --> 01:54:05,835
SOME DIRECTION OF WHERE TO LOOK.

3001
01:54:05,835 --> 01:54:10,639
SO WHICH I THINK IS A GREAT

3002
01:54:10,639 --> 01:54:11,607
DEMOCRATIZATION OF SCIENCE.

3003
01:54:11,607 --> 01:54:13,676
I THINK THAT'S REALLY A

3004
01:54:13,676 --> 01:54:14,677
FANTASTIC THING THAT'S HAPPENED

3005
01:54:14,677 --> 01:54:20,015
IN THE LAST 10, 20 YEARS THAT

3006
01:54:20,015 --> 01:54:21,517
WE'RE NOW FORCED TO MAKE ALL OUR

3007
01:54:21,517 --> 01:54:26,822
DATA AVAILABLE, AND THAT MAKES

3008
01:54:26,822 --> 01:54:28,157
IT POSSIBLE -- AS YOU POINTED

3009
01:54:28,157 --> 01:54:29,458
OUT AT THE VERY BEGINNING,

3010
01:54:29,458 --> 01:54:30,893
SOMETIMES SCIENCE CAN BECOME

3011
01:54:30,893 --> 01:54:34,029
SILOED, BUT THIS IS ACTUALLY ONE

3012
01:54:34,029 --> 01:54:36,532
OF THE WAYS THAT I THINK THIS

3013
01:54:36,532 --> 01:54:39,268
HAS ACTUALLY BEEN BROKEN.

3014
01:54:39,268 --> 01:54:43,072
AND ANOTHER ILLUSTRATION OF THAT

3015
01:54:43,072 --> 01:54:45,808
IS THAT, FOR INSTANCE, I'M NOT

3016
01:54:45,808 --> 01:54:47,243
AN IMMUNOLOGIST, BUT I WAS ABLE

3017
01:54:47,243 --> 01:54:50,246
TO ACCESS DATA FROM

3018
01:54:50,246 --> 01:54:52,982
IMMUNOLOGISTS AND WHEN I WAS

3019
01:54:52,982 --> 01:54:56,218
LOOKING AT -- CELLS EXPRESS

3020
01:54:56,218 --> 01:54:57,119
ONCOSTATIN M AND THE PATIENT

3021
01:54:57,119 --> 01:54:58,420
GROUPS THAT ARE ALL PUBLICLY

3022
01:54:58,420 --> 01:55:00,022
AVAILABLE DATA, WE CAN ACTUALLY

3023
01:55:00,022 --> 01:55:04,527
ANALYZE TO SEE WHICH

3024
01:55:04,527 --> 01:55:06,595
INTERLEUKINS ARE ACTUALLY

3025
01:55:06,595 --> 01:55:11,200
ELEVATED AND SEARCH FOR NEW

3026
01:55:11,200 --> 01:55:14,470
POTENTIAL TARGETS.

3027
01:55:14,470 --> 01:55:17,806
SO I WOULD BE QUITE HAPPEN TO

3028
01:55:17,806 --> 01:55:19,675
POINT IAN IF HE NEEDS ANY HELP

3029
01:55:19,675 --> 01:55:23,178
IN THE RIGHT DIRECTION FOR THOSE

3030
01:55:23,178 --> 01:55:24,847
THINGS.

3031
01:55:24,847 --> 01:55:28,784
AND I THINK THAT'S WONDERFUL,

3032
01:55:28,784 --> 01:55:33,255
THAT THAT CAN BE DONE.

3033
01:55:33,255 --> 01:55:34,957
>> SO IAN, DO YOU HAVE A
--

3034
01:55:34,957 --> 01:55:37,626
>> I AGREE, I THINK
SEARCHING

3035
01:55:37,626 --> 01:55:38,761
FOR DIFFERENT CHEMICALS AND HOW

3036
01:55:38,761 --> 01:55:42,064
THEY WOULD ACTIVATE OR INHIBIT

3037
01:55:42,064 --> 01:55:44,466
THE RECEPTORS AND THE PROCESSES

3038
01:55:44,466 --> 01:55:46,735
THAT MARK TALKED ABOUT AND THEN

3039
01:55:46,735 --> 01:55:48,270
I THINK WHEN YOU TALK TO A

3040
01:55:48,270 --> 01:55:50,339
PARENT WITH ATOPIC DERM AND YOU

3041
01:55:50,339 --> 01:55:52,174
SAY WHAT ARE YOUR NUMBER ONE

3042
01:55:52,174 --> 01:55:53,008
CONCERNS, NUMBER ONE THROUGH 10

3043
01:55:53,008 --> 01:55:53,375
IS ITCH.

3044
01:55:53,375 --> 01:55:56,712
THEY WANT THE RASH TO GET

3045
01:55:56,712 --> 01:55:57,713
BETTER, BUT ITCH MAKING THEIR

3046
01:55:57,713 --> 01:56:00,015
LIFE MISERABLE IS BY FAR THEIR

3047
01:56:00,015 --> 01:56:00,649
NUMBER ONE CONCERN.

3048
01:56:00,649 --> 01:56:03,786
AND SO IF THERE ARE NEW

3049
01:56:03,786 --> 01:56:05,321
THERAPIES THAT MARK'S GROUP IS

3050
01:56:05,321 --> 01:56:06,555
DISCOVERING THAT ARE GOOD AT

3051
01:56:06,555 --> 01:56:08,958
BLOCKING THE ITCH PART, EVEN IF

3052
01:56:08,958 --> 01:56:10,559
IT DID NOTHING TO THE RASH AND I

3053
01:56:10,559 --> 01:56:12,094
AGREE WITH MARK THAT YOU'D BREAK

3054
01:56:12,094 --> 01:56:13,629
THE ITCH-SCRATCH CYCLE SO YOU

3055
01:56:13,629 --> 01:56:15,898
SHOULD IMPROVE THE RASH ANYWAY,

3056
01:56:15,898 --> 01:56:19,835
BUT EVEN JUST BLOCKING THE ITCH,

3057
01:56:19,835 --> 01:56:21,036
PATIENTS WOULD TRIP OVER

3058
01:56:21,036 --> 01:56:24,206
THEMSELVES TO GO GIVE MARK A

3059
01:56:24,206 --> 01:56:25,107
HIGH FIVE.

3060
01:56:25,107 --> 01:56:26,809
SO I THINK IT IS A PATIENT

3061
01:56:26,809 --> 01:56:29,011
POPULATION THAT IT WOULD BE GOOD

3062
01:56:29,011 --> 01:56:30,212
TO VALIDATE SOME OF THE

3063
01:56:30,212 --> 01:56:35,117
MECHANISMS THAT HE TALKED ABOUT.

3064
01:56:35,117 --> 01:56:44,760
>> I'M ALL FOR THAT.

3065
01:56:44,760 --> 01:56:46,395
YOU WANT TO SAY A FEW WORDS,

3066
01:56:46,395 --> 01:56:50,132
IAN, ABOUT THE PRURITIS

3067
01:56:50,132 --> 01:56:54,003
ASSOCIATED WITH LIVER DISEASE,

3068
01:56:54,003 --> 01:56:55,638
LIKE PBC, WHAT'S YOUR VIEW OF

3069
01:56:55,638 --> 01:57:00,376
THE MECHANISM THERE?

3070
01:57:00,376 --> 01:57:02,511
>> I HAVE NO IDEA.

3071
01:57:02,511 --> 01:57:04,380
THAT'S WAY OUTSIDE MY

3072
01:57:04,380 --> 01:57:05,147
WHEELHOUSE.

3073
01:57:05,147 --> 01:57:05,614
THAT ONE IS FOR MARK.

3074
01:57:05,614 --> 01:57:07,716
>> OKAY, I CAN TAKE A STAB
AT

3075
01:57:07,716 --> 01:57:08,717
THAT.

3076
01:57:08,717 --> 01:57:11,220
SO I CAN TALK ABOUT OTHER

3077
01:57:11,220 --> 01:57:12,121
PEOPLE'S RESEARCH, IT'S NOT

3078
01:57:12,121 --> 01:57:16,558
SOMETHING THAT WE'VE WORKED ON.

3079
01:57:16,558 --> 01:57:17,626
THERE HAVE BEEN SOME -- I MEAN,

3080
01:57:17,626 --> 01:57:21,030
THERE'S BEEN A FEW PAPERS WHICH

3081
01:57:21,030 --> 01:57:22,131
HAVE SUGGESTED THAT ONE OF THE

3082
01:57:22,131 --> 01:57:23,532
FAMILIES OF RECEPTORS I TALKED

3083
01:57:23,532 --> 01:57:27,569
ABOUT, IN IS THE MAST-RELATED G

3084
01:57:27,569 --> 01:57:28,871
PROTEIN RECEPTORS MIGHT BE THE

3085
01:57:28,871 --> 01:57:34,643
RECEPTORS FOR SOME OF THE -- SO

3086
01:57:34,643 --> 01:57:38,313
THE COMPOUNDS THAT ARE ELEVATED

3087
01:57:38,313 --> 01:57:41,650
IN THE BLOOD THAT ARE ASSOCIATED

3088
01:57:41,650 --> 01:57:43,585
WITH THOSE LIVER CONDITIONS.

3089
01:57:43,585 --> 01:57:44,787
I CAN'T REMEMBER EXACTLY THE

3090
01:57:44,787 --> 01:57:45,988
NAMES OF THEM.

3091
01:57:45,988 --> 01:57:49,825
I'M BLANKING, I DON'T REMEMBER

3092
01:57:49,825 --> 01:57:51,660
EXACTLY WHAT THE CHEMICALS ARE,

3093
01:57:51,660 --> 01:57:56,365
BUT THEY ACTIVATE THE MAST

3094
01:57:56,365 --> 01:58:04,973
RELATED G PROTEIN -- RECEPTORS.

3095
01:58:04,973 --> 01:58:08,477
>> WELL, LISTEN, ON BEHALF
OF A

3096
01:58:08,477 --> 01:58:11,847
LARGE NUMBER OF PEOPLE WHO ARE

3097
01:58:11,847 --> 01:58:14,383
WATCHING THIS PROGRAM AND MANY

3098
01:58:14,383 --> 01:58:18,821
MORE WHEN THEY DOWNLOAD IT, I

3099
01:58:18,821 --> 01:58:20,456
WANT TO THANK BOTH OF YOU FOR

3100
01:58:20,456 --> 01:58:22,091
OPENING OUR EYES TO SOME REALLY

3101
01:58:22,091 --> 01:58:24,793
VERY EXCITING DEVELOPMENTS, BOTH

3102
01:58:24,793 --> 01:58:27,229
FROM THE STANDPOINT OF THE

3103
01:58:27,229 --> 01:58:30,933
NEUROSCIENCE, THE IMMUNOLOGY,

3104
01:58:30,933 --> 01:58:35,304
AND THE MICROBIOLOGY.

3105
01:58:35,304 --> 01:58:37,005
IT'S GOING TO BE VERY EXCITING

3106
01:58:37,005 --> 01:58:41,543
TIMES AHEAD, AND HOPEFULLY FOR

3107
01:58:41,543 --> 01:58:42,811
THE BENEFIT OF PEOPLE WHOSE

3108
01:58:42,811 --> 01:58:44,480
LIVES ARE MADE MISERABLE BY

3109
01:58:44,480 --> 01:58:48,917
PARTICULARLY CHRONIC ITCHING,

3110
01:58:48,917 --> 01:58:49,752
THAT HAS A GREAT DEAL OF

3111
01:58:49,752 --> 01:58:50,285
INTEREST.

3112
01:58:50,285 --> 01:58:51,420
SO THANK YOU VERY, VERY MUCH.

3113
01:58:51,420 --> 01:58:52,554
THIS HAS BEEN AN EXCITING

3114
01:58:52,554 --> 01:58:53,889
AFTERNOON.

3115
01:58:53,889 --> 01:58:56,391
AND I THINK WE HAVE RUN OUT OF

3116
01:58:56,391 --> 01:58:58,260
OUR TIME.

3117
01:58:58,260 --> 01:59:02,164
SO WE HAVE TO END THIS SESSION.

3118
01:59:02,164 --> 01:59:03,799
THANK YOU AGAIN.

3119
01:59:03,799 --> 01:59:05,200
>> YOU'RE WELCOME.

3120
01:59:05,200 --> 01:59:07,202
AND I THINK WE BOTH ENJOYED IT.

3121
01:59:07,202 --> 01:59:08,470
>> YEP.

3122
01:59:08,470 --> 01:59:10,005
TAKE CARE.

3123
01:59:10,005 --> 01:59:20,149
>> OKAY.