1 00:00:21,321 --> 00:00:22,289 So what I'm going to talk 2 00:00:22,289 --> 00:00:25,292 about, this morning is what I'll call 3 00:00:25,292 --> 00:00:28,045 a scandalously short history of research 4 00:00:28,045 --> 00:00:28,595 ethics. 5 00:00:29,229 --> 00:00:31,765 There's so much more I could say. 6 00:00:31,765 --> 00:00:32,299 Hopefully. 7 00:00:32,299 --> 00:00:34,352 What I, speak to you about this morning 8 00:00:34,352 --> 00:00:36,036 will give you some appreciation 9 00:00:36,670 --> 00:00:40,323 of the role of the past in shaping the rules for 10 00:00:40,323 --> 00:00:41,008 research 11 00:00:41,375 --> 00:00:44,079 that governed, the use of human subjects 12 00:00:44,079 --> 00:00:46,513 in research, you know, for decades. 13 00:00:46,847 --> 00:00:50,284 And as Doctor Grady so eloquently described. 14 00:00:50,984 --> 00:00:53,186 Require, 15 00:00:53,186 --> 00:00:55,477 vigilance because research changes, 16 00:00:55,477 --> 00:00:56,590 society changes. 17 00:00:56,957 --> 00:00:59,626 And, it's important to keep the fact that 18 00:00:59,626 --> 00:01:02,629 these are changeable in mind. 19 00:01:03,430 --> 00:01:04,831 So what I want to 20 00:01:04,831 --> 00:01:08,242 focus on today is why we have the particular kinds of rules 21 00:01:08,242 --> 00:01:08,936 that we had 22 00:01:09,303 --> 00:01:13,398 and the role of scandals, tragedies, revelations of 23 00:01:13,398 --> 00:01:14,041 abuses, 24 00:01:14,675 --> 00:01:18,011 shaped the particular, regulations. 25 00:01:18,645 --> 00:01:20,627 And I want to also make a broader 26 00:01:20,627 --> 00:01:21,648 historical point 27 00:01:21,915 --> 00:01:25,352 that US policy, health policy in general, 28 00:01:25,352 --> 00:01:28,519 over the course of the 20th century 29 00:01:28,519 --> 00:01:30,691 also was responsive to, 30 00:01:31,792 --> 00:01:33,961 to scandal and to tragedy. 31 00:01:33,961 --> 00:01:35,924 And I'm just going to go through, 32 00:01:35,924 --> 00:01:37,531 very briefly, a series of, 33 00:01:38,131 --> 00:01:41,101 examples to help put this in mind. 34 00:01:42,202 --> 00:01:44,658 Some of you may know that the first food 35 00:01:44,658 --> 00:01:45,272 and drug, 36 00:01:45,272 --> 00:01:47,874 regulation, occurred in 1906. 37 00:01:47,874 --> 00:01:49,779 There were concerns about the safety 38 00:01:49,779 --> 00:01:51,578 of patent medicines, for example, 39 00:01:52,546 --> 00:01:54,781 and the lack of safety. 40 00:01:54,781 --> 00:01:56,719 You could see cocaine, tooth products 41 00:01:56,719 --> 00:01:58,919 and the the wine is endorsed by the Pope. 42 00:01:58,919 --> 00:02:01,680 It actually contains, cocaine in small 43 00:02:01,680 --> 00:02:02,189 doses. 44 00:02:03,223 --> 00:02:07,554 But it was really the concern over the safety of the food 45 00:02:07,554 --> 00:02:08,161 supply. 46 00:02:08,595 --> 00:02:12,366 Some of you may have read, Upton Sinclair's searing 47 00:02:12,633 --> 00:02:15,025 indictment of the meatpacking industry 48 00:02:15,025 --> 00:02:16,536 in Chicago, The Jungle. 49 00:02:16,970 --> 00:02:20,807 And, as he famously said, he aim for the nation's heart. 50 00:02:21,108 --> 00:02:23,343 And he reached the stomach. 51 00:02:23,343 --> 00:02:25,078 But that pushed the U.S. 52 00:02:25,078 --> 00:02:29,270 Congress to pass the Food and Drug Act in 53 00:02:29,270 --> 00:02:29,883 1906, 54 00:02:29,883 --> 00:02:32,832 which was the first sort of regulatory 55 00:02:32,832 --> 00:02:33,453 venture 56 00:02:33,453 --> 00:02:37,386 to ensure the safety of food and drugs, used by American 57 00:02:37,386 --> 00:02:38,158 consumers. 58 00:02:38,725 --> 00:02:41,944 The major revision, a major revision of the Food and 59 00:02:41,944 --> 00:02:42,562 Drug Act, 60 00:02:42,562 --> 00:02:46,867 occurred in 1938 following this terrible tragedy. 61 00:02:46,867 --> 00:02:49,724 The Elixir of Self, an Elamite tragedy 62 00:02:49,724 --> 00:02:52,506 in which a chemist used as a solvent 63 00:02:52,506 --> 00:02:55,972 for the new sulfa drugs, diethylene glycol, which is also 64 00:02:55,972 --> 00:02:56,276 used 65 00:02:56,276 --> 00:02:59,980 in antifreeze, led to the deaths of more than 100 children. 66 00:02:59,980 --> 00:03:02,015 There was nothing the Food and Drug 67 00:03:02,015 --> 00:03:04,654 Administration could actually do to pull the drugs off the 68 00:03:04,654 --> 00:03:05,018 market. 69 00:03:05,852 --> 00:03:08,855 There were also concerns about the safety of cosmetics, 70 00:03:09,556 --> 00:03:12,172 you know, mascara that would blind women reducing 71 00:03:12,172 --> 00:03:12,492 drugs 72 00:03:12,492 --> 00:03:15,495 that would make you lose weight but also kill you. 73 00:03:15,862 --> 00:03:18,725 And it led to the first sort of major 74 00:03:18,725 --> 00:03:19,499 revisions 75 00:03:19,833 --> 00:03:22,703 of the, of the food and, 76 00:03:23,703 --> 00:03:26,740 Drug and Cosmetic Act for the first time, 77 00:03:27,908 --> 00:03:30,739 that drugs and cosmetics actually had to be tested for 78 00:03:30,739 --> 00:03:31,211 toxicity 79 00:03:31,211 --> 00:03:33,449 before marketing, that there had to be 80 00:03:33,449 --> 00:03:34,214 corrections, 81 00:03:34,581 --> 00:03:36,600 on the package, and that some drugs 82 00:03:36,600 --> 00:03:38,618 were too dangerous to be dispensed 83 00:03:38,618 --> 00:03:41,456 just over the counter, but had to be dispensed by 84 00:03:41,456 --> 00:03:42,556 prescription only. 85 00:03:43,523 --> 00:03:46,693 Children born with unusual birth defects, 86 00:03:46,693 --> 00:03:49,409 eventually connected to the prenatal use of 87 00:03:49,409 --> 00:03:50,230 thalidomide, 88 00:03:51,331 --> 00:03:53,827 which led to, amendments to the food, 89 00:03:53,827 --> 00:03:54,501 drug and, 90 00:03:55,135 --> 00:03:57,780 act in the Father Harris amendments 91 00:03:57,780 --> 00:04:00,273 that the FDA, for the first time 92 00:04:00,273 --> 00:04:03,243 could demand scientific data to, 93 00:04:03,510 --> 00:04:06,513 to determine that the Drug Act worked 94 00:04:06,880 --> 00:04:09,382 in a very different realm. 95 00:04:09,382 --> 00:04:11,914 Talking about, the regulation of animal 96 00:04:11,914 --> 00:04:12,953 experimentation 97 00:04:13,687 --> 00:04:16,590 for something like seven decades, 98 00:04:16,590 --> 00:04:19,893 Congress had been, revisiting 99 00:04:19,893 --> 00:04:22,896 potential legislation to protect animals, 100 00:04:23,230 --> 00:04:26,933 used in research after this photo essay 101 00:04:27,601 --> 00:04:31,104 that appeared in life magazine in 1966. 102 00:04:33,106 --> 00:04:37,043 Congress received more mail, about this. 103 00:04:37,043 --> 00:04:39,346 You know, the theft of dogs, organized 104 00:04:39,346 --> 00:04:40,013 pet theft, 105 00:04:40,013 --> 00:04:42,405 the treatment of animals before they got to the 106 00:04:42,405 --> 00:04:43,016 laboratory. 107 00:04:43,817 --> 00:04:46,117 Congress got more mail than they did 108 00:04:46,117 --> 00:04:46,820 about the, 109 00:04:47,821 --> 00:04:49,877 than it did about the Vietnam War 110 00:04:49,877 --> 00:04:52,058 and passed the Animal Welfare Act, 111 00:04:52,259 --> 00:04:54,710 which, like the National Research Act, 112 00:04:54,710 --> 00:04:56,129 has been amended over 113 00:04:56,129 --> 00:04:58,675 the years as animal experimentation itself 114 00:04:58,675 --> 00:04:59,766 has also changed. 115 00:05:00,634 --> 00:05:03,981 And finally, sort of the National Research 116 00:05:03,981 --> 00:05:04,938 Act, which, 117 00:05:06,339 --> 00:05:08,809 well, we'll be talking about today 118 00:05:08,809 --> 00:05:13,538 that was shaped by revelations, particularly in the 1960s, of 119 00:05:13,538 --> 00:05:14,080 abuses 120 00:05:14,080 --> 00:05:17,117 of human subjects, in American medical research. 121 00:05:19,486 --> 00:05:21,188 So even before the Tuskegee 122 00:05:21,188 --> 00:05:23,164 syphilis study, which I would argue 123 00:05:23,164 --> 00:05:25,592 was the tipping point for Congress to pass 124 00:05:25,892 --> 00:05:29,452 that legislation in 1974, there were Nazi medical 125 00:05:29,452 --> 00:05:30,397 experiments. 126 00:05:30,697 --> 00:05:32,971 And there was also, experimentation 127 00:05:32,971 --> 00:05:34,401 in the United States. 128 00:05:35,101 --> 00:05:38,672 Both the, history of human experimentation 129 00:05:38,672 --> 00:05:42,744 and and history of controversy and concern about the moral 130 00:05:42,744 --> 00:05:43,376 problems 131 00:05:43,376 --> 00:05:46,713 raised by human experimentation are much older. 132 00:05:47,113 --> 00:05:50,417 And I'm going to give you a very brief example. 133 00:05:55,555 --> 00:05:58,592 In 1900, the United States Congress 134 00:05:58,892 --> 00:06:01,862 actually entertained, 135 00:06:03,530 --> 00:06:04,831 legislation 136 00:06:04,831 --> 00:06:07,550 that would have, a Senate bill 3424 137 00:06:07,550 --> 00:06:09,569 that would have regulated 138 00:06:09,569 --> 00:06:13,356 human experimentation in the District of Columbia, 139 00:06:13,356 --> 00:06:14,341 that in 1900 140 00:06:14,341 --> 00:06:16,009 it would have required investigators 141 00:06:16,009 --> 00:06:19,470 to disclose in advance, you know, the purpose and 142 00:06:19,470 --> 00:06:20,247 procedures 143 00:06:20,247 --> 00:06:22,652 of any non therapeutic experiments 144 00:06:22,652 --> 00:06:24,351 involving human beings. 145 00:06:25,518 --> 00:06:28,288 And it also called for an, 146 00:06:28,288 --> 00:06:32,626 an explicit ban on using, people in studies, 147 00:06:33,026 --> 00:06:36,663 people who were deemed unable to and unable 148 00:06:36,663 --> 00:06:39,633 to consent to participation. 149 00:06:39,933 --> 00:06:42,672 This included children under the age 150 00:06:42,672 --> 00:06:45,639 of 21, infants and even pregnant women 151 00:06:45,639 --> 00:06:48,742 who were deemed unable to exercise 152 00:06:48,742 --> 00:06:51,745 sort of adult decision making capacity. 153 00:06:52,012 --> 00:06:55,015 That's another story. 154 00:06:55,015 --> 00:06:57,317 So then these bills did not pass, 155 00:06:57,317 --> 00:07:00,420 but it's it exhibits sort of a concern 156 00:07:00,420 --> 00:07:02,179 that people had about the direction 157 00:07:02,179 --> 00:07:04,291 in which medical research was developing. 158 00:07:04,758 --> 00:07:06,747 But I don't want to give you the idea 159 00:07:06,747 --> 00:07:07,661 that responsible 160 00:07:07,661 --> 00:07:09,655 medical experimentation was, in fact, 161 00:07:09,655 --> 00:07:11,164 not occurring at this time. 162 00:07:11,631 --> 00:07:14,234 And one of the best examples of this 163 00:07:14,234 --> 00:07:16,402 is the experiments that were conducted 164 00:07:16,402 --> 00:07:18,171 under the auspices of the U.S. 165 00:07:18,171 --> 00:07:21,174 Army, the Yellow Fever Board experiments 166 00:07:21,408 --> 00:07:24,577 in Cuba in 1900 and 1901. 167 00:07:25,578 --> 00:07:27,256 Some of you may know the name of Walter 168 00:07:27,256 --> 00:07:27,514 Reed. 169 00:07:27,514 --> 00:07:29,616 Walter Reed led a commission. 170 00:07:29,616 --> 00:07:33,258 They were interested in, establishing how yellow 171 00:07:33,258 --> 00:07:34,321 fever spread. 172 00:07:34,321 --> 00:07:37,453 Yellow fever was a, was a real threat, 173 00:07:37,453 --> 00:07:39,926 in the southern United States 174 00:07:39,926 --> 00:07:42,119 and Central America and South America 175 00:07:42,119 --> 00:07:43,363 in this time period. 176 00:07:43,730 --> 00:07:46,955 And they, were determined to establish 177 00:07:46,955 --> 00:07:48,568 sort of the vector 178 00:07:48,568 --> 00:07:50,797 of yellow fever, which they eventually did 179 00:07:50,797 --> 00:07:51,805 for that research. 180 00:07:51,805 --> 00:07:55,141 They had to expose human beings to considerable risk. 181 00:07:56,309 --> 00:07:58,745 They needed, 182 00:07:58,745 --> 00:08:01,652 they needed, people who were new to the 183 00:08:01,652 --> 00:08:02,248 island. 184 00:08:02,982 --> 00:08:05,112 Many of these people were newly arrived 185 00:08:05,112 --> 00:08:05,985 Spanish people. 186 00:08:06,219 --> 00:08:07,992 And but they needed naive subjects 187 00:08:07,992 --> 00:08:09,556 in order to see if they could 188 00:08:09,556 --> 00:08:11,771 spread the disease through various means, 189 00:08:11,771 --> 00:08:12,959 including mosquitoes. 190 00:08:13,360 --> 00:08:17,230 And Reed introduced a written permission form 191 00:08:17,230 --> 00:08:20,233 that was available in both English and Spanish. 192 00:08:20,433 --> 00:08:22,719 It, you know, it did not would not meet 193 00:08:22,719 --> 00:08:24,771 our standards of informed consent. 194 00:08:24,771 --> 00:08:27,129 But it was extraordinary for its time, 195 00:08:27,129 --> 00:08:28,308 warning of dangers 196 00:08:28,308 --> 00:08:31,483 to life and experiments with infected clothing and 197 00:08:31,483 --> 00:08:32,245 mosquitoes. 198 00:08:32,545 --> 00:08:36,783 It promised good medical care, and it also identified 199 00:08:37,117 --> 00:08:39,018 a considerable compensation ration 200 00:08:39,018 --> 00:08:41,366 that the men would receive if they signed 201 00:08:41,366 --> 00:08:43,256 and were selected for the study. 202 00:08:44,591 --> 00:08:46,760 Subjects who were selected actually 203 00:08:46,760 --> 00:08:50,753 receive $100 in American gold, which was a considerable sum at 204 00:08:50,753 --> 00:08:51,398 the time, 205 00:08:51,965 --> 00:08:54,734 and they promised to give $200 206 00:08:54,734 --> 00:08:57,737 to the surviving family if death occurs. 207 00:08:57,937 --> 00:08:59,372 Now, Frank, 208 00:08:59,372 --> 00:09:01,731 fortunately, none of the participants 209 00:09:01,731 --> 00:09:02,942 in the study died, 210 00:09:02,942 --> 00:09:04,912 although one of the investigators 211 00:09:04,912 --> 00:09:06,046 actually succumbed 212 00:09:06,046 --> 00:09:09,048 to yellow fever during the course of the study. 213 00:09:10,050 --> 00:09:13,653 So I want to begin with or I want to shift, 214 00:09:13,653 --> 00:09:17,079 if you will, to World War two, which does represent an 215 00:09:17,079 --> 00:09:18,158 important moment 216 00:09:18,158 --> 00:09:20,693 in the history of research in the United States 217 00:09:20,693 --> 00:09:23,219 and also in the history of research 218 00:09:23,219 --> 00:09:23,797 ethics. 219 00:09:23,797 --> 00:09:26,966 In 1941, President Roosevelt's Office 220 00:09:26,966 --> 00:09:29,663 for Scientific and Research was, was 221 00:09:29,663 --> 00:09:30,637 established. 222 00:09:31,237 --> 00:09:34,223 And importantly for medical research 223 00:09:34,223 --> 00:09:36,876 was the advent of unprecedented 224 00:09:36,876 --> 00:09:39,469 federal funding for medical research 225 00:09:39,469 --> 00:09:41,414 related to the war effort. 226 00:09:41,848 --> 00:09:44,100 And this was something that would continue 227 00:09:44,100 --> 00:09:44,851 after the war 228 00:09:45,151 --> 00:09:47,887 and was an important moment, sort of 229 00:09:47,887 --> 00:09:51,672 in the growing recognition of the importance of medical 230 00:09:51,672 --> 00:09:52,292 research 231 00:09:52,492 --> 00:09:57,709 not only to U.S., society, but, to our place in the world as 232 00:09:57,709 --> 00:09:58,231 well. 233 00:10:00,800 --> 00:10:01,634 Now, I also 234 00:10:01,634 --> 00:10:03,986 mentioned, if you will, sort of Nazi 235 00:10:03,986 --> 00:10:06,272 medical experimentation and again, 236 00:10:06,706 --> 00:10:10,710 in as in the United States, high ranking Nazi 237 00:10:10,710 --> 00:10:12,656 officials believed that medical research 238 00:10:12,656 --> 00:10:14,214 would help Germany win the war. 239 00:10:14,647 --> 00:10:17,784 And they undertook an ambitious. 240 00:10:17,784 --> 00:10:21,821 And if frightening, program of research 241 00:10:22,122 --> 00:10:25,658 in order to advance sort of their medical interests. 242 00:10:25,892 --> 00:10:28,761 Some of these may be familiar to you, 243 00:10:28,761 --> 00:10:30,743 but I also think it's it's useful 244 00:10:30,743 --> 00:10:31,764 just to briefly, 245 00:10:32,765 --> 00:10:35,001 briefly revisit them. 246 00:10:35,001 --> 00:10:37,095 Among the first that were undertaken were 247 00:10:37,095 --> 00:10:39,138 those at the Dachau concentration camp. 248 00:10:39,939 --> 00:10:42,085 They were interested in studying the effects of 249 00:10:42,085 --> 00:10:42,542 immersion 250 00:10:42,542 --> 00:10:46,412 and freezing water and and techniques of rewarming. 251 00:10:47,080 --> 00:10:50,424 These often ended with the, death of the, 252 00:10:50,424 --> 00:10:51,484 participant. 253 00:10:51,484 --> 00:10:51,784 Sort of. 254 00:10:51,784 --> 00:10:53,720 How long would it take to die 255 00:10:53,720 --> 00:10:56,198 if you were, you know, in the freezing water of wood 256 00:10:56,198 --> 00:10:56,723 equipment, 257 00:10:57,023 --> 00:10:59,261 for example, help you to survive longer 258 00:10:59,261 --> 00:11:01,728 so that you might be rescued and so forth. 259 00:11:02,428 --> 00:11:05,832 Also, at concentration camp, with death as an endpoint, 260 00:11:05,832 --> 00:11:07,780 there were studies of the effects 261 00:11:07,780 --> 00:11:09,669 of high altitude and low oxygen 262 00:11:09,669 --> 00:11:12,148 concentration and death as an endpoint was 263 00:11:12,148 --> 00:11:12,739 important 264 00:11:12,739 --> 00:11:16,709 because they wanted to study postmortem changes in the brain. 265 00:11:18,244 --> 00:11:18,778 As in the 266 00:11:18,778 --> 00:11:21,358 United States, the Nazis were interested 267 00:11:21,358 --> 00:11:22,649 in seawater studies 268 00:11:22,649 --> 00:11:25,391 how to quickly desalinate sea water 269 00:11:25,391 --> 00:11:26,252 to promote 270 00:11:27,820 --> 00:11:30,723 survival at sea against so that fliers, 271 00:11:30,723 --> 00:11:33,726 for example, could be rescued or Navy personnel. 272 00:11:34,861 --> 00:11:37,397 Here you see a victim of a Roma victim 273 00:11:37,397 --> 00:11:39,265 of Nazi medical experiments 274 00:11:39,265 --> 00:11:41,522 that also involved, among other things, 275 00:11:41,522 --> 00:11:42,969 you know, giving people, 276 00:11:43,736 --> 00:11:47,844 to see how long you'd survive with absolutely no water, 277 00:11:47,844 --> 00:11:48,441 forcing 278 00:11:48,441 --> 00:11:50,829 seawater on people, giving seawater 279 00:11:50,829 --> 00:11:53,012 flavored with a tomato extract, 280 00:11:53,313 --> 00:11:56,102 all involving great suffering, if not death to the 281 00:11:56,102 --> 00:11:56,883 participants. 282 00:11:58,051 --> 00:12:00,153 So the study of burns and wounds 283 00:12:00,153 --> 00:12:03,456 was also of great interest in the United States. 284 00:12:03,456 --> 00:12:05,866 A standard burn and wound was developed on 285 00:12:05,866 --> 00:12:08,161 animal subjects, chiefly pigs and dogs. 286 00:12:08,428 --> 00:12:12,189 The Nazis used Polish women at the Ravensbrück concentration 287 00:12:12,189 --> 00:12:12,565 camp, 288 00:12:13,099 --> 00:12:16,469 where they deliberately infect, you know, cut open 289 00:12:16,836 --> 00:12:20,730 to create a wound, infected it with bacteria, dirt, slivers of 290 00:12:20,730 --> 00:12:21,107 glass 291 00:12:21,441 --> 00:12:24,765 in order to study, sort of the natural history of 292 00:12:24,765 --> 00:12:25,511 the wound. 293 00:12:25,511 --> 00:12:28,715 Various ways to, to promote its healing. 294 00:12:30,149 --> 00:12:32,619 After the war, 295 00:12:32,619 --> 00:12:35,657 after the trials of the major Nazi war 296 00:12:35,657 --> 00:12:37,257 criminals, the U.S. 297 00:12:37,257 --> 00:12:40,593 military tribunal took on various groups 298 00:12:40,593 --> 00:12:44,735 in the first prosecution of various groups for war 299 00:12:44,735 --> 00:12:45,398 crimes. 300 00:12:45,865 --> 00:12:49,302 And the first group was the Nazi doctors. 301 00:12:50,203 --> 00:12:54,240 In 1946, the trial of United States 302 00:12:54,240 --> 00:12:57,377 versus Carl Brandt and all began. 303 00:12:58,111 --> 00:13:00,713 This was an action brought against 23 304 00:13:00,713 --> 00:13:03,316 high ranking Nazi medical personnel, 305 00:13:04,017 --> 00:13:07,797 22 men and one woman, a woman doctor who had presided 306 00:13:07,797 --> 00:13:08,154 over 307 00:13:08,154 --> 00:13:10,764 some of those burn and wound studies 308 00:13:10,764 --> 00:13:11,924 at Ravensbrück. 309 00:13:13,493 --> 00:13:14,560 There's much that can be said. 310 00:13:14,560 --> 00:13:17,235 And there are entire books written about the Nazi doctors 311 00:13:17,235 --> 00:13:17,563 trial. 312 00:13:18,031 --> 00:13:19,732 And what I'll just say here 313 00:13:19,732 --> 00:13:23,345 is that what among the issues for the tribunal, for the 314 00:13:23,345 --> 00:13:23,936 tribunal 315 00:13:24,437 --> 00:13:28,054 was how to judge these were these normal medical 316 00:13:28,054 --> 00:13:28,808 research? 317 00:13:28,808 --> 00:13:33,146 Were there rules about research, how to assess the guilt 318 00:13:33,513 --> 00:13:36,816 or innocence of the Nazi doctors on trial? 319 00:13:38,251 --> 00:13:40,453 And in so doing, they 320 00:13:40,453 --> 00:13:44,357 actually formulated, a list of principles 321 00:13:44,557 --> 00:13:48,204 that constituted permissible or acceptable human 322 00:13:48,204 --> 00:13:49,495 experimentation. 323 00:13:50,129 --> 00:13:53,091 I will say that, there was some squirming on the 324 00:13:53,091 --> 00:13:53,399 part 325 00:13:53,399 --> 00:13:55,878 of some of the American doctors who were 326 00:13:55,878 --> 00:13:58,171 called in to advise about the trial. 327 00:13:59,572 --> 00:14:01,541 The defense attorneys representing 328 00:14:01,541 --> 00:14:04,777 Karl Brandt, for example, sort of made a comparison. 329 00:14:04,777 --> 00:14:06,556 Well, what was so different with Nazi 330 00:14:06,556 --> 00:14:08,047 concentration camp experiments 331 00:14:08,047 --> 00:14:11,484 involving prisoners and the kinds of experiments, 332 00:14:12,018 --> 00:14:15,248 that were being conducted in American persons at the same 333 00:14:15,248 --> 00:14:15,588 time, 334 00:14:15,822 --> 00:14:19,427 experiments that involved deliberate infection with 335 00:14:19,427 --> 00:14:19,992 disease 336 00:14:20,226 --> 00:14:22,383 and experiments in which sometimes 337 00:14:22,383 --> 00:14:24,097 prisoners didn't fact die. 338 00:14:24,664 --> 00:14:27,166 One of the things that was actually, 339 00:14:27,166 --> 00:14:29,936 brought into evidence by the Nazi, 340 00:14:29,936 --> 00:14:32,501 excuse me, by the German, defense attorney 341 00:14:32,501 --> 00:14:33,906 was this issue of life 342 00:14:33,906 --> 00:14:38,644 magazine from June 4th, 1945 that featured malaria research 343 00:14:38,911 --> 00:14:42,982 at the Stateville prison in Illinois, where, 344 00:14:43,950 --> 00:14:45,785 some, 40 345 00:14:45,785 --> 00:14:49,589 or 50 inmates actually underwent infection 346 00:14:49,889 --> 00:14:53,493 with, loaded mosquitoes in order to study 347 00:14:53,493 --> 00:14:56,462 malaria and its treatment. 348 00:14:56,696 --> 00:14:59,532 So, as I already mentioned, 349 00:14:59,532 --> 00:15:01,734 when they delivered their verdict 350 00:15:01,734 --> 00:15:03,936 in the Nazi doctors trial, they, 351 00:15:03,936 --> 00:15:06,269 the judges, with the advice of several 352 00:15:06,269 --> 00:15:07,006 physicians, 353 00:15:07,273 --> 00:15:09,678 put together a set of of ten principles 354 00:15:09,678 --> 00:15:12,145 called permissible medical experiments, 355 00:15:12,445 --> 00:15:14,854 which we've come to know and it seems to 356 00:15:14,854 --> 00:15:17,383 be universally called the Nuremberg Code. 357 00:15:18,251 --> 00:15:21,354 Usually in discussions about the Nuremberg Code, 358 00:15:21,354 --> 00:15:24,524 it's the first principle that gets the, 359 00:15:24,524 --> 00:15:27,226 the attention and deservedly so. 360 00:15:27,226 --> 00:15:30,296 It sets an extraordinarily high standard 361 00:15:30,696 --> 00:15:33,499 that the voluntary consent of the human 362 00:15:33,499 --> 00:15:36,502 subject is absolutely essential. 363 00:15:36,869 --> 00:15:39,405 It does not permit proxy consent. 364 00:15:39,405 --> 00:15:42,475 It means, for example, that children are not legitimate 365 00:15:42,475 --> 00:15:45,611 subjects according to the Nuremberg Code. 366 00:15:45,611 --> 00:15:49,382 And it also excludes, you know, people in institutions 367 00:15:49,682 --> 00:15:51,506 and so forth, depending on one's 368 00:15:51,506 --> 00:15:52,418 interpretation. 369 00:15:53,452 --> 00:15:55,621 There were, of course, others. 370 00:15:55,621 --> 00:15:56,722 I'm not going to go through them, 371 00:15:56,722 --> 00:15:59,274 but just some that were seen as extremely 372 00:15:59,274 --> 00:15:59,959 important, 373 00:16:00,726 --> 00:16:03,851 to American physicians who wanted to defend medical 374 00:16:03,851 --> 00:16:04,463 research. 375 00:16:04,897 --> 00:16:07,180 That research had been based on prior 376 00:16:07,180 --> 00:16:08,167 animal studies. 377 00:16:08,534 --> 00:16:12,338 It was intended at the outset to avoid unnecessary suffering, 378 00:16:12,872 --> 00:16:14,640 should not have death as an endpoint. 379 00:16:14,640 --> 00:16:17,511 Studies risk should not exceed benefit, 380 00:16:17,511 --> 00:16:19,645 and that only scientifically 381 00:16:20,947 --> 00:16:23,950 qualified personnel were to conduct the studies. 382 00:16:24,851 --> 00:16:26,659 So it's in case you're interested, 383 00:16:26,659 --> 00:16:28,521 let me just tell you that seven of 384 00:16:28,521 --> 00:16:30,725 the Nazi doctors were actually acquitted 385 00:16:30,725 --> 00:16:32,158 on insufficient evidence. 386 00:16:32,692 --> 00:16:36,162 Seven received death sentences and nine received 387 00:16:36,162 --> 00:16:38,636 prison sentences ranging from ten years 388 00:16:38,636 --> 00:16:40,032 to life imprisonment. 389 00:16:40,399 --> 00:16:42,762 And I will say it was surprising to me 390 00:16:42,762 --> 00:16:44,503 that almost all of the nine 391 00:16:44,503 --> 00:16:48,841 who received prison sentences had their sentences, seriously, 392 00:16:49,141 --> 00:16:53,546 commuted to like one year or, only a few years. 393 00:16:53,546 --> 00:16:55,448 And they were back in medical practice. 394 00:16:55,448 --> 00:16:58,230 In fact, in Germany, Carl Brandt was among 395 00:16:58,230 --> 00:16:59,952 those sentenced to death. 396 00:17:00,286 --> 00:17:04,624 He actually offered his body for experimentation to the U.S. 397 00:17:04,624 --> 00:17:06,893 Army, which rejected his offer. 398 00:17:06,893 --> 00:17:10,062 And and he was, hanged at Landsberg Prison. 399 00:17:10,596 --> 00:17:13,430 So there is a real debate among my colleagues and 400 00:17:13,430 --> 00:17:14,066 interested 401 00:17:14,066 --> 00:17:16,082 in the history of research ethics 402 00:17:16,082 --> 00:17:18,037 and and the history of research 403 00:17:18,037 --> 00:17:22,141 in the 1950s and 60s and 70s in the United States, about 404 00:17:22,341 --> 00:17:25,583 what does the Nuremberg Code actually mean to medical 405 00:17:25,583 --> 00:17:26,379 researchers? 406 00:17:26,979 --> 00:17:29,437 And, you know, there are arguments 407 00:17:29,437 --> 00:17:31,317 sort of on on both sides. 408 00:17:31,317 --> 00:17:33,939 Some people have have made the claim that, you know, most 409 00:17:33,939 --> 00:17:34,353 American 410 00:17:34,353 --> 00:17:36,046 medical researchers did not even know 411 00:17:36,046 --> 00:17:37,557 that the Nuremberg Code existed. 412 00:17:38,758 --> 00:17:40,426 I do not support this. 413 00:17:40,426 --> 00:17:44,096 In 1953, for example, the journal science, the, 414 00:17:44,564 --> 00:17:47,867 you know, the scientific journal with the largest circulation 415 00:17:48,100 --> 00:17:50,937 actually published the code in a big article. 416 00:17:50,937 --> 00:17:53,201 They published the results of a symposium 417 00:17:53,201 --> 00:17:54,140 discussing this. 418 00:17:54,407 --> 00:17:57,058 It seems to me that that that's reaching a broad 419 00:17:57,058 --> 00:17:57,610 audience. 420 00:17:59,011 --> 00:18:02,014 I will also say that, in 1953, 421 00:18:02,348 --> 00:18:06,040 the secretary of defense, Charlie Wilson, actually, 422 00:18:06,040 --> 00:18:06,619 signed, 423 00:18:06,619 --> 00:18:09,594 you know, a memorandum requiring the code 424 00:18:09,594 --> 00:18:12,425 for all research conducted by the U.S. 425 00:18:12,425 --> 00:18:14,527 Armed forces. 426 00:18:14,527 --> 00:18:16,982 Curiously, and perhaps ironically, 427 00:18:16,982 --> 00:18:19,365 the document was also classified 428 00:18:19,365 --> 00:18:20,333 as top secret. 429 00:18:20,333 --> 00:18:24,675 So it seems to be something of an implement implementation, 430 00:18:24,675 --> 00:18:25,338 failure. 431 00:18:25,705 --> 00:18:29,147 But nonetheless, it came to the attention of many 432 00:18:29,147 --> 00:18:29,709 people. 433 00:18:31,577 --> 00:18:33,212 On the other hand, 434 00:18:33,212 --> 00:18:36,591 a number of, you know, commentators have 435 00:18:36,591 --> 00:18:37,183 argued 436 00:18:37,183 --> 00:18:41,218 that most American researchers kind of dismiss the Nuremberg 437 00:18:41,218 --> 00:18:41,554 Code 438 00:18:41,554 --> 00:18:45,005 as something that Germans and barbarians 439 00:18:45,005 --> 00:18:46,559 Nazis would need, 440 00:18:46,892 --> 00:18:49,677 but that American researchers did not need 441 00:18:49,677 --> 00:18:51,931 because they were already careful 442 00:18:51,931 --> 00:18:54,797 and concerned about both the safety 443 00:18:54,797 --> 00:18:57,336 and welfare of their subjects. 444 00:18:59,672 --> 00:18:59,972 I think 445 00:18:59,972 --> 00:19:01,965 it's important to keep in mind, though, 446 00:19:01,965 --> 00:19:03,242 that if you were to ask, 447 00:19:03,843 --> 00:19:07,448 what American researchers have, investigators have met the 448 00:19:07,448 --> 00:19:08,381 Nuremberg Code 449 00:19:08,581 --> 00:19:11,097 and its requirements in research that was 450 00:19:11,097 --> 00:19:13,552 going on both during the war and after. 451 00:19:13,753 --> 00:19:15,254 Absolutely not. 452 00:19:15,254 --> 00:19:18,257 Because, again, it's set an extra ordinarily 453 00:19:18,591 --> 00:19:21,394 high standard. 454 00:19:21,394 --> 00:19:24,140 So if I want to make the point here 455 00:19:24,140 --> 00:19:25,631 that in the 1950s, 456 00:19:25,631 --> 00:19:28,601 there was tremendous social support 457 00:19:28,601 --> 00:19:31,241 for the medical research enterprise 458 00:19:31,241 --> 00:19:32,071 and great, 459 00:19:32,972 --> 00:19:35,315 admiration for medical researchers 460 00:19:35,315 --> 00:19:36,142 themselves. 461 00:19:36,475 --> 00:19:39,278 And in part, it's because, 462 00:19:39,278 --> 00:19:42,748 medical research at this time was associated with volunteers. 463 00:19:42,982 --> 00:19:45,451 It was a voluntary action. 464 00:19:45,451 --> 00:19:47,822 There was actually sort of a society 465 00:19:47,822 --> 00:19:50,523 created for both these human guinea pigs 466 00:19:50,723 --> 00:19:53,492 in which they were honored for their willingness 467 00:19:53,492 --> 00:19:57,360 to risk their welfare and, and lives to advance medical 468 00:19:57,360 --> 00:19:58,064 research. 469 00:19:59,131 --> 00:19:59,498 There was 470 00:19:59,498 --> 00:20:02,535 also a long tradition of self-experimentation, 471 00:20:02,535 --> 00:20:06,906 which many, people in the public and I think some researchers 472 00:20:06,906 --> 00:20:08,874 saw as kind of the gold standard. 473 00:20:08,874 --> 00:20:11,903 If an investigator was willing to risk his 474 00:20:11,903 --> 00:20:13,345 or or her own body, 475 00:20:13,712 --> 00:20:17,370 then, you know, that was a test of how much they were invested 476 00:20:17,370 --> 00:20:17,783 in it. 477 00:20:18,384 --> 00:20:21,714 Today, of course, Self-Experimentation is not, 478 00:20:21,714 --> 00:20:22,655 recommended. 479 00:20:22,655 --> 00:20:25,144 And I'm sure you'll hear more about that, 480 00:20:25,144 --> 00:20:27,026 in, in the rest of the course. 481 00:20:27,860 --> 00:20:30,262 I also say the 1950s, there had been 482 00:20:30,262 --> 00:20:33,691 so many great advances in medicine 483 00:20:33,691 --> 00:20:34,800 associated 484 00:20:35,401 --> 00:20:38,473 with the wartime experience, primarily things like 485 00:20:38,473 --> 00:20:39,271 antibiotics, 486 00:20:39,271 --> 00:20:41,020 the importance of blood transfusion, 487 00:20:41,020 --> 00:20:42,575 that many people were confident 488 00:20:42,575 --> 00:20:45,811 that only great things were also going to come. 489 00:20:46,912 --> 00:20:49,051 And so, in part, I think it's important to keep 490 00:20:49,051 --> 00:20:49,415 in mind 491 00:20:49,415 --> 00:20:52,127 that the kind of the social, response 492 00:20:52,127 --> 00:20:54,620 to, to research and even research 493 00:20:54,620 --> 00:20:58,572 tragedy was very different than it would be only a decade 494 00:20:58,572 --> 00:20:59,058 later. 495 00:20:59,925 --> 00:21:02,895 I've always been surprised when I found this article. 496 00:21:02,895 --> 00:21:05,131 This is from the New York Times. 497 00:21:05,131 --> 00:21:08,083 As you can see, it's reporting the death 498 00:21:08,083 --> 00:21:10,002 in research of an 18 year 499 00:21:10,002 --> 00:21:13,078 old freshman at Seattle University 500 00:21:13,078 --> 00:21:14,073 in, he was 501 00:21:14,373 --> 00:21:16,442 he had had volunteered to take part 502 00:21:16,442 --> 00:21:17,743 in a blood substitute 503 00:21:17,743 --> 00:21:20,913 study, and, died, 504 00:21:22,214 --> 00:21:24,483 and his father was asked by reporters, 505 00:21:24,483 --> 00:21:26,508 was he going to sue the university or, 506 00:21:26,508 --> 00:21:28,320 you know, or sue the authorities? 507 00:21:28,621 --> 00:21:30,589 And his father said, of course not. 508 00:21:30,589 --> 00:21:32,291 This was a, you know, a project, 509 00:21:32,291 --> 00:21:34,938 a project that was intended to advance 510 00:21:34,938 --> 00:21:36,262 medical knowledge. 511 00:21:36,629 --> 00:21:38,717 He was going to treasure his son's, 512 00:21:38,717 --> 00:21:40,566 you know, heroic participation 513 00:21:40,866 --> 00:21:42,301 in such a study. 514 00:21:42,301 --> 00:21:44,296 And you could imagine it would be 515 00:21:44,296 --> 00:21:46,472 a very different response today if, 516 00:21:47,173 --> 00:21:49,612 you know, a freshman died in a research 517 00:21:49,612 --> 00:21:50,176 project. 518 00:21:50,376 --> 00:21:54,876 And that may also explain sort of the willingness to have large 519 00:21:54,876 --> 00:21:55,447 numbers 520 00:21:55,447 --> 00:21:58,617 of children participate in trials of the new 521 00:21:58,617 --> 00:22:01,754 polio vaccine in 1954. 522 00:22:01,754 --> 00:22:04,456 I'll remind you, polio, reversed 523 00:22:04,456 --> 00:22:06,857 the usual trend of infectious disease 524 00:22:06,857 --> 00:22:07,960 death in the 19. 525 00:22:08,360 --> 00:22:10,362 In the 20th century. 526 00:22:10,362 --> 00:22:12,698 Epidemic polio got only worse. 527 00:22:12,698 --> 00:22:15,673 It was it's, you know, terrified American parents and 528 00:22:15,673 --> 00:22:16,235 children. 529 00:22:16,535 --> 00:22:20,081 And 1952 was the worst, polio epidemic on 530 00:22:20,081 --> 00:22:20,773 record. 531 00:22:22,174 --> 00:22:23,242 Two years later, 532 00:22:23,242 --> 00:22:26,612 Jonas Salk and developed with 533 00:22:27,012 --> 00:22:29,677 with funding from the National Foundation 534 00:22:29,677 --> 00:22:32,017 for Infantile Paralysis, a vaccine. 535 00:22:32,518 --> 00:22:37,467 2000 American children participated in trials of the 536 00:22:37,467 --> 00:22:38,324 vaccine. 537 00:22:38,591 --> 00:22:41,571 So here you see a picture of those polio, 538 00:22:41,571 --> 00:22:42,661 pioneer years. 539 00:22:43,929 --> 00:22:46,615 And here you see, it's not an informed consent 540 00:22:46,615 --> 00:22:46,966 form, 541 00:22:46,966 --> 00:22:50,140 and it's actually a parental request form 542 00:22:50,140 --> 00:22:51,070 for a child 543 00:22:51,070 --> 00:22:53,630 to participate in this poliomyelitis 544 00:22:53,630 --> 00:22:55,407 vaccination field trial. 545 00:22:55,808 --> 00:22:58,824 But it represents sort of an early attempt 546 00:22:58,824 --> 00:23:00,045 to, at least in, 547 00:23:01,146 --> 00:23:03,851 in some ways not as advanced as Walter 548 00:23:03,851 --> 00:23:05,417 Reed's from 1900, but 549 00:23:05,417 --> 00:23:08,460 an early attempt to inform, you know, the, 550 00:23:08,460 --> 00:23:10,923 at least the parent of the child, 551 00:23:10,923 --> 00:23:14,360 the conditions of participation, the risks involved, 552 00:23:15,127 --> 00:23:17,810 and for the parent to authorize their 553 00:23:17,810 --> 00:23:18,897 participation. 554 00:23:19,098 --> 00:23:22,101 And, of course, it led to the successful, 555 00:23:22,701 --> 00:23:25,170 demonstration of an effective and 556 00:23:25,170 --> 00:23:28,173 mostly safe vaccine that, 557 00:23:28,607 --> 00:23:31,465 that was responsible for the eradication 558 00:23:31,465 --> 00:23:33,679 of polio in the United States. 559 00:23:33,979 --> 00:23:36,522 And, and again, sort of assumed the world, 560 00:23:36,522 --> 00:23:38,217 or at least that's the hope 561 00:23:39,885 --> 00:23:41,320 now for the 562 00:23:41,320 --> 00:23:45,391 medical research community, who are not unaware of 563 00:23:45,391 --> 00:23:48,478 some of the moral problems of medical experimentation in 564 00:23:48,478 --> 00:23:49,194 this period. 565 00:23:50,562 --> 00:23:52,498 They were concerned 566 00:23:52,498 --> 00:23:55,501 that the Nuremberg Code represented, too. 567 00:23:55,801 --> 00:23:58,771 It was an unworkable guide 568 00:23:58,771 --> 00:24:01,740 for their medical research. 569 00:24:02,341 --> 00:24:03,785 And again, as I've already said, it 570 00:24:03,785 --> 00:24:05,477 would not allow experiments on children. 571 00:24:05,778 --> 00:24:08,153 It would not allow experiments on people 572 00:24:08,153 --> 00:24:09,815 who were institutionalized, 573 00:24:10,149 --> 00:24:12,217 the dying and the mentally ill. 574 00:24:12,217 --> 00:24:14,286 And there were efforts. 575 00:24:14,286 --> 00:24:16,655 I'm most familiar with the efforts of the World 576 00:24:16,655 --> 00:24:19,191 Medical Association, which Doctor Grady already 577 00:24:19,191 --> 00:24:19,892 referred to. 578 00:24:20,693 --> 00:24:23,729 And it's a ten year effort from 1954 579 00:24:23,729 --> 00:24:26,732 to 1964 to create a kind of workable 580 00:24:26,732 --> 00:24:28,067 code of ethics. 581 00:24:28,701 --> 00:24:30,336 And again, this is the challenge. 582 00:24:30,336 --> 00:24:32,271 That is a perennial one. 583 00:24:32,271 --> 00:24:34,413 How do you protect human subjects 584 00:24:34,413 --> 00:24:35,841 and at the same time, 585 00:24:36,041 --> 00:24:39,044 enable medical research to advance, 586 00:24:39,345 --> 00:24:42,481 from which presumably all would benefit? 587 00:24:43,515 --> 00:24:44,450 So it was 588 00:24:44,450 --> 00:24:47,908 largely the Committee on Ethics of the 589 00:24:47,908 --> 00:24:48,454 LeMay 590 00:24:49,421 --> 00:24:51,250 and its American representatives, 591 00:24:51,250 --> 00:24:52,524 French representatives 592 00:24:52,524 --> 00:24:56,895 and British representatives who struggled over what would be 593 00:24:56,895 --> 00:25:00,032 an effective set of recommendations 594 00:25:00,265 --> 00:25:03,268 for clinical researchers. 595 00:25:03,736 --> 00:25:05,546 Well, this culminated and you've 596 00:25:05,546 --> 00:25:06,338 already heard 597 00:25:06,338 --> 00:25:10,270 in the 1964 Declaration of Helsinki, in 598 00:25:10,270 --> 00:25:10,976 which, 599 00:25:11,643 --> 00:25:13,619 physicians from all over the world 600 00:25:13,619 --> 00:25:15,013 unanimously recommended 601 00:25:15,013 --> 00:25:18,584 not a code of ethics, but recommendations guiding, 602 00:25:20,519 --> 00:25:23,522 guiding, clinical research. 603 00:25:24,123 --> 00:25:26,792 So this is refers to the original 604 00:25:26,792 --> 00:25:29,461 declaration of Helsinki in 1964. 605 00:25:29,461 --> 00:25:34,233 And as you know, it's undergone, significant revisions. 606 00:25:34,233 --> 00:25:36,603 And perhaps there's one under, happening 607 00:25:36,603 --> 00:25:37,669 even as we speak. 608 00:25:38,103 --> 00:25:42,086 But what was perhaps most important difference for 609 00:25:42,086 --> 00:25:43,041 researchers 610 00:25:43,041 --> 00:25:47,713 from the earlier Nuremberg Code was that it permitted proxy 611 00:25:47,713 --> 00:25:48,347 consent 612 00:25:48,881 --> 00:25:51,483 and it and, 613 00:25:51,483 --> 00:25:55,495 and so, for example, children could, could participate in 614 00:25:55,495 --> 00:25:55,988 trials 615 00:25:55,988 --> 00:25:58,008 of new vaccines, a number of new vaccines 616 00:25:58,008 --> 00:25:59,191 that are coming online, 617 00:26:00,359 --> 00:26:01,960 that, 618 00:26:01,960 --> 00:26:05,464 prisoner populations, which, could participate 619 00:26:05,798 --> 00:26:08,079 in trials of new drugs and sort of there's 620 00:26:08,079 --> 00:26:10,035 an explosion in the number of drugs 621 00:26:10,035 --> 00:26:14,373 that become available, in the 1950s, 60s and 70s. 622 00:26:14,740 --> 00:26:16,560 And I'll just remind you, sort of prisoner 623 00:26:16,560 --> 00:26:18,077 experimentation was not permitted, 624 00:26:18,744 --> 00:26:21,725 in, in countries like, the UK and France, 625 00:26:21,725 --> 00:26:23,615 but in the United States, 626 00:26:23,615 --> 00:26:26,538 every major pharmaceutical company 627 00:26:26,538 --> 00:26:28,687 had a major prison ward, 628 00:26:29,788 --> 00:26:32,491 facility for testing new drugs 629 00:26:32,491 --> 00:26:35,461 and other, interventions. 630 00:26:35,694 --> 00:26:38,096 This is just to show sort of, again, 631 00:26:38,096 --> 00:26:38,697 sort of, 632 00:26:39,097 --> 00:26:41,834 research and research ethics 633 00:26:41,834 --> 00:26:44,837 are, you know, are not stagnant. 634 00:26:45,137 --> 00:26:47,861 They change over time, both the way research is 635 00:26:47,861 --> 00:26:48,440 conducted 636 00:26:48,440 --> 00:26:50,579 and how it's understood and the context 637 00:26:50,579 --> 00:26:52,444 in which it's being, experienced, 638 00:26:53,312 --> 00:26:56,315 as well as, sort of 639 00:26:56,748 --> 00:26:59,083 the challenges, ethical challenges 640 00:26:59,083 --> 00:27:00,319 that confront us. 641 00:27:01,920 --> 00:27:04,527 So that's being done on the international 642 00:27:04,527 --> 00:27:06,625 level back in the United States. 643 00:27:07,192 --> 00:27:10,095 I want to return now to the, 644 00:27:11,697 --> 00:27:12,331 to the United 645 00:27:12,331 --> 00:27:15,300 States in its response to scandal and tragedy. 646 00:27:15,634 --> 00:27:18,437 What will precipitate the National Research Act 647 00:27:18,437 --> 00:27:21,440 in 1974? 648 00:27:21,874 --> 00:27:24,184 Well, as I've already indicated, by 649 00:27:24,184 --> 00:27:24,910 the 1960s, 650 00:27:25,310 --> 00:27:28,844 there's no longer sort of faith in the medical research 651 00:27:28,844 --> 00:27:29,615 enterprise. 652 00:27:30,249 --> 00:27:33,352 This is a time of challenge to all institutions. 653 00:27:33,352 --> 00:27:35,687 And physicians are no exception. 654 00:27:35,687 --> 00:27:39,428 And two things I think are largely responsible for 655 00:27:39,428 --> 00:27:40,325 propelling, 656 00:27:41,727 --> 00:27:43,795 Congress to act. 657 00:27:43,795 --> 00:27:46,532 One is the release of Doctor Henry Beecher's 658 00:27:46,532 --> 00:27:48,470 bombshell article in the New England 659 00:27:48,470 --> 00:27:49,601 Journal of Medicine. 660 00:27:49,601 --> 00:27:51,889 And again, sort of what represents the 661 00:27:51,889 --> 00:27:52,371 tipping 662 00:27:52,371 --> 00:27:55,574 point, the revelation in 1972 663 00:27:55,574 --> 00:27:58,677 of a 40 year study of untreated syphilis 664 00:27:58,677 --> 00:28:01,680 in Tuskegee, Alabama. 665 00:28:02,114 --> 00:28:03,929 So for those of you who have not read 666 00:28:03,929 --> 00:28:05,450 this article are not familiar. 667 00:28:05,450 --> 00:28:07,638 Henry Beecher is a very important, 668 00:28:07,638 --> 00:28:09,955 figure in the history of bioethics. 669 00:28:10,322 --> 00:28:12,414 He was a professor of anesthesia research 670 00:28:12,414 --> 00:28:13,792 at Harvard Medical School. 671 00:28:14,126 --> 00:28:18,490 He would go on and other, arenas as a convener of the Harvard ad 672 00:28:18,490 --> 00:28:18,830 hoc, 673 00:28:19,431 --> 00:28:20,632 Committee on Brain Death. 674 00:28:21,800 --> 00:28:22,634 But in 675 00:28:22,634 --> 00:28:25,324 in 1966, he published this article, 676 00:28:25,324 --> 00:28:27,706 which I encourage you to read. 677 00:28:27,706 --> 00:28:29,975 It's very short. 678 00:28:29,975 --> 00:28:32,945 And this article, Ethics in Clinical Research 679 00:28:32,945 --> 00:28:35,881 actually discusses, without naming names 680 00:28:35,881 --> 00:28:38,083 or naming the journals, talks 681 00:28:38,083 --> 00:28:40,470 about 22 examples of what he called 682 00:28:40,470 --> 00:28:42,721 questionable research practices. 683 00:28:43,021 --> 00:28:44,660 And they were questionable in that 684 00:28:44,660 --> 00:28:46,491 they were, insofar as they were being 685 00:28:46,491 --> 00:28:48,887 conducted without concern for the safety 686 00:28:48,887 --> 00:28:50,862 and welfare of the participants. 687 00:28:51,430 --> 00:28:53,944 And the overriding point the feature wanted to 688 00:28:53,944 --> 00:28:54,600 communicate 689 00:28:54,800 --> 00:28:58,370 was that this wasn't sort of from fringe or, 690 00:28:58,770 --> 00:29:01,875 researchers, but from people at the very 691 00:29:01,875 --> 00:29:02,341 heart 692 00:29:02,341 --> 00:29:04,533 of the medical research enterprises 693 00:29:04,533 --> 00:29:05,410 that the U.S. 694 00:29:05,611 --> 00:29:08,947 mainstream researchers at major institutions. 695 00:29:11,550 --> 00:29:14,353 And another point that Beecher wanted to make 696 00:29:14,353 --> 00:29:18,090 is that it involved populations that would certainly read, 697 00:29:19,191 --> 00:29:22,060 I think most people's definitions of vulnerable, 698 00:29:23,495 --> 00:29:26,231 who were the subjects mentally defective children? 699 00:29:26,231 --> 00:29:28,406 That's the term that was used at the time, 700 00:29:28,406 --> 00:29:29,234 quote, mentally 701 00:29:29,234 --> 00:29:31,424 retarded people and quote, juvenile 702 00:29:31,424 --> 00:29:32,237 delinquents. 703 00:29:32,704 --> 00:29:35,674 The very elderly, senile and demented 704 00:29:35,674 --> 00:29:38,176 soldiers in the armed forces, 705 00:29:38,176 --> 00:29:41,179 charity patients, the terminally ill. 706 00:29:41,613 --> 00:29:43,181 A group that we don't often see. 707 00:29:43,181 --> 00:29:46,318 Alcoholics, children and newborns 708 00:29:46,652 --> 00:29:49,621 and patients at the NIH Clinical Center. 709 00:29:50,689 --> 00:29:53,825 Now, two of his 22 examples, 710 00:29:54,393 --> 00:29:56,170 would have been well known to readers 711 00:29:56,170 --> 00:29:57,996 of the New York Times and other major 712 00:29:58,263 --> 00:30:01,295 newspapers in the US, and perhaps known to you as 713 00:30:01,295 --> 00:30:01,667 well, 714 00:30:02,000 --> 00:30:04,129 example 16, which was not identified 715 00:30:04,129 --> 00:30:06,672 as the, you know, the studies on hepatitis 716 00:30:06,672 --> 00:30:10,142 at the Willowbrook State School, but nonetheless involves them. 717 00:30:11,209 --> 00:30:13,311 Willowbrook was a large 718 00:30:13,311 --> 00:30:16,428 and underfunded a state institution on Staten 719 00:30:16,428 --> 00:30:16,982 Island. 720 00:30:17,315 --> 00:30:19,693 It was intended for mentally defective 721 00:30:19,693 --> 00:30:20,318 children. 722 00:30:20,952 --> 00:30:24,523 It, it was a terrible place by all. 723 00:30:26,224 --> 00:30:28,760 By all observers. 724 00:30:28,760 --> 00:30:31,530 At the institution, hepatitis was rife. 725 00:30:31,530 --> 00:30:34,666 And Saul Krugman, a, 726 00:30:34,666 --> 00:30:37,169 a pediatrician at NYU, proposed 727 00:30:37,169 --> 00:30:39,905 to use newly admitted children 728 00:30:39,905 --> 00:30:43,365 with their parents consent and actually give them 729 00:30:43,365 --> 00:30:44,142 hepatitis. 730 00:30:44,576 --> 00:30:47,212 Study them in a special ward 731 00:30:47,212 --> 00:30:49,989 at, Willowbrook for, to understand 732 00:30:49,989 --> 00:30:52,684 the natural history of hepatitis 733 00:30:52,684 --> 00:30:55,359 A, and also ways in which the disease 734 00:30:55,359 --> 00:30:57,456 might be effectively treated 735 00:30:57,456 --> 00:31:00,825 if they were using, for example, infusions of gamma globulin at 736 00:31:00,825 --> 00:31:01,359 the time. 737 00:31:01,760 --> 00:31:05,192 But it was the idea that testers are using, you 738 00:31:05,192 --> 00:31:05,630 know, 739 00:31:05,630 --> 00:31:07,704 the most vulnerable children actually 740 00:31:07,704 --> 00:31:10,001 giving them disease that disturbed many. 741 00:31:10,869 --> 00:31:13,004 So, again, here's 742 00:31:13,004 --> 00:31:16,308 Krugman is also, again, the idea was to work 743 00:31:16,308 --> 00:31:19,081 toward an effective vaccine and prevent the spread of this 744 00:31:19,081 --> 00:31:19,511 disease. 745 00:31:20,912 --> 00:31:23,448 Krugman through I mean, throughout his 746 00:31:23,448 --> 00:31:26,184 career, continued to defend the studies. 747 00:31:26,184 --> 00:31:29,449 I already mentioned parental concern, parental 748 00:31:29,449 --> 00:31:30,088 consent, 749 00:31:31,323 --> 00:31:31,923 which in 750 00:31:31,923 --> 00:31:34,630 some ways was sort of a, you know, he was in the 751 00:31:34,630 --> 00:31:35,193 vanguard. 752 00:31:35,761 --> 00:31:38,764 But critics have emphasized that it was group consent. 753 00:31:38,764 --> 00:31:42,213 He'd bring parents together and, you know, tell them about 754 00:31:42,213 --> 00:31:42,868 the study, 755 00:31:42,868 --> 00:31:46,685 have them sign sort of a brief, you know, brief 756 00:31:46,685 --> 00:31:47,172 form. 757 00:31:47,372 --> 00:31:50,375 And many people have found that problematic. 758 00:31:50,609 --> 00:31:54,646 And also issues about, you know, withholding gamma globulin from 759 00:31:54,646 --> 00:31:55,213 infected 760 00:31:55,213 --> 00:31:57,306 children, once they had established 761 00:31:57,306 --> 00:31:59,518 that would have a beneficial effect. 762 00:32:00,685 --> 00:32:04,393 The other the other one that's, would have been known to 763 00:32:04,393 --> 00:32:04,923 readers 764 00:32:04,923 --> 00:32:08,653 of the New York Times and again, other papers was the experiments 765 00:32:08,653 --> 00:32:09,227 conducted 766 00:32:09,227 --> 00:32:11,364 at the Jewish Chronic Disease Hospital, 767 00:32:11,364 --> 00:32:13,665 in which they were interested in studying 768 00:32:13,665 --> 00:32:17,877 sort of what live cancer cells do in the bodies of elderly 769 00:32:17,877 --> 00:32:18,603 patients. 770 00:32:19,471 --> 00:32:20,539 It was funded by the U.S. 771 00:32:20,539 --> 00:32:23,475 Public Health Service and the American Cancer Society. 772 00:32:23,475 --> 00:32:27,679 It, they did not get the consent of these elderly people. 773 00:32:27,679 --> 00:32:31,283 Some are, you know, identified as senile and demented. 774 00:32:31,550 --> 00:32:34,184 And the reason being that they didn't wish to 775 00:32:34,184 --> 00:32:34,653 stir up 776 00:32:34,653 --> 00:32:37,455 any, unnecessary anxieties. 777 00:32:37,455 --> 00:32:40,306 And the patients who had phobia and ignorance 778 00:32:40,306 --> 00:32:41,193 about cancer. 779 00:32:44,296 --> 00:32:46,498 Chester Southam was the principal 780 00:32:46,498 --> 00:32:47,432 investigator. 781 00:32:47,432 --> 00:32:50,168 He was at Memorial Sloan Kettering. 782 00:32:50,168 --> 00:32:53,104 He did not do his his case. 783 00:32:53,104 --> 00:32:56,107 Any favor when he gave and, 784 00:32:56,675 --> 00:32:58,595 he gave an interview to science again, 785 00:32:58,595 --> 00:33:00,212 the magazine of the triple A s, 786 00:33:00,579 --> 00:33:03,248 and the reporter asked, 787 00:33:03,248 --> 00:33:06,585 Doctor Southam, what would he have experimented 788 00:33:06,585 --> 00:33:09,081 on himself with these injections of live 789 00:33:09,081 --> 00:33:09,955 cancer cells? 790 00:33:10,655 --> 00:33:13,491 I'm not going to read the long quote. 791 00:33:13,491 --> 00:33:16,061 He basically said I would not have hesitated 792 00:33:16,061 --> 00:33:18,997 if it would have served a useful purpose. 793 00:33:18,997 --> 00:33:22,267 And then he goes on, he said, I did not regard the experiment 794 00:33:22,267 --> 00:33:24,506 as dangerous, but his the last sentence 795 00:33:24,506 --> 00:33:26,171 I'll call your attention to. 796 00:33:26,171 --> 00:33:28,425 But let's face it, there are relatively 797 00:33:28,425 --> 00:33:30,275 few skilled cancer researchers, 798 00:33:30,542 --> 00:33:35,029 and it seems stupid to take even the little risk, that did not 799 00:33:35,029 --> 00:33:35,680 win him. 800 00:33:35,680 --> 00:33:37,182 Friends at admirers. 801 00:33:38,884 --> 00:33:39,551 But again, 802 00:33:39,551 --> 00:33:43,188 perhaps the the singular most important moment, 803 00:33:43,488 --> 00:33:46,491 capping more than a decade of 804 00:33:47,525 --> 00:33:50,996 discussions about legislation to protect human subjects 805 00:33:51,296 --> 00:33:53,085 was the revelation of the Tuskegee 806 00:33:53,085 --> 00:33:54,032 Syphilis Study on 807 00:33:54,032 --> 00:33:57,035 July 25th, 1972. 808 00:33:58,536 --> 00:34:00,467 I think that many of you are familiar 809 00:34:00,467 --> 00:34:02,240 with the Tuskegee syphilis study. 810 00:34:02,240 --> 00:34:05,243 And so I just have a very a few very brief slides. 811 00:34:05,644 --> 00:34:08,237 You know, that the study actually, 812 00:34:08,237 --> 00:34:09,381 began in 1932. 813 00:34:10,515 --> 00:34:14,019 It was, intended to be a six month study. 814 00:34:14,552 --> 00:34:17,822 It was then extended and until it was formally ended 815 00:34:18,123 --> 00:34:20,250 by the Department of Health, education 816 00:34:20,250 --> 00:34:21,426 and Welfare in 1972, 817 00:34:21,993 --> 00:34:24,823 it was overseen by the Public Health 818 00:34:24,823 --> 00:34:25,530 Service. 819 00:34:26,431 --> 00:34:28,900 Surgeon General Thomas Perron. 820 00:34:28,900 --> 00:34:34,072 In the, you know, after, in 1936 to 1948, 821 00:34:34,472 --> 00:34:37,475 Perron was a crusader against this, 822 00:34:38,677 --> 00:34:40,712 syphilis and, 823 00:34:40,712 --> 00:34:43,462 other sexually transmitted diseases 824 00:34:43,462 --> 00:34:45,583 and intent on vanquishing, 825 00:34:46,084 --> 00:34:48,578 these diseases from the United States 826 00:34:48,578 --> 00:34:49,387 and sort of 827 00:34:49,387 --> 00:34:52,932 openly discussing sort of that the toll that this disease 828 00:34:52,932 --> 00:34:53,491 exerted. 829 00:34:56,227 --> 00:34:59,230 So, it turns out they did it, 830 00:34:59,464 --> 00:35:02,523 a study at six counties of the incidence of 831 00:35:02,523 --> 00:35:03,234 syphilis. 832 00:35:03,601 --> 00:35:05,392 They found Macon County had an 833 00:35:05,392 --> 00:35:06,705 extraordinarily high, 834 00:35:08,139 --> 00:35:09,074 incidence. 835 00:35:09,074 --> 00:35:12,377 And it was selected because there was a, 836 00:35:12,777 --> 00:35:16,548 veterans hospital for African American, servicemen 837 00:35:16,815 --> 00:35:20,251 in Tuskegee for the initial six month study. 838 00:35:21,586 --> 00:35:22,921 From the start. 839 00:35:22,921 --> 00:35:25,924 It involved deception of the participants. 840 00:35:26,658 --> 00:35:29,502 Doctor Raven Von Miller, who played an important role in 841 00:35:29,502 --> 00:35:30,061 the study, 842 00:35:30,662 --> 00:35:32,795 wrote letters to the men offering 843 00:35:32,795 --> 00:35:33,765 what he called 844 00:35:33,765 --> 00:35:35,871 last chance for special free treatment 845 00:35:35,871 --> 00:35:37,035 for their bad blood. 846 00:35:37,736 --> 00:35:40,472 And it turns out that, what he was 847 00:35:40,472 --> 00:35:44,109 offering was lumbar puncture, which was, 848 00:35:45,076 --> 00:35:47,946 undertaken to obtain spinal fluid for diagnosis. 849 00:35:47,946 --> 00:35:49,047 For diagnosis. 850 00:35:49,047 --> 00:35:52,117 It's a completely diagnostic procedure. 851 00:35:52,117 --> 00:35:54,719 There's nothing curative about it. 852 00:35:54,719 --> 00:35:57,088 The men found it very painful. 853 00:35:57,088 --> 00:35:59,225 And actually, one of the things I think 854 00:35:59,225 --> 00:36:00,759 is interesting and suggests 855 00:36:00,759 --> 00:36:03,228 that there's even some limited agency 856 00:36:03,228 --> 00:36:06,031 on the part of participants is that they, 857 00:36:06,931 --> 00:36:09,807 it was done one time only because the researchers 858 00:36:09,807 --> 00:36:10,335 realized 859 00:36:10,335 --> 00:36:12,884 if they wanted to do more spinal punctures 860 00:36:12,884 --> 00:36:15,373 in the future, their research population 861 00:36:15,373 --> 00:36:19,411 would completely absent itself from further participation 862 00:36:20,779 --> 00:36:21,913 in some to at. 863 00:36:21,913 --> 00:36:24,416 Sometimes Tuskegee was talked about a study of nature. 864 00:36:24,416 --> 00:36:27,786 These were men who were were very poor. 865 00:36:28,019 --> 00:36:29,554 They didn't have medical care. 866 00:36:29,554 --> 00:36:31,022 They weren't going to see a doctor. 867 00:36:31,022 --> 00:36:32,957 They weren't going to get treatment. 868 00:36:32,957 --> 00:36:34,025 But the public health service 869 00:36:34,025 --> 00:36:36,918 also took steps to ensure that they would not get 870 00:36:36,918 --> 00:36:37,862 treatment when, 871 00:36:38,229 --> 00:36:40,683 at least 254 of the men were called up 872 00:36:40,683 --> 00:36:43,201 for military service in World War two, 873 00:36:43,601 --> 00:36:47,041 and the Public Health Service intervened with the draft board 874 00:36:47,041 --> 00:36:47,605 and said, 875 00:36:47,972 --> 00:36:52,710 do not take these men because we they're in our study 876 00:36:52,977 --> 00:36:55,980 and we want to follow their untreated syphilis. 877 00:36:56,581 --> 00:36:59,017 If they had been inducted into the Army, 878 00:36:59,017 --> 00:37:00,618 or even if they hadn't found if once 879 00:37:00,618 --> 00:37:02,220 they were identified as syphilitic, 880 00:37:02,454 --> 00:37:04,753 they would have received free treatment 881 00:37:04,753 --> 00:37:06,758 for their disease, from the Army. 882 00:37:08,093 --> 00:37:09,727 Crucial to the success of the 883 00:37:09,727 --> 00:37:13,231 society of the study was Nurse Eunice Rivers. 884 00:37:13,832 --> 00:37:14,966 She was a trained nurse. 885 00:37:14,966 --> 00:37:17,480 She graduated from Bristol University, 886 00:37:17,480 --> 00:37:18,803 and she was crucial 887 00:37:19,170 --> 00:37:22,173 in bridging sort of the large cultural gap 888 00:37:22,173 --> 00:37:25,176 between these, unlettered farmers 889 00:37:25,477 --> 00:37:28,513 and, the Public Health Service 890 00:37:29,013 --> 00:37:31,264 researchers who came at irregular 891 00:37:31,264 --> 00:37:33,651 intervals over, over the 40 years. 892 00:37:34,752 --> 00:37:36,494 It was Nurse Rivers, for example, 893 00:37:36,494 --> 00:37:37,655 who was given the job 894 00:37:37,655 --> 00:37:40,658 of obtaining permission for postmortem, 895 00:37:41,259 --> 00:37:42,093 participation. 896 00:37:42,093 --> 00:37:43,261 It's always interesting to me 897 00:37:43,261 --> 00:37:45,272 that the one thing they asked them 898 00:37:45,272 --> 00:37:47,165 for was permission for autopsy. 899 00:37:47,832 --> 00:37:48,266 All right. 900 00:37:48,266 --> 00:37:51,882 And their families, her job became much easier when the 901 00:37:51,882 --> 00:37:52,737 Milbank Fund 902 00:37:52,737 --> 00:37:56,595 offered a burial stipend, initially $50, later raised to 903 00:37:56,595 --> 00:37:57,008 $100. 904 00:37:57,475 --> 00:37:59,725 And as she reported in public health 905 00:37:59,725 --> 00:38:01,412 reports in a 1953 article, 906 00:38:01,679 --> 00:38:06,084 she had only one refusal in 140 requests, 907 00:38:07,552 --> 00:38:09,320 so the study was not a secret. 908 00:38:09,320 --> 00:38:13,558 There were 13 publications between 1936 and 1974, 909 00:38:13,558 --> 00:38:17,162 in the open medical literature, but it's a 1954 910 00:38:17,529 --> 00:38:19,423 after things like the publication 911 00:38:19,423 --> 00:38:21,432 and science of the Nuremberg Code, 912 00:38:21,733 --> 00:38:24,607 that for the first time men in the study 913 00:38:24,607 --> 00:38:27,338 were identified as, quote, volunteers 914 00:38:27,338 --> 00:38:30,341 with social incentives. 915 00:38:31,209 --> 00:38:34,412 In an effort to kind of promote the, 916 00:38:34,779 --> 00:38:37,782 the knowledge that they were in a medical research study. 917 00:38:38,283 --> 00:38:41,553 In 1957, the Public Health Service, 918 00:38:43,388 --> 00:38:44,589 rewarded the men 919 00:38:44,589 --> 00:38:47,659 with a with a certificate signed by the surgeon general. 920 00:38:48,126 --> 00:38:52,530 And each man in the study received a dollar for every year 921 00:38:52,530 --> 00:38:55,600 they had participated. So they received $25. 922 00:38:55,900 --> 00:38:58,903 And this certificate that says, 923 00:38:59,270 --> 00:39:00,705 active participation 924 00:39:00,705 --> 00:39:03,808 in the Tuskegee Medical Research Study. 925 00:39:03,808 --> 00:39:06,372 Now, that did not translate necessarily 926 00:39:06,372 --> 00:39:08,279 to the men who who still may 927 00:39:08,279 --> 00:39:10,242 not have known that they were actively 928 00:39:10,242 --> 00:39:12,050 participating in medical research. 929 00:39:17,121 --> 00:39:19,691 So it's in 1972 that the, 930 00:39:19,691 --> 00:39:22,894 study is revealed, 1974. 931 00:39:23,394 --> 00:39:25,830 Oh, there were hearings, 932 00:39:25,830 --> 00:39:28,132 presided by, 933 00:39:28,132 --> 00:39:31,202 Senator Ted Kennedy, among others. 934 00:39:31,202 --> 00:39:33,371 And the creation of the National Commission 935 00:39:33,371 --> 00:39:36,708 to study the moral issues posed by human experimentation. 936 00:39:37,408 --> 00:39:41,813 And, this is the organization that also sponsors, 937 00:39:42,580 --> 00:39:44,573 the publication of the Belmont Report 938 00:39:44,573 --> 00:39:46,351 about what you've heard so much. 939 00:39:47,318 --> 00:39:48,931 One of the things that I will say 940 00:39:48,931 --> 00:39:50,788 is that I, I certainly hope that I've 941 00:39:50,788 --> 00:39:54,692 whetted your appetite for, an interest 942 00:39:55,026 --> 00:39:57,862 in the history of human experimentation.