 Today I'm going to introduce a friend, a colleague, and a fellow Chicagoan who's going to talk today. So this is Sidney Halperin, who's a professor emeritus at the University of Illinois at Chicago, and a lecturer in the medical humanities and bioethics program at Northwestern. Sidney Halperin is a historical sociologist who has written extensively about 20th century American medical institutions and biomedical science. Currently she serves as professor emerita at the University of Illinois and lecturer in the program on medical humanities and bioethics that's out of the Feinberg School at Northwestern University. For some time, Dr. Halperin's focus had been the framing of moral issues in the conduct of human research. She earned her doctorate in sociology at University of California at Berkeley with a concentration in historical analysis and has served as a full professor at both Vanderbilt and the University of Illinois at Chicago. She has been a visiting scholar for the Center of Bioethics, University of Pennsylvania School of Medicine, the Institute for Government and Public Affairs, the American Bar Association, and the University of Illinois. Her funding awards include investigator in health policy research from the Robert Wood Johnson Foundation, and she has had major grants from university fellowships from the National Endowment of the Humanities. Today she's gonna talk about, the title of her talk today is Parsing Risks and Benefits. Why should we care about human experiments from medicines past? And that's in line with some of her books. She's published a book last year called Dangerous Medicine, The Story Behind Human Experiments with Hepatitis. And she's also published two other books, one from the University of Chicago Press called Lesser Harms, The Morality of Risk in Medical Research. And she also has a book in progress called American Pediatrics, The Social Dynamics of Professionalism. It's my pleasure to welcome Sydney Halperin for today's talk. Thank you for coming, Sydney. Thank you so much for having me. So I am going to share my screen. Okay. So my talk today addresses moral complexities and judgments about experimental risks and benefits. My focus is calculations surrounding non-therapeutic studies, experiments with healthy subjects that offer them no possible benefits. Researchers pursue these studies to benefit science and future patients. The comparisons made in risk benefit assessments for these studies are fundamentally non-commensurate. Risk to subjects are being weighed against benefits for medical knowledge. Complexities in making these assessments are often overlooked, but they're revealed in experiments from medicines past and they remain with us today. I'm going to be drawing on historical material from my recently published book that you can see here. A very, very briefly, a brief overview of the book. For a 30-year period during World War II and the early Cold War, 1942, scientists in the US conducted hundreds of experiments that involved deliberately infecting people with hepatitis. Their goals were to better understand the viruses and prevent a disease that was afflicting soldiers. Researchers had no animal model for hepatitis and they resorted to experimenting on people. A unit of the US military, the Army Epidemiology Board, or its post-war successor, the Armed Forces Epidemiology Board, sponsored the entire program. 10 groups of researchers involving 60 investigators conducted these viral transmission experiments. The lead scientists of these groups, held positions at prestigious universities and laboratories. The researchers enrolled more than 3,700 human subjects. Some were infected with hepatitis A, others received hepatitis B, and even inadvertently hepatitis C, a strain not identified until the program had ended. In the book, I drew on in-person interviews and a very large volume of archival and other historical materials to examine the full course of America's Hepatitis Infection Program. My account addresses how this troubling research program came into being, what sustained it over time, and how and why it came into an end in the 1970s. Here's the book's major themes. Again, this is gonna be brief. Hepatitis, the program was part of a very broad mobilization of science for the national defense during World War II and the early Cold War. This mobilization created a new constituency of science, what I call a military biomedical elite. It was composed of military medical officers, science scientists, and the National Institutes of Health and more broadly the Public Health Service and researchers at major universities and laboratories. So you're seeing here a picture of a meeting in 1942 of this newly consolidated elite. Its members approved, oversaw, and served as lead scientists for the Hepatitis Infection Program and its particular projects. During the war and a early aftermath, government-sponsored researchers also protrude human infection experiments with a variety of other pathogens. These include dengue, sandfly fever, atypical pneumonia. They also use this general protocol challenge trials now called challenge trials to test the efficacy of vaccines against influenza, measles and dysentery and test pharmacologicals used for treating malaria and a variety of sexually transmitted infections. The Hepatitis Program was distinctive in both its 30-year duration and the variety of human subjects that scientists enrolled. The research participants included, you can see here the numbers of institutions and the number of subjects in each category. They included conscientious objectors to the military draft, prison inmates, mental patients and adults and children in facilities for the developmentally disabled. All were from marginalized groups and all resided in institutional settings. The 1,200 disabled persons listed here in the image included 800 children at Willowbrook State School and it was there that the last of the human infection projects took place. And a good portion of the inmates were African-American. The information on the race of subjects was very difficult to get. It's really basically considered patient records. But occasionally I did find a revealing document and on that basis I estimate that depending on the prison between 25 and 45% of inmates enrolled at that location were African-American. I found very little information about the use of other minority groups. Scientists and their military sponsors put a great deal of effort into advancing narratives justifying their interventions. They gain access to custodial facilities for recruitment by appealing to the ethos and management concerns of institutional directors. So actually when they went into the mental hospitals and institutions for this disabled, they argued that the experiments were in the subject's best interest. And they secured sympathetic coverage for the overall program for the mainstream press by drawing on the wartime cultural ethos that emphasize patriotic contributions to the common good. What you're seeing here is an example of this lotatory press coverage. So this is a headline and a photo in an article in a Philadelphia newspaper that reports conscientious objectors serving voluntarily in these experiments. Elite scientists were able to establish a dominant moral framework in which for a quarter century dangerous experiments with marginalized persons were legitimate. In the prevailing narratives, experiments were either in the subject's best interest as I just noted, or participants were making voluntary sacrifices for science and country. And those are the arguments made for prison inmates in the conscientious objectors. But in the 1960s, the biomedical elite could no longer sustain the dominance of their narrative. Rights activism created pressures from outside the profession and even entered medicine itself. Progressively minded young physicians and even members of the biomedical elite repudiated risky experiments with members of vulnerable groups and objections to the troubling experiments including the Willowbrook studies spilled into the public arena. The image you're seeing here gives examples of the altered character of press coverage on the right as a leaflet from the medical committee on human rights announcing demonstrations against Saul Krugman, the lead investigator at Willowbrook. And this was one indicator of a growing divide within biomedicine itself. I argue that the biomedical elite lost control of the public narrative. And it was at that point that hepatitis infection experiments came to an end. I'd be happy to say more during discussion about this period because there's actually a lot more to say. But I wanna move on to my findings about experimental risks and benefits. First harms, and there's a great deal to say about risks and benefits. The hepatitis program involved a great deal more harm than researchers had anticipated. When assessing risks, researchers primary focus is on short-term risk of death. And researchers, the hepatitis researchers were quite accurate on the score. There were four deaths of prisoners from fulminate hepatitis B. A fifth prisoner spent a week in a coma with this condition that managed to recover. These numbers were consistent with the expectations of researchers. In 1942, there was a massive outbreak of hepatitis B in the military. It was this outbreak that triggered the first human experiments. The death rate among hospitalized cases during this outbreak was between one and two per 1,000 cases. What researchers greatly underestimated was the long-term harm, particularly harms associated with the creation of hepatitis carriers. So carriers are individuals who failed to clear the virus after initial infection. Researchers were aware of the existence of carriers because they were aware that the serum of some blood donors generated hepatitis in people receiving transfusions. But their concern about carriers was mostly disease transmission. They were unaware that hepatitis is also a risk for those who are carriers who may develop cirrhosis and or liver cancer two or more decades after initial infection or to put it more accurately. Researchers didn't have systematic data linking the carrier status to cirrhosis and liver cancer and that wouldn't be available to the late 70s and early 80s. Scientists were also unaware of the existence of hepatitis C, as I mentioned before. Originally it was called non-A, non-B, but it would become clear later that researchers had actually transmitted the strain inadvertently. One occasion when subjects were infected with hepatitis C was a project that researchers called the blood sterilization project. After the war, scientists discovered that the supply of blood and plasma was contaminated with hepatitis B. And in the early 50s, the Armed Forces Epidemiology Board launched a project aimed at inactivating the blood-borne pathogens. Researchers took serum known to contain the virus, applied irradiation or chemicals and then injected the treated serum into research subjects to see if they would be protected by the treatment of the serum. None of their interventions worked. During the 70s, after the hepatitis program had ended, researchers at NIH analyzed the blood samples from this experiment that had occurred 20 years earlier. And those researchers analyzed the samples from 65 subjects in that earlier study and concluded that 35 of the 65 had received non-A, non-B. This is significant because of the carrier rate of hepatitis C, which is much higher than for hepatitis B, as you can see on my slide. So on average among adults who are exposed or infected with B, about five to 10% become carriers, but among adults infected with hepatitis C, 75 to 85% become carriers. But most disheartening was the later discovery about the long-term harm to children, some of whom were used as human subjects in transmission of blood-borne specimens. Researchers at the time thought that hepatitis was mild in children. Indeed, the symptoms are typically mild, but it would turn out that child subjects, given hepatitis B, would be especially vulnerable to becoming long-term carriers. And the younger the child, the more likely that a carrier status will arise. So the image you're looking at includes my estimates of a number of subjects receiving blood-borne hepatitis B or C. So I estimate that more than a thousand subjects were injected with serum containing one of these viruses and at least 150 were children. I do not provide estimates on the number of carriers, but in order to do so, I'd have to know how many of those receiving tainted blood received hepatitis C, and I'd also have to know the age of the children, which the documents did not reveal. So the scientific benefits. There were benefits, particularly during the World War II period. Studies during these years confirm the existence of two distinct strains, A and B. It identified their routes of infection, their incubation periods, and researchers used a variety of liver function tests to follow the course of the illness. They also used successfully gamma-goblin during outbreaks of hepatitis A, and they found that it created temporary immunity, passive immunity, but delayed the spread of new cases during epidemics. But after the war, researchers shifted their focus to durable disease prevention. It was at this point that the Armed Forces Epidemiology Board initiated the blood sterilization project, which I've already referred to. And investigators also put a great deal of effort into developing vaccines. But for two decades, they made virtually no progress. And I noted earlier that this was a period where three of the four research deaths occurred. In 1957, John Rodman-Paul, a Yale researcher and head of the Army Epidemiology Board's Viral Commission, lamented the disappointing post-war trajectory. These are his words. After rapid growth of knowledge about hepatitis from research conducted during World War II, advances slowed down and it was almost seemed as if they ground to a temporary halt, leaving certain basic questions as unanswered as they were in 1942. Researchers had tried, but repeatedly failed to identify an animal model for hepatitis or its various strains to isolate the viruses, develop tests for the virus's presence, which could be used to test blood, for example, to inactivate the pathogens, to find a stable growth media, or to introduce an immunizing agent. Now, I want to point out that there was a breakthrough in the mid-1960s. At that time, a researcher by the name of Burro Flumber discovered a blood-borne particle, a blood-borne particle he called Australia antigen, and it turned out to be the hepatitis B surface antigen. Sol Krogman's team at Willowbrook was one of several groups that confirmed that this particle was part of the B virus. An identification of the B virus allowed researchers to screen blood donors, and it was also the basis for the development of the first hepatitis B vaccine. But the advance was not a result of human infection experiments. Blumberg wasn't even a virologist. His background was biochemistry and population genetics. Meanwhile, deaths and injuries to subjects were never compensated, and the long-term harms were never acknowledged. So what you're seeing here is an example of a waiver and release document and the statement releasing the researchers and sponsors from any liability for injury. And these were standard issue during this period. They were required by military sponsors, and indeed the wording was approved by Defense Department lawyers. Researchers did provide medical care for subjects while the experiments were ongoing. After that, subjects received no further treatment or medical follow-up. The Defense Department made no provisions for the care of continuing illnesses or delayed harm, and it consistently refused to provide compensation for research injuries. There was one exception to this pattern. It would pay for burial costs for subjects who died, so long as funds were taken out of the principal investigator's research account. Now, this situation actually became a source of tension between researchers and their military sponsors. From work during the war, hepatitis researchers discovered that or realized that some of the subjects weren't recovering after six months, and they requested that they be allowed to buy health or disability insurance for their subjects. The Defense Department refused. So the bottom line on risks and benefits was that during this 30-year period, there was a dramatic underestimation of risk to human subjects, particularly long-term risks, a marked overestimation of scientific benefits, and all this done without a safety net for human subjects. I'm gonna have to speed up here. So what can be learned from this historical case about the dynamics propelling misrepresent or misestimation of risks and benefits? And how does present-day research bioethics weigh in on these matters? I'm gonna start by making a distinction between addressing the misestimation of benefit, and I'm gonna distinguish between the likelihood or perceptions of the likelihood that a given experiment is gonna yield useful knowledge and perceptions of the importance of the problem. So I'm gonna start with expectations of scientific advance. And I'd like to suggest that researchers have a highly skewed view about the pace of science. The histories of research that appear in publications highlight disparate contributions that seem to culminate in medical achievements. In these accounts, contributions that culminate in these accounts, scientists remember successes and they forget failures. I'm certainly not the first to point out that these histories of medical progress are a far cry from what actually happened in the past, but I wanna emphasize the implications for risk assessment because I think it basically results and researchers overestimating the likelihood of scientific benefit. Scientists can get enthralled by powerful ideas, and ideas sometimes are really powerful in biomedicine, and they can also get captivated by ideas that seem eminently workable. This leads, I think, to an overestimation of benefits and overconfidence about auspicious outcomes. Hepatitis strains have been damnably difficult viruses to study. Today, 80 years after laboratory and human experiments began in earnest, there's a cure for hepatitis C carriers, but there's no vaccine. There's a vaccine for hepatitis B, but no cure for carriers. Mid-century hepatitis researchers tried numerous techniques used successfully with other viruses. They tried cultivating hepatitis in chick embryos that work for influenza and measles, didn't work for hepatitis. They tried animal-based tissue cultures, worked for polio, didn't work for hepatitis. They even tried a medium derived from human cancer cells, which may very well have contained unrecognized cancer-causing viruses, but this didn't work either. Yet expectations of promising outcomes were repeatedly thwarted, and yet with one exception, scientists' belief in the scientific value of these hazardous human experiments didn't waver. The exception was a very brief period in which hepatitis infection experiments were halted following the death of the three subjects in the blood sterilization project. That moratorium lasted only 18 months, and after that, that Willowbrook study started. I noted earlier that comparisons between in non-therapeut experiments are fundamentally non-commensurate. So moving on now to perceptions of the importance of the problem. In these types of experiments, there's no grounding in expectation for benefits for subjects. And I'd like to suggest in these situations, it's inevitable that zeitgeist, the value of the time, the historical context, will powerfully influence assessments. And this is certainly played out in the history of hepatitis infection experiments. The wartime military medical office considered hepatitis among soldiers a major problem in national security. During the Korean War, the problem of hepatitis in the blood supply affected 20% of service personnel who received plasma, they contracted jaundice. And obviously the contamination of blood supply was also a problem for civilian healthcare. But narratives surrounding the blood sterilization project focus on nuclear preparedness. The Soviet Union had tested an atom bomb. The Truman administration was making plans for responding to a nuclear attack on the continental US. Cold war planners determined that a vast supply of blood would be needed and hepatitis contamination threatened the entire blood program. According to defense officials, the seriousness of the problem was such that research injuries could be tolerated. Unfortunately, I've seen a similar dynamic or a comparable, maybe analogous dynamic play out beginning two years ago, shortly after COVID-19 hit us. Again, some argue that the disease was such a serious problem. And it was so dangerous that very dangerous human infection experiments with this virus were justifiable. In addition to the pandemic, there were several other contextual factors operated. The use of the human challenge model had become mainstream and institutionalized in the infectious disease research world. Pathogens had been used in these types of experiments included Dengue, dysentery, typhoid, cholera, influenza, malaria, cholera, tuberculosis, neuroviruses, retroviruses and E. coli. And I think they were widespread in part because they could be done quickly and at relatively lower costs than doing large field trials. Meanwhile, there was an emergence of a new field of public health ethics along with an effort to revitalize a cultural emphasis on contributions to the common good. I'd just like to comment that there are two human challenge trials with SARS-CoV-2 currently ongoing in Britain. They began in the spring of 2021. But the point I wanna emphasize here, also in the slide you see that some things I think that advocates for this course are willfully ignoring to start off with the existence of long COVID and the availability of susceptible animals to conduct basic research. But the point I wanna emphasize here is the evaluation of benefits now referred to in among public health ethicists as social value is powerfully affected by social conduct, social context and assessments of the importance of the problem. I wanna move now on to the issue of underestimation of harm. Should mid-century hepatitis researchers have known better? I've said that they lack systematic information about the delayed consequences of the carrier status. But they encountered accumulating evidence of disease sequela, case reports of cirrhosis following hepatitis, subjects who didn't fully recover or subjects who recovered and then only to relapse. The original principal investigator of the blood sterilization project told prospective subjects, and this was in a recruitment pitch, that the chance of disability or a disabling injury from the experiment was one or two per 100, which is fairly high. Should researchers have a frame from human infection experiments because of growing evidence of disabling injuries? Should they have gone back to the laboratory and worked on developing animal models which were developed later, although for hepatitis A it's a pretty good one for B the available ones are less good. I'm gonna leave these questions on the table as open questions, but I'd also like to introduce a quite different line of argument. I'd like to point to the difficulty of making good judgments about risks when scientists are working at the boundaries of medical knowledge. Shouldn't we assume that when researchers go about studying a very poorly understood disease that human harm is a possible outcome? Or for that matter, that bad outcomes are gonna arise when investigators are testing really poorly understood pharmaceuticals or biologicals. Researchers have been testing antivirals for hepatitis B for years, and many of them have turned out to be highly toxic. In 1993, NIH investigators conducted a clinical trial, a field loridine FIAU for treatment of hepatitis B carriers. Among 15 subjects, there were five deaths and two other subjects survived as a result of liver transplants. I think we need to assume that when research takes place at the boundaries of medical knowledge, risk may be underestimated, and that we need to plan for how to handle these consequences. US does not have, and I feel very badly needs an organized system for caring for injured human subjects and for compensating research injury. I think it's a moral imperative to have such a system, particularly for subjects who have nothing to gain, who are healthy, have nothing to gain, and were asked to contribute to the greater good. But what do we have? Well, since the 1970s, some ethicist and policy analysts have been championing the introduction of a no fault compensation program for medical research injuries. But what we've had on this front is periodic advocacy and no meaningful action. Finally, I'd like to, before closing, raise another issue. And that is, who are the subjects in today's non-therapeutic experiments? And here I'm thinking about not only human challenge trials, but also non-therapeutic studies more generally, including phase one clinical trials. There's a growing literature revealing that commercialization of human research through contract research organizations points to the use of an economic underclass. Even where investigators are doing their own recruiting, subjects are drawn from the bottom of the economic hierarchy. These research participants are economically insecure and a large portion of them are persons of color. I'm drawing here on the excellent work of Jill Fisher, for example, in a recent book, Adverse Events. I'm also drawing my own reading of publications from small scale human challenge trials that I referred to before with a variety of other pathogens. I think on this matter, we need a norm of greater transparency in reporting recruitment practices for all non-therapeutic studies. But I'd like to suggest that current bioethic literatures see no fundamental problem in paying people for participation in non-therapeutic studies, so long as the wage is not an undue inducement. But of course it's an inducement. People without economic resources enroll in non-therapeutic experiments for the money. I think on this score, research ethics has been hampered by narrow frameworks that are half a century old. Since the designation of vulnerable groups for human research during the 1970s and 80s, social inequalities have become immensely steeper. And as of now, the field of research ethics has been toned to economic and social inequalities in the recruitment of human subjects. I think the field can and should do better. Finally, a question I've been asked a lot is what would have happened if scientists hadn't done or had stopped doing the hepatitis infection experiments? It's not really feasible to rearrange history or to tell an alternative history. But I do think scientists could have figured out, would have figured out through other means what they figured out with the human infection experiments, although probably not in the same timeframe. But maybe we should be posing other questions. For example, will experimental outcomes actually prevent any illness or help any patients? And are there other ways to answer questions, to find answers to pressing questions that don't put human subjects in danger? I wanna thank you for your attention. I've been poking the bear a bit and I look forward to a lively discussion. I'm gonna stop share. Great, well, thank you so much, Sidney. So your lecture was very interesting and really raised a whole bunch of fascinating questions that are really analogous to modern times. I'm gonna let Peggy start off with her question. Thank you so much. That was absolutely wonderful. I'm curious if you have any comments on research into orphan, what are often called orphan or let me rephrase that as rare diseases. And the economic incentives are not really what it's about, but it's society. And if in the cases where the orphan disease is inheritable, it also can have some impact on other family members that might- Different category. And I think that in those arenas too that there are dynamics going on between the subject groups and families and researchers that I think are really good. And that is, and I think this is one of the things I think we need more of in other arenas. And that is that subjects and researchers feel they're part of a common enterprise. And I think that's a way of undoing a lot of the problems we have in non-therapeutic human experiments. I also don't see these... Well, I'd have to think about particular experiments, but I don't think a lot of those I don't imagine are non-therapeutic. And if they are, they're really toward a common enterprise in which the families and the patients are part of and included. And I think that's one way of really improving the research process. Yeah, I agree. And I also think that there is a sense where these individuals with these rare disorders want to be understood and want to be... They want to understand themselves. They want other people to understand them. They want to be seen even medically, even scientifically. Yeah. Okay, thanks. And this is one of the ways to... I think we need broader participation in non-therapeutic trials. And I think one of the ways to do that is to really promote the idea that this can be a common enterprise. And also promote the idea that maybe we want to reward, socially reward contributions to the common good that people who aren't poor might want to be part of this or more people who don't need the money might want to do... I mean, we used to have a Peace Corps. Maybe we need a research corps, just some ideas that we don't have to pursue this the way we've been doing it. And just the other thing that's interesting to remember about this discussion is that some of this stuff was driven like the hepatitis experiments or things like that may have been driven by a desire to ultimately avoid having people get sick and not be able to work or not be in the military. So there's another agenda as opposed to what Peggy was talking about when you have family members or people who are really interested in some unusual situation. You know, it's interesting when Caleb Alexander came and spoke about like drug development because he does a lot of that stuff. He said one of the interesting things was these, not only these clinical trials, but the advocacy on the part of patients and their families. And you know, we've watched that grow up that started with breast cancer and AIDS, this old patient activism and activation. So that's another interesting piece, you know. Carolyn, you wanna take it away? Sure, thank you. Thanks for this talk. I was curious if you could speak at all about the geography of these kinds of studies. I mean, when we're thinking about equity and sort of the balance of participation it seems like the fact that it requires so much infrastructure to recruit patients and then keep up with them that, you know it sort of forces some of these studies to take place in more urban environments where the kind of disparity between available populations to test is maybe more pronounced. And I wonder if you have any ideas about moving these kinds of studies into other, what I'm calling geographies to sort of alleviate some of those challenges. Interesting, you know, I haven't done primary research on the contract research industry. So apparently it is all over the US. And although apparently recruitment methods and also who's serving as subjects varies when they're in different parts of the country. So I don't, I mean, what's happening for the human challenge trials, this, what I'm suggesting, there are a lot of them going on or have been they're usually small scale. And from what I can tell, mostly it's the university or laboratory that's handling the recruitment. They're not contracting these out. And usually it's the community around the institution say it's a university or a laboratory. So it's usually local recruitment. Yeah, so I don't really have any particular insights other than that. I mean, what happened with the hepatitis experiments in the mid-century was that researchers tried to find locations, institutions within proximity. The blood sterilization project was actually a collaboration of the Defense Department, the National Institutes of Health and PHS and also the Bureau of Prisons. And so the Bureau of Prisons designated three prisons around the country. And so one was off the coast of Washington, one was in Kentucky and another in rural Pennsylvania. And that actually ended up being a problem because the researchers were in Washington and when there were adverse events at the study sites it was hard for the researchers to get there to find out what was going on. So I think part of the problem is who are the responsible PIs and where is the study site? And that can be an issue. So equity in geographical locations may be hampered by the need for a responsible investigator to be in proximity to figure out what the heck's going on, if that makes sense. And the bigger question is, how do you get away from the fact that when people are really desperate, they will do a lot of things that other people who have more money will not do? You know, I remember when I was in, did my residency in Detroit, people would sell their skin, you know, like, you know, little things where, you know, for burn patients. And I don't know, it's interesting, you know. Yeah. Well, the literature on repeat, there are a lot of repeat human subjects today, serial human subjects. And they do it as a kind of, they do it as an informal labor market, basically. And, you know, the bioethics literature says, well, you know, we're not paying them more than they could get in another kind of job like this, but there are a lot of advantages for these, for enrolling. And one is that the subjects get lump payments. They can also spread out their participation when it's convenient. And also some people have trouble getting jobs because either their job record or quite honestly, their criminal justice record. And this is not a problem for signing up for any of these contract research organizations. In fact, they recruit people who are likely to have problems getting other kinds of jobs. So. That is really, that's absolutely fascinating. Peggy. Yeah, I really think we need more information on where the research organization, like the University of Laboratories during the recruitment. So I'm reading this literature and there's some investigators who are really responsible. They're saying like, here's who we recruited. Here many, here, this is many people who were minority, but most of them don't do that. Most of them say, well, we use community volunteers. It's completely unclear who these people are. It's completely unclear how they were recruited. So I think we need a norm. I'm not suggesting we want more regulation, but I think we need a norm. When you publish this kind of work, you need to say something, a paragraph on how you've got human subjects for non-therapeutic trials. Why, I think that's, I think that's a great way to end about non-humans. Can I just ask one more question? Sure, go ahead. Yeah. So, I mean, it's interesting what you just said and I just want to comment on that before I ask my question, which is, you know, if you knew how many subjects were in this or that demographic I still not sure quite what that would tell you. Because you want the demographic to reflect the population. You don't want it to be coerced, but you do want them reflected and seen. So I'm not quite sure where that's taking you. Okay, so I think with therapeutic trials we really want full participation of everybody. But non-therapeutic trials, I think we need more participation of more different segments of society. Let's put it that way. I'm not worried about representation on non-therapeutic trials. I'm worried about that for therapeutic trials. Does that make any sense? Non-therapeutic trials are fundamentally, I don't think they're good for human subjects. I mean, we do it for what? For the money or for altruism? I'd like more of it done for altruism. Let's put it that way. So, well, maybe that connects to my question, which is we look back on what happened at Willowbrook and other places, and we look back and say that was horrible and that's not occurring today, in that exact format at least. And in the equivalent amount of time, which is I guess 100 years, do we look back, will people look back on phase one trials and what else and say that was horrific, we're not doing that anymore? I think the answer is yes. And what beyond phase one would you group in that? I think the willingness to not raise questions about social equity and social inequality, okay, let me put it up more starkly. I think given that our society in recent decades has moved to escalating social inequalities, I think people at the bottom end of the socioeconomic strata are doing dirty work for all of us. And that includes dirty work in taking risks for human experiments that we all benefit from. And I think that's basically exploitative and that we're so inured to it because it's so widespread that we don't think that, we don't think there's anything wrong with it because we're like blind to it, and we're impervious to it, how's that? And I hope in 50 years we'll be at a place where we don't see that as okay, how's that? And I do think there are ways of approaching it differently. I hope there are ways of approaching it differently. I mean, some of the human subjects I look at were conscientious objectors to the draft. These were young men who were pacifists and didn't believe, they didn't believe in bearing arms, but they wanted to do good. And they were, I would say that they were genuine volunteers. And they understood, well, as much as a young person of 20 can understand that they could die from an experiment because I think young people think they're immortal. They understood what the risks were by making sense. And they wanted to do it because they wanted to show that they could make a contribution to the war effort without bearing arms. So maybe we need a little bit more of that. I'm not suggesting I wanna be a pacifist because I'm not a pacifist, but anyway, I just think there are other ways we can approach this. Caroline, you wanted to continue the conversation? Sure, just one follow-up on that point is you may not know some of some of this or you may not work with this literature, but it just strikes me that there might be relevant parallels with the literature on the ethics of organ donation and the ethics of like surrogacy and egg donation that there might be legal protections in place for some of those kind of participants in this larger kind of altruistic system that are not in place for participants in experiments, maybe a parallel. Thank you. Thank you. So anyway, I think it might be a natural place to take a break because I know Sydney will be back this afternoon and I really wanna thank you for a really interesting and thought provoking talk. It really made, I just, as we round this out, I think about the different topics that we've explored as part of like this ethics piece. We talked about Tuskegee in Guatemala. We talked about what to do if the president is incapacitated. We talked about radiation therapy. We got in a couple of weeks, we got to talk in the Nazis. And it's just really interesting to see these ethical problems in a historical context and realize that to get it really clearly and I think it's really useful. So Dr. Bob said, I wonder if they could have been given more rights like sex worker than other countries. So I'm gonna leave that for the afternoon and we'll continue the conversation. But Sydney, we'll give you a little time before the 130 session and on behalf of the McLean Lecture Series, that was really, really interesting and thank you for coming and I'm definitely gonna read that book. Thank you so much.