Alta Charo Considers Ethics for Stem Cells and CRISPR
A lawyer and bioethicist by training, Alta Charo has decades of experience in helping to formulate and inform science policy on new and emerging technologies, including stem cells, cloning, CRISPR, and chimeras. The Warren P. Knowles Professor Emerita of Law and Bioethics at the University of Wisconsin at Madison, she served on President Clinton’s National Bioethics Advisory Commission, was a member of President Obama’s transition team, was an advisor for the Food and Drug Administration, and served on more than a dozen study committees for the National Academies of Sciences, Engineering, and Medicine.
In the fourth episode of our Science Policy IRL series, Alta joins Issues contributing editor Molly Galvin to explore how science policy can and does impact people’s lives in real and profound ways. She also describes what it’s like to be one of the only non-scientists at the science policy table, how helping a close friend who died of ALS continues to inspire her work, and why science policy can help us become techno-optimists.
Is there something about science policy you’d like us to explore? Let us know by emailing us at [email protected], or by tagging us on social media using the hashtag #SciencePolicyIRL.
Resources
- National Academies Collection on Stem Cell Research
- Institute of Medicine. 2005. Review of the HIVNET 012 Perinatal HIV Prevention Study
- National Academies of Sciences, Engineering, and Medicine and National Academy of Medicine. 2023. Toward Equitable Innovation in Health and Medicine: A Framework
- National Academies of Sciences, Engineering, and Medicine. 2017. Human Genome Editing: Science, Ethics, and Governance
- The Issues Interview: Alta Charo
Transcript
Molly Galvin: Welcome to The Ongoing Transformation, a podcast from Issues and Science and Technology. Issues is a quarterly journal published by the National Academies of Sciences, Engineering and Medicine, and by Arizona State University. I’m Molly Galvin, a consulting editor for the journal.
Today, I’m joined by Alta Charo, the Warren P. Knowles Professor Emerita of Law and Bioethics at the University of Wisconsin-Madison for our next installment of our Science Policy IRL series where we’re pulling back the curtain to learn more about the community of people involved in making science policy happen by interviewing real people about their everyday experiences in the field. If you haven’t already, please check out our previous episodes below.
A lawyer and bioethicist by training, Alta Charo has decades of experience in helping to formulate and inform science policy on new and emerging technologies — from stem cells and cloning, to CRISPR and chimeras. She served on President Clinton’s National Bioethics Advisory Commission and was an advisor at the Food and Drug Administration from 2009 to 2011. She was also a member of President Obama’s transition team where she focused particular attention on transition issues related to the National Institutes of Health, the FDA, bioethics, stem cell policy, and women’s reproductive health. From 2021 to 2023, she served as the lead co-chair of the Safety, Security, Sustainability and Social Responsibility Unit of the U.S. Department of Defense. She is a member of the National Academy of Medicine and has served on more than a dozen National Academies study committees. She was also the inaugural David A. Hamburg Distinguished Fellow at the Nuclear Threat Initiative.
First thing I want to ask you seems like a basic question, but it could also be a very big question. How do you define science policy?
Alta Charo: Well, to give myself time, I’m going to say thank you for having me. It’s a pleasure to see you again. I think science policy has two sides of the same coin. One is the policy about how we are going to fund and perform scientific research and to deploy the results of that research. And so that’s really kind of the government role. The flip side of science policy is looking at the societal implications of what science can accomplish. And these are obviously related: what the government or the philanthropies choose to fund is influenced by what they’re hoping to achieve in terms of social effects. But they are different areas of analysis tend to call on different skills.
Galvin: Can you tell us how you got involved in science policy?
Charo: Well, I had a very confused childhood. I was fascinated both by the classic humanities, history and literature, and I loved to write. I wrote lots of really bad short stories. And I also loved science and I loved especially the kind of social policy implications of science. In the 1960s, we were in the middle of huge debates about nature versus nurture in the context of the civil rights movement. And so, I went to college originally, if you look at my freshman yearbook, announcing that I plan to double major in English and Mathematics and I compromised and I decided to major in Biology instead. And that turned out to be a very lucky choice because in addition to really liking the science, I lucked into classes on biology and social issues, biology and behavioral determinism, biology and evolutionary theory taught by people like E.O. Wilson and Stephen Gould and Richard Lewontin and Ruth Hubbard and George Wald. It was an incredible time to be watching these titans of the field debating one another in my classroom. So when I decided to use the biology degree more for social purposes than for basic science research, law became a tool more than a goal in and of itself. And so I don’t think it’s surprising I wound up doing science policy in many ways, although I thought it would be environmental policy and then it became therapeutics and reproductive genetics and such. It seems like there was always going to be a path that led to this place.
Galvin: You’ve been involved in advising on so many issues, including human genome editing, gene therapy, stem cell research, biosecurity. Can you talk a little bit about one or two projects that really resonated with you?
Charo: Sure. Let me mention briefly for each one I think three different things. So one has to do with stem cells and regenerative medicine. One of my best friends from childhood developed ALS (amyotrophic lateral sclerosis) when she was only 30 years old. And for the first six years of my time at Wisconsin, I flew back to New York very, very frequently to help take care of her and keep her company as she went through the six years of decline and paralysis before she died. And when the opportunity arose to take all the experience I had developed in the area of human reproduction, work on abortion policy and contraceptive policy at USAID (United States Agency for International Development) and the Alan Guttmacher Institute work on in vitro fertilization and surrogacy for the former Congressional Office of Technology Assessment and then academic research on so-called reproductive technologies.
It all came to a head when on my own campus, Jamie Thomson was immortalizing embryonic stem cells for the first time. And it was at the center of a debate that was about everything except embryonic stem cells. It was a debate about abortion. It was a debate about the role of women. It was a debate about the nature of personhood and human life, but it wasn’t actually about embryonic stem cells. It became a stand-in for everything. And it was clear we were at risk of having overreaction at the legislative level, at the state level or at the federal level, and that the scientific community would benefit from some consensus about how to proceed in this very tricky area. And I co-chaired the National Academies Committee on Embryonic Stem Cell Guidelines. And I do believe that the very extensive guidelines and continual revision of those guidelines that we developed helped to stabilize the field. And once there was a change in presidential policy on this with regard to funding, it also helped to shape the federal rules that now govern funding in this area. So, I feel like there was a very concrete outcome.
The second thing I want to mention is also something that came out of work with the Institute of Medicine and it’s not something that people talk about very much, but some of the research on preventing maternal to child transmission of HIV took place in parts of Africa where the American standard approaches simply were not feasible. They were too expensive. They involved too many visits and people were not actually showing up for prenatal care until very close to delivery. It was not going to work. And so there were tests to see which of these drugs that we were now working with could be used late in pregnancy in order to help save children’s lives. And it was a touchy area of research for all kinds of reasons, not the least of which is that women who were HIV positive were often stigmatized or even thrown out of their homes. They were at great risk. So you had to approach this research very carefully. And as a result, it was very carefully reviewed both locally and in the United States before it was started.
Despite that, there were critics of the research and complaints that in some cases, some of the paperwork to document these reviews had not been done. And there was the threat that some of the more successful interventions were going to be pulled out of the president’s PEPFAR (President’s Emergency Plan for AIDS Relief) program. And I was one of the people called in by Tony Fauci to review, yet again. this set of experiments and clinical trials in order to confirm that they were done ethically and that we could therefore use the results. And it was a very difficult task because were trying to recreate a lot of events that took place halfway across the world. And I remember sitting in the briefings and trying to point out that if you were sitting in an airplane and they forgot to do the checklist, they need to be disciplined because the checklist serves to reduce the risk of accidents. But if the plane still took off, it doesn’t mean that they didn’t actually fly the plane. And in this case, if they didn’t actually go through the checklist on the ethics reviews, it doesn’t mean that the experiment was unethical, but they do need to be told how to do it right the next time so that you reduce the risk of actually having an ethical experiment. And this turned out to be helpful in getting people to separate in their minds what the problems were from what the results should be. And I mean, it’s incredibly self-centered of me, but I do like to think that there are children that are alive today and healthy because I worked with other people to try to protect an area of research that had really concrete benefits for their mothers and themselves.
And the last is, I think going to be the genome editing report that again, I co-chaired. And here we were looking at a technology that was caught up once again in a conflation of debates around notions of reproductive autonomy and notions of eugenics and fears of eugenic eras and callbacks to World War II. And at the same time vast potential for advancing the diagnosis and the analysis and ultimately the treatment of a whole range of diseases and conditions. So our committee took this task very, very seriously. There were really very few guidelines to follow because the technology was so terribly new. I was fortunate that Jennifer Doudna had decided early on that she wanted to convene people to talk about this with her. She brought in Paul, the late Paul Berg, and David Baltimore who were veterans of Asilomar, and they put together a very small, very brief meeting in Napa Valley that I was included in along with Hank Greeley from Stanford as the two ethics people with scientists and journalists in a kind of mini replication of Asilomar.
And that set the stage in terms of having a background here and understanding that we needed to be very clear about separating heritable and non-heritable forms of this research. There’s a lot of science, regulatory science, needed to evaluate the science and its effects, but that we had the tools and that in the area of heritable that we had to actually challenge the comfortable consensus that you would never make heritable changes, a consensus that was developed at a time when you couldn’t do it. And to ask, is it absolutely ethically indefensible under every possible imagined circumstance to make a change that would be heritable? And after many months, we concluded the answer is no. But that finding such a circumstance and having the right preclinical evidence and regulatory apparatus to do it would be very, very hard to achieve. So we are miles away from doing it.
I think it was a valuable thing to trigger the regulatory apparatus around the world in every country to use their tools for somatic editing. And we are now seeing the success in approvals from the FDA of genome editing therapies that are profound and life-changing as well as being the victim of a business model that creates extraordinarily high upfront costs, may make sense over a lifetime, but we have to change the business model. And I think equally valuable was that we forced open the debate about heritable changes and force people to become more nuanced in their critiques and more precise in their predictions about the kinds of things that might happen if this were made available.
Galvin: You’ve been involved in so many of those different, really controversial, and very high level, important policy discussions. And most of the time it seems that your role is an advisory role. Could you talk a little bit about how that works as an advisor versus someone in the government implementing policy?
Charo: Well, I think I have to preface it by saying that even inside the government, many roles are advisory, including the roles I’ve played. I’ve worked for the Office of Technology Assessment as a staffer, and we wrote reports for Congress that were deliberately bipartisan and laid out options for congressional action that range from do nothing to do something dramatic and that were not geared to any particular political party’s agenda based upon our analysis of a technology and prediction of its effects and the advice of the advisory committees that we created. So there, the role as an advisor was to simply create in some great detail a set of options, but to let somebody else choose among them. So the great thing is that you become the people who really understand this business, but on the other hand, you have the frustration of not being able to express your opinion.
I worked for the US Agency for International Development. There, I was actually implementing. I was there as a AAAS fellow (American Association for the Advancement of Science Science & Technology Policy Fellow), which is something that people should definitely consider if they are thinking about moving from bench science to policy. And there, I was there to implement the executive policy in this case, having to do with access to family planning in Francophone Africa and Latin America. And I can tell you that there was at least one project I worked on, which I was not particularly fond of. I thought that the focus was unbalanced and reflected a set of priorities that I thought actually could backfire, but my job was to make that project work as well as possible, and that’s what I did. I wasn’t happy about that. And so I suppose it’s no surprise I wound up after the experience of not being able to express my opinion when I worked for Congress or not being able to actually follow through on my opinion when I worked for the executive branch, I went to academe where you could express your opinion all you want, very rarely having an effect on the world.
These are the trade-offs, right? These are the trade-offs. Once you get into academe, you either have to be so profound that you can become fundamentally influential. I mean, on the order of, you know, a Karl Marx starts an entire movement for the globe, or you can be fortunate enough to be plucked out to serve in these committee roles for the Academies, for government advisory committees. I served on President Clinton’s Bioethics Commission. And there you get to, once again, advise. Here allowed to express your opinion, because they’re getting you specifically for your expertise and opinions, but once again, having to then hand it off to see if somebody else will implement. Right. So on the Clinton Bioethics Commission, we wrote a number of reports with very strong recommendations for federal agency action to improve how human subjects research is done. They didn’t take all of our recommendations, but some of them they did, and some of them were influential on others, but there were other things where we were not influential at all. So we participated in yet another effort that’s been going on for many decades to have a better set of rules for research with people who’ve got impaired competence, like people who are developing dementia. And it has still never made it into public policy, formalized in federal regulation or funding rules. So it’s a lottery, whether or not your work will actually have an effect. And I think you have to just keep throwing that pasta against the wall, hope that some of it sticks.
Galvin: And how about working on these very controversial issues? Do you feel like you’re kind of drawn to those for any particular reason or is it just so happens that bioethics and biotech is such a huge issue in general that a lot of that does become controversial?
Charo: Yeah, I think it’s kind of the latter. I mean, we’re talking about biotechnology, life sciences technology, and so you’re talking about things that touch on what’s most personal to people. So I’ve worked on things having to do with human reproduction. I think that’s probably got the highest controversy associated with it because it is the most intensely personal thing that happens to most of us. I think that the work on, when I was at the FDA, I worked on, among other things, the approval process for engineered foods, bio-engineered foods. Again, highly controversial because food is something we all take into our bodies. It’s something that we feel intimate with because we touch it, we taste it, we make it, we grow it. And so even aside from its economic importance, there is just a kind of visceral sense that it is something that should be accessible to the ordinary person. If you’re going to talk about, I don’t know, a super collider, it’s just not something that most of us, myself included, can really understand and get emotional about because we don’t feel personally attached to it unless we’ve worked with one or we’ve been closely involved in the kind of research that depends upon its results. But the stuff I work on, because it’s about lives and food and babies and how we die and what it feels like when we get sick, these are things that everybody experiences. So everybody has an opinion.
Galvin: A lot of times when you’re involved in these projects, you are one of the few non-scientists in the room, and I was wondering if you could tell us a little bit about what it’s like for you to work so closely with scientists and how you have viewed that throughout your career.
Charo: I think that one of the reasons I’ve had as good a run for my money as I have in the area of science policy is I think science is cool, and I think scientists are cool. I see too many meetings where the non-science people around the table are either uncomfortable with or even somewhat suspicious or even hostile toward people who are embedded in the scientific world. And that just sets us up for failure. The fact that I think scientists are cool and that science is cool, doesn’t mean I think it should be done without any kind of public input, public guidance, et cetera. That’s not the point. But the point is you have to be on the same team, right? We have to both be rooting for the same thing, which is for science to flourish and do something good for the world. Now, how do we all get there together?
Both my older brothers became scientists. They’re both doctorates, one in bioengineering and the other one in physics. And so I grew up in a household where science was something that we talked about. My middle brother had a telescope and would bring it up to the roof of our apartment building and we would try to see the stars in the very overly lit Brooklyn, New York lighted skies. It was a very small apartment. I shared a bedroom with both my brothers. I remember late at night, it’s ridiculous, it’s coming to memory, late at night, and my oldest brother would be lying in the dark and he’d say things like, so if you’re sitting in a train and you throw a ball up in the air, how come you’re able to catch it instead of it just flying behind you while you keep going? And he was doing this to make me try to understand what he was already studying.
He was almost 10 years older than me. He was already studying physics and learning about the theory of relativity. Now I’m struggling to understand what happens in a train. So for me, it was a game and it’s part of what made the whole thing fun. So I don’t feel uncomfortable at those tables. Having the biology undergraduate degree and then having sat through so many scientific meetings and really trying to hear what they’re saying and to grasp as much as I can and to read the scientific journals, I feel like I’ve had a continuing education program, does not make me a scientist, but it has helped me to hear, understand enough to be able to figure out how that might affect something that I need to know about and to ask questions. I have to say that asking questions is probably the most important thing at the table.
Galvin: I think different people and different disciplines just think differently and questions that a scientists might be asking, sometimes they’re not thinking about the practical applications of science and the real world effects. One thing that we talk about a lot is how to bring the public perspective into these big questions for genome editing or stem cell research. We talk a lot about public participation. I wonder if you have thoughts about how we can really do that on a practical level, how to make the public part of policymaking.
Charo: Yeah, I have had some thoughts about that. Having sat through many different settings in which there’s some form of public participation, whether it’s the public hearings where people could testify before the Bioethics Commission or it’s sitting in an IRB meeting where you’ve got one public member who’s supposed to somehow represent the world out there. So a couple of things. I think the first is that it’s almost always a mistake to have one public member, one non-specialist member. It puts that person in a terrible position because somehow he or she is supposed to represent all other people besides the experts, and it can feel like you are being drowned out, and the conversation can also get away from you as it gets hyper-technical and all the people who are in the field start using their acronyms and they’re making references to experiments and you’re sitting there like, “What are they talking about?” And it can make you very wary about even participating.
So I think the first thing is that you have to have a critical mass so that you have a range of people who are the non-experts and also people who can help give each other kind of the emotional wherewithal to wade into this thing. The second is to be clear about what you’re expecting from them. And I’m going to draw now on the IRB experience because in a sense that’s also policymaking. And actually along with that, the same thing when it comes to this issue about how you talk to people about end of life care. I think it’s a big mistake to ask somebody, let’s talk about end of life actually. First, it’s a big mistake to ask somebody, do you want to continue antibiotics or do you want to be put on a ventilator? Because these are technical questions. What you really want to be getting from somebody who’s not a physician or a bioengineer is do you want to continue if it’s going to be painful? Do you want to continue if it means you’ll never leave the hospital? Do you want to continue if it means you will be attached to a machine for as long as we can tell? In other words, you ask people about how they want to live and then you tell them, well, if that’s how you want to live, then this is the machine that we should use or shouldn’t use, or this is the drug we should use or shouldn’t use.
In some ways, I think bioethicists have created a monster in the form of informed consent because they’ve now driven it to the point where there’s the sense that somehow the individual patient has to make all the decisions, but the whole reason that they’re seeing a professional medical provider is because they’re looking for professional advice. What the patient is an expert on is what the patient’s life preferences are, not on the tools that will achieve that.
Similarly, if you’re in a committee or in an IRB or something, I think what the public members are there to do is to bring back the human element. So you can have people, let’s say, talking about the genetic technologies that might reduce the severity of some early onset disease, but it’s the non-experts who may be the ones who are in the best position to say, let’s talk about the family dynamics. Let’s talk about how this affects the way in which somebody is going to grow up or their relationship with their siblings. This is not to say that I’m telling you you should do it or shouldn’t do it, or it’s good medicine or bad medicine, but let’s broaden the picture so that instead of treating bodies as if they are machines with a broken part, we recognize that human beings have both a physical and an emotional and a psychological component that has to all be considered together, and in that you can actually get help if it’s in a more kind of public policy, what should we be doing about biospecimen gathering, et cetera.
Again, the scientists will be able to tell you lots about what they could learn from the specimens and how that might be usable in this area or that area of research, but it’s going to be from the non-scientists that you’re more likely to have somebody talk about, well, what if somebody uses that for something that I think is horrible? I mean, what if they want to do, I don’t know, intelligence research, and I think that’s terrible stuff. I want to be able to say no to that.
Galvin: One question that we’re asking everybody participating in this series, and we’ve kind of already talked about this a little bit, but what are the big questions that motivate you to do this work?
Charo: Well, what motivates me is two things. I mean, one is this just kind of human curiosity that started back, as I said in the 1960s with the debates around nature and nurture and all that that led to, and the second is again, what I mentioned before, which is that really tragic six years of watching my friend die slowly from ALS and the frustration at the randomness of the universe. There’s no particular reason why she should have gotten this, and there’s no reason in the world that I can imagine that somebody should have to suffer like that. It’s one of those diseases that just makes you question the point of the universe. And the idea that anything I do like trying to save embryonic stem cell research and regenerative medicine research from being squelched by overreactive legislation, anything I can do that may help to make that situation something that’s only a matter of the past is incredibly motivating.
And so whether it’s testifying about the use of fetal tissue in research before Congress, or it’s in the work on regenerative medicine and genome editing for the Academies or the Bioethics Commission on sensible regulation of research, that doesn’t stop. It feels like I’m doing it, in a weird way I feel like I’m doing it all for her. The second is that I’ve been quoted this way before. I really do kind of divide the world into bio-pessimists and bio-optimists, and I’m a bio-optimist. I’m not foolish enough to think that technologies are all good, every technology is dual use. If we were to have imagined before there was fire, all the things that fire could do, we would’ve gone, wow, that’s great, and oh my God, that could destroy whole swaths of Canada and could send smoke flying all the way down to Washington D.C..
But overall, I do feel like science and technology can be gathered and made into a force for good and progress, and we do see life expectancies increasing, disease rates dropping, famine rates dropping. I mean, we live in a better world as human beings than we would have 20,000 or 10,000 years ago, 5,000 years ago. We just do. So I’m waiting for the world in which we use biology for so many more things. I’m waiting for the world where our buildings are not built out of bricks, but they are grown from the ground up, in which we have living skins that react to the external environment, in which our parks are lit by bioluminescent plants instead of eating up fossil fuel that increases the greenhouse gas problem, where foods are cultivated in ways that don’t involve the use of animals to the point of animal torture and are actually healthier for us anyway. I see this world of possibility. It’s probably the Star Trek coming out in me, but the thing that frustrates me more than anything else is that I’m now old enough to know that I’m not going to see a lot of this and I really want to be around to see it all happen.
Galvin: What role do you see science policy playing in making that innovation happen? How important is it and how can science policy be crafted to both protect people’s interests and protect from risks, but also maximize those benefits?
Charo: I think we’ve made tremendous strides in having a set of ethical principles and actual governing rules to protect people and the environment while we do scientific research. I do think we’ve made vast progress, not only in the United States, but around the world, in doing that. I think there’s a different challenge and it’s a more difficult challenge, and that is figuring out how to marshal the power of technology and innovation in a way that quickly makes its benefits more evenly and more equitably distributed among people and its risks and burdens more equitably distributed among people. We live in a largely capitalistic globe. That’s the dominant system, and it has had vast, vast benefits for us because of the way it has incentivized innovation. But, even the most purest capitalist economist will tell you that it’s not perfect and that there are places where you need to intervene in order to direct innovation and human efforts in ways that the profit motive will not, at least not initially.
And so the National Academies has embarked on an effort to look at ways that we can better embed ethical principles into the innovation process, and recently released a report specifically on embedding equity into the innovation life cycle and looking at ways that government and funders, including nonprofit funders, as well as the individual scientists and the private equity, all of them, can be thinking early on about ways either to direct research with an anticipation of how to make sure that its benefits are going to flow out more equitably or to create parallel lines of research. Now, I’ll give you a very concrete example. At the Second International Summit on Genome Editing, we were already hearing about the possibility of developing a treatment for sickle cell disease. Now, sickle cell disease is endemic in West Africa, although we have plenty of it here in the United States, especially in the African-American population, and the technology was going down the road of an ex vivo methodology. You take cells out of a human body, you edit them and you put them back in the human body. It’s incredibly difficult, can be very painful, very expensive, requires very elaborate facilities, et cetera, but it made more sense because it gets away from the problem of trying to do something in the body without the genome editing going wild and going into organs and systems you don’t want it to go in. It makes sense to do that research.
The Gates Foundation was thinking, well, we need to have a parallel line of research that will slowly get us to the point of, so-called in vivo editing where you don’t have to do all that because otherwise it’s unlikely that we will ever be able to see this work in places like West Africa who have far fewer medical facilities. That is the kind of thinking I think we need to encourage so that we can all see the benefits of science flowing out to as broad a population as possible as early as possible, and in that sense, I think that we can really help to promote science policy for the public’s benefit.
Galvin: Alta, it’s been such a great conversation. Really appreciate you taking the time. Thank you so much for joining us.
Charo: Oh, it was really my pleasure. You’re very welcome.
Galvin: If you would like to learn more about Alta Charo work, check out the resources in our show notes. Is there something about science policy you’d like to know? Let us know by emailing us at [email protected] or by tagging us on social media using the hashtag #SciencePolicyIRL. You can subscribe to The Ongoing Transformation wherever you get your podcasts. Thanks to our podcast producers, Sydney O’Shaughnessy and Kimberly Quach and our audio engineer Shannon Lynch. I’m Molly Galvin, contributing editor at Issues and Science and Technology. Thank you for listening.