Roundtable: The ethics of human enhancement

What is a patient’s baseline and how does that affect how we think about treatment vs. enhancement?

Dan: This is framed around a series of hypotheticals - the major question being, how do we deliver treatment; and how do we distinguish between treatment and enhancement, and how does that affect the science that we do?

Rahul: A wild Kait appears! Are you coming in from clinic?

Kait: [very obviously wandering around a hospital lobby] Yes.

Dan: Alright, let’s get into it.

Hypothetical 1A: ​​Mr. Smith is a 64-year-old man with a 40-pack-year smoking history and COPD (on 2L of home oxygen). He was admitted to your service three days ago for worsening shortness of breath (up to 4L of O2), cough, and sputum production. Following treatment with nebulizers and azithromycin, he is now back to his baseline level of oxygen.

Dan: I feel like this is a very typical medicine story - I’m not even sure there’s much to discuss here. But let’s look at the second hypothetical:

Hypothetical 1B: Mr. Smith is a 64-year-old man with a 40-pack-year smoking history and COPD (on 2L of home oxygen). He was admitted to your service three days ago for worsening shortness of breath (up to 4L of O2), cough, and sputum production. Following treatment with nebulizers and azithromycin, as well as diuresis, he is now off oxygen with good oxygen saturation.

Dan: Is this something that anyone has ever seen in the hospital - someone with a home O2 requirement come off oxygen?

Rahul: I have seen that, but the person probably needed oxygen and just refused it.

Dan: Regardless, I feel like so much of medicine is about baselines; we are aiming to get them back to baseline rather than improving their baseline.

Preston: Do you feel like that is because we spend so much time in the inpatient setting in training as opposed to seeing folks in the outpatient setting?

Carla: I think that’s a great point. Inpatient is different than outpatient.

Dan: True, but I think that even in the outpatient setting, most of the guideline-driven treatment is at least in some ways proactive, while most of the medicine that I actually practice during clinic is reactive. A patient comes in with a concern, and I am trying to get them back to baseline.

Carla: The immediate thought that I have is that most of the medicine that we practice is indeed reactive, but with something like GLP-1s, it is much more proactive. We are entering an era where we really are trying to bring people past their baseline - like trying to generate a new baseline for our patients.

Deb: I agree, I think that’s a great example of doing more than we would have done before. Aging is also another example, with anti-aging treatment. There is this whole slew of research about prolonging life and prolonging fertility - do you consider that enhancing? A similar consideration might be for dermatology, something such as botox.

Rahul: But that, delaying the aging curve, that is really not that different than returning to baseline. We are preventing the bad changes that are associated with aging.

Carla: I think Botox in some ways fits into that category as well - for most people, it is really about anti-aging.

Kait: What about transplant? You are going back to a baseline before you had the disease. Theoretically you are bringing someone back to their baseline, but the rate of change seems to matter as well.

Deb: I think that the organ transplantation example is a good one to point out, that perhaps we focus on improving from a baseline because of resource and knowledge limitations. To take liver disease, we are not very good at preventing complications and death from advanced liver disease, so maybe it is fair that we are focusing on deadly disease before shifting our attention to “enhancing humans”. We would not give someone a super liver before we are able to give someone with a sick liver a chance. Though maybe this might change with the ability to transplant non-human organs to humans [1].

Dan: Jumping to gene therapy, taking gene therapy for sickle cell [2], is there some fundamental difference between doing this for an embryo versus a child? There doesn’t seem to be a fundamental ethical difference between correcting this disease in utero vs. in vivo. Or similarly probabilistically trying to conceive a child that did not suffer from a hemoglobinopathy.

Rahul: I do feel like there is a difference - there is something about the probabilistic nature that removes some of the intentionality, some of the causality.

Deb: I think that the probabilistic thinking is really a psychological trick, that fundamentally there is not a significant difference between these scenarios.

Rahul: One thing I do want to flag when asking why we don’t do more augmentation is that it might just be really hard. People are probably working hard to make super soldiers.

Dan: To jump ahead:

Hypothetical 2A: Mr. Pidcock is a 45-year-old man w/ a PMH of severe burns secondary to a kitchen accident 10 years ago. He has multiple keloid scars. He presents today to your clinic as he wishes to undergo laser therapy.

Hypothetical 2B: Mr. Pidcock is a 45-year-old man w/ a PMH of severe body dysmorphia. He presents to you today in clinic as he wishes to undergo laser therapy for perceived disfiguring scars that are not apparent on exam.

Hypothetical 2C: Mr. Pidcock is a 45-year-old man w/ no significant past medical history. He presents to you today in clinic as he wishes to undergo laser therapy for resurfacing of his skin in order to appear more youthful.

Carla: I feel like this hypothetical, particularly for the gentleman with body dysmorphia, really points to our feelings about nonmaleficence. I think we do know that doing procedures on someone with body dysmorphia can worsen that psychiatric condition or would lead to the point where we are harming them. The other two I think are easier.

Preston: I think the problem with 2B is that we are not treating the underlying cause. We should be treating body dysmorphia as a psychiatric condition. The intervention would not help them.

Dan: I would say that, as a medical community, we give lots of interventions that are either not data-driven or probably non-inferior to placebo.

What is the role of augmentation in athletics, and how does that differ from “natural” ways of improving performance?

Hypothetical 3A: An athlete comes to you for EPO versus (3B) an athlete comes to you for a hyperbaric oxygen chamber. Is there a difference between these, assuming that the risks are pretty similar?

Rahul: I think that sports are quite different than the other hypotheticals. We as a society agree (and this might also apply to a discussion around intellectual ability to some extent) that we want to see the best that nature has to offer, and so we want sports to be free of exogenous supplementation. If people do this stuff through brute force of will, that is evidence of someone’s natural talent.

Preston: I think I agree with most of that. We are, though, ok with athletes spending a ton of money to surround themselves with a team. Fundamentally, what is the difference between that and Epo shots - someone spending thousands of dollars a year on a physio team and coaching team? We do like this idea of people competing and pushing themselves, but to some extent it’s not just their own biology. We are, for some reason, more ok with spending money than with medications. What makes that different?

Rahul: You’re saying that people are, effectively, augmenting themselves.

Kait: I agree - there is an interesting tension. I wonder if something has to do with the rate. It feels unnatural that you can immediately boost some talent, where we really feel like you need to suffer for some amount of time to get that reward.

Preston: Even if you do surround yourself with a great coaching team you still have to put in the legwork.

Rahul: I do think that’s one of the reasons why people love Kobe Bryant; because of that grinding mentality. He was always grinding, and people looked up to that. A lot of people can be very good at certain sports. Another interesting case is bodybuilding, where a lot of people take steroids - that’s not a widely loved part of the sport.

Carla: Bodybuilding is an interesting example. People now are very open to being “natty” vs. “non-natty” that has now become part of the sport and so it really is ingrained in the culture.

Rahul: That’s true, so now the competition is really stratified based on taking or not taking steroids.

Dan: Natty vs. not natty is interesting - it almost comes back to the cosmetic aspects of enhancement. So much of bodybuilding is about appearance and performance, and so maybe it’s almost less about the sport and about shaping or sculpting your body to look how you want it.

A related argument is about natural variation being itself very imbalanced in the population - athletes like Pele have a cardiac output that is far greater than other athletes.

Rahul: Who is that?

Dan: One of the most famous soccer players, don’t worry about it. Tadej Pogacar, if that makes more sense to you.

Preston: It’s hard to argue that there isn’t some component of genetics or natural giftedness, since if you look at the top level of a sport, like the 100th best tennis player vs. the best tennis player, it is generally not the case that the 100th best player is trying less hard or working less hard. Is it more unfair for someone to be gifted with natural talent vs. someone taking Epo? Why is that less morally grey - they didn’t work hard for the genetics? We see it as OK to be born with natural talent but not ok to augment with Epo.

Kait: For some reason, as part of the human experience it feels very different - theoretically everyone can run outside, but not everyone has access to Epo.

Rahul: Humans love competition - a lot of society is competition. Social hierarchy is based in competition. It does not depend on everything being fair, but the nature of competition is that it can take any bell curve, no matter the absolute standard of deviation, and expand the observed dynamic range. This is like the differences between the worst NBA player and the best - the NBA is a league created to magnify these very small differences on the bell curve. The rules of sport are designed to generate winners and losers.

Preston: It reminds me of Roger Federer giving Dartmouth’s commencement speech[3]. The point that he was making is that he has only won 54% of his points throughout his career but won almost 80% of his matches.

Rahul: Exactly. I don’t buy this argument that enhancements will equalize people. Society will exaggerate differences between us.

Dan: In a world where everyone is between 6’ 1” and 6’ 5”, the 6’ 1” people are still short.

Kait: One related hypothetical - in the sport sense, everyone is competing against each other. Let’s say that we are preparing for an alien invasion and we want to create the best possible human. Would we be ok performance enhancing beyond the natural bell curve because we feel like the benefits outweigh the harms?

Rahul: I do feel like people love an exoskeleton. If there was an Iron Man suit, I think society would eat it up.

Carla: Should we take a general poll on who is for and against enhancement?

Kait: I feel like it depends so much on the context.

Carla: Why does it depend on the context?

Kait: I don’t have a great framework for this, but I think it depends on both the side effects and the benefit.

Carla: Let’s say that there is a risk - like braces. There is a minimal risk.

Preston: Or maybe even coffee. There was a recent paper that came out that showed that, for coffee drinkers, continuing to drink coffee reduces the risk of recurrent Afib[4].

Rahul: That goes against everything I know.

Carla: Kait, let’s talk about an example - a treatment that brings you back to baseline without side effects, versus a treatment that brings you above the baseline. The latter seems bad to you even if there are no side effects?

Kait: I guess if there are no side effects then I’m ok with it.

Dan: The flaw in the general logic relates to cosmetics.

Carla: I think that there is significant stigma related to cosmetic procedures.

Dan: True, though I don’t think we view it as an ethical wrong.

Carla: I think that some people do view it as an ethical wrong. People make the argument that it is bad for society if, say, Rahul has cosmetic surgery and therefore skews your view of beauty.

Experimentation and augmentation - does the provenance or motivation of augmentation change whether we find it acceptable?

Dan: Let’s jump into a random set of hypotheticals.

Hypothetical 4A: A researcher is working on trying to understand the role of alpha-synuclein in alpha-synucleinopathies such as Parkinson’s. In doing so, he finds a single nucleotide variant that, when introduced into mice, greatly improves their Morris water maze time.

Hypothetical 4B: A researcher is working on trying to understand the role of heritable intelligence. In doing so, he finds a single nucleotide variant via GWAS that, when introduced into mice, greatly improves their Morris water maze time.

Dan: Are these fundamentally different scientific questions with different ethical considerations?

Rahul: Maybe the subtlety here is lost on me.

Preston: In the first one, you find it unintentionally, while in the second one you are working on enhancement. I think I fundamentally don’t like when people are working on heritable intelligence.

Rahul: A large part of that issue is that we don’t have a good quantification for “intelligence.” If there were a good metric, I think it would be ok to work on that.

Carla: But there are lots of quantifiable metrics that exist already, like reading speed. What if a researcher wanted to work on understanding the genetic basis of reading speed. It wouldn’t be passing judgement on whether or not someone is intelligent.

Rahul: My issue is not with the label; my issue is that the metrics used for this (IQ, educational attainment) probably are at least partially heritable; which then people use as an argument that these are real biological characteristics. I do think that in science, the outcome can matter more so than the path - so to me, these are very similar.

Dan: Let’s say that this researcher is studying IQ, finds this gene, and shows that there is a quantifiable difference in the outcome. To me, the fact that the outcome is meaningful does not justify that the scientific question is garbage. Just because you got a good answer doesn’t mean that the process was justified (or even that it made any sense at all).

Rahul: Like the discovery of lithium [5]. They thought that some ions in urine might be important, and so they trialed lithium.

Preston: The reason why the work on heritable intelligence is problematic is that it is not necessarily just the intrinsic problem with the science itself; it’s the societal implications of it. A lot of the findings are co-opted by people who, almost regardless of the science, will invariably use these findings to make arguments about race. This kind of research does lead to societal effects that are inevitably bad for society.

Dan: I agree. I put in another hypothetical that we can discuss.

Hypothetical 5A: A food scientist, working for a large multinational corporation, uses cross-breeding to select for an apple varietal with similar taste, but with a much longer maturation cycle throughout the year.

Hypothetical 5B: A food scientist, working for a large multinational corporation, uses a CRISPRi screen to identify genes that increase the rate of apple growth at low temperatures. He eventually identifies a gene with that phenotype, introduces it into the strain, and finds that it leads to a varietal with similar taste but a much longer maturation cycle throughout the year.

Hypothetical 5C: A food scientist, working for a large multinational corporation, uses a CRISPRi screen to identify genes that affect apple flavor. He eventually identifies a gene with that phenotype, introduces it into the strain, and finds that it leads to a much more flavorful varietal.

Hypothetical 5D: A food scientist, working for a large multinational corporation, uses a CRISPRi screen to identify genes that affect apple color. He eventually identifies a gene with that phenotype, introduces it into the strain, and finds that it leads to identical apples with a rainbow of colors.

[everyone agrees that all of these are fine]

Rahul: I actually think that the step I find most concerning is the A to B. The use of CRISPR is the biggest risk. Though that’s fundamentally a scientific risk, rather than an ethical question.

Kait: Going back to the intelligence - cross-breeding vs. genetic editing feels similar from an ethical perspective. But going back to the intelligence - I do think that there’s some fundamental difference between say, genetic editing, and a new behavioral intervention that leads to the same outcome. Between those two things, the behavioral intervention feels more ok to me.

Rahul: I wonder if it’s true that the variance matrix of where breeding goes is such that the most probable outcomes are fine. The way that variation is introduced at random with a CRISPR screen could be outside the norms of what is tolerable evolutionarily. Maybe it’s more likely that those would be harmful. Maybe in cross-breeding you assume that the process is “natural” and so there is less likelihood of toxicity.

Dan: I feel like this is an argument for evolutionary optimization. Just because something is an apple and another thing is an apple doesn’t mean that they are optimized to prevent production of toxins. We know they don’t make toxins; so the argument there is that when you take two things that don’t make toxins and cross them, you are less likely to make toxins. But apples are not perfect; we can build a better apple.

Preston: Like Honeycrisp.

Carla: Or Evercrisp. [When asked if Evercrisp apples are better]. No, they taste the same.

Carla: It seems like we are getting bogged down in methodology. What is the point you are trying to get to?

Dan: Is there difference between academic and commercial science? Both in the sense of regulation and safety, but also the idea that commercial interests are trying to optimize the world through science.

Carla: I think the apple and intelligence are very different.

Dan: There was a presidential council on ethics in 2003 [6] where they made the point that physicians stand as a barrier between biomedical technologies and patients. The flaw here is that we have (1) tremendous trust in the biomedical system (maybe more true in 2003 than now) and (2) we have a tremendous trust in capitalism, that it is generating good ideas and outcomes for the world. The system is thus set up so that the only barrier between an individual and a treatment is the doctor. As you move into the world of enhancement, the person who is deciding if someone deserves to be enhanced is the doctor.

And so maybe one difference between CRISPR and the apple is that at least there is a person; a doctor; standing in between. Regarding apples, there is no person being thoughtful about implementation.

Carla: Maybe the incentives are more perverse because they are trying to make money. There are regulators though, like the FDA.

Rahul: Maybe the regulators are like the doctors in that scenario.

Dan: In some ways, biotechnology is very poorly regulated. We as doctors can prescribe any medication for any indication.

Carla: Presumably we as doctors are trained to do evidence-based medicine. Our training is such that we should be the gatekeepers.

Rahul: But also evidence-based is also a flawed concept; there are so many situations that do not have an evidence-basis.

Carla: I take great solace in that. There are many correct answers - that is the art of medicine.

Kait: I think we are mainly practicing norm-based medicine rather than evidence-based. If someone came in septic and you gave a sugar pill, that would not be a reasonable move. Regarding enhancement, perhaps it’s that there is not really a norm around enhancement, and so we reject it out of hand. But if we lived in a society where there were more norms around enhancement.

Dan: There’s this argument around whether we should be doing science that allows us to enhance. A lot of this centers around “dual-use” science - science that we do that is in theory to treat a medical condition, but is in reality around enhancement. When you do enhancement, you buy into this argument about the perfectability of humans. By arguing that there is a “better,” you argue that there is fundamentally a “worse.” You are attempting to genetically optimize a human.

Dan: Rawls made a similar argument writing in the 1970s - as a society, we are perfectionists. We are always selecting for descendants that are better than us. A direct corollary of this - if you think that parents have a duty to have their children do their best, then parents have a duty to enhance their children.

Rahul: To the conversation we were having earlier, commonly we hear about immigrant parents that come to the US that spend all their money on tutoring for their children. Is that perfectionism? That’s essentially paying money to enhance your children to succeed in society. We all feel like that’s fine.

Dan: Why do people not feel fine about somatic genetics?

Carla: There is something fundamentally changing about who you are in a genetic sense.

Preston: Isn’t who you are not just your genetics but also your lived experience, your abilities, your environment in general?

Kait: I wonder if part of it is the magnitude difference. One tutoring session is not as big as one gene intervention. Part of it is our ability to predict that something is actually beneficial. A change in your genes is a large change and could have very large effects; one tutoring session is unlikely to have adverse effects. Tutoring feels more reversible in some ways.

Dan: It’s more of an autonomy argument then.

Kait: Autonomy yes, but also reversibility. Consequences that we don’t fully appreciate.

Genetics and augmentation - what are the ethical considerations for genetic manipulation in augmentation?

Dan: Let’s take a vote. This came up at a Crick Society meeting - what geneticists in the field feel is justified ethically. It’s actually a scale, but we’ll just vote yes/no. The assumption here that the risk is all the same.

Do you think somatic treatment for a genetic condition causing physical disability is ethically allowed?

[Everyone votes yes]

Rahul: Just to clarify, this is for somatic mutations? Then yes.

Preston: Why would that affect your decision?

Rahul: I think there’s a consent argument here somewhere; now you are making decisions that affect future offspring.

Carla: But an argument by induction would say that the same logic applies to the next generation.

Rahul: It’s a really interesting point, though I still think you need a higher bar. The effect of germline mutation could have an immense societal impact. Even assuming that the risks are the same.

Preston: In a society where we allow parents to consent for their children, you would also want your kid to be treated now.

Do you think somatic treatment for a genetic condition causing intellectual disability is ethically allowed? For improvement of appearance? For improvement of physical abilities? For improvement of cognitive abilities?

Kait: I would say yes to everything if somatic. Even cognitive and physical abilities.

Preston: I would say yes to all of these except for maybe 3.

Rahul: Arguably 3 is the one that we actually do in society, at least as doctors. Many things we do improve cosmetic appearance.

Carla: Where I’m getting hung up is will this be universally accessible and the answer is no. Though that is true of basically all of our healthcare now (including, say, statins), and so I’m not sure why this would be fundamentally different. I would say yes to all 5.

Kait: I change my mind - no to appearance.

Rahul: My gut is yes to the first two and no to the last three. But I can’t find a good argument for why that would be true.

Dan: I think I’m closer to Preston - maybe on 3 and maybe on 5. Something about the genetics of cognition that I cannot necessarily justify.

Preston: I think because we live in a world in which cognition is more rewarded in our society.

Rahul: People also argue that GLP1 agonists allow people to be more productive by reducing food noise. That surely also improves your cognitive ability. Maybe 5-10 years from now such a medication exists - that reduces extraneous thoughts and allows for improved focus - it is hard to imagine that medication not being approved. Similarly, we worked as a society to eliminate lead.

Kait: I think that appearance and cognition feel like they have a greater risk of perversion. Regarding appearance, what about things that affected the skin color of their children. Similarly, what if you could engineer everyone to be incredibly bigoted. This would have a huge impact on society.

Dan: Related to enhancement, have you guys heard of the “Enhanced Games?” [7] There was founded by a guy in Australia who wanted to make a sporting event where people would break records while taking performance-enhancing drugs.

Carla: I think this is very compelling for some reason.

Dan: I find it compelling for two reasons. (1) I would like to see the limits of human performance. And (2) the IOC is very puritanical - the reason why we don’t want people to do PEDs is because PEDs are bad for you. But the fundamental premise that all things that enhance you are bad for you in some way that is not outweighed by the benefits seems illogical. As long as people understand those risks.

Kait: I agree.

Preston: I was mostly thinking about this from a safety perspective - though if people are aware of the side effects, I guess that it makes sense.

Carla: Are you against body-building?

Preston: I don’t like it but I’m not gonna stop people from doing it.

References