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Can Human-Grown Organs De-Liver?

photograph of surgeons conducting procedure on operating table

Despite the majority U.K. shifting from an opt-in to an opt-out donation system, there is still a vast shortage of viable organs. According to NHS figures, there are currently over 7,000 people on the organ transplant waiting list, and just last year 420 died because a suitable organ was not available. And this is not just a U.K. problem. Similar shortages occur across the EU, the U.S., and Canada. In fact, the organ shortage problem is global, with most countries reporting a deficit between the number of donors and the number of hopeful recipients.

Writers at The Prindle Post have already explored and critiqued some solutions to this problem, including harvesting organs from the imprisoned, 3D printing the necessary body parts, xenotransplantation, and paying people to donate non-vital organs. Last month, I wrote a piece about OrganEx, a novel technology that might reverse posthumous cellular damage, thereby making more organs viable for transplant.

But hot on the heels of that innovation came news of an upcoming trial by biotech company LyGenesis, a trial which might have truly radical implications for the organ transplant landscape. In short, the company will try to grow new livers inside the bodies of people with end-stage liver disease.

This is wild in and of itself. But it gets better: twelve volunteers will be given increasingly potent doses of the treatment over the trial period until the final study participants will potentially grow not just one but five mini livers throughout their bodies.

While still highly speculative, the potential to grow livers, or even other organs, within the body of the hopeful transplantee could dramatically reduce global demand. People would no longer have to wait for a whole organ to be available. Instead, they could grow a new one. This would improve health outcomes, ease pressure on healthcare systems, and ultimately save lives.

The procedure involves taking healthy liver cells from an organ donor and injecting them into the lymph nodes of the sick recipient. As the nodes provide an excellent environment for cellular division and growth, the team at LyGenesis believe that the transplanted liver cells would start to divide and grow within the node, eventually replacing it.

Over time, the transplanted cells would develop into one or several miniature livers and start compensating for that person’s damaged original.

The team have already conducted animal trials over the last ten years, growing mini livers in mice, pigs, and dogs, and now believes it is time for human trials. Each trial participant will receive regular check-ups over the following year to ensure doctors pick up on any adverse side effects as soon as possible. In total, the study should take just over two years to complete. If the trial goes well and the results prove promising, LyGenesis plans to implant other cells and grow other types of organs.

But, the donor cells have to come from somewhere – the team do not magic them into existence. The source of these cells will be, unsurprisingly, donated livers. So, organ donation will still be needed even if the trial proves to be 100% effective. However, the proposed technique could vastly increase the number of sick people a single donated liver could help. Currently, when a perfectly healthy liver is donated posthumously, it is split into two, and surgeons implant each half into a different sick person. As such, one liver can help up to two people.

However, the LyGenesis researchers believe that, because only a (relatively) limited number of cells is needed to start the organ growing process, they could get up to seventy-five treatments out of a single donated liver.

Arguably, the LyGenesis cell transplant technique should be the first port of call regarding ethical organ donation processing, as helping more people than less is ethically required.

Now, the prospect of growing organs rather than harvesting them from altruistic donors has been around for several centuries in the dream of xenotransplantation – taking tissues and organs from animals and putting them in people. In fact, the first recorded attempt to use animal material in a human’s body was in the 17th century, when Jean Baptiste Denis transfused lamb’s blood into a patient to surprisingly little harm (i.e., the person did not die). Since then, harvesting animal tissues and organs for human transplantation has become more sophisticated, with scientists employing genetic modification techniques to improve the compatibility of organs and recipients.

However, xenotransplantation comes with a whole host of potentially intractable ethical issues. These include the potential dangers of zoonotic disease transmission (which caused David Bennett Sr.’s death), animal welfare concerns, and reflections upon our ever-increasing capacity to alter the natural world around us for our needs.

When compared to these ethical objections, LyGenesis’ human-growth liver technique seems justifiable on human-interest grounds and on a broader range of bioethical considerations.

Not only does it seemingly have the potential to maximize the net benefit each donated liver can provide, but it also helps avoid many of the issues that come part-and-parcel with growing human organs within non-human animals.

For example, there is no worry about cross-species disease transmission as all the genetic material involved is human. Similarly, beyond the animal’s use in the research, there is no worry about organ farming producing suffering on a comparative scale to the industrial farming complex. Questions regarding our ability to alter the world around us and, in essence, play God remain. However, such criticisms can be levied by critics against practically every medical procedure used today and, as such, fail to be specific to the topic of organ farming. Indeed, complete devotion to such a stance would seemingly paralyze an individual to complete non-action, as everything we do can be interpreted as playing God in one form or another.

Ultimately, while still very experimental, LyGenesis might be on the right track to tackling the organ donation shortage, at least in liver disease cases. Time will tell whether growing organs within one’s body is the way forward. However, compared to the potential issues xenotransplantation raises, human grown livers certainly seem to have a distinct ethical advantage.

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Rise of the Human-Animal Hybrids: The Ethics of Xenotransplantation

black-and-white photograph of pig in a cage

On January 7th, 2022 David Bennett was implanted with a pig heart. His doctor was not Moreau, but rather Muhammad Mohiuddin, a surgeon at the University of Maryland Medical Center and expert in xenotransplantation – the implantation of animal organs into humans.

While pig parts have been used medically for decades, such as the use of pig heart valves as replacement valves, the implantation of a whole organ is an incredible clinical achievement. The donor animal is genetically modified and raised in careful conditions to minimize the chance of pathogen transmission and rejection, that is, the human immune system attacking the heart as foreign tissue. Whole organ xenotransplants been performed before, but without effective technology to prevent rejection, results have been bleak.

The life-saving surgery was done under special FDA authorization given the lack of other options. How Bennett will fare long-term remains unclear, and like most transplant patients he will need to take immunosuppressant drugs even with the genetic modifications done to the pig. Transplant patients are followed for both physical and psychological concerns, as the feeling of becoming hybrid or chimera, or taking up aspects of the donor, is well established, and may be especially acute in xenotransplantation. (Regardless of the physiological legitimacy of this feeling.)

The organ donor list is long in America, and the supply of organs short. Xenotransplantation represents a potential lifeline for thousands of patients in need. Nonetheless, as amazing as new xenotransplantation technology is, it comes with longstanding ethical concerns.

Modern medicine heavily instrumentalizes animals, their bodies becoming objects of research and testing, and now harvested for organs. From an animal welfare perspective, xenotransplantation is clearly not good for the pigs – although perhaps not any worse than factory farming. Xenotransplantation research also involves extensive use of non-human primates, especially baboons, as they are considered the best animal model to test the viability of cross-species transplants for humans.

Beyond animals, xenotransplantation research makes use of brain-dead humans as test subjects. Death is a tricky designation, and some people, while deemed dead from the perspective of brain death, are nonetheless biologically stable enough to support a transplant for some period of time. In September of 2021, for example, a genetically modified pig kidney was attached to a brain-dead woman and supported for 54 hours. The idea is that data like this is of more relevance to human recipients than that from baboon trials, although the condition of the test subjects renders it all but impossible to do longer term studies. Such research practices invoke complex questions about human subjects, and the status of brain death. The very idea that the body is declared dead, yet somehow alive enough to test organ transplantation, challenges our intuitions. And for communities for whom the body or the breath are more important in the designation of life and death, brain death is a thin justification for such research.

These research practices may be defensible, but they should be done carefully, with attention to the animal welfare implications, the alternatives, and the expected benefits of xenotransplantation. This ethical question is made more complicated by the empirical fuzziness, for we do not yet know what the clinical payoff might be.

The more sensational ethical concerns of xenotransplantation research come from the ick factor. One can all too easily imagine Jeff Goldblum informing Dr. Mohiuddin that he is playing God, and that humans should stay well away from the creation of chimeras.

From a scientific perspective, this is tricky. Humans are never pure. Not only are humans, like all organisms, a cobbled together pile of old parts assembled by evolution, but even during the course of our life we are a blend of different species. Just ask the 100 trillion bacteria living inside your gut.

Nonetheless, this is all at least “natural,” whereas xenotransplantation most certainly involves some kind of additional level of “unnatural” intervention. There are two ways, I believe, we can make this concern more precise.

The first involves an express embrace of the sacred or the natural. For example, a Christian theological perspective in which the body is explicitly treated as sacred, may provide clear grounds for ethical objection to xenotransplantation. This may be an even greater concern in Jewish and Muslim communities with their specific injunctions against the eating of pork, although some Jewish and Muslim religious authorities have been open to uses of porcine parts when clinically necessary.

The limitation of this approach is that it argues against xenotransplantation based on the acceptance of specific religious or spiritual premises, or ontological claims, about what is natural, as opposed to general ethical principles.

The second characterization of the concern is about the implied values. Xenotransplantation embraces a conception of medicine such that all research and interventions are okay as long as they are ultimately in service of prolonging life. A more humble ethical framework, one that is more accepting of death, may not value xenotransplantation to the same extent. The Harvard political philosopher Michael Sandel has developed a perspective of giftedness regarding intervention. His idea is that we should not strive for mastery of every aspect of our biology, but should be open to the arbitrariness of life as something which makes it worth valuing. Sandel, to be clear, is not against healing, and believes that healing disease helps our natural capacities flourish. But where we draw the line is fuzzy, and one possible objection to xenotransplantation is that it fails to appropriately acknowledge the messiness of life and the ways to cope with that, and instead is highly technocratic, seeking mastery and intervention. (At the expense of animal life.)

Finally, xenotransplantation is new, expensive, and technologically demanding, and ethical issues will no doubt arise in the specifics of implementation. How should it be handled with insurance? How should patenting work? Who deserves access to these organs? For instance, concerns have been raised about Bennett who was guilty of a 1988 stabbing. Organ donation in the United States is administered by the United Network for Organ Sharing (UNOS) and policies are in place to facilitate the equitable distribution of organs. Although even these are imperfect, and wealthier, better-connected patients can use strategies like signing up at multiple transplant centers to receive organs faster. How whole organ xenotransplantation will fit into the existing scheme is not yet clear, but should be done in a way that preserves as far as possible equity of organ donation.

Personally, I worry an overly restrictive ethical response would be premature, as we are still in the research stage with xenotransplantation and therefore have an unclear decision to make from an outcome perspective. David Bennett’s case may be important for public perception, but as a single instance, it is limited in how scientifically informative it can be. Nonetheless, we should continue a parallel conversation about animal welfare, research ethics, and highly interventionist medicine. And above all, we should avoid celebrating a medical marvel as an ethical one without careful reflection.

 

Note: David Bennett died March 8th, 2022, two months after the procedure.

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The Heartless Matter of Organ Transplantation and COVID Vaccination

photograph of surgery

Boston’s Brigham and Women’s Hospital has removed one of its patients from its transplant list because he refuses to get the COVID-19 vaccination. 31-year-old DJ Ferguson, who suffers from a hereditary heart issue that causes his lungs to fill with blood and fluid, had previously been prioritized for a life-saving heart transplant. However, according to his family, he has been removed from the transplant list due to his vaccine hesitancy. DJ’s father, David Ferguson, said, “[i]t’s kind of against his basic principles; he doesn’t believe in it. It’s a policy they are enforcing and so because he won’t get the shot, they took him off the list [for] a heart transplant.” DJ’s family are currently considering moving him to another facility but are unsure whether he would survive the trip.

The fair distribution of scarce resources has been an issue throughout the pandemic. For example, in its early days, there was considerable discussion about distributing life-saving ventilators when the number of people needing them outstripped hospital reserves. States such as Alabama, Kansas, and Tennessee all produced guidance recommending, suggesting, or explicitly stating that a patient’s disability status could be considered a reason to withhold — or even withdraw — ventilation. In other words, they deprioritized the disabled in favor of the non-disabled. This problem has, to a degree, eased with the development of effective vaccines and the production of more ventilators.

However, unlike ventilators, we cannot simply manufacture more bodily organs, such as hearts (at least, not yet). The supply of hearts is dictated by how many people donate them. Unlike other donatable organs, like kidneys or livers, donating a heart isn’t something one can do as a kind act during their lifetime. If you’re donating your heart, you’re already dead. As such, hearts are incredibly precious resources. They possess value born from the life that the donor no longer lives and the organ’s potential for its recipient – heart transplantation both takes and awards life.

Because someone must die for a transplantable heart to be made available, there is rightfully an ethical imperative to ensure that the ‘right’ person receives the organ. Giving such a vital and scarce resource to someone who would treat it improperly squanders its potential and disrespects the person who donated the organ. Turk, from the sitcom “Scrubs,” summarizes this well when he refuses to perform surgery on another character’s longtime patient when he finds out that the person has continued to drink, saying:

Dr. Cox, I know it’s really hard on you medical guys, because you spend most of your time with your patients and you get emotionally attached. But as a surgeon, the person I’m closest to is the guy who’s giving us the liver, because it’s a gift, and I think it’s important that it goes to the person that’s proven they’re up to the responsibility.

While the phrase ‘responsibility’ clouds the water here somewhat, the general message remains the same: some people are more deserving of organs than others. While we may wish to save everyone, this isn’t possible given the global shortage of organs. Roughly 17 people die each day because of a lack of organs in the U.S. alone. So for each person who receives an organ, there are numerous others deemed less worthy who must miss out.

In “Scrubs,” it comes down to a matter of responsibility and the ability of potential recipients to demonstrate they will treat the organ with the regard it demands. In a sense, they have to earn that organ. In DJ Ferguson’s case, the point of contention is slightly different. As Arthur Caplan, Head of Medical Ethics at NYU Grossman School of Medicine, states, “Organs are scarce, we are not going to distribute them to someone who has a poor chance of living when others who are vaccinated have a better chance post-surgery of surviving.” So, the concern here isn’t whether Ferguson’s shown he is responsible enough (although you could make a case that his actions demonstrate he isn’t). Instead, it is simply a matter of maximizing outcomes and minimizing risks. Being vaccinated against COVID-19 means you’re less likely to die from the disease, and a reduction in this risk improves the chances of getting the best ‘value-for-money’.

Pinning so much on the vaccination status of a potential organ receipt might strike some as odd. After all, there are countless ways to act that might jeopardize an organ’s recipient but which would seem unreasonable to use as exclusion criteria (denying a transplant to someone who enjoys extreme sports, for example). However, it is essential to remember that individuals are at substantial risk from infections post-transplantation as their immune systems are compromised. This is because the body’s immune system sees donated organs as a foreign entity that must be destroyed, causing organ rejection. To help prevent this, organ recipients take drugs to suppress their immune systems. While allowing successful organ implantation, it means that the recipient is at greater risk from infections. Even something as innocuous as a cold can be fatal, and the same goes for COVID-19. With this increased risk comes an accompanying increase in the threat posed to the positive outcome of transplantation. Therefore, a vaccinated person is a much less risky investment than a non-vaccinated person. Given our interest in maximizing the benefits someone will receive from a donated organ, it seems reasonable (even prudent) to make vaccination a requirement for anyone to receive an organ.

David Ferguson has said his son “is fighting pretty damn courageously, and he has integrity and principles he really believes in, and that makes me respect him all the more… It’s his body. It’s his choice.” David may be right. His son may indeed be acting bravely by exercising his right to bodily autonomy in a dire situation, which might make him deserving of respect. But this does little to change the fact that, when deciding who should receive a heart transplant, DJ is a risky investment. If we’re concerned with making sure that the consequences of a transplant are as positive as possible — “positive” meaning conferring the most amount of life — a person’s choice to be unvaccinated must be taken into consideration.

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Re-Thinking the Nature of Bodies

close-up photograph of Body Worlds Exhibition

Human beings are constantly growing and shedding cells. This means that very few of the cells that any person has as an adult were the cells that they had as an infant. Over the years, as we’ve learned more about cell growth and death, we’ve learned that our bodies aren’t fixed objects that simply change shape over time. Bodies are ever-shifting collections of physical stuff. To co-opt a phrase from Heraclitus, no one occupies the same body twice.

We can also contribute to the set of cells in our bodies by growing them in laboratories outside of the confines of the body. Scientists have already transplanted cell-cultured bladders into people who were born with bladders that do not empty properly. Our improved understanding of cells motivates new questions about bodies. What does it mean to say that I occupy my body? What is a body? What is the relation between my body and my identity? How does emerging technology change and inform our concept of bodies? Why does any of this matter?

In the early 20th century, when scientists first began to experiment with cell culturing, some were quick to point out the implications the technology could eventually have for organ transplants. We’ve long had fewer available organs than are required to save the lives of people experiencing organ failure. For some reason, people are hesitant to donate organs, even after they are dead and are no longer using them. When it became clear that we could cultivate cells in a lab, an incredible life-saving solution appeared to be on the horizon. One initial challenge is that cell-culturing is fairly easy to do when the expected outcome is merely flat plates of cells. But organ cells require a more complex kind of architecture, and this has proven to be a difficult nut to crack. 3-D printing technologies have provided some pathways forward, leading some scientists to conclude that the technology to grow new organs for transplant might well be available within the next decade.

One virtue of producing organs in this way is that a person’s own cells can be used to grow them. When an organ donation recipient has an organ grown in someone else’s body transplanted into their own, the recipient’s body will often reject it. To keep this from happening, doctors put patients on regiments of immunosuppressants to prevent the body from treating the organ as something it should fight. If the organs are grown by culturing a patient’s own cellular material, their body will not interpret it as foreign and the transplant is more likely to be a success. One consequence of all of this is that, once this technology is developed and assuming it becomes widely available, a person’s cellular material is capable of generating many livers, hearts, kidneys, and so on. The organs with which a person was born are just the initial set that the material provided by the body can produce under the right conditions.

These considerations present the raw material for a special form of the Ship of Theseus puzzle. The Ship of Theseus leaves a port on a long voyage. As it travels from one place to the next, it loses its pieces which fall to the bottom of the ocean. We can imagine that by the time the ship reaches its final destination, every part of it has been replaced. Is this still the Ship of Theseus? If not, at what stage did it cease to be the ship that left the port? When it sheds its first nail? When it sheds more than half of its parts? What if we were able to construct a ship using the parts found at the bottom of the sea? Would that be the ship that left the port?

If it becomes possible to grow any part of a human body by culturing cells, we could, in principle, replace a human body plank by plank, so to speak, with material that is cellularly identical to the material that was there before. When these parts have been implanted, what, if anything, has changed about the person’s body? Is there anything either morally or metaphysically important about the fact that cells were grown outside of the body rather than inside of it?

With all of this in mind, you might ask yourself: what does it mean to say that one of your organs is part of your body? After all, at any given time, an organ produced by your cellular material could either be inside of you or in a lab somewhere awaiting implantation or both. One initial way to answer the question may be that your body occupies an identifiable, though somewhat arbitrary, location near the seat of your consciousness. One unique, identifiable feature of occupying your body is that wherever you go, your body goes too. One shortcoming of this kind of position is that it might capture too much; the definition might be too broad. Imagine that a person has shrapnel inside of them from an explosion or has a piercing. These objects occupy the body or adorn the body, but we aren’t typically inclined to say that they are part of the body.

Another proposal is that the organ shares an origin story with the other parts of you, and that’s what makes it part of your body. According to this kind of view, the various parts of a person’s body came into existence as a result of a shared set of causal mechanisms. One shortcoming of this view is that we can, and do, make changes to a body, resulting in sets of physical features that do not share an origin. For example, intuitively, a transplanted organ becomes part of a person’s body after it is implanted, even though it was not grown in that space.

A third, perhaps more plausible, way of thinking about bodies is functional. Your body is your body because of the way the parts work together to play essential roles in keeping you alive and flourishing. So, imagine that you have contributed cellular material dedicated to the creation of a new liver to replace the one that you currently have. The new liver has not yet been implanted and it is currently on ice on the doctor’s office, ready for surgery. The liver that is currently in your body performing the function of a liver (even if it is doing so poorly) is part of your body. Even if the new liver is made of your cellular material, it is not part of your body until it is implanted and serving the function that a liver serves. One consequence of this kind of a position is that functional accounts of the body are not constrained to any particular kind of physical stuff. On this view, a pacemaker or an artificial hip counts as part of a person’s body. This functional account opens up all sorts of possibilities when it comes to how we think about the intersections of body and technology.

The ways that we think about bodies have moral implications at least in part because living beings stand in unique moral relations to their own bodies. Harm done to a person’s body affects that person in a first-personal way that no one else can experience. The things that happen to a person’s body can dictate the course of that person’s life. A person makes choices for their own body that would be either impossible or inappropriate for them to make for anyone else’s. All of this may give rise to unique rights and/or obligations.

For instance, if a person’s organs can be re-grown, are we obligated to provide space and resources for re-growth? Should it be possible for a person to die as a consequence of organ failure simply because they didn’t have the resources to re-grow their organs? Should the number of re-grown organs a person can produce be dependent on their financial resources? Does this technology pave the way for the rich to live forever while the poor die when their original organs fail? Does the potential for the re-growth of organs extend the human lifespan indefinitely and, if so, would this be a desirable state of affairs?

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The Ethics of Chimeric Research

microscopic image of human embryos

Recently, various news outlets covered the creation of the first human-monkey chimeras in China. A chimera is an organism whose cells come from two or more species. Researchers managed to develop monkey embryos containing human cells after previous attempts relied on pig and sheep embryos. While this type of research is prohibited in the U.S., the work was legal in China. 

Such projects have been conducted with the hope of developing human organs which can then be transplanted into humans and for conducting research into neurological and psychiatric diseases in humans. Even though such embryos do not progress past one or two weeks of growth, these efforts have been controversial. This is because it is difficult to restrict human cell growth to just one organ. According to Robin Lovell-Badge the concern is that without some way to restrict the contribution of human cells they could contribute to the animal’s central nervous system.

Such scientific endeavors present several ethical issues. These include concerns about animal ethics. For example David Shaw, Wybo Dondorp and Guido de Wert argue that given the limited number of organs for transplant, harvesting organs from human/non-human chimeras is a valid option so long as there is a substantial potential benefit to humans and if there are no reasonable alternatives present. 

Unlike other forms of animal research where the benefits may be less certain, harvesting human organs from a chimera would in most cases save a human life, so there is a large proportional benefit. Also, while there may potentially be other options for saving the life of a human requiring an organ transplant (such as research into artificial organs or changes to public policy requiring that people opt-out of organ donation), those options have not been established. For specific people who will die without an organ transplant there is no established alternative option. Thus, with these two conditions met, Shaw et al. argue that it is permissible to kill chimeras for their organs.  

César Palacios-González has argued that while harvesting organs of a human/pig chimera may be acceptable on such grounds, the case for great-ape/human chimera is more problematic. He argues that from a species-neutral standpoint great apes who possess qualities of self-awareness, complex social structures, and the potential to form rudimentary cultures are “borderline persons.” Because of this, great-ape/human chimeras are deserving of moral protection. 

Killing such animals for their organs would be no more morally justified than killing humans who possess less psychological capacities such as infants, toddlers, and adults with less mental capacities than great apes. Palacios-González suggest that we either accept that it is morally acceptable to kill great apes, great-ape/human chimeras and some human borderline persons for their organs, or we must reject harvesting the organs of any of them. 

While the animal rights argument covers some of the ethical issues involved with human/non-human chimeras, ethicists and philosophers also recognize the distinct ethical concerns presented by chimeric research. One of these concerns is whether it is wrong to cross species boundaries to create part-human beings. Is there some fixed line that distinguishes the human species from other animals, and should this boundary be breached?

According to some, crossing the boundary line of the human species is wrong because it is a challenge to God’s existence, however such arguments will not satisfy those who do not believe in a god. For others, crossing the species boundary is inherently wrong because it is unnatural. There are also those who would argue that is morally wrong because it would create too much moral confusion as we must determine the moral status of human-animal hybrids (for discussion, see Meredith McFadden’s “Moral Standing and Human/Non-human Hybrids”). 

On the other hand, such arguments are difficult to pin down because the concept of species is complicated. For example, according to Jason Robert and Françoise Baylis, “Biologists typically make do with a plurality of species concepts, invoking one or the other depending on the particular explanatory or investigative context.” 

One concept of species holds that species are defined in terms of reproductive isolation. If two populations of creatures do not successfully interbreed, then they belong to two different species. However, this definition only applies to species that reproduce sexually. Another definition considers the lineage of a population of organisms and its continuity over time. Such a definition is more encompassing but also more vague. Operationally it can be very difficult to arrive at a set of traits or qualities that completely distinguishes one species from another.  

The scientific conception of species, therefore, is not fixed. There are many ways to describe species, and it can be very difficult to arrive at a specific and distinctive definition of what makes homo-sapiens a distinct species. Because of this, the notion that it is immoral to cross species boundaries is problematic because it is difficult to define the human species in a fixed way. 

On the other hand, as Robert and Baylis point out, the fact that scientists do not have an account of fixed differences between species does not mean that the ethicist couldn’t employ a fixed account. They explain, “notwithstanding the claim that biologically species are fluid, people believe species identities and boundaries are indeed fixed and in fact make everyday moral decisions on the basis of this belief.” They use the example of race as an analogy; where race is not a biologically useful concept, but it can be a socially useful concept. 

If there are good reasons to adopt fixed notions of species for ethical purposes, then there may be a basis to claim that it is wrong to cross the species boundary, particularly because of the moral confusion it could create. Settling some of these issues will likely require that the public take note of the tension that can exist between a scientific account of something and an ethical account. Should we pursue a more open concept of species and of moral status in line with an experimental approach to these issues, or should we rely on the concept of fixed distinctions when it comes to moral matters. The issue of animal/human chimeras asks us to consider what, ethically, does it mean to be human and what does it mean to be a person?

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Moral Standing and Human/Non-human Hybrids

photograph of lab rat perched on human's arm

In a groundbreaking development towards the goal of growing human organs viable for transplant, Japanese scientists announced that they have government approval to create animal embryos containing human cells in them. The experiments could consist of mice and rat embryos, adjusted to grow with human cells that hopefully will grow into organs once the embryos are implanted into mouse surrogates. 

This is the first such experiment since the government adjusted its stance in March. Before this change, studies were banned that developed embryos that contained human cells beyond 14 days, and scientists were not permitted to implant such embryos into uteruses. One reason to be cautious of implanting an embryo and allowing it to develop to full term is the possibility that the human cells may extend past the initial point and function of their hybridization. So, the unpredictability of developing hybrids even with smaller organs composed of human cells has been met with restraint by the scientific community.

The “14 day rule” has widespread use either in strict policy or soft adherence (though in the past few years some experts have proposed doubling it). Embryos typically implant in the uterus around day seven so it is only recently that the technology to develop embryos past the 14 day rule without implanting them has even been a serious possibility. At around 14 days, the “primitive streak” appears: “a faint band of cells marking the beginning of an embryo’s head-to-tail axis.” Why does this matter?

“The formation of the primitive streak is significant because it represents the earliest point at which an embryo’s biological individuation is assured. Before this point, embryos can split in two or fuse together. So some people reason that at this stage a morally significant individual comes into being.” 

The 14-day rule arguably provides a helpful legal doctrine in its clarity and its non-arbitrary grounding. Most scientists and laypeople alike would prefer to have some such standard so that embryonic research is both possible but regulated. 

There are certainly other, more philosophically popular, standards for moral status – the status that grants a being the cluster of rights and responsibilities as a member of the moral community. Moral status is a difficult quality to codify: while it is pretty intuitive that I cannot be wronged by a table and don’t owe it anything, this is decidedly not the case with my partner of a decade. So what about a pet kitten who scratches me? Does she wrong me? What sorts of behavior and treatment might I owe a pet kitten? These questions get at the moral status of the table, my partner, and a kitten. 

Typically, theories of moral standing have a difficult time including humans at early stages and excluding non-humans (at mature stages of development). This makes the moral status of human/non-human hybrids potentially interesting. If it is, for example, our ability to experience complex pain and pleasure that makes us morally significant, there is great evidence that a number of non-human animals share these capacities (as well as our intellectual abilities). 

For bioethicists and layfolk alike, embryos may possess moral standing for a few reasons. It could be species membership itself that grants humans in early development their status. Or, it could be the potential for developing into a creature with advanced capacities of emotionality and rationality. 

If the experiments proceed as designed, the human cells will stay focused to organs such as the pancreas. Given this, hardline pro-lifers may say these aren’t human enough to have moral value, depending on what’s driving their intuitions: if the moral status is grounded in the religious view that god implants a soul into a zygote, they might simply reject this as human-made, without a human soul, and assign no moral value. If their intuitions are driven by the notion that human embryos have the potential to develop into a creature with special capacities such as intellectual, relational, or emotional capacities, then the moral status of the embryo would depend on what capacities these hybrids would have once developed. It is unlikely that the capacity to produce insulin and regulate blood sugar is the morally significant capacity that grants humans their status in our moral community. 

If it’s “sanctity of human life” that drives one’s intuition of moral status and the status of embryos, the presence of living human cells, and eventually organs, may lead to different positions. For such a position, it is not intellectual, emotional, or sentient abilities that ground the status, so the lack of overall capacities of the hybrid is no drawback. The presence of living human cells seems to be enough of a grounding, but in the hybrid’s case, it doesn’t qualify as “human” overall, only partly, hence “hybrid”. For such a circumstance, one could admit of a scalar model of moral standing, so the hybrid could have whatever percentage moral status that it is made up of human organs, or keep a binary understanding of moral status that the hybrid must cross a threshold of composition to meet.  

For most thinkers, having a human organ is insufficient for qualifying for full moral standing of a mature human. These mice and rats that are implanted with organs will have the standing that mice and rats normally have. The monkeys that scientists are using to perform similar hybridization for organ development will similarly have whatever status monkeys normally do. To contrast, consider the experiments begun earlier this year to make chimeras of brain cells. In such experiments, we aim to alter monkeys’ capacities and manner of experiencing the world by adding human brain cells. Here it becomes more difficult to determine the moral status of the resulting animal.

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Death and Consciousness: The Prospect of Brain Resuscitation

3D image of human brain

Recently published by Nature, Yale School of Medicine completed a study where they were able to revive disembodied pig brains several hours after death. In their study, they looked at 32 brains from pigs that had been dead for four hours. The brains were separated from the body and hooked up to a machine called BrainEx. On this system oxygen, nutrients, and protective chemicals were pumped into the organ for approx 6 hours. The study found that the brain tissue was largely intact and functional compared to those that did not receive the BrainEx treatment. The cells were alive, able to take up oxygen and produce carbon dioxide, but there was no further brain communication between the cells.

These findings are considered a breakthrough for the scientific community because they challenge the previously believed fact that brain cells are irreversibly damaged after a few minutes from being oxygen deprived. In general, when an organ is oxygen deprived for about 15 minutes, it should die. Nenad Stestan, a Yale neuroscientist explained during a press conference, “Previously, findings have shown that in basically minutes, the cells undergo a process of cell death. What we’re showing is that the process of cell death is a gradual step-wise process, and some of those processes can either be postponed, preserved, or even reversed.” BrainEx, a tool developed to study the living brain beyond the confines of the body, has allowed researchers a new way to look at brain cells. Previously, studies were limited to slices of the brain from dead animals, which explains our lack of knowledge on the complex organ. We now have the means to study the interrelational association between the many parts of the brain.

Bioethicists have been equally excited and alarmed with the new means of brain research. This kind of study in is uncharted territory. Technically, because the brain is taken from a dead animal, it doesn’t fall into the category of animal research. Animal research is protected through the ethical guidelines that animals should not be subjected to unnecessary harm. However, do we know enough about consciousness to truly know if the pig is experiencing harm in the process? If the pig were to feel harm during this experiment, would it make it an unethical practice?

The scientists took a measure of steps to be proactive in protecting the possibility of the pig gaining consciousness. A series of chemicals were pumped into the brain by the BrainEx machine, one of which was supposed to stop any possibility of neural interaction that would lead to consciousness. An electroencephalogram (EEG) monitored the brains throughout the whole study. Researchers said that if they had detected any levels of consciousness, they would shut down the experiment immediately. In addition, they were standing by with anesthesia to administer. Luckily, the only findings were that cell metabolism could be recovered and no consciousness was detected. With little well known about consciousness in general, can we even be sure that an EEG should be the only indicator of consciousness or perception? It is still unknown how many neurons are needed to be activated for the pig to have any feelings at all.

Weighing the cost of the unknown harm with the benefits is one step for researchers to consider with this project. Ultimately, we will gain expertise of the interactions of a mammalian brain. Understanding the internetwork of relations between the many parts of the brain can point scientists towards new cures for dementia, brain diseases, or injuries that were once considered irreversible. Future studies can include testing drugs, studying neural pathways, and furthering general knowledge of neuroanatomy.

What cannot be ignored with these studies are the implications for long-term changes in the medical community. These findings could challenge the definition of death as it is right now. According to MedicineNet, the current law standard for death is the following: “An individual who has sustained either (1) irreversible cessation of circulatory and respiratory functions, or (2) irreversible cessation of all functions of the entire brain, including the brain stem is dead. A determination of death must be made in accordance with accepted medical standards.” This definition was approved and accepted by the American Medical Association in 1980. With the findings from the Yale study, it challenges the notion that all brain cells are irreversibly damaged. Could doctors continue with this assessment if these studies lead to a means to reverse the damage, and if so, how do we now declare when someone has died?

Another worry is related to organ transplant. According to the United Network for Organ Sharing, someone is added to the transplant waiting list every 10 minutes. In the US, 18 people die every day while waiting for a transplant. Described in a commentary by Stuart Youngner and Insoo Hun, is the worry that doctors would feel reluctant to harvest organs for donation. If people could become candidates for brain resuscitation rather than donation, when, where, and for who do doctors make this decision? There is already the struggle for when do doctors switch from saving someone’s life to saving their organs for the benefit of another person. The answers only come down to moral decision making and the possibility of brain resuscitation further complicates the answers.

The continuation of these studies have the potential to make a huge difference for our expertise of neural anatomy and the process of cell death. For now, researchers have weighed the perceived benefits to outweigh the possibility of harm to the research subject. With the means to learn more about the definitions of consciousness and death, it is necessary for after each study to reevaluate the process of BrainEx in order to continue the study in an ethical manner.

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The Transplant Scenario in Fiction and Film

A photo of an operating room during surgery

Ethicists make many uses of the story of the transplant surgeon—the surgeon who uses one healthy patient as an organ bank and saves five lives.  Surely this must be a villain, not a hero, but why? Most of us think it would be right, not wrong, to flip a switch so a train didn’t head toward five people lashed to a track but instead toward one. The scenario helps raise questions about killing and letting die, doing and allowing, and also poses a problem for act utilitarianism, which assesses actions in terms of outcomes.  

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