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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.

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.

A Cross-Species Solution to Organ Donation?

A photo of surgeons operating on a patient.

When thinking of genetically modified organisms, vast fields of corn and large confined animal feeding operations might come to mind. However, a recent development in medical technology has moved us one step closer to modifying animals for purposes other than agriculture. Xenotransplantation is the practice of transplanting cells, organs, or tissues across species. Previously, the largest obstacle to xenotransplantation was the potential infection of viruses between species. However, a new experiment successfully eradicated the threat of such viruses, opening the door a little wider in terms of pig-human transplantation.

Continue reading “A Cross-Species Solution to Organ Donation?”