Chimeras with benefits? Transplants from bioengineered human/pig donors

By Brad Segal

In January of this year, Cell published a study modestly titled, Interspecies Chimerism with Mammalian Pluripotent Stem Cells. It reports success bioengineering a mostly-pig partly-human embryo. One day before, Nature published a report that scientists had grown (for lack of a better word) a functioning genetically-mouse pancreas within the body of a genetically-modified rat. The latest study raises the likelihood that before long, it will also be scientifically possible to grow human organs within bioengineered pigs.

The implications for transplantation are tremendous. But hold the applause for now. Imagine a chimera with a brain made up of human neurons which expressed human genes. Would organ procurement without consent be okay? That troubling possibility raises  questions about whether manufacturing chimeras with human-like properties for organs is even appropriate in the first place. Here’s what University of Montreal bioethicist Vardit Ravitsky told the Washington Post:

“I think the point of these papers is sort of a proof of principle, showing that what researchers intend to achieve with human-non-human chimeras might be possible … The more you can show that it stands to produce something that will actually save lives … the more we can demonstrate that the benefit is real, tangible and probable — overall it shifts the scale of risk-benefit assessment, potentially in favor of pursuing research and away from those concerns that are more philosophical and conceptual.”

I respectfully disagree. Saving more lives, of course, is good. Basic science is also valuable – even more so if it might translate to the bedside. This line of research, though, is positioned to upend our entire system of transplantation, and so its implications go beyond organ supply. In this post I will argue that to assess this technology’s implications for organ procurement in particular, there is good reason to focus on harms, not benefits.

To start, there is a distinction between two major aspects of transplantation. They are related, but each operates under a different set of professional and ethical norms.

First, there are the problems in transplantation of organ allocation. The supply of organs available for transplantation is limited, and there are more people who stand to benefit from a transplant than available organs. Thus, as a result of scarcity, we require a fair system of rationing to determine who will receive an organ and in what order. The priority for adults on a transplant wait-list in the United States differs by organ system. Allocation for kidneys, for instance, largely depends on the length of time the patient has been listed for a transplant (this is a “first-come first-serve” system of rationing). Livers, on the other hand, are allocated to the patient with the highest MELD-Na score (which predicts risk of mortality over a defined time period; it is a “sickest first” system of rationing).

At any rate, eligibility for organ allocation relies on a utilitarian calculation. From a public health standpoint, organ allocation should maximize the benefits of the scarce resource (especially among those in need of help). Yet for an organ recipient to realize the benefits of a transplant, he or she must take immunosuppressive drugs everyday – for life. Though these might cause severe side effects, without them the recipient’s immune system will likely reject the organ and cause it to fail. Therefore, the reasoning goes, to be listed for a transplant, a candidate needs some capability of adhering to the post-transplant treatment regiment. Otherwise, the organ will fail, and overall more good would have resulted had the organ been allocated to a recipient who then provided the adequate level of care. If a person needs a liver but is actively addicted to drugs and alcohol, a request to be listed for a transplant would likely be denied on the grounds that it would not maximize overall benefits.  The point I’m making here is that this all feels rather utilitarian. But for allocation, from a public health perspective, it is not unreasonable to frame the acceptability of chimeric organ supply by its potential benefits.

In contrast, the second set ethical considerations in transplantation deal with organ procurement. Here, a focus on the benefits is problematic because the questions pertain to non-recipients; the people who donate vital organs are not the same people who benefit from them. In absence of medical benefit for donors, commensurate organ procurement would inflict no harm to donors. In other words, the principle of nonmaleficence is particularly stringent in the context of organ procurement because the donors themselves do not directly benefit from rather-invasive surgery.

Notice that focus has shifted from benefits to harms – but for good reason. Merely because a technology will increase the supply of transplantable organs does not mean it is good or right; the ends do not necessarily justify the means. Treating someone merely as a means fails to respect that person’s humanity. This might be philosophical and conceptual, but it matters. That is why saving the lives of eight people listed for a transplant by taking vital organs from a healthy person without consent would violate countless moral, professional, and legal norms. Particularly in the context of organ procurement, society holds transplant surgeons accountable to a non-utilitarian standard.

No one is going to deny the potential benefits of organs supplied by pig-human chimeras. It could save lives! But the utilitarian appeal of increasing the organ supply is one of the reasons why deontological norms like the dead donor rule (DDR) are put in place. This stipulates that donors cannot be killed in the process of organ procurement. The DDR is upheld regardless of the number of lives a violation might save. Its point is to protect donors from wrongs inflicted in the name of potential benefit.

In the wake of the report in Cell, I feel the focus should not be on the benefits of providing chimeric organs to transplant candidates; it ought to be on whether it harms donors. As it turns out, that gets at the thorny bioethical issues underlying the report. Do part-human part-pig chimeras have the same moral status as people; or, would vital organ procurement not violate medicine’s credo, “First, do no harm”?

Leave a comment below and let me know what you think, or you can Tweet me @bradsegal. I’ll pick this up again in my next post.