By Gary Evans

The next frontier in transplant medicine includes bioengineered organs, which raise ethical issues but could help alleviate a critical shortage that leaves more than 100,000 people on organ wait lists annually in the United States.

A critical aspect of advancing bioengineered organs is the ability to bridge the research gap between animals and man by conducting research on patients declared brain-dead, who technically would not meet the ethical thresholds for human research subjects. For example, the idea is to test bioengineered lungs or kidneys for short periods in the recently deceased, who would agree to such medical research much like consent to organ donation.

“Although such studies do not pose risk to human subjects, they pose unique ethical challenges concerning the previous wishes of the deceased, rights of surviving family members, effective operation and fair distribution of medical services, and public transparency,” the authors of a new study reported.1

The researchers acknowledged the elephant in the room, as there is no avoiding the cultural taboos around death and the ghoulish aspect of experiments involving those whose brains are blank but hearts are beating.

“Manipulation of recently deceased bodies for research purposes can seem frightening or abhorrent,” the authors conceded. “Reported abuses involving use of bodies of the recently deceased without permission to either obtain transplantable tissue or train medical students underscore this reality.”

To move forward in this research, the acceptable definition of death that all parties must agree on is based on neurological rather than cardiopulmonary criteria.

“Continuation of organ support for short, experimental studies — hours to a few days — can be ethically permissible if the appropriate criteria are employed for selection of the deceased and the procedure conducted in such a manner that is respectful of both the deceased and their authorized decision-makers,” the authors wrote.

IRBs stand as a model for ethical oversight, although the recently deceased would not be human subjects under the provisions for research in the Common Rule. A more appropriate model is the University of Pittsburgh’s Committee for Oversight of Research Involving the Dead (CORID), which in 2002 became the first panel dedicated to reviewing protocols for research involving deceased subjects, the authors reported.

Q&A

IRB Advisor spoke with lead study author Brendan Parent, JD, an assistant professor of bioethics at NYU Langone Medical Center in New York City. The following interview has been edited for length and clarity.

IRB Advisor: Can you comment further on this contention that IRBs could be a model of infrastructure and oversight, but would not be the appropriate ethical stewards of bioengineered organ research?

Parent: As we stated in the paper, we don’t think it is appropriate for the IRB to take on this additional kind of research oversight — specifically because the purview of the IRB is human subjects research, and we do not believe that this is human subjects research. The IRB can serve as a model for the kind of oversight and structure for deliberation and review process in terms of weighing risks and benefits and the rights and duties of the involved stakeholders. With the key difference being that perhaps the most prominent stakeholder in human subjects research — the human subject — is completely absent from this conversation [due to brain death]. We propose that there should be some other kind of oversight body, more in tune to other issues like the rights of surviving family members, the benefits of the potential research, and the allocation of scarce resources, including the hospital staff or personnel who might help facilitate the research.

IRB Advisor: Can you comment on the type of bioengineered organs that are under research and may eventually be tested on brain-dead subjects?

Parent: The applicability is over a broad range. There are a lot of different versions being pursued by different companies. Some are going to be entirely 3D printed plastic-like scaffolding populated with entirely human cells. Others are going to be a little bit of human and a little bit of animal. Some are going to be primarily nonhuman animal that might be somewhat genetically engineered to be more compatible with human bodies. There is even the entirely artificial, noncellular equipment. It runs the full gamut based on which company, but I think they are all applicable in that the body of the recently deceased — declared dead by brain-death criteria — will be a useful test subject.

IRB Advisor: What about the ethical issues of informed consent? Does that defer to any surviving family?

Parent: Ideally, the consent already would be obtained from the deceased prior to their death when they signed up to be organ donors. The question is whether we can use consent to organ donation as sort of a proxy. When you register to be an organ donor in most states, you are simultaneously registering for the use of your body parts for purposes of transplant, education, and research. There is some nuance to that, in that different states have different levels of specificity. In a lot of places, it is sort of an all-or-nothing checkbox. In those circumstances, you technically are authorizing for something like this [research] in the event that your organs are not viable for transplant — this might become a sort of backup use that you are authorizing.

There is another question, which is how many people are aware of something like this — that this might be an alternate use? I think it is important to educate that this is a possibility, and also go to families and get what I would call surrogate or informed authorization as opposed to consent, which implies something more specific.

IRB Advisor: There are a lot of cultural issues and stigma surrounding death. Can this emerging field navigate these negative perceptions?

Parent: I think the concerns aren’t much different than what we already face with issues like brain-death determinations or present practices regarding organ procurement, which include ensuring adequate education and transparency about what is taking place. This is not going to affect or be performed on living people. That is very important to know. Just as the field of organ transplant is trying to combat myths like, “I am not going to register to be an organ donor because that means emergency response is not going to try as hard to save my life.” It’s just not true. There are firewalls in place. The people who perform lifesaving practice — that is what they went to school for, that is their livelihood. There also is separation of teams. The clinical team that performs lifesaving efforts and knows how to declare death [is separate] from the organ procurement transplant team.

It’s similar with this, and that needs to be a strong description and focus of this research. We have exhausted all the useful information we get from animal models. Before we try these manufactured organs in living humans, this is a potential research field where we can get very useful information. We can get the research to a higher quality, so that when we do the first human trials there is a better chance of success. [It is important] to point out that value and describe how this will take place; we are not just going to do this on anybody who dies. It has to be people who die in controlled circumstances at the hospital, and we will make sure that family members know all through the authorization process. We need to make people aware that we are still going to prioritize the availability of organs for purposes of transplant because that can save immediate lives, while still acknowledging that when people are ineligible — when they die and their organs are unavailable for transplant — there still is potentially a very valuable legacy that they can leave. This research could save tens, hundreds, thousands of lives in the future.

REFERENCE

1. Parent B, Gelb B, Latham S, et al. The ethics of testing and research of manufactured organs on brain-dead/recently deceased subjects. J Med Ethics 2019; Sept. 28. pii: medethics-2019-105674. doi: 10.1136/medethics-2019-105674. [Epub ahead of print].