Episode 8: Organ Donation Models: Eijkholt and Fleck

No Easy Answers in Bioethics logoEpisode 8 of No Easy Answers in Bioethics is now available! This episode on organ donation models features Center Assistant Professor Dr. Marleen Eijkholt and Center Professor Dr. Len Fleck. Combining their clinical ethics and health policy expertise, they sat down together to discuss ethical issues within current organ donation models, stemming from recent legislation passed in the Netherlands to implement an opt-out system of organ donation. Drs. Fleck and Eijkholt discuss positive and negative aspects of opt-out and opt-in systems, also drawing from other countries around the world. Additionally they discuss reasons why individuals may choose not to be organ donors, and the types of situations that can emerge at the bedside when grieving individuals do not want their loved one’s organs to be donated.

Ways to Listen

This episode was produced and edited by Liz McDaniel in the Center for Ethics. Music: “While We Walk (2004)” by Antony Raijekov via Free Music Archive, licensed under a Attribution-NonCommercial-ShareAlike License. Full transcript available.

About: No Easy Answers in Bioethics is a podcast series from the Center for Ethics and Humanities in the Life Sciences in the Michigan State University College of Human Medicine. Each month Center for Ethics faculty and their collaborators discuss their ongoing work and research across many areas of bioethics—clinical ethics, evidence-based medicine, health policy, medical education, neuroethics, shared decision-making, and more. Episodes are hosted by H-Net: Humanities and Social Sciences Online.

Humanity in the Age of Genetic Modification

Bioethics in the News logoThis post is a part of our Bioethics in the News series

By Jennifer Carter-Johnson, PhD, JD

Scientists have recently announced that they had used the new gene editing technique, CRISPR, to remove remnants of ancient viruses that had integrated into the pig genome. An amazing feat of genetic engineering to be sure—but the article is notable as a first step in “humanizing” pig organs for use in organ transplant by removing pig-specific viruses before they can infect human organ recipients. The idea of humanizing pigs should make us wonder—what does it mean to be human? How much genetic modification can pigs undergo and still be pigs? How do we define humanity for our neighbors and ourselves? How much genetic modification would it take to remove the label of humanity?

These questions are not asked in a vacuum nor is the research being conducted solely for philosophical inquiry. We need organs to save lives. There are over 116,000 people on the organ donor list and only 33,611 organ donations each year. About 20 people die every day in the U.S. waiting for a match so that they can receive a new heart, kidney or lung. Additionally, not everyone who actually receives a transplant has a successful outcome.

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Image description: a Lego figurine of a person dressed in a pig costume is shown in the foreground against a yellow and white background. Image source: clement127/Flickr Creative Commons.

Transplant rejection occurs because each person has a fairly unique set of signal markers on their cells that allow the immune system to identify “self.” Bacterial or viral infections trigger immune responses in part because they change the infected cell’s signal markers from “self” to “foreign.” A transplanted organ also looks “foreign” to the recipient’s immune system due to the difference in signal markers, and this immune response leads to transplant rejection. For instance, identical twins would have very little risk of transplant rejection, while two unrelated people of different backgrounds would likely be unable to donate to each other. Thus, doctors search for the greatest amount of match between recipient and donor, and then suppress the recipient’s immune system to further decrease the risk of transplant rejection.

Using animal organs introduces yet more foreign signals to the organ recipient, leading to the desire to humanize those organs with markers that signal “human” and “self” to the recipient. In fact, doctors have been using pig heart valves in transplants since the 1970s. These hearts valves are extracted and then stripped of live cells to decrease the risk of rejection. This preparation procedure limits types of transplants that can be performed, and even with preparation, rejection issues may eventually arise.

Therefore, today’s scientists are working to use genetic engineering to modify pig organs to express the same cell markers that signal “self” to a human recipient. The referenced article described the development of pigs without endogenous retroviruses that some fear could infect recipients. From that basis, scientists could use several different techniques to develop pigs with humanized organs. One technique would be to genetically modify an embryo such that the pig’s cells express more “human” markers and less “pig” markers. Another technique that has been pioneered recently would be to inject human cells into a pig embryo such that the resulting chimeric pig would grow a genetically human organ.

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Image description: three pigs are shown outside through metal fencing. The main pig appears to be smiling. Image source: Peppysis/Flickr Creative Commons.

Both of these techniques raise the question of what it means to be human. Merriam-Webster defines the noun human as “a bipedal primate mammal (Homo sapiens) : a person.” Furthermore, the adjective definition of the word human, “having human form or attributes,” broadens that definition in an ambiguous way that leaves us no closer to an answer than before. After all, the point of humanizing cells is to give them human attributes for organ transplantation. Surely, that isn’t enough to make the pig a human? Pigs with genomes edited to have organs that look more “human” will likely still act like pigs. But we don’t truly know how multiple genetic changes will present. Looking to the chimera technique, would a chimeric pig with the heart and kidneys of a human still be a pig? What if some of those human cells colonized the brain and some percentage of neurons were human? How do we answer the question of humanity? Do we ask what percentage of the body is human? Do we see if the animal still acts like a pig or test its skills on the SAT?

In contrast, does a person who receives a pig heart transplant cease to be human and become a pig? Humans do not have a great track record of recognizing humanity in others. Perhaps in recent times, we in the United States have not had to consider what qualifies as human. A baby born from a human mother is a human. But this concept has not always been so straightforward. Constitutional definition of a slave as 3/5 of a person and the idea of blood quantum to limit Native American rights go back to the beginning of our country. More broadly, Hitler wanted to develop a master race and viewed Jews as subhuman – leading to horrific abuses and mass murder. Today, some countries still view women as property rather than humans with rights.

Genetic technologies will challenge how we view ourselves, our neighbors, and the next generation. Genetic testing has revealed Neanderthal genetic code in many of us due to interbreeding thousands of years ago. CRISPR-based tools will eventually allow parents using artificial reproductive technologies to select genetic traits for their children. How many modifications would it take for a child to cease to be human? Perhaps super strength or gills to breathe under water sound like fantastic science fiction now, but so too did the tablets and communicators of Star Trek in the 1960s and the watch phone/TV from Dick Tracy in the 1940s. Returning to the idea of organ transplants, would a skin bag full of organs derived from a human’s cells but with no brain be considered a human? Would your answer differ if there was a brain but no higher order brain function? Such an option could reduce organ rejection to nil if a person’s cells could be used to create their own replacement organs.

The dangers of relegating a population to second tier status because they are genetically different from the norm have been explored across fiction from Animal Farm to the X-Men. Humanity’s history suggests that those stories are rooted in our inability to see humanity in those we deem as other. Advances in science mean that we need to define what it means to be human in order to avoid abuses equal to slavery or Nuremberg. Our world is changing and so too will humanity – whether or not we are prepared.

j-carter-johnsonJennifer Carter-Johnson, JD, PhD, is an Associate Professor of Law in the College of Law at Michigan State University. Dr. Carter-Johnson is a member of the Michigan State Bar and the Washington State Bar. She is registered to practice before the U.S. Patent and Trademark Office.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, November 9, 2017. With your participation, we hope to create discussions rich with insights from diverse perspectives.

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Dr. Eijkholt published in ‘Journal of Emergency Medicine’

CMarleen Eijkholt photoenter Assistant Professor Dr. Marleen Eijkholt is the co-author of an article in the April 2017 issue of the Journal of Emergency Medicine. The article, “Enabling Donation after Cardiac Death in the Emergency Department: Overcoming Clinical, Legal, and Ethical Concerns,” is co-authored by Michael Dailey, MD, Sean P. Geary, MD, Stefan Merrill, MD, and Marleen Eijkholt, PhD.

Abstract
Background: In light of the growing gap between candidates for organ donation and the actual number of organs available, we present a unique case of organ donation after cardiac death. We hope to open a discussion regarding organ procurement from eligible donors in the prehospital and emergency department setting.

Case: This case study, involving an otherwise healthy man who, after suffering an untimely death, was able to successfully donate his organs, highlights the need to develop an infrastructure to make this type of donation a viable and streamlined option for the future.

Discussion: Given the departure from traditional practice in United States transplantation medicine, we bring forth legal and ethical considerations regarding organ donation in the emergency department. We hope that this case discussion inspires action and development in the realm of transplant medicine, with the aim of honoring the wishes of donors and the families of those who wish to donate in a respectful way, while using our medical skills and technologies to afford candidates who are waiting for organs a second chance.

Conclusions: We believe that this case shows that donation after cardiac death from the emergency department, while resource-intensive is feasible. We recognize that in order for this to become a more attainable goal, additional resources and systems development is required.

The full article text is available on the ScienceDirect website (MSU Library or other institutional access may be required to view this article).

Regulated Organ Market: Reality Versus Rhetoric

moniruzzamanCenter Assistant Professor Monir Moniruzzaman, PhD, has a new article in the October issue of the American Journal of Bioethics. Read “Regulated Organ Market: Reality Versus Rhetoric” here (a subscription may be required to view this article).

Individual vs. Public Benefit in Liver Donation

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Hannah Giunta

Earlier this month, the United Network for Organ Sharing (UNOS) announced it would hold a public hearing regarding concerns about disparities in donated liver access across U.S. geographic regions. (Q13 Fox News 2014) While donated livers are supposed to go to the sickest patients first, geography is still taken into consideration. So, the person closest to death is not always the first to get a donated liver. Rates of liver donation are highest in the Midwest and South where centers often serve predominantly rural areas and see less overall demand. Patients on the coasts commonly have to wait longer before qualifying for a transplant. This disparity has resulted in patients with means flying across the country to get an organ while lower income patients have to simply wait at home. UNOS considers the number of waiting list deaths resulting from this disparity serious and is entertaining various solutions. One proposal under consideration would involve redrawing regional boundaries to decrease the total number of regions. Those larger regions would then each serve a more equitable number of patients. To date, this proposal has drawn intense criticism, with lawmakers in the U.S. House of Representatives signing an opposition letter in an attempt to stop any map redrawing. (WIBW 2014)

UNOS Region Map
UNOS Region Map

Yet, both critics and proponents of the changes seem to be arguing from self-interest instead of from a well-grounded public health-focused perspective. On the one hand, critics worry that organ-rich areas will become organ “farms” for those areas of the country where grassroots efforts to increase donations have been less successful. Dr. Sean Kumer, a transplant surgeon at the University of Kansas, expressed this sentiment, noting, “What they are attempting to do is say, ‘Hey, those guys have all the organs. Let’s go over and poach those’ instead of having their own grass-roots campaign to identify new donors.” (Q13 Fox News 2014) The University of Kansas publicly announced its opposition to the proposed changes (Bruce 2014), and at first glance, it does seem intuitive that regions where more effort is expended for organ donor recruitment and procurement have a right to increased access. Yet, this view is actually problematic. First, this claim might stand up if transplant centers did not receive support and benefits from belonging to a national network, but I believe they likely benefit from information sharing, training, and system-wide resources. Secondly, it is difficult to tease out just what a needy individual’s responsibility is for circumstances in the larger population. If an individual lives on one of the coasts and personally advocates organ donation but others choose not to donate, then is that individual less deserving of an organ? What about areas where certain religious or cultural groups oppose organ donation? Should needy patients who might support donation themselves bear the burden of others’ different choices? Conversely, what if a patient lives in a region where organ donation is high but they personally are not donors? Should they enjoy the benefit of increased access?

Proponents of map changes also argue from a predominantly self-interested position. Surgeons at the University of Pittsburgh signed on in favor of the proposal—but not really because they see it as a more equitable way to allocate scarce medical resources. (Smydgo 2014) Rather, Pittsburgh surgeons work in an area that stands to gain the most from redrawing the map. It’s unclear whether they would support a proposal that might not be advantageous to their own region. Neither side seems concerned about the broader public implications of liver transplant inequities.

Obviously, any question about the allocation of scarce medical resources is certain to reignite age-old controversies pitting the welfare of individual patients against equitable access for all those in need. I believe this line of thought creates a false dichotomy—one where physicians operate independently of the larger health care system and patients are completely autonomous agents who are not impacted by complex social issues and practices. While seeing one’s duties as specific to an individual patient is helpful in the everyday practice of medicine, it is too narrow a conception when navigating one’s role in a complex public system. Indeed, I would argue that because pervasive inequality has been shown to negatively impact all involved, including one’s current and future patients, physicians have a duty to promote larger public health goals (see Wilkinson 2011 for more on how social inequality impacts us all). By taking a narrow stance on what constitutes one’s ethical obligations, physicians like Dr. Kumer assume their actions impact only their patients, and equally, they then assume they are selflessly fighting to insure access for the needy. However, transplanting an organ into one patient inevitably means it is not available for some other person. In a case where a less seriously ill patient receives an organ ahead of a more critical patient, the sicker individual could be left to die when both lives might have been saved if the healthier patient had waited a bit longer for a transplant. I am dubious that physicians are as willing to acknowledge their indirect role in a disadvantaged patient’s death as they are to take credit for a life saved.

In the narrowest sense, a physician has an obligation to an individual patient. Dr. Kumer articulates this sense of obligation. Especially when making time-sensitive medical decisions, physicians commonly do not have the luxury of considering broader social implications. But, when a physician is operating within the context of a specific allocation system and that entire system is under review, he can and ought to fairly analyze policy implications. Such analysis does not ethically conflict with his duties to individual patients. Yet, it would be unfair not to acknowledge that Dr. Kumer’s position is held by a large and increasing number of physicians. Despite the Institute of Medicine’s recommendation that more physicians earn public health degrees, the proportion of physicians in public health programs continues to decline (cited in Donohoe and Martin 2014). Biomedicine has become increasingly separated from the social and cultural dimensions of patients’ lives and from a broader ethical commitment to the public’s overall health. It therefore is understandable that individual physicians are reticent to engage in these types of discussions, but their complacency cannot be ethically justified. Part of a physician’s professional duties should involve taking an interest in system-wide inequalities, including those perpetuated by the medical system itself. In this case, neither the critics nor the proponents are discharging their ethical obligations.

Those who disagree with my position will undoubtedly contend that asking physicians to serve two masters is unfair; am I advocating that physicians should focus on their role as public health advocate instead of their daily responsibilities to patients? My answer is a resounding “No.” When a patient is on the operating table, the responsible surgeon is and should be focused solely on what actions can be taken to insure that individual’s survival. But, in broader discussions of public policy, there is no reason that carrying out one’s professional obligations as a physician obviates one from considering societal implications and the public’s health. It is just as much of an ethical lapse not to fulfill this obligation as it would be not to promote a patient’s interests in the operating room. Until we can conceive of a world where patients and physicians can operate without being impacted by broader social structures, individual patient welfare and system wide justice are not antithetical to one another. At the very least, individual welfare and social justice are not separate considerations. In my opinion, they are intimately intertwined.

References:

hannah-giunta-100Hannah Giunta is a sixth year DO-PhD student pursuing a PhD in Philosophy and Bioethics.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, October 9, 2014. With your participation, we hope to create discussions rich with insights from diverse perspectives.

You must provide your name and email address to leave a comment. Your email address will not be made public.

Lungs for Sarah Murnaghan Raise Ethical Questions

Bioethics-in-the-News-logoThis post is a part of our Bioethics in the News series. For more information, click here.

By Tom Tomlinson, Ph.D.

Sarah’s Murnaghan’s sad predicament. has been much in the news the last several weeks. Sarah is a 10-year-old girl with advanced cystic fibrosis (CF) who was critically ill in an intensive care unit in Philadelphia. Seeing a double lung transplant as her only hope for survival, her desperate parents made a highly public appeal to Health and Human Services Secretary Kathleen Sebelius and members of Congress to suspend the policies of the Organ Procurement and Transplant Network (OPTN), which don’t permit children younger than 12 to be put on the waiting list for lungs from adult donors.

Expressing sympathy for Sarah and her parents, Secretary Sebelius nevertheless refused to change the rules, leading Eric Golub at The Washington Times to call her a “death panel bureaucrat.” Sarah’s parents then went to a Federal District Court judge, who issued an injunction ordering the OPTN to put Sarah on the adult list, and later another child with CF. In response, OPTN developed an interim policy on June 10, which is set to expire on July 1.

Sarah quickly received a double-lung transplant from an adult donor on June 12. As of this writing, she remains on a ventilator in the intensive care unit at Children’s Hospital in Philadelphia.

Most discussion of this case has focused on the plight of Sarah and her parents, who have been especially adept at using social networks to capture media attention on behalf of their daughter. Related worries have been expressed about having the organ distribution system driven by sympathy for individual patients who manage to capture the public’s heart.

But there is a larger problem in which Sarah’s story is embedded: how to design a fair and effective system for distributing a scarce resource that falls far short of the need. In 2011, 351 patients needing lung transplant died on the waiting list. Until we have the capacity to grow a new set of lungs from our stem cells, not everyone who needs a lung transplant to survive will receive one. In the meantime, how should we decide who goes to the front of the line?

Well, speaking of lines, how about “first come, first served”? We use this method all the time to guard against favoritism. If I want to secure tickets to a very popular play, I get in line, whether at the box office, or on the Web. Whether I get tickets or not will depend on nothing else about me—not how rich or famous or educated or influential I happen to be. Of course we know that in real life I have a better chance of getting tickets if I know the producer. But that observation just emphasizes how much we think real life falls short of the ethical ideal that “first come, first served” exemplifies.

Why not do this with lung transplants? Transplant centers put candidates on the OPTN waiting list, and when a lung becomes available, the person who’s been on the list longest gets first dibs. In fact, this is the system that was used for distributing lungs to both adults and children up to 2005. The reasons for changing it are instructive.

First, time on the waiting list may have little to do with how badly someone needs a transplant, and it turns out this is especially true for patients needing a lung transplant. Mr. Smith at #1 may be healthy enough to wait quite a little longer, while Mr. Jones at #10 will surely die within weeks without the transplant. So is it “fair” to Mr. Jones if we give the transplant to Mr. Smith? We will have considered each of them equally with respect to time on the waiting list. But we’ve not treated them equally with respect to the urgency of their need, because if we did, the transplant would go to Mr. Jones.

OK, then, urgency of need is a very compelling consideration when without the transplant the patient stands at the brink of death. So let’s make that our rule. Transplants will go to the sickest first. Mr. Jones is still on the ventilator in the ICU, and is not expected to survive to leave the hospital without a lung transplant. Mr. Smith is at home with increasing difficulty breathing due to his lung disease, and is clearly on a downhill trajectory. But he is managing to survive out of the hospital. Urgency of need dictates that Mr. Jones should get the next available lung. But because he’s already so sick, Mr. Jones is much less likely than Mr. Smith to survive the transplant procedure and leave the hospital, and if he is discharged, he is also likely to die sooner despite the transplant. So we will have treated our two candidates equally with respect to the urgency of their need, but not with respect to extending their life. We count the shorter time that Mr. Jones is given for more than the time Mr. Smith could have had.

And here’s another complication. Setting concerns for fairness to one side, we should also guard against making people worse off. That’s what happens when those who “need” a transplant are transplanted too early. The transplant procedure itself is a risky business, and life with the transplanted organ can be a precarious affair, with survival complicated by the serious and sometimes lethal side effects of immunosuppressive drugs. More than half of lung transplant patients are dead 5 years later. Many patients with slowly progressing disease will live longer if they wait longer.

Rather than picking just one of these conflicting criteria, and thereby sacrificing the other ethically important factors, a group of lung disease and transplant experts developed the Lung Allocation Score (LAS), which OPTN adopted in 2006. Supported by evidence from OPTN and other sources, they identified a number of clinical measures that predict the length of two kinds of survival: survival without transplant; and survival post-transplant. The LAS is basically the difference between these: (survival post-transplant) – (survival without transplant x 2). The higher the LAS score, the higher the priority to receive a donated lung. This calculation incorporates two ethical criteria at once. First, it gives a higher priority to those with a predicted higher net benefit. And second, because survival without transplant is subtracted twice, it also gives weight to urgency of need.

This system, which is continually being refined as more evidence is accumulated, applies to all recipients 12 years old and above. Because there aren’t very many patients younger than 12, there wasn’t a solid base of evidence on which to extend the LAS scoring to them, and so those patients were prioritized based on waiting list time. Until Sarah Murnaghan, that is, who got put on the adult list with an LAS score. We can hope she does at least as well as adults with similar scores, despite the lack of solid evidence that she will.

To end, let’s bring this back to Sarah and pediatric patients like her. Suppose that we develop the evidence to support extending LAS scoring to younger patients, who will then go on the list alongside adults with equal or higher LAS scores. The fact that she is a child will make no difference. A 5-year predicted net survival for a 10-year-old gets no more weight than a 5-year survival for a 35-year-old. Should it get more weight?

References:

tomlinsonTom Tomlinson, Ph.D., is the Director of the Center for Ethics and Humanities in the Life Sciences and a Professor of Philosophy at Michigan State University.

Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made between July 3 and July 12. With your participation, we hope to create discussions rich with insights from diverse perspectives.

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