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Shortage of organs for transplantation – is more research on human–animal chimeras the right approach?

12 September 2016
By Dr Silvia Camporesi and Giulia Cavaliere
Department of Global Health & Social Medicine, King's College London
Appeared in BioNews 868

It is time to discuss, once again, the lifting of a moratorium on research. We are not talking about the CRISPR genome-editing moratorium, but about the 20 August announcement by the US National Institutes of Health (NIH) to lift the moratorium on research involving chimeric human/non-human embryos (see BioNews 863). The use of federal funds for this kind of research had been previously banned by the NIH in September 2015.

Although it does not state it explicitly, the NIH announcement seems to have been triggered by Harvard professor George Church's research on growing humanised organ models in non-human animals, namely pigs.

Insoo Hyun, a bioethicist at the Case Western Reserve School of Medicine in Cleveland, Ohio, followed with a perspective piece in PLOS Biology, stating that the benefits of this kind of research are so great that we should no longer hesitate to fund it. He addresses traditional concerns in animal ethics, such as safety, the moral status of the non-human animal (in this case, the human/non-human chimera) and the exploitation of non-human animals in research.

We agree with his precautionary stance, which is consistent with the existing ethical standards for chimera research developed by the International Society for Stem Cell Research in 2007 and which has more emphasis on animal welfare than on speculative concerns about moral humanisation of the human/non-human animal chimera.

Ultimately, we find that Hyun's conclusions that 'most, if not all, of these [traditional] concerns can be reasonably addressed' are plausible. However, Hyun fails to address the elephant in the room: why should we invest significant resources in the creation of humanised animal models in the first place?

Let's take a look at the two main assumptions in Hyun's piece.

First assumption

'The shortage of human organs for donation is a pressing problem worldwide ... The humanitarian importance of this research is both apparent and urgent. There is currently a dire shortage of organs for transplantation in the United States, leading to approximately 22 deaths per day among patients waiting for organs.' 

Hyun is right about the numbers, but we believe that the urgency of the research is not by any means self-evident. What he fails to examine is whether the creation of humanised animal models is the best way to address this pressing matter, and he fails to acknowledge the existence of viable alternatives, such as opt-out policies to increase organ donation from human to human. One notable example is Austria, which has a more than 90 percent organ donation rate; a similar law was approved in Wales in December 2015.

Second assumption

'Given the noble aims of this research, it is puzzling to some why the NIH is so nervous about providing federal funds to researchers with a track record of success in this area.'

When put in this way, it is difficult to object to research that aims to save lives and relieve suffering. The argument goes: we have the opportunity to save lives and we should do that. If we fail to do that, we are equally morally responsible (acts and omissions are morally equivalent). Such beneficence-based arguments are common when it comes to new and emerging science and technologies, but they risk the uncritical acceptance of scientists' assumptions. In this case, the assumption is that the research has the noble aim of solving the shortage of human organs and, as long as precautionary measures are taken to ensure safety and respect for the welfare the animals, then research should be allowed to go ahead.

In the UK, any research of this kind would need a specific licence granted on a case-by-case basis from the HFEA. In 2007, two research groups in the UK (the stem cell biology laboratory directed by Dr Stephen Minger at King’s College London, and the group headed by Dr Lyle Armstrong at Newcastle) applied independently for a licence to the HFEA to carry out interspecies somatic cellular nuclear transfer for the creation of 'cybrids', which were eventually granted after a period of deliberation and public consultation.

These applications, and the research itself, were motivated by the need to create to develop patient-specific embryonic stem-cell lines through interspecies somatic cellular transfer using oocytes derived from non-human animals (rabbits or cows), to avoid the scarcity of human oocytes. According to HFEA rules, research on 'human admixed embryos' can only be conducted in vitro, and these embryos cannot be placed in non-human animals or humans. In spite of the high hopes, and of the HFEA approval, the cybrid experiments did not yield the expected results, in part because of lack of funding (see BioNews 491), and in part because another more promising technology came about – namely, iPS (induced pluripotent stem) cells, discovered by the Nobel-prize winning Japanese scientist Shinya Yamanaka in 2007 (see BioNews 476).

It remains to be seen how much funding research groups working on humanised animal models for organ transplants will be able to attract. But at these early stages of deliberation, it is important to reflect that investing in this research is a deliberate choice that will shape our collective future. By choosing to invest in this kind of research, we are actively deciding to how allocate scarce resources to address the social problem of shortage of human organs for transplants.

While we do not necessarily believe that the existence of viable alternatives should be used to ban humanised animal models outright, it is certainly a matter that deserves ethical attention. We need reflect on the fact that, by ignoring other potential solutions – or at least prematurely supporting one solution over another – we are actively privileging a medical/scientific solution over a political solution of devising and implementing policies to facilitate human-to-human transplants.

Historical reasons to be skeptical of scientific/medical solutions to social problems abound – the sterilisation of those considered a burden to society instead of investing in disability accommodations; the widespread use of Ritalin and Adderall to manage unruly children in schools instead of investing more resources in education; the use of expensive pharmaceutical solutions to epidemics in low-income countries that could be solved with basic public health measures. What we need is further critical reflection. Technical feasibility alone should never drive a change in law and policy.

19 April 2021 - by BioNews 
The director of the Progress Educational Trust is interviewed by 5 News about embryos containing material from both monkeys and humans...
14 August 2017 - by Cara Foley 
Ancient viral genes have been eliminated from pigs using the genome editing tool CRISPR, according to research...
30 January 2017 - by Arit Udoh 
Insulin-producing cells from pancreases grown in rats can cure diabetes when transplanted into mice, according to a study...
19 December 2016 - by Giulia Cavaliere 
It's not enough to just talk about the benefits of extending the 14-day rule, we must also consider the views of those who believe that human embyros are persons...
30 November 2015 - by Dr Silvia Camporesi and Dr Lara Marks 
It is important to engage the public in the debate about genome editing as early as possible, and in a way that is as open as possible, to make sure that all possible voices are included...
12 October 2015 - by Dr Silvia Camporesi and Dr Lara Marks 
The UNESCO International Bioethics Committee has released a statement reaffirming an earlier moratorium called by a group of US scientists on the use of CRISPR/Cas9 in human embryos. We argue that the current framing of the debate in terms of dystopic or imagined futures is too narrow and constrains the boundaries of the debate to germline applications...
27 April 2015 - by Dr Ross Cloney 
The image of eugenics often portrayed in the media is reminiscent of the horrors of the early to middle 20th century. Legions of identical blond-haired, blue-eyed ubermenschen, backed by an authoritarian state with no room for diversity or difference. In 'From Bench to Bedside, to Track and Field: the context of enhancement and its ethical relevance', Silvia Camporesi demolishes that image...
Author Response ( - 15/09/2016)
Thank you for your feedback on my PLoS Biology article. That Perspective piece had a very tight word limit, so I was not able to delve into the complexities and full range of issues that I ideally would have liked.  Perhaps as a result of this, your commentary above (to my surprise) attributes to me views that I do not actually hold. Thank you for this opportunity to clarify my own ideas.

First, I completely agree with you that there are many viable social and policy alternatives that ought to be pursued rigorously to increase the pool of available organs. I certainly did not mean to suggest that we should promote chimera research as the BEST or ONLY way to address this dire shortage.  But it can potentially help relieve some of the shortage, should it prove to work. Let a million flowers bloom -- all avenues should be pursued simultaneously.

Second, and on a related note, I also do not believe that NIH funding for chimera research and social and political efforts to increase donor organs are locked in some type of zero sum game.  The science budget for the NIH and state and national budgets for organ donor education, outreach, and procurement do not come from the same financial well such that the funding of one will lessen the funding for the other.  Personally, I think funding for both areas should be increased, and that the funding of one should never come at the expense of funding for the other.  One could engage in an interesting debate about national prioritization of basic and translational biomedical research vs. social welfare and health care budgeting, but that is a complex issue that takes us far from the focus of the PLoS Biology Perspective piece.  That said, I suspect you and I will agree on much more than we might disagree regarding this array of issues.

You conclude your commentary by saying that, "Technical feasibility alone should never drive a change in law and policy." I completely agree, and explain why this is the case in my book Bioethics and the Future of Stem Cell Research (Cambridge, 2013).  Cheers!
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