Center for Ethics professor Dr. Leonard M. Fleck is among a group of seventeen international co-authors of “Heritable Human Genome Editing: The Public Engagement Imperative,” published in the December 2020 issue of The CRISPR Journal.
Abstract: In the view of many, heritable human genome editing (HHGE) harbors the remedial potential of ridding the world of deadly genetic diseases. A Hippocratic obligation, if there ever was one, HHGE is widely viewed as a life-sustaining proposition. The national go/no-go decision regarding the implementation of HHGE, however, must not, in the collective view of the authors, proceed absent thorough public engagement. A comparable call for an “extensive societal dialogue” was recently issued by the International Commission on the Clinical Use of Human Germline Genome Editing. In this communication, the authors lay out the foundational principles undergirding the formation, modification, and evaluation of public opinion. It is against this backdrop that the societal decision to warrant or enjoin the clinical conduct of HHGE will doubtlessly transpire.
The full text is available with free access on the publisher’s website.
Delighted to post our latest contribution on the public engagement imperative re: remedial germline genome editing. Published in the The CRISPR Journal with @CohenProf & 16 contributors from around the world, the paper delineates the ways by which public opinion is formed. pic.twitter.com/whTP3ezVUf
The excitement and potential of CRISPR to treat severe genetic conditions by editing disease-causing DNA has taken an unexpected hit. A recent Wall Street Journal article highlighted the unexpected results from a CRISPR study in which attempts to edit a human gene responsible for blindness resulted in the loss of the entire chromosome from the cells in the embryos. These results echo another study conducted in human cell lines published earlier in 2019.
CRISPR is a targeted gene editing process that allows scientists to direct genetic modifications with far more precision than prior procedures. CRISPR has been touted as a gigantic leap in the ability to modify DNA by creating or repairing pinpoint DNA mutations without affecting other areas of the chromosome on which the gene resides. The recent study indicates that the technique might not be as straightforward in humans – and thus neither will be its use to fight disease.
Image description: A partially assembled puzzle that is an image of blue double helix DNA molecule structures. Image source: Arek Socha/Pixabay
CRISPR Technology – Promise and Problems
The value in CRISPR mediated genetic modification can be seen in a wide variety of biotechnology products, such as genetically modified crops and new biologics. But perhaps the most exciting and most controversial potential for CRISPR can be found in the desire to modify embryonic genomes to remove genetic abnormalities for which we currently have no cure.
This promise of embryonic gene editing is appealing not only because it would remove the condition from the child born from the gene-edited embryo, but also because the offspring of that child would also be free of the condition. CRISPR gene editing – because it is done at the embryonic stage – creates germline mutations that are passed to future generations. In a therapeutic use of CRISPR, those mutations would be cures for often untreatable diseases.
However, it is this very promise that raises many of the problems with CRISPR embryonic gene editing. Much debate has surrounded embryonic gene editing. Until this recent news, there were fears that CRISPR may make gene editing too easy. The technological development of CRISPR in embryonic gene editing is moving at a breakneck pace as scientists around the world are working on procedures. Biohackers work in their garages and livestream the use of CRISPR to edit their own genomes.
Many are debating which genes should be targeted and how fast the research into actual trials should proceed. Most agree that severe diseases would be the best place to start, but should the technology be deployed for cosmetic benefits such as eye color, or diseases for which a treatment exists? The dangers of CRISPR editing are unclear, and there has been an informal moratorium on the use of the technology to create children. Despite that, there has been at least one rogue scientist who has created genetically modified embryos and brought them to full term birth.
International Policy on Human Gene Editing
The scientific research is not occurring in a vacuum. Each country decides how CRISPR can be used in its medical system – both when the technique is safe enough and on which diseases it should be used.
An international commission recently pronounced that the technology is not ready for clinic implementation because scientists don’t understand the full safety issues surrounding its use in human embryos. The commission described some of the potential clinical uses in the future and outlined a basic safety protocol for approval.
One of the creators of CRISPR, Jennifer Doudna, has also spoken out against applying CRISPR too hastily to embryonic gene editing.
Based on the recent studies showing loss of chromosomes, the international commission and other scientists are correct to call for a moratorium on clinical embryonic gene editing.
Image description: An abstract image of blue and green double helix structures and binary code (zeros and ones) against a black background. Image source: Gerd Altmann/Pixabay
CRISPR – The Path Forward
The setback in CRISPR gene editing does not mean that the technology and research should be discarded. The potential to change lives is too great; however, the dangers of use with our current understanding are even greater. So how do we move forward with CRISPR in embryonic gene editing? The answer must include balance – in research strategies and in voices.
While the technology is not ready for clinical use, and we have not yet determined which uses would be appropriate if it were available, the science should not stand still. The research surrounding CRISPR gene editing will yield insights into human biology that we cannot predict. For example, the loss of chromosome length in human embryonic cells undergoing CRISPR treatment seems to be different than the response of other species of embryonic cells. And debates about the appropriate use of the technology will allow us to discover more about ourselves as humans.
As we debate the best way to develop and deploy CRISPR technology, we should look to a variety of stakeholders. Scientists have a solid track record in understanding when recombinant DNA technology has potentially hazardous implications. In the 1970s, the Asilomar Conference allowed scientists to put together research guidelines that allowed the technology to be developed without harming public health. In fact, the international scientific consensus not to use the technology such as described above indicates that scientists are beginning that work. Such a moratorium on clinical uses gives us time to understand how to deploy the technology in the safest manner.
Additionally, there is a role for the voices of the patients whose lives could be changed by the technology. Patients may not be in the best place to judge when the technology should be deemed safe enough to deploy, but they certainly will have input about which mutations cause hardships that merit the risk of germline editing. Many of these patients already work with scientists on potential treatments for their diseases. CRISPR discussions may open another avenue for many.
Finally, there is a role for legal regulation of the use of CRISPR. Governments should listen to the voices of scientists and potential patients in drafting these regulations. But as shown by the example of at least one rogue scientist, there needs to be teeth to the moratorium on CRISPR clinical use at this time. CRISPR and its use in human gene editing raise complicated issues and hold great promise as a powerful tool to defeat genetic diseases. The development of those technologies will not be straightforward or without risk and will require more basic science research to achieve clinical efficacy. But with proper planning, we may learn more about ourselves as humans on the path to a cure.
Jennifer Carter-Johnson, PhD, JD, is Associate Dean for Academic Affairs and Associate Professor of Law in the Michigan State University College of Law. Dr. Carter-Johnson is a member of the Michigan 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 Tuesday, December 15, 2020. 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.
Center Assistant Professor Dr. Laura Cabrera and co-author Dov Greenbaum have written an editorial published in Frontiers in Genetics, titled “ELSI in Human Enhancement: What Distinguishes It From Therapy?”
The open access editorial, published June 23, is available in full from Frontiers in Genetics.
In 2017, Josiah Zayner live-streamed himself injecting a gene therapy construct designed to edit the DNA in his muscle cells to give him bigger muscles. This moment was noteworthy because the gene therapy construct had been created entirely by Zayner in his garage laboratory. Such work is called biohacking or DIY biology.
These actions do not come without consequences. He has recently been investigated for practicing medicine without a license, and the state of California recently passed a law to require all such kits to include a notice “stating that the kit is not for self-administration.”
What is Biohacking?
Zayner is not alone; in fact, the biohacking movement is growing across the country. Zayner also sells kits that allow other biohackers to experiment with DNA and gene editing from his website, The Odin. There are also laboratories across the country that allow interested people to have space to conduct biology experiments without having to build a home laboratory.
Biohacking at its core is bringing science out of the laboratories of academia and industry and into grasp of citizen scientists. But the exact definition of what is included in biohacking differs among people. Biohacking includes a diverse variety of science experiments such as tracking of sleep and diet, under-skin implantation of computer chips and other technology, ingestion of “smart drugs” and sub-clinical levels of LSD, transplantation of gut and skin microbiomes, infusion of “young blood” to reverse aging, and genetic modification of bacteria, yeast and human cells.
Image description: an equipment setup called a “makerbay” in a Hong Kong biohacking makerspace. Image source: Athena Lam/Flickr Creative Commons.
Each type of biohacking brings its own risks and rewards. This blog post will focus on genetic modification of cells using new gene editing techniques such as CRISPR. Advances in gene editing technology over the past five years have made accessible science that was once confined to expensive, high-technology laboratories. For a broader look at CRISPR and gene editing by researchers and bio-hackers, Netflix has a new documentary series, Unnatural Selection.
Benefits of Biohacking
First and foremost, the benefit of biohacking is access to science. Not everyone can afford an advanced degree biology or wants to work full time in a laboratory. Biohacking democratizes science for people who have a passion for learning about the world and how it works. It also has the potential to increase access to medicine. One endeavor, the Open Insulin Project, attempts to find a cheaper and intellectual property-free way to produce and distribute insulin to make it available to people who have a hard time affording the drug.
In addition to access, biohacking communities are also hubs of outreach and education. The laboratory spaces often hold classes and meeting spaces for like-minded individuals to network. There are competitions that bring together student and citizen scientist teams who work on using synthetic biology to create biological solutions to local and international problems.
Biohackers are taking these responsibilities seriously as a whole. The community has even developed its own code of ethics emphasizing open access, transparency, education, safety, environment, and peaceful purposes.
Risks of Biohacking
Although biohacking has many benefits, there are risks of which the world and individual citizen scientists should be aware. Perhaps the largest potential threats are the lack of education and regulation within the biohacking community.
Image description: two people are gathered at a table containing various types of scientific equipment. Image source: Martin Dittus/Flickr Creative Commons.
While Josiah Zaynor holds a PhD in biopohysics, not all biohackers are so well educated. Community laboratories help with classes and mutual support, but home-based biohackers must rely on their own knowledge and understanding, though websites are available for questions and discussions. Education and outreach to biohackers is also the strategy of the FBI in recent years, though many biohackers are reticent to accept its help. Additionally, while the community does have a code of ethics, there is little formal ethics training in concepts such as informed consent or using animals in research.
Due to the open definition and decentralized structure of biohacking, regulation is almost impossible. Lack of regulation leaves laboratory safety in the hands of the biohackers. As with any scientific endeavor involving genetic engineering, accidents can occur that could lead to the release of environmentally destructive organisms. Biohackers injecting themselves or others could cause any number of infections or adverse reactions. Additionally, the risk of the development of dangerous or ineffective gene therapies and other products by biohackers has led the Food and Drug Administration to issue warnings to the public about untested products. This risk is especially relevant in an era of rising drug costs.
Other dangers, such as specific threats to biosecurity, are real but attenuated. While it is possible biohackers could genetically engineer a bacteria or virus, there are far easier ways for a small-scale terrorist group to attack.
Future of Biohacking
Highly technical equipment and processes are becoming more accessible. People are looking for ways to take control of their health and provide access to medicines. Curiosity about the natural world should be encouraged.
The risks are real, but we can deal with them by working together. By having community leaders willing to confront the risks and help develop community norms, we can shape the application of biohacker energies. Zayner himself has realized that other biohackers may seek to emulate his self-experimentation and get hurt.
In the end, biohacking is here to stay.
Jennifer Carter-Johnson, PhD, JD, 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. 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 14, 2019. 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.
In November of 2018, a Chinese scientist announced that he had edited the embryos of twin girls and that the twins had been born. The scientist, He Jiankui, used CRISPR, a revolutionary method of editing sequences of genes, to delete the gene CCR5 from the embryos’ sequences. The intention was to make the twins resistant to HIV. Editing human embryos and allowing those embryos to develop into living, breathing babies was widely condemned. However, now it appears possible, likely even, that the twins’ cognition was impacted, perhaps improved. This, however, was an off-target effect—it was unintended. On March 13, Nature published a comment from a group of scientists calling for a moratorium on clinical uses of human germline editing. This call is only for a moratorium on clinical uses, not on research on editing the human germline.
Despite the moratorium, I think a good argument can be made that tolerating the clinical use of human germline editing is morally permissible. Here is one such argument. The fact that He Jiankui edited the girls’ embryos suggests that it is inevitable that some scientists are going to engage in this behavior. Imposing a moratorium is unlikely to change this—the cat’s out of the bag. Given that the behavior is inevitable, we should ensure it is performed as safely as possible in order to reduce the risk of harm.
Image description: an illustrated image of a strand of DNA with a piece being inserted, representing CRISPR-Cas9 technology. Image source: NIH Image Gallery/Flickr.
The Inevitability Argument
I’m claiming that because clinical use of human germline editing is now inevitable, we should tolerate and regulate it. Generally, arguments of this type don’t work. It isn’t generally true that just because something is going to happen anyway, we should not only tolerate that behavior, but also make sure that it is done safely. For example, it’s true that humans murdering other humans is inevitable (unless we can cognitively or morally enhance people through, for example, gene editing!). Despite prohibitions on murdering, it still happens and probably always will. But its inevitability doesn’t mean that we should tolerate it but ensure that it is done safely. We shouldn’t, obviously.
Sometimes the argument does work, though. Sometimes the inevitability of a behavior suggests that we should tolerate it under regulation. For example, people using IV drugs is, for the foreseeable future, inevitable. Given this inevitability, it is morally justifiable to tolerate the behavior and do what we can to ensure that it is done safely. One way we do this is through needle exchanges. More recently, similar arguments support the widespread availability of naloxone for overdoses. So, sometimes, but not generally, the inevitability of a behavior justifies the tolerance of the behavior in order to ensure it is performed safely.
Reducing Harm
Why does the Inevitability Argument work in the case of needle exchanges? Why does it fail in the case of murder? One difference is that we know murder is wrong. You can’t have the concept of murder without also having the concept of wrongness. To tolerate murder would be to tolerate something that is morally prohibited. But we should be more skeptical of the wrongness of IV drug use—it may not be wrong at all, to say nothing of policies that permit or prohibit it. Even if it is wrong, our confidence that it is so should be lower. Another difference is that in the case of needle exchanges with IV drug users, the tolerance and regulation is meant to reduce harm, not only to the users, but to society. On the face of it, it seems implausible that one could anticipate a parallel policy of tolerating and regulating murder to reduce harm. Rather, tolerating and regulating murder would increase harm.
Inevitability of Clinical Use of Human Germline Editing
Is the clinical use of human germline editing more like IV drug use, or more like murder? Supposing that whether the Inevitability Argument works depends on whether we know the behavior being tolerated is wrong, and whether tolerating it is intended to reduce harm, the clinical use of human germline editing seems much more similar to IV drug use than it does to murder. First, we don’t know whether the clinical use of human germline editing is wrong, unlike our knowledge that murder is wrong. Whether it is wrong or permissible or obligatory depends on a lot of factors, including on whether embryos have a moral status and whether we have a duty to future persons.
Second, what would tolerating the clinical use of human germline editing look like? It would require scientific and political oversight of methods, data, and follow-up clinical care. But more importantly, the tolerance and regulation of the clinical use of human germline editing would require that we know more about what the effects of it will be. The only way we can acquire this knowledge is by conducting research on the clinical consequences of editing the human germline. This is all to say that the intention of tolerating the clinical use of human germline editing is to reduce as much as possible any potential harms, both to the person whose embryo was edited as well as to society.
Tolerating and Regulating Clinical Use of Human Germline Editing
By these criteria, the clinical use of human germline editing looks much more like needle exchanges for IV drug use. If so, then the Inevitability Argument may work, suggesting that we should tolerate and regulate its practice. But this tolerance and regulation impose further requirements: we must closely monitor the behavior and support research on the effects of editing the human germline.
Scientists assert (without sufficient foundation, I think) that the behavior is wrong. Do we really know that the clinical use of editing the human germline is wrong? If so, what general principle grounds this knowledge? What are the consequences of this general principle for other lines of scientific research? Is the clinical use of human germline editing really inevitable?
Parker Crutchfield, PhD, is Associate Professor in the Program in Medical Ethics, Humanities, and Law at the Western Michigan University Homer Stryker M.D. School of Medicine, where he teaches medical ethics and provides ethics consultation. His research interests in bioethics include the epistemology of bioethics and the ethics of enhancement, gene editing, and research.
Join the discussion! Your comments and responses to this commentary are welcomed. The author will respond to all comments made by Thursday, April 18, 2019. 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.
Give God a rest; do your own gene editing (and thinking). On August 2, 2017 the New York Times headline read, “In Breakthrough, Scientists Edit a Dangerous Mutation from Genes in a Human Embryo.” The mutation was of a gene called MYBPC3, and the result of that mutation is a disease called hypertrophic cardiomyopathy. This disease affects 1 in 500 people. Its victims are typically young athletes. CRISPR-cas9 is the technology used to accomplish the gene editing. More precisely, a synthetic healthy DNA sequence was injected into an egg cell fertilized by a sperm cell with the mutated gene. This healthy DNA sequence was supposed to be copied into the newly created embryo. In fact, however, the maternal DNA was copied, thereby correcting the paternal mutation in 72% of the resulting embryos. A total of 54 embryos were created, later destroyed, after genetic analysis had been done. The remaining embryos were genetically mosaic. This research received worldwide attention.
Image description: a black and white image of an 8-cell human embryo, day 3. Image source: Wikimedia Commons.
I want to raise two questions. How should we assess this research and its future possible uses from an ethical perspective? How should we assess public policies designed to regulate this research now and in the future? I am going to give more attention to this latter question in the context of a liberal, pluralistic, democratic political culture because many people would demand that the research itself be outlawed, not just regulated. The relevant question to ask is this: What sort of justification must be given for regulating or banning gene-editing technologies used to create or modify human embryos? The short answer I will defend in response to that question is that regulations must satisfy public reason and public interest requirements (as explained below).
From an ethical perspective, gene-editing technology represents considerable potential benefit, as the example of hypertrophic cardiomyopathy above suggests. At least 200 single-gene disorders could be corrected at the embryonic or pre-embryonic level, thereby preventing premature death or substantial diminishment of quality of life in these future possible children (as well as potential descendants of those children). To be clear, no gene-editing technology is ready for clinical application. Off-target effects remain a problem. From an ethical perspective, the risk-benefit ratio of such interventions today weighs too heavily on the risk side. Researchers, however, are confident that these risks can be overcome.
Assuming that the safety issues can be effectively managed, another ethical objection is that these future possible children (maybe for several generations) would not have consented to such fundamental interventions. I do not see this as a compelling objection. Parents today must consent to very risky surgery or other medical interventions in a two-year old child that could result in the death of that child or substantial lifelong impairment. We have to trust the judgment of parents and physicians in such circumstances. We have to believe they are all acting in the best interests of that child (absent compelling evidence to the contrary). This seems perfectly analogous to what would be occurring with gene-editing of an embryo. (For a broad overview of relevant ethical principles, see Wolpe et al., 2017.)
I now want to switch to concerns in the context of public policy. What sort of political justification would be needed to legitimize the complete banning of gene-editing research on human embryos? Here are two answers that are entirely “out of bounds” in a liberal, pluralistic society: (1) doing gene-editing of embryos is “playing God,” and (2) destroying embryos should never be regarded as an acceptable part of medical research.
The phrase “playing God” invokes amorphous religious associations, deliberately and arrogantly engaging in some life-or-death activity that is the exclusive prerogative of God. However, if this is supposed to be a compelling argument for public policy purposes, then large areas of medical practice would have to be outlawed as well. It might well be the will of God that I die from my heart attack, but I still want my surgeon to be agnostic and do the bypass surgery needed to save my life. God is typically described as being omnipotent, though millions of embryos are created annually with thousands of serious genetic disorders. Allowing those future possible children to suffer the awful consequences of those disorders by forbidding the development of the technology that could correct those disorders looks like willful social negligence, not impiety.
Critics of gene-editing rail against the possible, speculative harms this technology could unleash on future generations of children, all the while ignoring the very real harms current actual children are having to suffer as a consequence of these genetic disorders. This is not just shortsighted; it is ethically and politically perverse. Virtually everyone agrees that it would be premature today to do embryonic gene-editing with the intent of bringing that future possible child to birth. However, nothing would justify laws that would forbid going forward with the research until such time as it would be safe to introduce into the clinic.
Some religious critics will object to the destruction of embryos that will be integral to the development of this technology. We noted above that 54 embryos were created and destroyed in connection with the hypertrophic cardiomyopathy research. Some religious critics will see those embryos as having the moral status of persons with the same rights as you and I. However, this is where public reason must be invoked as the appropriate basis for formulating policy in a liberal, pluralistic society.
Public reason (Rawls, 1996) must be neutral or agnostic with respect to all religious belief systems or other comprehensive worldviews. From an objective, scientific perspective embryos have no capacity to feel pain, no consciousness, no interests, and no personal identity. Embryos are not mini-persons. Some religious adherents may believe otherwise. They are free to affirm that belief in the private social space of their religious community. However, they may not seek to create laws that would effectively impose that belief on citizens who did not share that belief. This would be an illegitimate, illiberal use of the coercive powers of government unless they were able to justify such laws through an appeal to public reasons and related public interests.
Public reasons are reasons that all free and equal reasonable citizens as citizens can accept as reasonable, as consistent with the best science and fair terms of cooperation in a just society. Public reasons are the currency of rational democratic deliberation. Public interests are interests that all citizens have, and that could not be adequately protected or enhanced without the use of the coercive powers of government to control those who would threaten those interests. Protecting air and water quality would be a clear example of a public interest.
A liberal, pluralistic society recognizes and respects many reasonable ways of living a good life. Individuals are free to order their lives in accord with many different reasonable values that do not represent a threat to the rights of others or to various public interests. Consequently, such a society will accept that some people will refuse to use gene-editing technology in the future to alter the genetic endowment of their future possible children. This is political respect for procreative liberty.
It would be illiberal and illegitimate for some political group to use the coercive powers of the state to force religious individuals to use gene-editing technology, contrary to their religious beliefs. Likewise, these religious individuals must be mutually respectful of the procreative liberty rights of others to use gene-editing technology to alter the genetic endowments of their future possible children. This would include paying taxes to support the medical and scientific research needed to develop safe and effective versions of embryonic gene-editing, keeping in mind the taxes needed to pay for the health care needs of children born with cystic fibrosis or muscular dystrophy or any number of other medical problems that could have been avoided with judicious gene-editing.
In conclusion, there can be reasonable disagreement regarding various uses of embryonic gene-editing technology. However, that disagreement will have to invoke public reasons and public interests. God’s will and God’s won’t are not public interests.
Leonard M. Fleck, PhD, is a Professor in the Center for Ethics and Humanities in the Life Sciences and the Department 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 by Thursday, December 14, 2017. 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.
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.
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.
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.
Jennifer 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.
You must provide your name and email address to leave a comment. Your email address will not be made public.
Center Assistant Professor 
This post is a part of our 
MSU Bioethics 