This 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.
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.
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.
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References
- Michael Daly, How Dick Tracy Invented the Apple Watch, The Daily Beast, https://www.thedailybeast.com/how-dick-tracy-invented-the-apple-watch
- James Gallagher, Human-pig ‘chimera embryos’ detailed, BBC NEWS, http://www.bbc.com/news/health-38717930
- Gina Kolata, Gene Editing Spurs Hope for Transplanting Pig Organs into Humans, New York Times, https://www.nytimes.com/2017/08/10/health/gene-editing-pigs-organ-transplants.html
- Merriam-Webster Dictionary, https://www.merriam-webster.com/dictionary/human#h2
- Star Trek, http://www.startrek.com/database_article/star-trek-the-original-series-synopsis
- S. Constitution, Article I, Section 2, Clause 3, University of Chicago, http://press-pubs.uchicago.edu/founders/tocs/a1_2_3.html
- S. Department of Health and Human Services, Organ Donation Statistics, https://www.organdonor.gov/statistics-stories/statistics.html
MSU Bioethics 
This topic seems to be a sensitive one for many people and it is not a subject that is straight forward. I definitely understand that it is important to advance medical technology and anything related to that but I personally think there is a fine line that can easily be crossed. The ambiguity of what makes someone a human is confusing to say the least. I thought it was interesting to pose the question of if a person receives a pig heart transplant cease to be human and becomes pig. It sounds silly to say out loud but technically speaking it makes sense. I also agree that humans do not have a great track record in recognizing humanity in others. As a result, it can make it extremely difficult to distinguish the boundaries between ethics and medical technological advances.
Thanks for the comments. Sometimes I feel like we have to say the silly question out loud to help us focus on the technical details that do really matter. Glad it got you thinking!
Bioethicist Alex Mauron tackles this question in his 2003 essay “Renovating the House of Being: Genomes, Souls, and Selves” Ann New York Acad Sci. 1001: 240. Cogent arguments against the genome-as-eidos view of humans, yet introduces equally brain-based arguments. Worth a look!
Great suggestion! Thanks!
Very interesting post! When thinking only about organ transplants, that in itself seems fairly harmless- why not use the available technology to help those people who can’t get organ transplants (which as you wrote, there are many)? If a loved one needed a transplant, I would want to look at all available resources, including pigs(!). However, when you examine the “slippery slope”, it does bring up many more ethical questions. How far will this new technology go? Will parents be able to create “super babies”? And will our definition of what makes us human evolve as this new technology evolves? I wonder if there are existing guidelines in the scientific community to guide future research/technology. Are there some areas of science that we just shouldn’t pursue b/c of ethical considerations? But on the flip side of that, are there areas that were considered unethical 50 years (or more) ago that we have explored/researched/advanced and are now considered acceptable/ethical?
I am not against the use of the technology in organ transplants (though I know some are). I just want us to start thinking about the issues in advance rather than reacting to them. Perhaps there are technological solutions to head off some issues. I believe the group who recently published the pig human chimera embryo studies said that they had some sort of fail safe switch if the human cells began to migrate to the brain.
The ability to create genetically modified children is coming, IMO. For a great novel based around potential impacts of such children, I highly recommend Beggars in Spain by Nancy Kress.
Thanks for the comments!
I found this post very interesting because I was not aware of the idea of genetically modifying pig organs so they can be used for human organ transplants. As you talked about in your post, I believe that this topic does bring up a lot in regards to ethics. I liked the question you posed about the possibility of genetic modification making pigs human. When reading this question I initially thought “well of course pigs wouldn’t be human”, then after thinking about it more it is a viable question. Scientist can’t 100% predict how the genetic modifying is going to impact the pig overall. What if this genetic modifying did somehow effect the pigs brain. Although when thinking about this it may seem far-fetched I do think this is something very important to consider. I also believe that this could be a slippery slop in the field of science. If we start to genetically modify animals for our own human health use where is the line drawn? More and more people could want to begin to use genetic modification for their own benefit. Will this lead to parents being able to design their “perfect” child? What policies and guidelines do you think would need to be set in place so that the use of genetic modification can be monitored and not be abused?
Research to enable parents’ ability to design their perfect child is also proceeding. Right now the researched is focused on repairing genetic mutations that lead to disease, but even that is fraught with questions. I wrote a blog post about this topic last year, questioning how to define a disease in light of this advancing technology. You might find it interesting (https://msubioethics.com/2016/10/20/defining-the-spectrum-of-normal/).
The first thing I think we need to do is think about when the technology should be used. This is a difficult question that not all countries will agree upon, and differences could lead to medical tourism as people country hop to get what they want.
Thanks for the comments!
You definitely pose a lot of very interesting questions. Something that I found to be particularly interesting was that pig heart valves have been used in human transplants since the 70’s. I worry about the reliance on animals for organs because as our population grows, our meat and animal industries are becoming more corrupt and exploitative. While these technologies are cool and life-saving, I think the more we explore genetic modification, it becomes difficult to draw that line between ethical and unethical behavior. I would like to see more public health and prevention initiatives as a solution to organ transplants. These may not be feasible with all transplants, but many heart valve transplants and general heart surgeries are the result of chronic health conditions like obesity. Risk factors like poverty play a significant role in nutrition and other health outcomes. As we take more steps towards preventing and/or providing solutions to these problems, hopefully we will see a decrease in the necessity of some of these major surgeries.
Thanks for the comments. One other issue that we need to think about is access. As much as poverty plays a role in some diseases that lead need, lack of access to any of the solutions is also a huge problem. Additionally, the idea of less need for transplants ties back into Eve’s comments about genetic edits to the human genome that could reduce the incidence of some diseases that lead to organ failure. Such research also makes it difficult to draw that ethical line.
A thought provoking topic!
Perhaps a little bit of a stretch, though your ideas cause me to consider humanity, I am also drawn towards questioning our culture’s peception of death and mortality. This is likely due to my own personal interest in end-of-life care, but based on the number you put forth regarding organ transplants and the length of the list, I cannot help but think about how physicians, family members and patients are understanding the reality of their health status. Is our culture, by advancing the progress of genetic testing, like you are describing, helping us cope with mortality or doing just the opposite?
It seems to me that the unfortunate reality of the wait for an organ accompanied by the “successful” genetic testing of non-human species, is providing false hope. This not to suggest that there shouldn’t be a transplant list, but perhaps to suggest the slowing of genetic testing in non-human species for the sake of humanity. Thus, I am wondering if we are providing false hope in the face of diminishing humanity? Humans are mortal… we know this, always have. Is subjecting hummanness worth the fight against ever prevailing mortality? Can there really be a fight against the mortality of the human?
Definitely not something that will happen tomorrow or next year. But as I tell my Biotechnology class, the things that I began discussing as science fiction 10 years ago are now today’s cutting edge science papers. Better to think about them in advance.
I do take your point about morality, though. Humans are mortal but the fight against mortality also seems to be a very human trait. We should never give false hope, but I also hope we continue the fight. Great thoughts. I leave you with the words of Dylan Thomas:
Do not go gentle into that good night,
Old age should burn and rave at close of day;
Rage, rage against the dying of the light.
Though wise men at their end know dark is right,
Because their words had forked no lightning they
Do not go gentle into that good night.
Good men, the last wave by, crying how bright
Their frail deeds might have danced in a green bay,
Rage, rage against the dying of the light.
Wild men who caught and sang the sun in flight,
And learn, too late, they grieved it on its way,
Do not go gentle into that good night.
Grave men, near death, who see with blinding sight
Blind eyes could blaze like meteors and be gay,
Rage, rage against the dying of the light.
And you, my father, there on the sad height,
Curse, bless, me now with your fierce tears, I pray.
Do not go gentle into that good night.
Rage, rage against the dying of the light.
This post was very interesting when I think of organ donations I think of humans donations not animal donations. Using a pig organ inside of the human body does raise the question as stated as to what it means to be human. It was interesting to learn that doctors have been using pig heart valves in transplants since the 1970’s. Using pig organs is alarming to me growing up in the farming community and being around agriculture knowing what viruses and diseases that pigs can have I feel would be harmful to the human body. It would useful to know how scientist’s are modifying theses viruses. This topic does draw the line to whether or not a human becomes pig or pig become human.
That fear of pig-human virus transmission was the reason for this study. The heart valves currently used are treated to minimize any such transfer but that would be more difficult with a fully functioning organ. My guess is transplant pigs would be raised in far different conditions than the farms you and I grew up with. Thanks for the comments!
Very interesting read! Great point on the ethical concerns on if the pig becomes a human or is it still considered a pig. Looking forward to future studies.
The future is here – in rats. News out just this week is that scientists have implants human brain cells into rat brains. Take a look at https://www.technologyreview.com/the-download/609354/tiny-human-brains-inside-rats-are-sparking-ethical-concern/.
When thinking about saving the life of a human, I think most people would agree that we should do whatever it take to make sure they stay alive; and I would agree but I find it difficult to sacrifice the natural biology of a innocent creature in the process. The evolution of science is extraordinary, however I also feel like genetically modifying a creature for the soul purpose to fix a human is not enough. After reading this, it made me think of out current nutrition battle (Genetically modified organism versus organic foods) before we were all about GMO’s and now we are seeing the side affects in our health. Ethically, I do not think it is right to modify an innocent creature for our selfish gain. In addition, we really do not know what side effects it may cause them. Look forward to reading new studies on this topic.
Thanks for the comments. In some ways we have been genetically modifying crops and animals as long as we have had agriculture. The differences we see as we begin to use direct molecular techniques are interesting, though.
A few years ago my mother’s best friend underwent heart surgery to replace a dysfunctional heart valve. My mother’s friend informed her that the surgeon gave him two options: a mechanical valve and a pig valve. Both valves had their pros and cons and ultimately my mother’s friend chose the mechanical valve because it lasts longer than a pig valve. Now in my mind whenever I have thought about organ donations I have only considered organs donated from other humans, even in the instance of my mother’s friend I did not consider the pig’s valve as an organ transplant. This blog post opened my mind to the possibility of genetically modifying pig organs to reflect human organs. This could potentially change the world of donations if in fact it worked. However, it is important to consider that there are multiple issues with organ donation between humans let alone what could happen between a human and genetically modified pig/human organ. From my understanding, the pig valves that are used to replace heart valves only last up to five years, so would a pig/human heart only last for a limited amount of time. I guess this would be one of my questions along with how would these new pig/human organs be tested appropriately?
I hope your mom’s friend is doing well. Thanks for your comments.
The pig valves don’t last as long due to all pig antigens leading to eventual rejection but they don’t damage red blood cells as badly so clotting is less of an issue than in mechanical valves. It really is a trade-off. The pig/human organs would theoretically last longer because the organs would be modified to look more human to decrease rejection.
These organs would undergo clinical trials like many other medical devices and drugs. Likely sick people with little other hope would received them first and if the organs proved successful then the clinical trials would widen. There are likely to be special protocols to look not just at outcomes but also pig-human cross infection risks as well.
I posted a link in a comment above but wanted to leave this description in its own comment in case anyone is interested. Just this past week, la story was published describing how labs are implanting human brain cells into rat brains in order to conduct research on numerous human brain diseases. If you are interested in learning more about the technology, check out the original article at https://www.statnews.com/2017/11/06/human-brain-organoids-ethics/