Alien Organs

Article Written by Cerdan Lopez
Illustration by Savio Aquino
Posted 12 November 2021

Coming from a family with a history of both diabetes and hypertension, I live in fear of one day acquiring them. And, one day, one of my organs may fail because of them. Causing me to require an organ transplant, putting me on a waitlist. A waitlist that, unfortunately, has about 20% to 35% of people on it die without ever getting a transplant. [1]  But what if you didn’t need the waitlist? Because you can have an organ made for you. [2] An organ grown in an animal. This is the dream of xenotransplantation. [3]

Xenotransplants are not a new concept. [3-5]. While ancient humans had myths of humans gaining animal organs, it was only in the 17th Century, when Jean-Baptiste Denis performed blood xenotransfusions, that the idea took hold. [3,5] And it was only on the 26th of October 1984, when Leonerd Bailey gave a dying baby a baboon’s heart, that xenotransplantation was proposed as a solution to organ shortages. [5,6]

Of course, today, the most common animal talked about in xenotransplants are pigs. [3] This is due to the deletion of the antigen galactose-⍺-1,3-galactose in 2003. [7] With improvements in genetic engineering, such as developments in CRISPR-Cas9, there is more and more talk about the very real possibility of xenotransplantation as a common medical procedure. [7-9]

While pig valves are already widely used as a common xenograft, xenotransplantation, specifically from pigs, has recently been in the news due to Dr Robert Montgomery and his team. [3, 10] They had done something incredible. Not only had they transplanted a porcine kidney into a patient, along with a bit of porcine thymus, they had done so successfully. After closely monitoring the patient for about two and a half days, it was declared a success. 

Despite this success, there are multiple worries and concerns.

One such concern lies in a delayed rejection response. [11] While most xenograft rejections occur within a few hours to a few days after the surgery, a rejection can occur weeks after the surgery. [11, 12] Since the organ is foreign, immune cells can and do attack them unless the immune system is mitigated by immunosuppressants. 

Another large concern has to do with pig biology itself. For one thing, pigs live a much shorter lifespan than humans, only up to fifteen years. Thus, there are concerns as to if these organs would even last the lifespan of a human. There is also the problem of differing needs between organisms such as the enzymes, nutrients, and even internal body temperature. [13]

Of course, there is the possibility of zoonotic transmission of diseases to humans. If ever a pig infected with a disease has its organ transplanted into a human, there’s a chance that the disease will mutate and start infecting humans. This is, in part, due to the organ being directly placed inside the body instead of going through the normal external routes first, such as the digestive system. [3, 14] Given this, there are concerns as to the ethical nature of such a procedure if it can potentially endanger the lives of not just the recipient but also society as a whole. [15]

When Leonard Bailey successfully transplanted the baboon heart, ethical concerns were raised. One of which has to do with animal rights. Since animals do feel pain, is it right to breed an animal merely to harvest its organs? There are arguments made that killing any animal life to save a human one is unethical. Although there are those who believe in a line that can be drawn, where primates are not okay but pigs are. [6]

There is also the manner of informed consent. [16-20] A huge part of informed consent is that the patient must be fully aware that they are receiving the organ from a non-human source. The patient must know the potential side effects of such a procedure as well as any dangers. Above all, the patient must be able to back out at any moment. There is an emphasis on bridging the knowledge gap between patient and doctor, trust between patient and doctor, as well as the agency of the patient. This is important since, as stated earlier, there is a risk of zoonotic transmission. [3, 15] Thus, there is a real possibility that the patient must be closely monitored for the rest of their life. They must disclose their status to others, such as healthcare professionals and even sexual partners. These, however, may violate the ethical code that states that patients are guaranteed anonymity for procedures such as these.

Of course, when talking about informed consent, one must never forget to tell the patient of options. There’s the obvious option of being on the waitlist for a human organ but there’s also the possibility of cloning or even printing your own. While organ cloning and printing are not the topic of this article, I will briefly discuss them.

 Cloned organs can be 100% genetically identical to the recipient as stem cells can be taken from the individual who needs the transplant. [21, 22] However, one can also easily get DNA from someone who is a close genetic match and grow the organ from there. These stem cells are grown in a medium and are induced to differentiate into the organs needed. 

Printing organs is a different affair. Using biodegradable materials, a machine is used to print the organ needed. [23] These materials can be natural, synthetic, a hybrid of both, or even the adult stem cells of the patient. The idea is that one only needs code and materials in order to print any organ.

However, in the face of all this new technology, we must remember that we aren’t quite there yet. We aren’t at a point where these can be regular medical procedures. But what if we were. Let’s say we’ve done it. We’ve perfected all of these technologies. You can simply request to print or clone or have an organ grown in an animal. No side effects, no scientific reason not to use them. What do we do?

Yes there are ethics involved but all of these ethics boil down to one question: “To what measure is a non-human?” Or, in other words, where do we draw the line?

When we print organs that perform, objectively speaking, better than the original, is that fine? A heart that never fails, muscles that are stronger, eyes that see better… Is it fine that some people, inherently, will have access to this technology while the rest of us scramble with our genetically random organs? 

When we clone organs, are they ours for the taking? A clone, a true clone, is an individual in their own right. Copying errors, environmental factors, and differing experiences make clones distinct from their clone parents.What if one has cloned enough organs and cells to make an individual, is that fine as long as a person isn’t cloned all at once?

If you create an animal for the sole purpose of harvesting its organs, is that still okay? We’ve genetically manipulated pigs to make xenotransplantation easier. What if we find a way to make organs that can be transplanted into a human with no discernable genetic difference between the human organs and the animal ones? At what point does the animal become human?

These are difficult questions to answer and, thankfully, we’re not there yet. But we’re at a crossroads. We are at a point in history where we can decide whether to continue pursuing this technology or not. 

In all of these, we must remember that science is neither good nor bad. It is ultimately what we do with science that matters. And even though ethical concerns involving this technology may delay or even stop its progress, that is, ultimately, a good thing. Because progress is not measured in how many inventions we have, in how much knowledge has been acquired. Progress, true progress, is measured in how much value we give a life. It is measured in the decency we place in a life that we would consider insignificant.

We just have to decide what that means.

References

  1. Healy D, Lawler Z, McEvoy O, Parlon B, Baktiari N, Egan J, Hurley J, McCarthy J, Mahon N, Wood A. Heart Transplant Candidates: Factors Influencing Waiting List Mortality. Irish Medical Journal. 2005;98(10):235–237. PMID: 16445141
  2. Tönshoff B. Immunosuppressants in Organ Transplantation. Handbook of Experimental Pharmacology. 2019;:441-469. DOI: 10.1007/164_2019_331
  3. Ekser B, Li P, Cooper D. Xenotransplantation. Current Opinion in Organ Transplantation. 2017;22(6):513-521. DOI:10.1097/MOT.0000000000000463
  4. Reemtsma K. Xenotransplantation: A Historical Perspective. ILAR Journal. 1995;37(1):9-12. DOI: 10.1093/ilar.37.1.9
  5. Shayan H. Organ Transplantation: From Myth to Reality. Journal of Investigative Surgery. 2001;14(3):135-138. DOI: 10.1080/089419301300343282
  6. Rémy C. The Animal Issue in Xenotransplantation: Controversies in France and the United States. History and Philosophy of the Life Sciences [Internet]. 2009 [cited 8 November 2021];31(3/4):405-428. Available from: https://www.jstor.org/stable/23334492
  7. Cooper D, Ekser B, Ramsoondar J, Phelps C, Ayares D. The Role of Genetically Engineered Pigs in Xenotransplantation Research. The Journal of Pathology. 2015;238(2):288-299. DOI: 10.1002/path.4635
  8. Perkel J. Xenotransplantation Makes a Comeback. Nature Biotechnology. 2016;34(1):3-4. DOI: 10.1038/nbt0116-3
  9. Xenotransplantation 2.0. Nature Biotechnology. 2016;34(1):1-1.DOI: 10.1038/nbt.3466
  10. Roberts M. US Surgeons Test Pig Kidney Transplant in a Human [Internet]. BBC News. 2021 [cited 8 November 2021]. Available from: https://www.bbc.com/news/health-58993696
  11. Hryhorowicz M, Zeyland J, Słomski R, Lipiński D. Genetically Modified Pigs as Organ Donors for Xenotransplantation. Molecular Biotechnology. 2017;59(9-10):435-444.DOI 10.1007/s12033-017-0024-9
  12. Lu T, Yang B, Wang R, Qin C. Xenotransplantation: Current Status in Preclinical Research. Frontiers in Immunology. 2020;10. DOI: 10.3389/fimmu.2019.03060
  13. Candinas D. Xenotransplantation: Postponed by a Millennium?. QJM. 2000;93(2):63-66. DOI: 10.1093/qjmed/93.2.63
  14. Takeuchi Y, Weiss R. Xenotransplantation: Reappraising the Risk of Retroviral Zoonosis. Current Opinion in Immunology. 2000;12(5):504-507. DOI: 10.1016/S0952-7915(00)00128-X
  15. Kaiser M. Xenotransplantation–Ethical Considerations Based on Human and Societal Perspectives. Acta veterinaria Scandinavica Supplementum. 2004;99:65–73. PMID: 15347151
  16. Ellison T. Xenotransplantation – Ethics and Regulation. Xenotransplantation. 2006;13(6):505-509. DOI: 10.1111/j.1399-3089.2006.00352_3.x
  17. Cohen S. Nudging and Informed Consent. The American Journal of Bioethics. 2013;13(6):3-11. DOI: 10.1080/15265161.2013.781704
  18. Millum J, Bromwich D. Informed Consent: What Must Be Disclosed and What Must Be Understood?. The American Journal of Bioethics. 2021;21(5):46-58. DOI: 10.1080/15265161.2020.1863511
  19. Manson N, O’Neill O. Rethinking Informed Consent in Bioethics. Cambridge: Cambridge Univ. Press; 2008.
  20. Dougherty T. Informed Consent, Disclosure, and Understanding. Philosophy & Public Affairs. 2020;48(2):119-150.DOI: 10.1111/papa.12164
  21. Seedhouse E. The Human Clone Market. Beyond Human. 2014;:51-64. DOI: 10.1007/978-3-662-43526-7_4
  22. Cascalho M, Platt J. The Future of Organ Replacement: Needs, Potential Applications, and Obstacles to Application. Transplantation Proceedings. 2006;38(2):362-364. DOI: 10.1016/j.transproceed.2005.12.055
  23. Ventola C. Medical Applications for 3D Printing: Current and Projected Uses. P & T : a peer-reviewed journal for formulary management. 2014;39(10):704–711. PMID: 25336867

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