Every 8 minutes, one more person in America is added to the organ transplant waiting list. Sadly, many never make it off that list; 17 patients die everyday waiting for an organ donor.⁵

Richard Slayman, a 62-year old man from Weymouth, Massachusetts, was one of these patients. After having had a kidney transplant in 2018, Slayman had been experiencing advanced kidney failure once again four years later. Even after many surgeries to improve his transplanted kidney’s function, it seemed that nothing was working.¹

Slayman was in dire need of a human kidney donor, or another solution. 

That was when a transplant nephrologist, Dr. Leonardo V. Riella, suggested sourcing the kidney from a pig instead of a human donor.¹ A pig kidney was chosen due to the fact that the size as well as function of their kidneys are very similar to human kidneys.

The idea was not new, so-called ‘xenotransplantation,’ or “ transplantation . . . into a human recipient of . . . live cells, tissues, or organs from a nonhuman animal source . . .,” has been researched for many years.² 

In fact, xenotransplantation has been attempted many times in the past as well, including an attempt with a genetically modified pig heart in 2022.⁷

Thus, Dr. Riella was hopeful that a pig kidney transplant for Slayman would be successful. The procedure with a genetically modified porcine (or pig) kidney had already been tested on several brain-dead patients, as well as successfully in monkeys.⁴

Beyond that, the researchers had found ways so that the patient’s body would not reject the organ, otherwise known as “hyperacute (or immediate) xenograft rejection [HAR response]”.³These obstacles were overcome by ultimately editing 128 genes in the pig’s genome with CRISPR-Cas9.⁴

Pig cells contain various sugars that the human body contains antibodies against (the human body naturally recognizes and defends against). One such sugar that the pig cell contains is galactose-α (1–3) galactose, which is very similar to a human gut bacteria, thus the human body has developed an immune response (antibodies) against this sugar and bacteria. Thus, when a pig organ is inserted into a human patients, the sugars present on the pig cell triggers an immune, or HAR response, which results in destruction of the transplanted organ, or graft in the patient.³ Genes related to three such sugars in the pig were knocked out using CRISPR. Furthermore, “seven genes were added because they produce human proteins that help to prevent organ rejection”.⁴ 

Additionally, the pig was grown in a sterile environment to prevent bacterial and viral infection in the human patient. However, the pig still contained pieces of viral genetic elements that could become activated when transplanted and elicit an immune response in Slayman. 59 CRISPR edits were made in order to also inactivate these viral genes.⁴ 

With all this background research and additional precautions, the transplantation surgery for Slayman was performed on March 16, 2024.  “Once the surgeons restored blood flow to the transplanted pig organ, it immediately became pink and started to produce urine . . . a sign that the transplant had been successful”.⁴

Although the operation was successful, the patient’s doctors continue to be cautious. Slayman continues to be monitored for symptoms of a healthy kidney through metrics such as creatinine level (low levels indicate that the kidney is filtering waste efficiently). Doctors are also administering immunosuppressive drugs before Slayman is discharged so that his body does not have an immune response to the transplant.⁴ 

Nonetheless, with this preliminary success, his surgery and continued recovery brings hope for an end to the organ donor crisis and all those on the organ transplant waiting list.

Certainly, the idea of xenotransplantation is not without ethical concerns. If xenotransplantation becomes a more common practice, many are already concerned on issues of animal welfare, as well concerns of inaccessibility to certain demographics of patients due to cultural and religious practices.⁶ 

Nevertheless, xenotransplantation provides at least a possible solution to the organ donor crisis. Slayman himself summed it up best: “ ‘He [Slayman] saw this as not only a way to help himself, to improve his own quality of life . . . he thought it was also a way to provide hope for the thousands of people in need of a transplant themselves, and he thought that it was worth this experimental effort’”.¹

References

1. “A milestone”: Harvard affiliated physicians perform first-ever pig kidney transplant: News: The Harvard Crimson. News | The Harvard Crimson. (n.d.). https://www.thecrimson.com/article/2024/3/26/first-kidney-pig-transplant/ 
2. Center for Biologics Evaluation and Research. (n.d.). Xenotransplantation. U.S. Food and Drug Administration. https://www.fda.gov/vaccines-blood-biologics/xenotransplantation 
3. Galactose-alpha-1,3-galactose. Galactose-alpha-1,3-galactose – an overview | ScienceDirectTopics. (n.d.). https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/galactose-alpha-1-3-galactose#:~:text=In%20the%20case%20of%20a,destroying%20the%20graft%20via%20HAR 
4. Mallapaty, S., & Kozlov, M. (2024, March 22). First pig kidney transplant in a person: What it means for the future. Nature News. https://www.nature.com/articles/d41586-024-00879-y
5. Organ donation statistics. (n.d.). https://www.organdonor.gov/learn/organ-donation-statistics 
6. Rollin B. E. (2020). Ethical and Societal Issues Occasioned by Xenotransplantation. Animals: an open access journal from MDPI, 10(9), 1695. https://doi.org/10.3390/ani10091695
7. Siems, C., Huddleston, S., & John, R. (2022, March). A Brief History of Xenotransplantation.
8. The Annals of Thoracic Surgery. https://doi.org/10.1016/j.athoracsur.2022.01.005 

Image References

Cover Image: https://medicine.wustl.edu/news/covid-19-boosters-important-for-patients-who-undergo-solid-organ-transplants/

 Figure 1 source: https://www.nytimes.com/interactive/2018/11/14/magazine/tech-design-xenotransplantation.html