Author: Genevieve Doctor

As of April 4, 2025, there are 103,223 people in the United States waiting for an organ transplant that could save or greatly improve their life. Of those 103,223 people, seventeen of them will be dead by the end of the day. Tomorrow, seventeen more. Every eight minutes, another person is added to the transplant list at the United Network for Organ Sharing (UNOS), the only organ procurement and transplantation network in the United States. Eighty-six percent of those on the list need a kidney, but livers, hearts, lungs, pancreases, and other organs are needed as well. While over 170 million people in the United States are registered donors, only three out of a thousand people will die in a way that allows for deceased organ donation. The simple truth is this: we do not have enough organs. 

The need for organs has only grown in America, largely due to increased longevity and higher rates of obesity associated with organ failure. Both science and public policy changes have offered a variety of creative potential solutions. One concept adopted in parts of Europe is known as “presumed consent,” where citizens choose to opt out of being an organ donor upon death, as opposed to the American system of opting-in. Another idea is to broaden the pool of cadaver donors by expanding the brain death requirement to a “persistent vegetative state” or allowing a potential donor who is soon to die to choose to donate their organs and experience a “death by donation.” While these potential solutions are ripe for controversy and ethical concerns about consent, they only slightly expand the donor pool—and, still, very few people are likely to die in a manner conducive to organ transplantation. A newer idea offers a different set of questions and controversies while having the capacity to almost completely solve the organ shortage crisis: xenotransplantation. 

Xenotransplantation is already progressing in the United States. On March 21, 2024, Mass General Hospital performed the first successful kidney xenotransplantation into a living recipient, done under compassionate use for the recipient with no other option, and extended his life by two months. Furthermore, just recently on February 3, 2025, the FDA approved a clinical trial for patients with end-stage renal disease and the first transplant is expected to take place mid-year 2025. So, what is it? 

Xenotransplantation is a process that uses organs from genetically modified pigs rather than human organs. The genetic modification is done using CRISPR/Cas9, the leading gene editing technology. Pigs are an ideal candidate for xenotransplantation for multiple reasons, including the similarities between pig and human organs, their short gestation period, their large litter sizes, and the present common acceptance of pigs being used as meat animals. Furthermore, the widespread use of pigs for organ transplants would present numerous benefits, including providing a near-unlimited supply of organs, reducing illegal organ trafficking, and allowing “borderline” candidates who would otherwise be denied a transplant an opportunity to have a new organ. 

All this being said, xenotransplantation certainly presents a slew of complications and concerns. On the medical side, there is a possibility of transmitting animal viruses to the recipient and loved ones near the recipient. Furthermore, while pig kidneys are similar to human ones and both filter waste from blood and make urine, human kidneys have many important roles and it is currently unclear if pig kidneys can fulfill these functions long-term (though the longest-living recipient of a pig kidney says she is currently doing very well, months after the transplant). As for the pigs, they must be raised in sterile conditions to reduce the likelihood of infection to the human recipient. The pigs are also genetically modified to make their organs more suitable for humans and reduce the likelihood of animal viruses being transmitted, which has presented a debate on the ethics of using animals in such a way. 

With the FDA giving the green light to clinical trials and the purported success of recent kidney xenotransplants, xenotransplantation appears to be gaining speed. It may present a unique solution to the organ shortage crisis while posing interesting questions about the consequences of using such technology. 

The 21^st century has ushered in an era of incredible advancements in medicine. From the first uses of online patient portals to nanomedicine, how people are treated for their health has changed drastically. It then follows that as medicine itself develops, the regulations and protocols surrounding medicine change with it. In the United States, the Food and Drug Administration (FDA) is the gatekeeper of all new medicines. Each year, the FDA approves only dozens of novel drugs, approving fifty-five in 2023 and thirty-seven in 2022. At the end of 2023, the FDA approved the first CRISPR/Cas9-based gene therapy for treatment, implicating new questions surrounding regulations of the powerful yet controversial technology and its other applications. 

CRISPR/Cas9 is the nickname for “Clustered Regularly Interspaced Short Palindromic Repeats” and “CRISPR Associated Protein 9.” It is the leading technology for editing the human genome. The applications of CRISPR are virtually limitless, from treating genetic diseases to organ transplantation to altering the genetic code of future generations. The FDA approved clinical trials of CRISPR for treating genetic diseases in 2021, effectively treating patients with sickle cell disease. In just a few short years, these treatments were greenlit for treatment in the United States. However, as CRISPR technology advances, regulations have limited its other uses. Currently, there is a ban in the United States on using federal funds for editing the genes of future generations while embryos (i.e., “germline editing”), prohibiting the FDA from approving any clinical trials for such modification and the National Institute of Health (NIH) from funding research. However, germline editing is not technically illegal in the United States—any research must use only private funding, though it is globally discouraged. The question is: are the existing regulations on germline gene editing proper? 

There are clear ethical concerns about editing human embryos that make it widely acceptable amongst researchers that the brakes have been pumped on developing the technology, which isn’t quite ready for human trials. The lack of a specific ban on embryonic research has led some to push for stricter regulations to eliminate it altogether. There are concerns about genetic diversity becoming limited over time, which would not be seen within the first generation of genetically modified persons but later on. While a parent may undoubtedly want to edit a genetic disease out of their child, it becomes a public policy concern about generations down the line that may be adversely affected by dwindling genetic material. Further, unborn children cannot consent to alterations—and those alterations aren’t always accurate, and could lead to additional health issues. 

Conversely, some have argued for looser regulations on germline gene editing, specifically in favor of research forthree-parent embryos. This involves using DNA from the father and the mother as well as mitochondrial DNA from a donor mother to prevent mitochondrial diseases from being passed onto the child. Properly done, it would help couples conceive while mitigating or eliminating the risk of passing on genetic diseases. This is a less controversial use of the technology already approved for clinical trials in the United Kingdom, but research has been dampened in the United States by the above regulations. 

While CRISPR has recently received FDA approval for some applications, its use has been hindered in others. As the technology produces more treatments, it will gain efficiency and accuracy with increased research on the new type of medicine. With this increased accuracy, it may come time to reevaluate the current regulations regarding germline editing. Some may argue that Congress, the FDA, and the NIH have not done enough to restrict it and need to ban research on germline editing immediately. Others may argue to allow federal funds to be used for research and increase reproductive freedoms. Regardless, there is a growing conversation surrounding the use of CRISPR gene editing in medicine that has only become louder following FDA approval for one application.