Insights from the scientific literature with inspiration from a recent groundbreaking surgery of a mature age man with kidney failure give hope to scientists and the public.
I have closely observed progress in health sciences and technology for many years. In a recent story titled Be an Innovator, Not a Laggard, I explained the “diffusion of innovation” theory within a public health context to inform and inspire my readers.
My key message was based on learnings from the successful implementation of public health initiatives to leverage and expedite emerging technologies' value for better health outcomes, which I will cover one important requirement in this article.
One of the items I discussed was precision medicine with gene editing. It might have sounded too radical or scary to some readers, but the idea is not far-fetched and will save millions of lives when it becomes mainstream.
Scientists, including Nobel Laureates, have made remarkable progress recently (especially in the last two years), which I want to highlight and explain the reasons behind in this story.
Exciting Scientific and Clinical Progress of Xenotransplantation in the Last 2 Years
These scientists, published in the New England Journal of Medicine in 2022, highlighted the critical shortage of organs available for transplantation and worked on genetically modified pig organs, recognizing them as a promising solution. However, they faced the daunting challenge of hyperacute rejection.
They engineered pigs with specific genetic alterations through meticulous breeding, offering hope for overcoming this hurdle. In a groundbreaking study, they transplanted kidneys from these genetically modified pigs into two brain-dead human recipients, sustaining their bodies with ventilators throughout the experiment.
The transplanted kidneys started working immediately, making urine and giving doctors hope. During the 54-hour study, the kidneys worked better and better, with tests showing they were functioning well in both recipients. Creatinine levels showing kidney health dropped after the transplant, indicating the procedure was successful.
Biopsies conducted at regular intervals revealed no signs of rejection, instilling confidence in the viability of the transplanted organs. Throughout the study, the transplanted kidneys continued functioning robustly, surpassing expectations with their high urine output.
As the study concluded, it became evident that genetically modified pig kidney xenografts had survived and thrived within the human recipients, offering a glimmer of hope in the quest for viable organ transplantation solutions.
According to the Physicians Committee, “In January 2022, a 57-year-old man with a life-threatening heart attack received a pig heart. Two months later, though, he died, and while it’s unclear what went wrong, there are many risky complications associated with xenotransplantation.”
A year later, in October 2023, these scientists published in Nature that they had made kidneys from pigs with particular changes in their genes. These changes made the pig kidneys more like human kidneys.
When they put these pig kidneys into monkeys, they found that kidneys with specific gene changes lasted longer. This suggested that these changes could make pig kidneys better for human transplants. Researchers concluded that these findings bring us closer to testing pig kidneys in humans.
Last week (March 2024), the first pig kidney transplant was made to a human at Massachusetts General Hospital in Boston, as documented in a scientific report in Nature on 22 March 2024 and BMJ.
Slayman, a 62-year-old with end-stage renal failure, received a kidney from a miniature pig carrying 69 genetic edits aimed at preventing organ rejection and viral infections.
The key point is that researchers made genomic edits to prevent rejection and inactivate viruses, ensuring safety and reducing the risk of infection in the recipient. Refinement of genetic edits is necessary to eliminate the need for immunosuppressive drugs, potentially revolutionizing organ transplantation.
This groundbreaking surgery might address the critical shortage of human organs for transplantation, with thousands of people dying each year while waiting for organ transplants. So, initial results suggest that pig organs are safe and function like human organs in the short term, paving the way for larger clinical trials.
They informed us that all US transplants of animal organs into humans, including Slayman’s, were approved for compassionate use. However, researchers hope that the FDA will approve full-scale clinical trials to provide hope for patients and their families.
After this exciting background, which gives us hope, I want to introduce a concept/process called xenotransplantation in biotechnology briefly.
What is xenotransplantation in simple words?
Xenotransplantation involves transplanting cells, tissues, and even organs from one species to another. Xeno means foreign. In my story context, xenotransplantation involves transferring organs from one species (animals) to another (humans).
The basic idea behind xenotransplantation is to take organs from animals, like pigs, modify them to make them more compatible with humans, and then transplant them into human recipients.
The key enablers of this process are gene editing and genetic disenhancement, which prevent the rejection of the transplanted organ and reduce the risk of transmitting diseases from animals to humans.
The organ's genetic makeup is modified to prevent or stop rejection by the recipient’s immune system and minimize the likelihood of transmitting diseases from animals to humans.
Through targeted genetic alterations, the organ becomes better suited for transplantation, ensuring compatibility and reducing the risk of complications post-transplantation.
Xenotransplantation has been explored for decades as a potential solution to the shortage of human organ transplantation. Early attempts date back to the 17th century, but scientists began experimenting with animals like pigs, primates, and baboons as potential human organ donors in the 20th century.
As this 2024 Frontiers review paper informs, the first published attempts at xenotransplantation occurred with xenotransfusion in the 1600s. In the 1800s, xenoskin transplants were attempted prior to more ambitious attempts at kidney xenotransplantation.
There has been a long line of endeavors as advancements in medical science and technology have brought the prospect of xenotransplantation closer to reality. This 2017 paper by Dr David K. C. Cooper (MD/PhD) explains the history of cross-species organ transplantation.
Recent advancements in genetic engineering, particularly with technologies like CRISPR-Cas9, which got a Nobel Prize in 2020, have brought xenotransplantation closer to reality.
Scientists have made significant progress in modifying animal organs to make them more compatible with humans, and some successful transplants have been performed in experimental settings.
Xenotransplantation could revolutionize organ transplantation by providing a potentially limitless supply of organs for patients in need. It can save lives and reduce the long waiting times for organ transplants.
Why do we need animal organs rather than human ones?
We need animal organs for transplantation primarily because there is a severe shortage of human organs available for donation.
Despite efforts to increase organ donation rates, the demand for organs far exceeds the supply. Many patients die while waiting for a suitable organ from a human donor to become available.
In the US, another person is added to the waiting list every 10 minutes. According to the FDA, currently, ten patients die each day in the US while on the waiting list to receive lifesaving vital organ transplants.
You may wonder about the use of dead people. Obtaining organs from deceased human donors is limited due to the availability of suitable donors, consent issues, and the quality of the organs. Additionally, not all organs from deceased donors are suitable for transplantation due to factors such as age, medical conditions, and the cause of death.
Animal organs offer a potential solution to this shortage. By using organs from animals, particularly pigs, which have similar anatomical and physiological characteristics to humans, we can potentially increase the supply of organs for transplantation. However, this approach also has challenges and raises concerns.
What are the key concerns and challenges with animal organs?
While xenotransplantation offers hope for addressing the organ shortage crisis, it raises ethical, safety, and regulatory concerns. There are worries about the risk of transmitting diseases from animals to humans (known as zoonotic diseases) and the potential for organ rejection despite genetic modifications.
This February 2024 review paper on Frontiers highlights that xenotransplantation holds great promise in addressing the severe shortage of human organs. However, it also faces significant ethical concerns that need careful consideration. The key concerns are xenozoonosis, public and regulatory challenges, and ethical treatment of animals.
Patients, their families, and the community must realize that if there is a confirmed case of transmitting a xenozoonosis to a xenotransplant patient, it could have serious consequences for everyone involved.
However, these concerns must be weighed against the tremendous benefits it offers to countless patients in need. For many, the potential cure provided by xenotransplantation far outweighs the ongoing health issues, complications, and even death they face without it.
They use patients with type 1 diabetes as an example. The shortage of human donor organs means that many could benefit significantly from islet cell xenotransplantation, which could be life-changing and even life-saving.
Who really needs organ transplantation?
Patients with various diseases may require organ transplantation to address their medical conditions.
Some common diseases necessitating organ transplants include end-stage kidney failure, chronic liver disease or cirrhosis, heart failure, chronic obstructive pulmonary disease, cystic fibrosis, type 1 diabetes, certain types of cancer, and autoimmune diseases affecting organs.
Each of these conditions can severely impair the function of vital organs, leading to life-threatening complications and significantly reducing a patient’s quality of life. Let me briefly explain each and provide links to various book chapters from NIH that you can freely access and read.
End-stage renal disease results in the complete failure of the kidneys to function correctly, leading to dangerous levels of waste buildup in the body.
Chronic liver disease can progress to cirrhosis, where scar tissue replaces healthy liver tissue, impairing liver function and causing liver failure.
Congestive heart failure occurs when the heart cannot pump blood effectively, leading to fluid buildup in the lungs and other parts of the body.
Chronic obstructive pulmonary disease causes progressive damage to the lungs, resulting in difficulty breathing and decreased oxygen levels in the blood.
Cystic fibrosis is a genetic condition that affects the lungs and digestive system, leading to respiratory and digestive complications.
Type 1 diabetes with severe complications can damage multiple organs, including the kidneys, heart, and eyes, necessitating transplantation in severe cases.
Certain cancers may require organ transplantation if the disease has spread to vital organs like the liver or lungs.
Autoimmune diseases can cause the immune system to attack healthy organs, leading to organ damage and dysfunction, which may require transplantation to restore normal function.
So, organ transplantation offers a potential solution by replacing a diseased or failing organ with a healthy one from a donor, improving the patient’s health and well-being.
How about brain transplantation?
I have been investigating these aspirations since the 1990s, but the concept of brain (head) transplantation remains theoretical and highly speculative. The brain is a unique organ that manages the entire body and possibly hosts the mind and consciousness.
While some experimental procedures have involved transplanting the heads of animals, particularly rodents, these experiments have faced significant ethical concerns and scientific skepticism.
The concept of a human brain transplant faces many hurdles, like reconnecting nerves and blood vessels, preventing immune rejection, and maintaining brain function. There are also significant ethical concerns, such as questions about identity and consciousness.
Many scientists have discussed brain transplantation and associated issues. However, the most outspoken and bravest one I have met so far is Dr Sergio Canavero, an Italian neurosurgeon who believes that whole brain transplantation in man is technically feasible.
Dr Sergio Canavero wrote an interesting paper about it published in the Surgical Neurology International in 2022.
Conclusions and Takeaways
This recent breakthrough surgery of a 62-year-old man brings xenotransplantation closer to reality, offering new hope for patients in need of life-saving organ transplants.
With ongoing advancements in genetic engineering and medical technology, xenotransplantation could become a viable option for patients in need of life-saving organ transplants in the future. In addition, transplantation of cells and tissues can also be useful.
Recent evidence has suggested that transplantation of cells and tissues may be therapeutic for certain diseases, such as neurodegenerative disorders and diabetes, where human materials are not usually available.
While xenotransplantation holds promise as a solution to the organ shortage crisis and offers hope for tackling it, it raises ethical, safety, and regulatory concerns.
Scientists and the public are concerned about the risk of transmitting diseases from animals to humans (zoonotic diseases) and the possibility of organ rejection despite genetic modifications. Therefore, these solutions require meticulous studies and substantial refinement.
According to CNN Health, “More than 100,000 people in the US are on the transplant waiting list, and an average of 17 die every day while waiting. Doctors have spent decades experimenting with alternatives, and many now see potential in replacing failing human organs with genetically modified pig organs.”
The Physicians Committee urges us to register as organ and tissue donors. Donors can provide life-saving transplants and contribute to groundbreaking research that helps reduce and replace the use of animals. Interested readers in the US might register through organdonor.gov.
Thank you for reading my perspectives. I wish you a healthy and happy life.
If you found this story helpful, you may also check out my other articles on NewsBreak. As a postdoctoral researcher and executive consultant, I write about important life lessons based on my decades of research and experience in cognitive, metabolic, and mental health.