BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: Xenotransplantation

Pigs Leading The Way In Organ Transplants

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On April 17, 2024

In Student Post

Bio Threats- FDA's A-Team (6355) (9806964753)

Scientist looking at pig cells

Imagine waiting for a phone call that could save your life, but you never get the call. This is a reality for many patients that are on an organ transplant list. Recently scientists have found a way to make it possible for a patient to get a transplant without waiting for the rest of their lives. Richard Slayman is a 62 year old man from Massachusetts who, went through xenotransplantation, received the first pig kidney transplant while still alive. How would you feel about receiving an organ from a pig?

In recent years scientists have been genetically engineering pigs for human organs to address the lack of human organs available for transplant surgeries. Many of past transplants have been unsuccessful. Some of the transplants included “hooking a kidney up to a brain-dead organ donor’s body, and another involved performing a double-kidney transplant in a brain-dead patient. In addition, in 2022, a man underwent the first pig-heart transplant but died shortly thereafter”

Richard Slayman faced type 2 diabetes and high blood pressure which lead him to seven years of dialysis before his first human kidney transplant in 2018. This transplanted organ began to fail five years later which pushed him back to dialysis in 2023. This lead Richard to receiving the kidney transplant. The wait for another human transplant would have been too long. Richard was presented with an opportunity to get a transplant using a kidney from a genetically engineered pig. What would you do wait or get the transplant? The genetically engineered pig was developed by eGenesis using CRISPR technology. The total number of gene edits in the DNA was 69.

Dr. Ehtuish Performing An Organ Transplant.

Doctors performing an organ transplant

The scientists removed three genes responsible for creating carbohydrates that trigger human immune responses. They also added seven human genes to prevent potential immune system rejections, and they deactivated certain viral DNA sequences known as endogenous retroviruses that could pose risks to human health. These adjustments were done to ensure the organs are safe for transplantation into the human body.

Richard Slaymans pig transplant has been a huge success. So are pigs going to lead the way in organ transplants? So far it seems to be the case. Richard Slayman in the past few days has left the hospital. Now the doctors need to continue to check in with Richard to make sure all is going well. This is very important because it is common for the transplanted organ to be rejected and also possible infection. To prevent this the doctors have to give the patient a perfect balance of immunosuppressive drugs. “too low a dose can lead to rejection, while too much can make a patient vulnerable to infection”

In AP Bio we learn about the importance of DNA and RNA function and the manipulation of it. DNA determines the production of RNA, and the RNA then allows for the production of proteins that carry out all the functions we need it to. CRISPR technology uses guide RNA, which is specifically made to match particular DNA sequences. This allows CRISPR to harness a cell’s mechanisms to precisely target and alter genetic data. This process demonstrates roles of DNA and RNA in genetic expression and regulation, and being able to do this will allow for a lot more possibilities. This topic also relates through the impact of the immune system when the organ transplant happens. The immune system plays a role in distinguishing between self and non-self cells. When a foreign organ is transplanted, the recipient’s immune system may recognize it as a threat. This leads to organ rejection. This immune response is lead by T cells that identify mismatched human leukocyte antigens on the donor organ. To prevent rejection, patients will undergo immunosuppressive therapy, which will lower the immune system’s activity but this also increases susceptibility to infections and other diseases. What do you think about the process of organ transplants. Is it efficient the way it is or will new science make it more efficient with the help of animal organs?

Pig Kidneys and CRISPR: A Swine-Tific Breakthrough! 🐖

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On April 17, 2024

In Student Post

The groundbreaking transplant occurred at Massachusetts General Hospital, where surgeons successfully implanted a pig kidney into a 62-year-old patient, Richard Slayman. Slayman, who had been on dialysis for seven years due to complications from type 2 diabetes and high blood pressure, faced a challenging prognosis. Traditional human organ transplants presented a daunting wait time, rendering them an impractical solution. However, the advent of genetically engineered pig organs offered a glimmer of hope.

The pig kidney transplant represents the culmination of years of research and development in xenotransplantation. Scientists have meticulously engineered pigs with modifications to mitigate immune rejection in human recipients. Why pig organs? Egenesis wrote, “Pigs have been identified as a good species for xenotransplantation due to their similarity to humans in terms of organ structure and physiology, in addition to the abundance of the species” (eGenesis). Researchers have tailored pig organs to be more compatible with the human immune system by employing advanced gene-editing techniques such as CRISPR. What is CRISPR gene editing, you might ask? Mr. Anderson has a great in-depth explanation, but I will give you a brief overview. There are a number of genes associated with CRISPR called Cas-genes which make Cas proteins , which in general are helicases and nucleases. In AP Bio, we learned that helicases unwind DNA. Nucleases cut the DNA. The system will transcribe and translate proteins and transcribe DNA to make CRISPR RNA (crRNA). This is a way to fight the viral DNA by breaking it apart, so “before the infection starts, the infection has essentially ended” (Bozeman 2:45). Also note that the “spacers” are basically a history of old infection so that we won’t be infected again. Why is this so popular in the science world? Scientists thought that if we hijack the system, they could use it to inactive genes or embed new genes.CRISPR-Cas

EGenesis, a biotechnology company, spearheaded these efforts by implementing 69 genetic edits to enhance compatibility. To ensure the success of the transplant, Slayman underwent comprehensive preoperative preparations, including antibody-based treatments and immune-suppressing drugs. The procedure’s apparent success offers promising prospects for the future of transplantation medicine. Dr. Leonardo Riella of Massachusetts General Hospital expressed optimism that such transplants could revolutionize treatment paradigms, potentially rendering dialysis obsolete.

A Future without Dialysis? Oink-credible!

Mass General Hospital also released an article. They specifically stated, “Additionally, scientists inactivated porcine endogenous retroviruses in the pig donor to eliminate any risk of infection in humans.” (This was not previously mentioned in the first article).CRISPR illustration gif animation 1In AP Bio, we did an entire unit on DNA, gene expression, and gene regulation. To understand what CRISPR is and how it works, you need to know this unit’s steps. CRISPR facilitates the study of gene function by enabling researchers to manipulate gene expression patterns precisely. Scientists can elucidate the mechanisms governing gene expression and regulatory networks by targeting specific regulatory elements within the genome. We discussed gene expression, where CRISPR plays its role by looking into specifics, such as translation and transcription. It involves using a Cas enzyme (such as Cas9) guided by a small RNA molecule (gRNA) to target specific DNA sequences for modification. While CRISPR itself doesn’t directly involve transcription, it can indirectly manipulate gene expression. By targeting particular regions of DNA, CRISPR can disrupt or modify genes, thereby affecting mRNA transcription from those genes. For example, CRISPR could knock out a gene of interest, decreasing or abolishing the corresponding mRNA transcription.

Moreover, the implications extend beyond medical innovation. The breakthrough holds the promise of addressing systemic disparities in organ transplantation. Dr. Winfred Williams highlighted the potential for increased health equity, particularly for ethnic minority patients facing barriers to accessing donor organs. 

The successful pig kidney transplant represents a triumph of scientific endeavor and human perseverance. As we navigate the complexities of organ shortage and healthcare disparities, innovations in xenotransplantation offer hope. By fostering dialogue and collaboration, we can chart a course toward a future where life-saving treatments are accessible.

As we piggyback into the future of medicine, let’s remember that every breakthrough comes with a side of questions. But with CRISPR in one hand and pig kidneys in the other, who knows what’s next? One thing’s for sure: the future’s looking mighty swine-tastic! 🐖✨

What are your thoughts on the ethical implications of xenotransplantation? How do you envision the future of organ transplantation evolving in light of recent advancements? 🧬🧬

**Used Grammarly as a tool***

Quit Hogging All the Kidneys

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On November 1, 2021

In Student Post

Xenotransplantation is defined as the process of transplanting organs between members of different species. Saying it out loud it sounds like mad science but the it’s not as crazy you might think. Xenotransplantation has actually been a process that has been used for many years, even dating back to the 1960s. This journey began with apes and monkeys. Scientists believe that it would make the most amount of sense to use because they were essentially the most promising source of organs and tissue due to their being primates. However, this unraveled into a series of problems that were due to them being contaminated with viruses that are pathogenic to human beings. Baby monkeys were also researched but the idea was dismissed due to ethical reasons. This consequently led to the study of pig tissue.

We have actually been utilizing things from pigs that most people may not even be aware of. One example of this is pig insulin. It would replace the insulin that your body would usually make in order to get blood sugar into your cells. We obviously can’t take just any part of a pig and use it. We can, however, utilize a pig’s kidneys and transplant it into a human body. On September 25th, scientists and researchers  successfully transplanted a kidney from a genetically altered pig into a human patient and discovered that it functioned normally.

Little piggies

How Did It Work?

According to the an article by the New York Times, the pig needed to be genetically altered in order to be transplanted into the patient. What was altered? Essentially the kidney in the procedure was obtained by removing a pig gene that encodes a sugar molecule that elicits an aggressive human rejection response. Interestingly enough, the genetic difference between pig DNA and human DNA is 98 percent.

What Were The Risks?

While pigs and humans may share a lot of DNA, they are not a match right away. A non altered pig would cause many risks if any part of it were transplanted into the human body. A way it could pose an issue is through the viruses they may contain. Pig viruses may not cause disease in pigs, but they can in fact be pathogenic to humans. The human proteins that are expressed onto the transgenic pig cells can be receptors for viruses. An article on pig DNA from PMC explains that CD55 is a receptor for human Coxsackie B and ECHO viruses (these are relatives of poliovirus), and these cause a disease called myocarditis. The protein CD46 can act as as a receptor for the measles virus, so it is possible that morbilliviruses of animals could be preadapted in the same pigs used for xenotransplantation.

Another way that these transgenic pigs may heighten risk of virus is through viruses with lipid envelopes that are from host cell membranes would be less likely to inactivated by human compliment. What could have been a protective mechanism against infections from viruses derived from farm animals could be broken down in attempts to make xenografts for humans (The tissue or organ being transplanted from the other species).

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Diagram of a pig kidney

The future of xenotransplantation looks promising. While it may have worked, scientists are still doing studies and still trying to find out more about the viruses pigs may carry. While we can weed out the viruses we are aware of, we still can’t account for the ones we don’t know exist. There is a reason this topic is somewhat new and that is because of ethics. Apes and Monkeys could’ve actually been genetically altered the same way these pigs were, however it was deemed unethical. I personally agree that apes and monkeys shouldn’t be harvested, but that begs the question of whether harvesting organs from pigs is ethical. And with that I ask you what you ate for breakfast, lunch or dinner. Pigs and other animals are already being harvested for food and I believe that if there is a problem with xenotransplants, there would be a problem with the food industry. With that being said, if you’re ever in the market for a kidney, you have options.

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