BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: #transplant

Human Body Pig Kidney

For decades, scientists have been trying to figure out an alternative to conventional organ transplants due to the overwhelming need for human organs. With advancements in technology, a few experiments have been conducted with pig organs as an alternative, but mostly on brain-dead patients for safety. The exceptional pig-heart transplant on a living patient was unsuccessful, as the patient died shortly after the transplant. However, just recently, surgeons at Massachusetts General Hospital transplanted a pig kidney into a 62-year-old living patient, Richard Slayman. National Guard Kidney Transplant 099This surgery may be the first successful example of pig organ transplantation of many to come in the future, as he is expected to be discharged from the hospital soon. Slayman, who is recovering well after the kidney transplantation, sees his surgery not only as a way to help himself but also to provide hope for thousands of people in need of a transplant. Slayman has been on dialysis for the previous seven years after being diagnosed with type 2 diabetes and high blood pressure before a human kidney transplant in 2018, which showed signs of failure just five years later, restarting dialysis in 2023 and causing serious health problems. With the massive population in need of a human kidney, Slayman couldn’t have survived the wait time, according to his doctor Winfred Williams. The opportunity to receive a pig kidney became Slayman’s only hope as he later consented to the operation. Biotechnology company eGenesis uses the gene-editing system CRISPR to tweak the genes of pigs to make the pig organs suitable for people. With a total of 69 genetic edits in the pig’s DNA, the scientists took out sections of pig genes that the human immune system attacks and added seven human genes that help prevent immune-related problems possible of causing transplant rejection. In addition, they also disabled endogenous retroviruses in pigs’ genomes as they can hurt humans. This CRISPR technology has always been used in recent years to produce a solution to treat sickle cell disease, first approved in the U.K. and later in the U.S. in December 2023. CRISPR technologies have also been used to modify immune cells to attack tumors and cancerous cells in personalized cancer treatments. The apparent success of Slayman’s surgery represents not only a breakthrough in organ transplantation but also a potential solution to solving the unequal access for ethnic minorities to organ transplants and resources due to organ shortage and other problems. This connects to what we’ve learned in AP Biology on how different blood types can only receive blood donations of certain other blood types for their antigens exhibited. Carrying this to organ transplants means for some blood types, it’s extremely hard to find a matching organ for transplant. With this CRISPR pig kidney transplant marks a breakthrough in solving this problem. If you were to face an organ transplant, would you want to wait for years for a matching human organ or take the risk for a CRISPR pig organ?

 

CRISPR Gene Editing Provides Hope for Patients on Transplant List

Do you know anyone who has needed an organ transplant? Hopefully, the answer is no. However, many medical dramas on television have shown us the awful process patients go through when waiting on a transplant list for a heart, lung, kidney, etc.

For years, scientists have experienced many trials and errors. They explored pig parts and ways to supplement them as human organs. However, a huge advancement in gene editing has just reinstated hope for many suffering patients.  On March 16th, Richard Slayman received a pig kidney. He had type two diabetes and had been on dialysis. He had a transplant several years ago, but the organ showed signs of failure. Doctor Winfred Williams explained that Slay would not have survived if he had to wait another five years for a human kidney transplant.

National Guard Kidney Transplant 099

Eventually, the idea was proposed for Slayman to receive a genetically engineered pig kidney from eGenesis, a biotechnology company.  Their goal is to generate human-compatible organs that can be used in transplants. In Slayman’s case, this kidney had been genetically altered 69 times using the CRISPR-Cas9 gene editing system, which allows certain parts of a genome to be removed or even added. Slayman’s new kidney was made suitable for him in a very meticulous way. Firstly, three genes that are typically found in pigs that attack human immune systems were removed. These were genes that code for the synthesis of certain carbohydrates. Additionally, seven human genes were added to the genome that prevent an immune response that may lead to transplant rejection. Certain pig viruses were also removed as they pose a harm to humans.

This is very relevant to one of our last AP Biology units. We just learned about mRNA processing. This step occurs following mRNA transciption, with the goal of making certain proteins. After the nitrogenous bases are transcrribed from template DNA, the mRNA is processed in several ways. A Guanine cap is added to the front of the strand and a Poly-A tail is added to the end. Additionally, parts of the mRNA are cut out. In CRISPR editing, this same process is done by scientists artificially, rather than our natural processes. The parts of mRNA that are cut out that will not make a protein are called introns, while the kept parts of mRNA are called exons. mRNA splicing can also take place where different combinations of bases are organized to make certain amino acid chains.

4.5. The CRISPR Cas 9 system as a laboratory tool

This new advancement will not only help patients receive new organ quicker, but it is the doctors’ hope that this will solve a larger cultural issue, in that ethnic minorities often struggle to receive organ transplants. This new process will hopefully benefit the healthcare system both medically and culturally.

Transporting Organs from Pigs to People!

The shortage of human organs for transplants is one of the biggest problems facing the medical field, about 22 people die on waitlists for organs die every day in the United States. But there is a newfound hope! A recent discovery using CRISPR-cas9 gene editing may address this challenge.

Scientists have been dreaming about transplanting organs from pigs into people for years, a process called xenotransplantation, but they have been held back by threatening viruses in the pigs DNA called PERVs. PERVs are present throughout the pig genome and would infect a person who receives a pigs heart, lung, kidney, etc. This infection could be fatal and may cause a human epidemic. Scary right? However, scientists at well-known laboratories had a breakthrough this past summer using CRISPR-cas9 and created healthy pigs with no traces of PERV genes!

It was, in fact, the two early developers of that gene-editing technology, Harvard University’s George Church, and Luhan Yang, who first believed CRISPR’s guide RNA and a DNA-slicing enzyme could make precise, genome-wide changes to pig cells. Their results showed that CRISPR could “knock out” PERV genes at all 62 sites in the pig genome. However, there were some flaws in their experiments, they used a line of “immortal” pig kidney cells, which were chosen for their ability to survive in the dish. Earlier the team had tried to use genetically “normal” pig cells, but once the cells were edited they failed to grow normally. Yang says, “CRISPR’s hacking job of the DNA may have prompted them to stop dividing or self-destruct.” But when they exposed the cells to a “chemical cocktail” making them “immortal,” the growth of PERV free cells in the dish rose to 100%.  The next step was to actually produce piglets. The researchers inserted DNA containing the nuclei of the edited cells into the eggs taken from the ovaries of pigs in a slaughterhouse. They allowed each egg to develop into an embryo and implanted it in the uterus of a surrogate mother. Boom, healthy, PERV-free piglets!

https://commons.wikimedia.org/wiki/File:Cute_Piglet.jpg

After this huge finding, Church and Yang co-founded a company called eGenesis which focuses on the engineering of transplant organs and projects in laboratories around the world exploded. Currently, a transplant surgeon at the University of Maryland is gearing up to swap a pig heart into the chest of a baboon! However, obstacles still remain in regard to humans; the rejection of the organs once in humans, the physiological incompatibility, how to insert genes that will prevent toxic interactions with human blood, and (what I believe is most important) the ethical question.

 

 

 

 

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