BioQuakes

AP Biology class blog for discussing current research in Biology

Author: andrewsarchus

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?

 

Where Did Father’s Mitochondrial DNA Go?

Evolving from free-swimming bacteria engulfed by forms of humans’ earliest ancestors billions of years ago, almost every human cell is powered by mitochondria, which use oxygen to create usable energy for our body’s daily needs. Originating from free-floating bacteria, mitochondria have unique DNA different from the 23 pairs of chromosomes in our body. Although our chromosomes come from both parents, 23 each, nearly all humans’ mitochondrial DNA (mtDNA) comes from the mother’s egg. What about the mtDNA in the sperm cell then? DNA rendering

Scientists figure that sperm’s mitochondria are soon broken down by molecular processes after fertilization in other animals, but the reason behind why this happens to humans has been unknown. Now research has found that human sperm’s few mitochondria contain virtually no DNA at all. This mtDNA elimination process might play a role in human infertility and mitochondrial diseases, according to molecular biologist Dmitry Temiakov of Thomas Jefferson University in Philadelphia. Coming up with the same conclusion, Shoukhrat Mitalipov, Ph.D., director of the Center for Embryonic Cell and Gene Therapy at OHSU, said, “We found that each sperm cell does bring 100 or so mitochondria as organelles when it fertilizes an egg, but there is no mtDNA in them.” Using molecular biology, researchers found that sperm’s mitochondria did contain some DNA, along with an important protein called mitochondrial transcription factor A (TFAM) that acts to protect that DNA. But after the sperm cells mature, chemical changes happen which prevent TFAM from entering mitochondria, and as it enters the nucleus instead, it no longer prevents the mtDNA from degrading. The fact that DNA damage in sperm from oxidative stress is common could be another reason why mitochondrial DNA disintegrates. Having mitochondrial DNA doesn’t help fertility either; if the sperm’s mitochondrial DNA sticks, it could become a source of infertility. Previous studies showed that sperm cells with elevated amounts of mtDNA experience decreased sperm counts and motility. A new study found that other animals “show multiple mechanisms that may contribute to maternal mitochondrial inheritance in different organisms,” said Xinnan Wang, a mitochondrial cell biologist at the Stanford University School of Medicine. This study connects to our lesson in AP Biology on the concept of genetics and how our DNA is passed on from our parents. Specifically, we previously learned how our mitochondrial DNA is almost completely from our mother, as the egg contains way more mitochondrial DNA than the sperm, allowing us to track ancestry by maternal mitochondrial DNA. This study expands our understanding of this concept. According to Temiakov, there are probably other unidentified mechanisms in sperm cells that regulate mtDNA, as a future area for research as it is crucial to better understand mitochondrial diseases and how to treat them. What do you think would happen if the mtDNA is passed on equally from both parents?​​​

Novavax: A Revolutionary Change to Covid Vaccines

Medical company Novavax introduced a new FDA-authorized COVID booster shot in early October, expanding the options of available COVID vaccines. This booster specifically targets the XBB.1.5 SARS-CoV-2 variant, a descendant of Omicron, distinguishing itself as the first protein vaccine in over a year. Unlike other mRNA vaccines, such as those developed by Pfizer and Moderna, Novavax employs a more traditional method, directly injecting proteins resembling those in SARS-CoV-2 into the body. The Novavax vaccine includes Matrix-M, a proprietary compound extracted from Chilean soapbark trees, enhancing the immune system. Matrix-M has also been integrated into other vaccines, including one endorsed by the World Health Organization for malaria.

Similar to the updated shots from Moderna and Pfizer, the Novavax vaccine is not optimized for newer virus versions like Eris and Pirola, as it is specifically designed to target the XBB.1.5 variant. Unlike mRNA vaccines, the Novavax vaccine is more convenient for distribution and storage, as it can be kept at normal refrigeration temperatures. However, the development of new formulas for emerging variants in protein vaccines takes longer compared to the adaptable mRNA vaccines.

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Novavax demonstrates effectiveness similar to other COVID vaccines, with its booster being approximately 55% effective at preventing symptoms and 31% effective at preventing infection. Studies indicate that mixing and matching different vaccine types yield comparable antibody responses, with some studies favoring the use of both boosters, taking the mRNA after protein vaccines. The longevity of antibodies from the Novavax booster, which lasts longer than those from mRNA vaccines according to research, remains inconclusive due to confounding variables of preexisting immunity.

In terms of safety, the Novavax booster poses a lower risk of causing myocarditis or pericarditis compared to mRNA vaccines and shows fewer side effects in the initial 48 hours after vaccination. The booster is currently available in pharmacies, distributed to numerous locations, and is recommended as a single dose.

In AP Biology, we learned how mRNA vaccines for COVID work, as the vaccine introduces antigen-encoding mRNA into immune cells. These cells utilize the mRNA as a guide to produce foreign proteins resembling those created by the COVID virus. These protein molecules then trigger an adaptive immune response, instructing the body to recognize and eliminate the actual COVID virus.

Is the Novavax booster the real deal? mRNA vaccines, such as Moderna and Pfizer, have been proven effective and have worked extremely well in the past. Their contributors, Katalin Karikó and Drew Weissman, were recently awarded the Nobel Prize in Physiology or Medicine. Novavax has just been approved with not much prior history in its effectiveness or side effects open to the public. Personally, I believe that the mRNA vaccines are way safer options regarding their previous successes, however, the benefits and pros of the Novavax listed by scientists and researchers might as well outweigh its uncertainty. If you have the choice of taking the new Novavax booster or the mRNA boosters, which one would you choose considering their pros and cons?

A Child of Three Parents?

In 2015, the United Kingdom became the first country to legalize a procedure called Mitochondrial Replacement Therapy (MRT), which was used to prevent inheritable health conditions involving the heart, brain, and muscles caused by mitochondrial mutations. This MRT procedure, sometimes called three-person in vitro fertilization (IVF), involves transferring genetic material from the nucleus of the egg or embryo with mitochondrial mutations to a different healthy donor egg with its genetic materials previously removed, allowing the child produced to have three parents.

Early human embryos

Eight years later, the Human Fertilization and Embryology Authority (HFEA) of the United Kingdom confirmed that at least one UK child had been born using the procedure as of April 2023. Although this is the first successful case of a fully legalized MRT procedure, it has previously been done successfully unregulated as well. A US doctor used MRT successfully to prevent mitochondrial disease in a baby in Mexico in 2016. Another US doctor, John Zhang, and his team successfully performed IVF on an embryo at New Hope Fertility Center in New York City in 2016. Greece and Ukraine have also conducted MRT to treat infertility. Despite many successes and new countries such as Australia approving MRT in 2022, MRT remains restricted in most areas, including the United States. The extent of IVF’s effectiveness is still to be tested. When, inevitably, a small number of mitochondria are transferred into the donor egg or embryo, it’s unclear whether or not very low levels of mutation-bearing mitochondria cause health problems. Additionally, scientists estimate a 1 in 50 chance of a mismatch in mitochondrial DNA and nuclear DNA could result in mitochondria problems. In some cases, a phenomenon known as reversal, where the carried-over mitochondria can increase markedly over time, replacing donor mitochondria in cells and bringing back the mutation. From scientist Wells’ observation in Greece, of the 6 children born with MRT, 1 child experienced reversal, though the reversal seems to have had no effect on the child’s health. The reason for this phenomenon is not clear, but scientists hypothesize that, due to efficiency reasons, matching donor and recipient on their mitochondrial DNA or freezing the mother’s eggs before transferring the nuclear genetic material into fresh donor eggs could prevent reversal. The process of Mitochondrial Replacement Therapy (MRT) is related to our understanding of mitochondria. From what we’ve learned, mitochondria are passed down only by females and mothers, as a significant amount of mitochondrial DNA exists inside eggs from mothers, whereas no mitochondrial DNA exists in the sperm of males, and all mitochondria are lost during fertilization. This leaves the mitochondrial DNA of the embryo and child originating solely from the mother’s egg. This explains why it is not possible to be treated with simple medicine, as the mutations are passed down genetically, requiring this procedure. Although I think the other side of natural selection should be considered by scientists before widely spreading the use of this procedure, the fact that MRT is life-saving and allows families to be formed outweighs the natural philosophies, and it should be widely used one day. If you needed MRT to give birth to a healthy child, would you do it?

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