Is Heart Failure a Thing of The Past?

Failure? What's that?

In the modern day some strokes and heart attacks are able to be treated with no lasting symptoms if treated withing 2-3 hours of the event, but there are still those events where treatment simply isn't enough to get people back on their feet. Whether you are put on a beta blocker, an Ace Inhibitor, or diuretics, the heart doesn't fully recover in some cases. This is where newly discovered gene therapy comes in. Researchers had previously found a gene that produces a protein called cardiac bridging integrator 1 (cBIN1) that is integral in allowing the heart to perform at full functionality. Hearts that are low on cBIN1 are found to have trouble contracting, and have a severe risk of heart problems. Recently tested on pigs was this protein embedded in a virus, being shot into the blood vessels of pigs with heart failure. These pigs, prior to the treatment, were expected to die withing the 6 month window of the period. In fact they were slated to die much sooner, within 2-3 months. All of the 4 pigs survived the research window and were found to have a 30% improvement in heart function. A far shout from the results of current treatments, which range from 5-10%. FDA approval is being applied for to obtain permission to test on humans, but it isn't expected to go through until 2025 at the earliest. 

I am excited for this to develop into later stages. As somebody who has a genetic heart condition, seeing that heart failure and it's aftereffects may become a thing of the past is greatly comforting. I can't wait to see where this research goes, and I will be personally following this subject. Once this protein is successfully implanted in humans, I'm hoping we can find an enzyme that helps control the gene expression and protein production, so we could possibly make a pill for people who are found to have cBIN1 deficiencies. 

Links

https://www.nature.com/articles/s41536-024-00380-0

https://www.nhs.uk/conditions/heart-failure/treatment/

Genetically Modified Pigs Aiding in the Shortage of Organs for Transplants

Over 100,000 individuals remain on the waiting list for an organ transplants, and tragically, about 17 individuals perish daily due to the unavailability of suitable organs. In response to this critical shortage, scientists are diligently researching the feasibility of utilizing genetically modified pigs to address this pressing medical need.

Nestled discreetly near Blacksburg, Virginia, lies a secret farm comprising 22 meticulously maintained buildings housing roughly 300 pigs. These pigs serve as subjects for extensive research aimed at exploring their potential in human organ transplantation. Referred to as a "barrier facility," these buildings must maintain absolute sterility to shield the pigs from any potential pathogens. The journalist working on the article emphasized the rigorous sterilization process implemented before entering the pig-containing premises. 

The process of genetically modifying these pigs involved sophisticated technology to edit the DNA in their skin cells. Following editing, similar techniques that were used on Dolly the Sheep are utilized to generate cloned pig embryos. A tiny pipette is employed to penetrate the egg and extract DNA, removing the majority of genes. Subsequently, edited cells are fused with emptied eggs using electrical stimulation, initiating cell division and resulting in the formation of new embryos. These embryos are then surgically implanted into female pigs, and within a span of four months, cloned piglets are born. These piglets contain ten genetic modifications ensuring their suitability for organ transplantation and compatibility with recipients. 

However, amidst the potential medical breakthroughs, ethical concerns arise. Many question the morality behind modifying, breeding, and ultimately slaughtering these animals for human benefit. L. Syd Johnson, cited in the article, denounces the process as an act of "hubris," likening it to the treatment of animals as mere machinery. I agree with this statement; the entire process is deeply disconcerting. While modern medicine continues to extend human lifespans, we must pause and reflect on the ethical boundaries we are willing to transgress. Though this procedure holds promise in saving lives and mitigating transplant wait times, it compels us to confront the profound moral implications of our technological advancements.

Scientists grow humanized kidneys in pig embryo

 Scientists grow humanized kidney in pig embryo 

    Scientists have recently been able to successfully grow a kidney made mostly of human cells in pigs' embryos. This is a big step for research pertaining to creating viable organs for transplants. This is the first time that an organ containing mostly human cells has grown inside of an organism of another species. Stem cell biologist Liangxue Lai and his team at the Guangzhou Institutes of Biomedicine and Health in China were able to make this possible after 5 years of research and refining models. The problem at first was that nobody was able to induce the embryos to make organs because they contained multiple cell types. Lai and his team found the solution when they realized they could modify the human cells using the gene-editing tool CRISPR/Cas9 to increase the activity of multiple genes. This change made it so that the human cells were able to fight back the pigs' cells. 

    A little part of me does think it's a bit weird they are growing inside of pigs and I wonder if this could be a gateway to diseases that are carried by pigs. However, I really believe that this is truly a ground-breaking discovery. Research shows that there are over 100,000 people on the transplant list in the United States and most of those people need kidney transplants. This is definitely a really important advancement and it is a great help to those who need it. It's amazing that after all these years of research, a team was able to modify something to change the whole course of this research. It would be interesting to see other organs being grown in pigs or even other organisms in the future.

LINKS:

https://www.sciencenews.org/article/grow-human-kidney-pig-embryo

https://www.science.org/content/article/early-stage-human-kidneys-grown-pigs-first-time

The Future of Organ Donation: Genetically Engineered Pigs

Should you ever find yourself in need of a replacement for a vital organ, your ability to receive one will depend on some factors that have nothing to do with how badly you need that heart or lung or pancreas. Your age and blood type will figure, as will your ability to afford the immunosuppressant drugs and lifelong care needed to keep the organ functioning. If your lucky day ever comes, it will come only because someone else had an extremely unlucky day: A healthy and immune-compatible donor will have died in a way that leaves a healthy target organ unscathed. But thanks to scientists that are doing their best to find an option rather than wating for a person to die. There is a probability of using other animals to help us. There is one abundant and quick-breeding species that in crucial respects bears an almost uncomfortable resemblance to humans: Sus scrofa domesticus, the common pig. A 150-pound pig is uncannily humanlike in organ size and function. But this is not that easy. In fact, humans are not molecularly compatible with pigs, their organs will never work in a human body. So, scientists are working to comprehend the mechanisms that guide the human immune system to distinguish friend from foe, and to persuade it to regard the pig as friend.

Xenotransplantation has always been around the corner, pigs have been quietly insinuating their way into our bodies for some time now. Their pancreas glands have been used to make some types of insulin, and their intestinal tissue has been used to make the blood thinner heparin. Cardiac surgeons reach for pig heart valves to replace leaky and hardened human plumbing, and eye surgeons have affixed pig corneas to damaged human eyes. But those are not the only organs that people are waiting for, unfortunately there are many organs that are not compatible with us.

In 2013, a 27-year-old Harvard graduate student named Luhan Yang co-authored a study that demonstrated how the genome-editing tool known as Crispr-Cas9 could slice through mammalian genes and edit sequences to remove some characteristics and alter others. Yang’s team developed a technique to edit genetically normal cells from a living pig, then embed the DNA-containing nuclei of these modified cells into egg cells taken from the ovaries of a normal pig. A few months later, the team witnessed the birth of the first pig born without the endogenous viruses. 

With the PERV gene knocked out of their pigs, Yang and her team are experimenting with knocking in dozens of human genes to make the organs more humanlike: Some would buffer the pig tissue from assault by the human immune system; others would tweak its coagulation system to diminish the risk of clotting. In my opinion this could safe many lives because there is a chance that your lucky day to receive an organ donor will never come, that you’ll become one of the 20 Americans who die each day waiting for an organ. The ability of scientist to manipulate many genes opens new possibilities and innovation. And some day the organs of those pigs could be in someone that we know or even us.

Sources :
https://www.nytimes.com/interactive/2018/11/14/magazine/tech-design-xenotransplantation.html ttps://www.google.com/search? Pig Organs
https://www.google.com/searchq=pig+transplant&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiZno3BgefeAhWFl-AKHfhZDiQQ_AUIDigB&biw=1280&bih=610#imgrc=IsDo59d5_Ivg1M:

Engineering the Livestock of Tomorrow

According to the article “Scientists on brink of overcoming livestock diseases through gene editing”, by Hannah Devlin, UK geneticists at the Roslin Institute in Edinburgh have been making significant progress in genetically engineering disease resistance and resilience into livestock species. Although still in its trial stages, the director at the Roslin Institute, Prof Eleanor Riley, believes that in the very near future, the farming industry will be able to save millions every year once these resistant/resilient animals are successfully introduced into the live stock population. The first and most promising experimental trial is currently producing blue ear disease resistant swine, who may be introduced into the live stock population as soon as in three years’ time. Blue ear disease can cause the effected swine to produce stunted offspring or still births, resulting in significant monetary loss in the farming industry. By identifying the gene that codes for the surface receptor, in pig cells, that the virus needs in order to bind and spread, the scientists at Roslin, were able to select and remove a small section of this gene, therefore causing the link from the blue ear virus to the pig cells to be removed entirely. This in turn means that this small genetic intervention would make the resulting swine immune to this ailment  
                    (pig with blue ear)         

            Furthermore, this type of genetic identification and alteration research is also under way for other significant live stock illnesses, such as the avian flu, oyster herpes, and amoebic gill disease in salmon. Geneticists at Rolsin have also begun investigating the genetic foundation for E coli and campylobacter resilience, as they are believed to be the cause of hundreds of thousands of food poisoning cases in the U.K. alone each year. Yet the public seem slow to come around to the idea of eating genetically modified animals (even though they have had no qualms with GMO crops for decades). However, once they realize the benefits genetically engineered livestock will bring to animal welfare and environmental impact mitigation, both the professionals at the Roslin institute and myself believe, the publics opinion will sway much faster in its favor.

Link to article

 https://www.theguardian.com/science/2018/mar/17/scientists-on-brink-of-overcoming-livestock-diseases-through-gene-editing

And for more on Blue Ear Disease

http://www.pigprogress.net/Health/Health-Tool/diseases/Porcine-Reproductive-and-Respiratory-Syndrome-PRRS-

Scientists Breed Pigs with Life-Saving Gene Alteration

Piglets are the main focus for PRRS prevention.

Great leaps have been made in research of the pig farming industry as scientists at University of Edinburgh have managed to use gene-editing techniques to halt the infection of one of pig-farmers' worst enemies: Porcine Reproductive and Respiratory Syndrome. Porcine Reproductive and Respiratory Syndrome (PRRS) is a costly and deadly disease that plagues the domesticated pig population with high death rates for both pregnant sows, their fetuses, and young piglets. The virus can cause abortion and mummification of fetuses, as well as severe respiratory issues and extreme weight loss, which causes a large percentage of the piglet population to die before reaching adulthood. This article summarizes the discoveries and the mechanisms behind them.


The pathway for the PRRS virus has now been linked to a scavenger receptor on macrophages known as CD163, a receptor also responsible for managing inflammation and removing hemoglobin. Scientists have managed to pinpoint CD163 as the infection site for PRRS, but due to the other important contributions of CD163, they could not delete the receptor as a whole. However, in the originally published journal detailing the research, the structure of CD163 is described as "pearls-on-a-string", with nine scavenger receptor crysteine-rich domains (SRCR), and from this, the team of Edinburgh managed to pinpoint SRCR5, the domain responsible for the infection of pigs with PRRS.

Using gene-editing technologies, researchers injected 24-39 zygotes with the SRCR5 deleted genes and ended up with 32 live piglets. From this, they took the two pigs that showed the desired deletion of the exon 7 (which is linked to SRCR5), crossed them, and resulted in a mixture of different genotypes, all of which had deletion of exon 7 in varying forms. Exposing these individuals to the PRRS virus did not result in infection, while still maintaining normal functions within the CD163 scavenger receptor. From this experiment, not only did the team at Edinburgh prove that the deletion of SRCR5 can prevent infection of one of the deadliest viruses in domestic pigs, but also that it can be safely and successfully passed on to other generations.

Human-Pig Hybrid Chimera Study

Scientists have created more than 2,000 human-pig hybrids in the hopes of using the information gained to one day grow human organs inside of animals for transplants. The hybrid embryos were allowed to develop to 28 days before being removed. This short time frame allowed scientists to see how the human and pig cells mix together.The study has come under fire as ethical concerns from the US National Institutes of Health had put a temporary  ban on funding for this controversial experiment last year.  One ethical concern brought about during the ban was that hybrid creatures could theoretically have humanized brains,  and what that could mean if they were accidentally released into the wild. Although i understand the ethical dilemma faced with chimera research I feel as though there is many advantages that this research could bring that cannot be ignored. Not only is this study bringing us closer to understanding how different cells can interact it also allows us to learn the information that can one day lead us able to grow human organs ready for transplant.

https://www.theguardian.com/science/2017/jan/26/first-human-pig-chimera-created-in-milestone-study
http://www.counselheal.com/articles/31719/20170130/human-pig-chimera-embryo-development-grow-donor-organs.htm

The Next Heart Transplant Could be from a Pig!

Thanks to research that is currently being done, people waiting for organs may soon be able to receive organ donations from pigs.  The current research is housed at the National Institute of Health in Bethesda, Maryland.  Over the last 10 years they have been transplanting pig hearts into baboons to see if they could survive with them.  On a daily basis, about 22 people die waiting for an organ that they need.  The researchers at the NIH have been able to keep a baboon alive for 3 years!! These shocking results do not mean that they can start using pig organs in humans yet, but they are one step closer.  People never believed in transplanting organs from one species to another, which is known as xenotransplantation.

When an organ is moved from one species to another, it may provoke an intense attack from the host’s immune system. The researchers have been working with different drugs to try to stop such an intense immune response.  One they found to work the best was CD40.  This drug blocks the communication that occurs between certain immune cells. It works by binding to a receptor in the surface of the cells.  They were using CD40 along with Heparin, a blood-thinning drug, to see if it would prevent the immune response in the baboons with the implanted pig hearts.  It worked while the baboons were on the drug, but once the researchers took the drug away and it left the system, they started to reject the hearts.   These experiments proved that if humans started to receive pig organs, they might have to be on a drug to support their immune system and prevent infection.

This is one step closer to being able to save more lives.  I knew that they were trying to get pig organs to be able to be transplanted in humans, but I never knew that they were this far into the research. Hopefully someday they will be able to make the pig organ work in humans without an immune response.  They are working diligently to delete the gene that causes the response in the host's body.  

Human organs may be created by editing pig DNA

Beginning in 1990, researchers began experimenting with transplanting pig organs into humans. This is known as xenotransplantation. They began this research so humans would not have to wait for another human to die to use their organs. The experiments were halted in 1998 due to the discovery of “viral genes” in the pigs DNA known as PERVs. Further research has shown that humans host the same endogenous retroviruses. When pig cells were mixed with human cells in a petri dish, they observed that the pig cells had infected the human cells. The researches tried to rid the pigs of the retroviruses, it seemed impossible because they seemed to be a part of the pigs’ genomes’.

                Beginning of 2013, scientists lead by Dr. Church have been using the Crispr technique to edit the genes of PERVs, and turned out that they could contain them within the pigs genome. With more thorough testing, they found 62 PERVs within the genome. They also found out that the DNA was almost identical from each human and pig virus. The scientists then engineered genes that produced specific enzymes to hunt the PERVs and eradicate them of their viral DNA. After two weeks, the viral DNA was destroyed. The biggest accomplishment came after the genomic surgery, where the pig cells began to grow normally and chromosomes had no mutations.

                Dr. Church and the scientists have finally discovered one molecule that could change all 62 genes singlehandedly. The next step in their research is to edit genes that wouldn’t alert the human immune system so the organ transplants can be successful. Dr. Dunn said “This work brings us closer to a realization of a limitless supply of safe, dependable pig organs for transplant.”  These scientists hope to be able to transplant pig organs into humans in the near future.

                This research in particular is incredibly fascinating to me that they can edit genes in different animals and have it translate into humans. This could solve the problem of people being stuck on waiting lists and potentially losing their lives for not having a match. Although this will take decades, it’s amazing to see the direction that this research is headed towards.

The link to the original article can be found here.

Pigs Could Be the Perfect Organ Donors

More than 123,000 people wait on transplant lists in America alone that if received, could save their life. It is said that on average every 12 minutes another person is added to a life saving organ transplant list. 

Scientists have been manipulating and editing the genes of pigs for years in order to potentially making them the perfect organ donors for humans. After modifying 62 different genes in pig embryos, scientists think they have finally found a way to make pigs the ideal and suitable organ donors. Although pig organs are similar in size to humans, pig embryos posses 62 porcine endogenous retroviruses (PERVs) which once in humans is not treatable (potentially causing more issues in the human body such as blood clotting). Companies are working together to attempt to breed pigs genetically edited before even born in order to try and reduce the amount of PERVs in the pig embryo.

With more research throughout the years, I believe that this is a great step taken to possibly use pig organs for human transplants. The pigs organ size is already ideal, it is just the genetics that need to be altered. With the right genetic editing and modifying this could lead to an increase in available organs for transplant and the saving of thousands of lives.

Link to Article:

http://www.popsci.com/edited-genes-could-make-pigs-perfect-organ-donor

Link to supporting article:

http://exclusive.multibriefs.com/content/powerful-gene-editing-could-make-pigs-perfect-organ-donors/medical-allied-healthcare

Gene-Editing Record Smashed in Pigs

According to an article published in Nature, a study has been underway for the creation of a steady supply of organs for humans from pigs. In the past issues have arose with the rejection of the organs by the human immune system as well as the possibility of infection. A research team at Harvard Medical School led by geneticist George Church has modified 60 genes from pig embryos and now believes that they have created a suitable nonhuman organ donor.


The modification of 60 genes was ten times more than have ever been previously edited in any animal. This was accomplished by using CRISPR gene-editing technology to inactivate 62 porcine endogenous retroviruses (PERVs) in pig embryos. The group also modified more than 20 genes in a separate set of embryos. Among these was a gene that encodes for proteins that sit on the pig cell and cause blood clotting or triggers an immune response in humans.


Eventually the pigs that will be used to grow organs for humans will have both of the modifications as well as the deletion of PERV. Although the edited embryos are not yet ready to be implanted into the mother pig, Church believes they are close. The organ donor pigs will be kept in isolation away from pathogen. I found this article to be very interesting. It is impressive that they were able to edit that many genes and still produce good results. This could lead to many benefits in the future, especially in human therapies.

Dr. George Church of Harvard Medical School dropped a bombshell in the middle of his presentation. In a typical experiment scientists use Crispr to alter a single gene. Church and his colleagues used Crispr to alter 62 genes at once in pig cells. They hope this will lead to using pig organs for human transplants. This also raises the question is this experiment could be used to altered multiple human genes at once. In 1990s researchers explored the possibility of using pig organs for human transplant. There is a major risk with pigs DNA called porcine version also known as PERV can affect human cells as well. In 2013 they asked Dr. Church to discover a way to edit the genes of PERV. He agreed to give it a shot even though he thought it wouldn’t work. Dr. Chruch had failed several times only killing the cells.  In the last experiment Dr. Church and colleagues found that there were 62 PERVs in the genome. The DNA was nearly identical from virus to virus. Chruch engineered a new set of genes and inserted them into pigs cell. Two weeks went by and the modified pig cells had altered all of their own viral DNA. Chromosomes showed no abnormalities and the cells grew normally. This could be the answer to endless supply of safe dependable pig organs for transplant.  

       This finding could save thousands of lives! We wouldn't have to wait for someones life to be cut short to save another one. There's always a down side to new findings. This is the first time scientist were able to change multiple genes at once. This could be another huge step to creating designer babies. 

People Might Be Genetically Programmed to Eat More Than Others

Researchers from the University of Copenhagen have discovered big differences in the variability of eating habits amongst pigs.  The study looked at pigs with comparison to humans genetic mapping to reveal specific genes on the human genome known to be involved with obesity.  The researchers monitored the eating habits of pigs rather than humans because it would be nearly impossible to monitor that many humans hourly for that extent of time.  Basically, the research team wanted to figure out and understand why when some people get hungry they over eat, while others have control over how much they eat.  Pigs are a popular study model for researchers studying human obesity because they have similar genomes and digestive systems with humans.  Over a thousand pigs were given an abundance of food supply during a time span of four years, and each of the pigs were monitored daily.  The results were very interesting, there were big differences in the variability of the pigs eating habits. Some pigs with certain genetic variants were overeating as a normal behavior, proving they were genetically programmed to eat more food than other pigs. Kadarmideen states, "This is the first study in the world looking at pig to human comparative genetic mapping to reveal key genes on the human genome (e.g. on chromosomes 6 and 17) that are known to be involved in human obesity and some new genes; together they may explain why we crave for (more and sometimes unhealthy) food and why some of us overeat, so consequently developing obesity and diabetes, both of which are key societal and public health problems".  In the future it is possible that a simple blood test could determine if that person is more likely to have unhealthy eating habits, which could lead to diseases such as diabetes or obesity.  I believe this would be quite remarkable if people were able to take a simple blood test to figure out what kind of eating behaviors they geneticaly have.  It would allow for better understanding of the obseity genes and why some individuals eat like they do.  Although, I firmly believe that even if people know they might have genetically unhealthy eating habits, it all comes down to the individual person on changing these bad habits.

http://www.medicalnewstoday.com/releases/267024.php
http://obesityinamerica.org/

Androstenone Levels and the Taste of Pork

Several months ago, Science Codex published an article that highlighted a study relating the taste of pork to genes associated with scent.  The study was a collaboration between Hiroaki Matsunami of Duke University and scientists in Norway.  The Norwegians were interested in working with Matsunami because in a previous study he discovered the OR7D4 gene which codes for an odor receptor for androstenone.  Androstenone is a compound commonly found in the urine of swine (pigs).  Currently, the pork that is sold in Europe comes from female or castrated male swine.



The Norwegians wanted to see if consumers would be able to detect androstenone from noncastrated swine.  The scientists were interested in studying this because the European Union will be banning piglet castration by the year 2018 in all European countries.  It was found that noncastrated pigs contained a 6.4 ppm level of androstenone while castrated pigs contained only a 0.1 to 0.2 ppm level of androstenone.  The study used 23 participants, 13 who were consumers and 10 who were professionals.  Each participant was divided into a group based on whether they could or could not detect androstenone.  According to an article in Time, each person detects androstenone in different ways.  It can be perceived as having a scent ranging from urine to the sweetness of vanilla.  The participants who detected androstenone had two functioning copies of the OR7D4 gene.  Those who could not detect androstenone contained only one functioning copy of OR7D4 or none at all.  The important finding was that 70% of the participants had two functioning copies of the OR7D4 gene and thus were sensitive to androstenone.

This study shows that the upcoming ban in 2018 may negatively impact many people living in Norway.  More studies should be completed to see if the proportion of people impacted in Norway correlates with the rest of the population in Europe.  If 70% of all Europeans have two of the OR7D4 genes, meat producers may have to alter some of their practices.  Pork from females or imported pork from castrated swine may become prevalent in European grocery stores.  The study as a whole illustrates the importance of genetics and how a single gene can alter one’s perception of the world.  Further studies should be completed to see if other genes affect taste or scent.