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:

Ancient Organs

Researchers may have discovered the 700 million year old mutation that allowed for the production of lungs, forelimbs, and inner ear.  In an article found on Science Daily, many organs in vertebrates have been linked back to multiple mutations.  The regulatory protein called ESRP acts as a molecular switch to splice and rejoin genes, they are also involved with morphogenesis and cell to cell interactions which generate different protein variants.  At first the evolutionary significance of these genes were not known, however until recently it is thought that this group of regulatory proteins mutated and began to create the proteins assigned for the lungs and other organs specific to the vertebrates.
This article is interesting because it shows what could have caused the mutation resulting in the coding for the inner organs.  The evolutionary significance for the ESRP would make sense for it to be important for our history but there had to have been something else alongside this mutation to correct the formation and placement over time for the organs such as the lungs.

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.  

Sexuality Beyond Our Gonads

A new article published in the international journal Nature  has presented a new and intriguing perspective on the potential sexuality of organs. Up until now, it had been widely accepted that differences in an organ's sexuality was strictly limited to the sex organs of the species in question. Recent genetic tests on Drosophila melanogaster (fruit flies) at the MRC Clinical Science Center based at Imperial London College have shed new light on this belief.

The intestines were the organ tested by the researchers, and the results they found were more than interesting. The researchers used genetic tools that allowed them to turn the expression of a gene "on" or "off," which allowed them to manipulate the femininity or masculinity of the stem cells of the intestines being observed. They found that the sex differences in intestinal stem cell behavior rely on a doublesex- and fruitless-independent branch of sex differentiation pathway downstream of transformer. These mechanisms are believed to be intrinsic mechanisms that control cell cycle duration. The researchers suggest that based on this newly observed cascade of sex differentiation, "a new sex determination pathway is at play." It should also be noted that differences between the organs were controlled for hormonal differences.

The major difference found between the masculine and feminine intestines was that the females intestines had a greater rate of proliferation. The enhanced ability of growth is believed to allow the female gut to grow during reproduction, but also makes them more prone to tumors. The enhanced rate of growth was noted by researchers to allow easier creation of genetically induced tumors. Overall, the increased plasticity of the gut is believed to make reproduction possible for the female.

This new discovery raises the question of whether or not this translates to humans, and how it can be applied to medicine. If we do discover that our organs are aware of their own sexuality, this could explain differences between men and women's health beyond the affect of differing levels of hormones. This would hopefully lead into a greater and more accurate scope of practice by health care providers. More tests will need to be done in the future on whether or not our organs have differences in sexuality, and how medicinal treatment can correspond accordingly.

Fly intestines showing genetically induced tumours (in green). Growth is significantly greater in female guts (right) than male (left). The cells shown in red are those that are multiplying.

Credit: MRC CSC

Reasearchers Find the Gene that Makes Us 3D

Researchers at the the University of Bath in England found that the YAP gene plays a role in the 3D body shape of vertebrate. YAP gene helps to regulate organ size, tissue tension, direction and alignment of organs in humans and other vertebrates. Researchers first experimented on the YAP gene in an embryo of a medaka fish, or Japanese rice fish, by mutating the gene. Researchers found that embryos with YAP mutation were flatter in the direction of gravity and tissues did not align correctly, especially the tissues in the lens of the eye. After, researchers tried the mutation on 3D clusters of human cells and found tissues to be unable to maintain the right amount of tension to be the correct shape and properly function. If human tissues were unable to hold up against gravity, many of our organs would not function at all or improperly. Researchers hope the discovery may lead to further growth and advancement in the field of regenerative medicine.

If this study is helpful in the field of regenerative medicine, this could be another alternative to organ transport. People would not have to depend on an organ donor to live. Most people would not have to die waiting for an organ transplant and the survival rate of those on the waitlist would increase.

Original Link: http://www.popsci.com/researchers-find-gene-makes-us-3d
Related Link: http://www.genecards.org/cgi-bin/carddisp.pl?gene=YAP1

Some immune cells only defend one organ

In this article, scientists have discovered a new way the immune system may fight cancers and viral infections. Research has been done on mice and in mice it shows that some organs have the immunological equivalent of "neighorhood police" speacialized squads of defenders that patrol only one area, a single organ, instead of an entire body. If one group of cells absolutly needs a transcription factor to exist, while another group of cells dosent care if that factor is gone, that strongly suggests that the two groups of cells use disticnt developmental pathways and are therfore different. The results point to at least four types of natural killer cells rather than just one major type long recongnized by immunologists. After discovering this new addition to the body this changes some of the concepts and thoughts of many reaserchers and may help with different cancers.


http://www.nature.com/icb/index.html