Closing the Gap Between Organ Transplant Scarcity and the Countless Patients in Need

Annually, 150,000 people around the world join the waiting list for an organ transplant but half of them die before they can get one.

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Why are there Organ Shortages?

Only a very small number of people die in a way that allowed their organs to be suitable for transplantation. Such as in the hospital, in an intensive care unit, following a road accident or a stroke. Or some people haven’t made it clear that they want to become an organ donor when they die, and relatives may be too distraught to give the doctors permission.

Xenotransplantation

Xenotransplantation is the process of transplanting organs or tissues between members of different species.The transplant can be carried out between concordant species , which are closely related and have a lot of the same genes. Or it can be carried out between discordant species that aren’t closely related, therefore having few genes in common. Transplants carried out between discordant species result in more violently rejected transplanted organs. This is because all animals have ‘flags’ on their cells that tell what species they are.

Why are transplanted organs rejected?

Majority of people with transplanted organs suffer from rejection, even if they’re from the same species. Rejection happens because the recipient’s immune system realizes that the new organ is not its own. Thats why transplant patients must take anti-rejection drugs. On the other hand if the organ being donated comes from a different species it is rejected quiet quickly in a process called hyper acute rejection. “In hyper acute rejection pre-programmed antibodies in the recipient’s bloodstream target the xenoantigens, “the flags”,  all over the transplanted organ and trigger a destructive chain reaction. The blood supply to the transplanted organ is blocked, cells die, and the organ stops working.”

 Ways we’ve tried to prevent hyperacute rejection of xenotransplants?

In 1992, British scientists successfully breeder a pig with human “flags” on its cells in hopes to prevent hyper acute rejection of xenortansplants. “The scientists did this by putting DNA for the human flags into the pig embryos then put them into the wombs of surrogate sows. They had to do it multiple times before they were finally successful in creating a ‘transgenic’ pig with a DNA  0.000001% more human than other pigs.”

Dilemma 

But, this still didn’t get rid of the rejection problems for xenotransplant because when monkeys were given these “transgenic” pig organs the longest they survived was only a few months. Many people asked why the British scientists didn’t transplant the “transgenic” organs into humans, because after all they did have human “flags” now. And the answer was because it was unethical and “they were worried that the pig organs could carry potentially dangerous pig viruses into their human recipients, such as PERVs.” In 1997, British scientists discovered PERVs, Porcine Endogenous Retroviruses, could infect humans, and even though they didn’t have any evidence proving that, they didn’t want to risk spreading the disease. For example, “every species has its own type of endogenous retrovirus which is harmless to the species it lives in.”

We currently use pigs insulin to treat diabetes, and their heart valves to replace diseased human valves. To this day, the closest we’ve gotten to actually using “transgenic” pig organs for human transplants was when the livers of transgenic pigs were used to keep two patients alive in the USA while doctors searched desperately to replace them with human organs. “The two patients – one of them Robert Pennington – were connected to transgenic pig livers on trolleys at their bedside. The pig livers took over the work of their own failed livers, cleaning their blood and keeping them alive. Both procedures were successful and the two patients are alive and well after human livers were found for them and transplanted. ( this was all done before scientists discovered that PERVs could infect humans)”

The Big Step Forward

Until, the landmark study by George Church and his team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School where they used the gene editing system known as “CRISPR–Cas9” to genetically engineer pig DNA in 62 locations. “By using CRISPR–Cas9 like a pair of molecular scissors Church and his team have inactivated all 62 repetitive genes containing a PERV in pig DNA, surpassing a significant obstacle on the path to bringing xenotransplantation to clinical reality.”

 

Work Cited

http://wyss.harvard.edu/viewpressrelease/222

http://www.pbs.org/wgbh/pages/frontline/shows/organfarm/etc/faqs.html