Cooking up a Chimera: The Future of Organ Transplantation

Cooking up a Chimera: The Future of Organ Transplantation

Since the first skin autograft transplantation in 1823 by German surgeon Carl Bunger, the list of transplantable organs has grown to include almost everything we find in the human body. In the United States an average of 79 people receive lifesaving organ transplants every day, but sadly an average of 22 people die daily while waiting for transplants due to a global shortage of donated organs.

Although artificial organs can support a patient as they wait for a successful transplant, such devices are rarely capable of replacing real organs. A team of researchers from the University of California, Davis, are attempting to tackle this problem by exploring the possibilities of growing human organs inside pigs with the goal of transplanting the organs to patients.

 

Gentle Chimeras

The team, led by Professor Pablo Ross, revealed this week how they used a gene-editing technique known as Crispr (Clustered regularly interspaced short palindromic repeats), to alter the genetic makeup of pig embryos and prevent the development of the pancreas. Human cells known as induced pluripotent stem cells (iPS) were injected into the pig embryo, replacing the original pig cells and enabling the embryo to develop into a predetermined tissue type (in this case the pancreas). The human cells were not rejected by the embryo as it had not yet developed an immune system. The team decided to terminate the test embryos for analysis after 28 days, but in theory the embryo should develop into a normal pig foetus, albeit one with a human cell derived pancreas.

This is not the first time research has been conducted into gene-editing techniques. In 2010, a team of scientists were able to generate a rat pancreas in a mouse model, while another team successfully developed a mouse model with a liver comprising of 95% human cells. The existence of two types of DNA  in an organism is known as genetic chimera and can naturally exist in both humans and animals. However, the purposeful creation of genetic chimera has been subject to strong criticism.

 

Ethical Enquiries

The U.S. National Institutes of Health, the main source for medical research funding in the US, said last September that it would not back research into genetic chimera until it better understood the implications. Citing fears that the presence of human cells in an animal’s biology could have an effect on the animal’s brain and behaviour, the NIH voiced concerns that genetic chimera gene-editing could potentially make the subject animal more humanlike, and imposed a moratorium on providing funds for this type of research.

The team were able to acquire funding from a number of alternative sources including the California Institute for Regenerative Medicine and the Universidad Católica de Murcia, Spain. Professor Ross commented on the NIH’s concerns, saying there was a “very low potential for a human brain to grow”, and that the team hopes “this pig embryo will develop normally”.

Other concerns include the fact that the human host may reject the organ due to the presence of pig cell types or the modification of the human cells within the pig embryo, and that the transplantation of organs from animal to human hosts could introduce animal viruses. The second concern was addressed by a team from Harvard Medical School last year who modified and inactivated more than 60 retrovirus genes in pig embryos, but the possibility of organ rejection is still a reality.

There is also the ethical question of using animals to supplement an organ shortage and if there should instead be a focus on encouraging more people to become organ donors. Animal rights organisations oppose experiments like genetic chimera gene-editing due to the suffering caused to animals and the anticipation of organ farms where animals are reared solely to provide organs for transplantations. However, one could argue that there’s isn’t much difference between rearing a pig for human consumption and rearing it for organ harvesting.

 

An end to organ shortages

A 2007 article on xenotransplantation (transplanting organs from one species to another) from Carl G. Groth examines the potential advantages of transplanting organs from pig to man. While xenotransplantation is different in that it uses pig organs instead of genetic chimera organs, the arguments regarding the benefit of this procedure are the same.

The article reiterates the fact that organ shortages will no longer be a problem for prospective transplantation patients and death on waiting lists will be avoided. More liberal age limits could be applied to allow currently unsuitable elderly patients to make the list. Non-optimal human organs are often used in transplantations due to the shortage of suitable replacements, but using gene-edited pig organs could ensure that the organ is the right match for the patient.

Groth also argues that the aforementioned problem of graft rejection could be avoided by using modified donor tissue and that xenotransplantation, and by extension pig grown human organs, could bring significant cost savings and render existing organ donation organizations obsolete.

 

Practicality vs Ethics

While it seems that the practical advantages of genetic chimera production far outweigh the cons, the ethical debate is a much more difficult subject to navigate. Some worry about the dangers of interfering with gene pools, while others are concerned about the potential suffering caused to animals who exist solely to provide organs for humans. However, it is in our collective interests that this research continues, as it could quickly turn the tide on organ transplantation shortages and prevent the deaths of thousands of people each year. As for Orwellian pigs overthrowing farmsteads, we’ll have to wait and see what happens.

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