On the recent episode of Genetics Unzipped 'Have a heart: the science of xenotransplantation', Dr Sally Le Page talked about the process of transplanting organs from animals into human bodies. The first proof-of-consent pig to human heart transplant was conducted in January 2022, leaving the world impressed by this achievement and its implications (see BioNews 1128). I was in awe of this milestone, which really makes me think no challenge is big enough for mankind.
Dr Le Page discussed with consultant cardiologist Dr Rohin Francis, and livestock biotechnology specialist Professor Angelika Schnieke. It was an interesting and thorough conversation between specialists that covered many exciting points about this groundbreaking procedure. Questions about organ rejection, genome editing, risks of diseases jumping between host species, ethics, and the future of this experimental technique were debated.
Dr Francis, who also runs the science YouTube channel, MedLife Crisis, explained that organ rejection is a key consideration in any transplant, even when the donor is the same species as the recipient. Each individual has specific molecules on the cells' surface and, when transplanted into a different body, these can become targets for the immune system. The difference in these cell surface molecules is greater between different species, leading to catastrophic and immediate rejection in past experimental transplants.
Dr Francis commented on the development of 'ten-gene-pigs'. These are animals where genome editing has been used to remove four pig genes that were triggering important human immune responses, and to add six human genes that intend to mask the foreign tissue. These pigs provided the heart for the surgery in January 2022 and are being currently bred to provide more organs in the near future. It is outstanding how we have become able to create custom-made animals to satisfy our needs of organs, in a near sci-fi way.
One of the fears Dr Le Page and Dr Francis (and myself, and most likely many of you) had about xenotransplantation was the passage of infections with the organ, that could be detrimental to the recipient. Especially retroviruses that insert their genetic material within the DNA of the host species and use their cellular machinery to replicate. The pig organs could contain viral DNA that could inadvertently be introduced into the recipient's body.
Professor Schnieke reassured Dr Le Page that the risk of porcine viral DNA passing to humans is theoretical and has not happened in vivo so far. She clarified the possibility of inactivating such viruses using genome editing, silencing not only the original four genes in the 'ten-gene-pigs', but also the viral genes that may be present in the cells.
My favourite part of the podcast was when Professor Schnieke explained how these unique animals are created. The process starts with porcine cells that come from a skin or renal biopsy, for example. These are cultured and their genomes edited, then their genetic material is extracted and transferred into an oocyte, and finally implanted into a pig, to be grown in the womb and born as a state-of-the-art animal. It is a complex and sensitive process that, if perfected, has the potential for endless opportunities to treat many diseases.
The specialists debated that many challenges still exist to improve xenotransplantation. It is uncertain if all genes that may be detrimental to humans are being silenced, and the risk of transmitting diseases is certainly not ruled out either. But even if the techniques are improved, the ethical implications are not to be forgotten. Is it ok to manipulate other species, raise them in artificial, highly controlled settings, and then kill them to provide us with organs? Is it safe to edit other species' genetic information and create novel, chimeric animals? These questions are yet to be answered and need cautious consideration.
Shortly after the release of this podcast, the death of David Bennett – the man who received the pig transplant earlier this year – became public. The cause of death is still uncertain, however, his doctors recently reported that a porcine virus was found in the patient's blood, and this may have been associated with the short viability of the heart (see BioNews 1144). This news has prompted both hopes and distress in the scientific community: on one hand, having found a possible cause of transplant failure gets us closer to finding a cure and refining the technique for future patients, with improved infectious control in animals and thorough screening. On the other, it raises awareness of viral infections being indeed (fatally?) transmitted through the organ and possibly passed on to other human beings.
I'm intrigued to find out what developments time and experience will bring in the field of xenotransplantation. I found Dr Le Page's podcast complete and clear, providing all the relevant information on the topic. I look forward to the second part of this episode, to hear about the current research status and what is next on the horizon.