If a new medical technology increased the risk of a new zoonotic pandemic – even marginally – how would society decide the balance between risk and benefit? If you needed new lungs that are only available in another country, would a health ban on transplant in your own country stop you?
New developments in organ transplant technology may have simplified the path to new zoonotic diseases, but biotechnology innovators and medical research institutes have failed to educate the public about the risks. Failure to do so may jeopardize the potential of a promising therapy.
More than 4,400 Canadians are on the waiting list for lifesaving new kidney, liver or lung transplants. In 2019, 250 dead pending. In the United States and elsewhere, the supply gap is more extreme and great hopes rest on xenotransplantation: the transplantation of cells, tissues or organs of animals.
Preclinical trials of pig organ transplants have addressed technical barriers to xenotransplantation, reducing the likelihood of rejection. Last summer, surgeons at the Maryland School of Medicine reported a baboon’s 31-day survival after receiving a lung of a genetically modified pig.
A few weeks later, a team from New York University transplanted a kidney from a genetically modified pig into a brain dead person. In December 2021, surgeons at the Maryland School of Medicine transplanted a genetically modified pig heart into a 57 year old living man.
All projects have been approved under US Food and Drug Administration (FDA) regulations, and corporate funding has been completed by the US National Institutes of Health. The next step with the FDA is to approve clinical trials. Normalization of xenotransplantation could take place before the public knowingly accepts the benefits and risks.
A potential zoonotic pathway
As a developmental geneticist, it has been exciting to follow these advances. The designer gene-editing revolution (known as CRISPR-Cas9) makes these amazing advances possible. CRISPR makes it possible to modify the molecules on the surface of porcine cells thus the human immune system will not trigger tissue rejection.
To prevent human transplant recipients from being infected by pigs retroviruses (viruses capable of integrating their genetic material into host cells), the retroviruses hidden in the pig genome have been removed by CRISPR editing. The risk of transmitting disease directly from a genetically modified donor pig to the human host is negligible.
However, healthy transplanted pig organs could become infected after transplantation. Bacteria and zoonotic viruses most easily enter hosts through the delicate airway surfaces, as with COVID-19. Live porcine cells in a transplanted lung could easily be infected with an inhaled porcine virus, including a new virus from a wild animal host that has evolved to infect pigs.
After entering the human body, a replicating zoonotic virus could generate millions of mutations per day, because their gene copying mechanism is naturally error prone. A porcine virus replicating in a lung transplanted into a human could produce variants which may be able to recognize and infect human cells. Although this is likely a rare event, it is not impossible that it could trigger a new zoonotic pandemic.
Risk, fear and polarization
The scenario described above could evoke the risk and fear of a complex new medical technology. It parallels the thinking involved in vaccine hesitancy or the distrust of genetically modified foods. Both are well entrenched in today’s political culture. In both cases, citizens are increasingly demanding prior consent and the choice not to participate, despite possible risks to public health. Vaccine hesitancy increased the death toll from COVID-19 and delayed economic recovery from the pandemic.
On the other hand, distrust of the industrialization of food has discouraged the introduction of genetically modified foods that improve nutrition or support agricultural productivity in a warming climate. Consumers wonder whether genetically modified organisms (GMOs) exist for the public good or for corporate profit.
Increasingly, health problems such as vaccinationvaping or genetic testing generates disinformation platformspolitical debate and influence. Social media algorithms amplify extreme positions and elicit strong emotional responses to to the detriment of the middle ground. When communications from the scientific community are reactive, poorly targeted or incomprehensible to ordinary mortalsthe influence of science in the political process is diminished.
In 2022, advances in xenotransplantation technology good news. The immense pressure to solve the growing shortage of organs for transplantation may cause biotech companies and public regulators not to be critical enough when seeking permission to conduct clinical studies. They must prepare for the nature and extent of backlash from those who are fed up with experts and mistrust corporate motivation and institutional authority.
The concern about zoonosis of transplants has been expressed more than twenty years agolong before CRISPR transformed the field. Since, there does not appear to be any hard facts or even a call for research on zoonotic infection by xenotransplantation after transplantation. Bioethicists are report the problem now, but the silence on xenotransplant zoonosis from biotech companies and their affiliated preclinical research institutes leaves the door open for a narrative driven by skepticism and mistrust. It is their responsibility to lead a public dialogue on managing the risk of new zoonotic diseases resulting from post-transplant infection.
J Roger Jacobs is a professor in the Department of Biology at McMaster University.