The Significance of the Report of the November 1997 - National Forum on Xenotransplantation
Xenotransplantation: A Pandora's Box for Launching the Next Pandemic
Image 1. Where to get your free copy of the “Report of the National Forum on Xenotransplantation: Clinical, Ethical and Regulatory Issues, November 1997”.
https://publications.gc.ca/site/eng/9.686126/publication.html
I was a key player on the Health Canada’s organizing committee for this forum on xenotransplantation including the selection of participants and manager of operations. Moreover I compiled and edited the Report of the National Forum on Xenotransplantation: Clinical, Ethical and Regulatory Issues, November 1997 (see url above to get a free electronic copy) although somehow this was not captured in the publication.
This forum led to public consultation with Canadians who indicated the pandemic risks to the population would not justify the very short term benefits to few individuals, and so at the time a voluntary moratorium occurred. However it has been since lifted (but I don’t know when, sometime before October 21, 2022).
This forum received many accolades including by Dr. Robin Weiss who had been warning about animal retroviruses permanently integrated into the human genome since March 1997 [see Weiss, 2001] and the threat to human health of xenozoonoses: animal zoonotic agents transmitted to humans through the exposure of- or implantation into- humans of animal tissues or cells (xenografts).
This is yet another potential source of the next pandemic virus aside from lab leaks from gain-of-function research or bioweapons.
Many if not most people do not realize that in part the mass vaccination with COVID-19 mRNA vaccines opened a pandora’s box enabling xenotransplantation clinical trials to proceed …see below (a quote from a chapter I had been writing on vaccine controversies) which the FDA jumped on December 31, 2021.
“From the get-go, those in power knew that a safe and effective adaptive immunity vaccine against SARS-CoV-2 was highly unlikely. However, the agenda was to trial the notion that the mRNA vaccine platform technology was an acceptable means for governments to enable the rapid protection of its citizens against acts of viral bioterrorism, accidental lab leaks of novel pathogens related to ‘gain of function’ research, or the xenozoonoses that potentially might emerge from xenotransplantation clinical trials or compassionate use xenografts. It may not be a coincidence that the latter was unexpectantly authorized by the FDA on December 31, 2021 in the USA[1]“
[1] Potentially signifying that the FDA had accepted the notion that mRNA technology without safety studies could be used during epidemic/pandemic emergencies as was demonstrated for SARS-COV-2. See articles by Kozlov 2022 (compassionate EUA for pig heart transplant January 2022) and Rabin 2022 (for January 2022 University of Alabama at Birmingham kidney transplant on legally dead patient [Porrett et al, 2022] and Rabin 2021 (for September 2021 kidney xenotransplants on a legally dead ventilated accident patient at NY University Langone Transplant Institute under Dr. Robert Montgomery). It is not clear as to whether the FDA authorized EUAs for the xenotransplantation experiments on the legally dead patients. Despite the fact that the modified pigs of Revivicor had 10 genetic modifications, the live recipient of the pig heart on January 7, 2022, suffered a porcine CMV infection which lead to his demise on March 8, 2022.
On June 29 and 30, 2022 the FDA held a Cellular, Tissue and Gene Therapies Advisory Committee Meeting [Docket FDA-2022-N-0784, FDA Advisory Committee Meeting on “Cellular, Tissue, and Gene Therapies Advisory Committee June 29-30, 2022. https://www.fda.gov/advisory-committees/advisory-committee-calendar/cellular-tissue-and-gene-therapies-advisory-committee-june-29-30-2022-meeting-announcement-06292022] concerning xenotransplantation.
In the meeting the presentation by Judith Arcidicono of the FDA touched on the issue of porcine CMV (slide 17).
However, the issue of xenozoonosis did not seem to be high priority of the FDA as captured by these minutes:
Question 1. Please discuss any other known or emerging viruses that should be considered in the context of human xenotransplantation.
Summary of Discussion: The committee discussed the multiple known porcine viruses that impact organ function, directly cause disease in humans, or may cause complications, such as coagulopathy in humans. There were discussions of the need to identify or develop tests for specific viruses, although no single platform exists to test for all of the diseases mentioned. The committee noted that while many porcine viruses have not been shown to infect normal healthy human cells, the recipient of a xenotransplantation product will be immune-compromised or immune-suppressed, so that current data may not be representative of transplant conditions. The committee discussed patient monitoring and recommended that testing be performed frequently immediately after transplant and tapering off over time.
Lets not fool ourselves about what the roll-out of the mRNA COVID-19 vaccines was all about. It wasn’t about saving lives.
REFERENCES:
Kozlov M. Clinical trials for pig-to-human organ transplants inch closer. US regulatory agency signals willingness to allow first xenotransplant trials. Nature July 6, 2022. https://www.nature.com/articles/d41586-022-01861-2.
Porrett PM, Orandi BJ, Kumar V, Houp J, Anderson D, Cozette Killian A, Hauptfeld-Dolejsek V, Martin DE, Macedon S, Budd N, Stegner KL, Dandro A, Kokkinaki M, Kuravi KV, Reed RD, Fatima H, Killian JT Jr, Baker G, Perry J, Wright ED, Cheung MD, Erman EN, Kraebber K, Gamblin T, Guy L, George JF, Ayares D, Locke JE. First clinical-grade porcine kidney xenotransplant using a human decedent model. Am J Transplant. 2022 Apr;22(4):1037-1053. doi: 10.1111/ajt.16930. Epub 2022 Jan 20.
Rabin RC. In a first, surgeons attached a pig kidney to a human and it worked. New York Times, October 19, 2021. https://www.nytimes.com/2021/10/19/health/kidney-transplant-pig-human.html.
Rabin RC. Patient in groundbreaking heart transplant dies. New York Times, March 9, 2022. https://www.nytimes.com/2022/03/09/health/heart-transplant-pig-bennett.html.
Weiss RA. The Leeuwenhoek Lecture 2001. Animal origins of human infectious disease. Philos Trans R Soc Lond B Biol Sci. 2001 Jun 29;356(1410):957-77. doi: 10.1098/rstb.2001.0838.
Interestingly, when I became the Research Manager of the Blood Zoonotics Unit at the Public Health Agency of Canada in 2004 I was tasked with the development of 1) a screening test that would indicate the presence of a potential xenozoonosis and 2) potential countermeasures to its spread. The screening test was the real time PCR ddCt test for HERV-K102 pol activation (24 log range) performed on DNA extracted from plasma [Laderoute M et al., AIDS, 2007] and or HERV-K102 envelope antibodies. The countermeasure to xenozoonosis was the activation of HERV-K102 prior to and during the early days of the xenotransplant. Should the virus escape and start a local epidemic, HERV-K102 activation would be enhanced by a) lysine support, and the reversion of immunosenescence in the most vulnerable by daily supplementation with zinc, flavonoids, and vitamin D (now also including ivermectin) with the exclusion of anti-inflammatories including statins, corticosteroids and melatonin over 2 mgs daily. The evidence substantiating the countermeasure approach was given in Laderoute M et al, Open AIDS J, 2015 which showed HERV-K102 5-fold increased genomic integration in the HESN associated with sterile immunity (HIV exposed and seronegative) and resistance to HIV-1 acquisition.
There is a case that HTLV arose from SLV, when chimp brains were used to culture virus for an experimental polio vaccine in Africa in the early 1950s. Supposedly, the towns involved became unpopulated in the nect 30 years.
https://pubmed.ncbi.nlm.nih.gov/7935079/