Xenotransplantation

Xenotransplantation Information & Postings - Mixing of human and animal cells/parts can produce new retroviruses

(This is from one of my e-mails and I am the original source for finding this reference article in 2015.)

Timestamp from original e-mail I sent:  Tue 10/20/2015 9:10 AM
(explained and sent to others via e-mail and detailed on facebook)

Source:  American Anti-Vivisection Society (AAVS) - AV Magazine

Source date: 9/1/1996

Summary

p.14-17. "Xenotransplantation and Primates - Threats Masquerading as Cures." Dr. Susan Ildstad wants to transplant healthy bone marrow stem cells from baboons into the bodies of terminally ill AIDS patients. Ildstad believes this procedure will produce an entirely new andfully functional immune system that will combat and kill the AIDS virus. Based on experiments involving mice, Dr. Ilstad claims to have discovered a new type of bone marrow cell (a facilitator) which, when mixed with typical stem cells from the marrow of a donor, allows survival of the transplant and avoids the problems associated with graft versus host disease. Stephen Rose,* director of AIDS funding at the NIH, said, "Having seen her data -- there are no underlying data to make me believe this is going to be successful". David Sachs*, Harvard University xenotransplant specialist, agreed, saying, "there was no evidence from the data she presented to show that facilitator cells were present in primates." Despite scientific skepticism, the FDA supported the clinical experiment to transplant baboon cells into AIDS patient Jeff Getty. Prior to this decision, the FDA convened lengthy hearings of the National Academy of Sciences' Institute of Medicine and its own Biological Response Modifiers Advisory Committee. Dr. Marion Michaels*, from the University of Pittsburgh, told the committee that despite rigorous screening, "the donor organ, the tissue or the accompanying hematopoietic cells can also be the source of infection. Most often these infections are latent organisms and are often clinically silent in the donor." Dr. John Coffin*, a leading expert on recombination in viruses, concluded "the infection is a virtually inevitable consequence" of xenotransplantation and "This is a very serious worry because the animals that have been chosen for doing this -- the baboon and the pig -- are both known to carry endogenous viruses, replication competent, but very poorly studied, that are capable of infecting human cells." He further suggested baboon bone marrow experiments could make the HIV-AIDS infection "worse by spreading the host range." 

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(This is from one of my e-mails and I am the original source for finding this reference information in 2016.)

Timestamp from original e-mail I sent: Sun 2/21/2016 8:28 PM
(explained and sent to others via e-mail and detailed on facebook)

http://www.aabb.org/advocacy/comments/Pages/xenofda050802.aspx

(This is my wording from original e-mail): Coffin was part of this and so was Varmus ( Varmus reinstated xenotransplatation and Coffin was part of the workgroup who had meetings and I have meeting minutes of their discussions)

Guidance for Industry
Precautionary Measures to Reduce
the Possible Risk of Transmission of
Zoonoses by Blood and Blood
Products from Xenotransplantation
Product Recipients and Their
Intimate Contacts

U.S. Department of Health and Human Services
Food and Drug Administration
Center for Biologics Evaluation and Research
February 2002

(This is my wording from my original e-mail) They withdrew in (sic) on: Withdrawn May 2015 ( Coffin was part of the meetings where they said partners of xeno were not at risk when all previous research said they were. They didn't want it to show that close contact relatives could catch something from a xeno recipient)

Withdrawn - Draft Guidance for Industry: Precautionary Measures to Reduce the Possible Risk of Transmission of Zoonoses by Blood and Blood Products from Xenotransplantation Product Recipients and Their Intimate Contacts

The guidance document entitled "Draft Guidance for Industry: Precautionary Measures to Reduce the Possible Risk of Transmission of Zoonoses by Blood and Blood Products from Xenotransplantation Product Recipients and Their Intimate Contacts” was withdrawn on May 8, 2015. Please visit: http://www.gpo.gov/fdsys/pkg/FR-2015-05-06/html/2015-10477.htm for additional information. that link goes to this:


[Federal Register Volume 80, Number 87 (Wednesday, May 6, 2015)] [Notices] [Pages 26059-26061] From the Federal Register Online via the Government Publishing Office [www.gpo.gov] [FR Doc No: 2015-10477] ----------------------------------------------------------------------- DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2015-N-1419] Withdrawal of Draft Guidance Documents Published Before December 31, 2013 AGENCY: Food and Drug Administration, HHS. ACTION: Notice.

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May 10, 2019 - This is a compilation of information I discovered through my online and other source research since 2009. This page includes my writings and postings explaining xenotransplantation research and it's uses and dangers.  

The history on xenotransplantation, what it is, and zoonosis it can cause:

"Xenotransplantation is any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivocontact with live nonhuman animal cells, tissues or organs. The development of xenotransplantation is, in part, driven by the fact that the demand for human organs for clinical transplantation far exceeds the supply. 

Currently ten patients die each day in the United States while on the waiting list to receive lifesaving vital organ transplants. Moreover, recent evidence has suggested that transplantation of cells and tissues may be therapeutic for certain diseases such as neurodegenerative disorders and diabetes, where, again human materials are not usually available. 

Although the potential benefits are considerable, the use of xenotransplantation raises concerns regarding the potential infection of recipients with both recognized and unrecognized infectious agents and the possible subsequent transmission to their close contacts and into the general human population. Of public health concern is the potential for cross-species infection by retroviruses, which may be latent and lead to disease years after infection. Moreover, new infectious agents may not be readily identifiable with current techniques.
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This is the group who campaigned to stop Xenotransplantation. They were successful until Harold Varmus as NIH Director moved to re-implement it's use in research and biologicals:

The Campaign for Responsible Transplantation

The Campaign for Responsible Transplantation (CRT) was launched on January 20th, 1998, out of concern over the irresponsible rush to commercialize animal-to-human organ and tissue transplantation (xenotransplantation). Xenotransplantation poses a grave danger to human health because of the risk of transferring deadly viruses to the human population. There are safer and more cost-effective ways to reduce the shortage of human organs for transplantation that are not being explored by the US government. CRT has grown to include 70 organizations from around the world, representing over two million people. 

https://web.archive.org/web/19990428134047/http://www.crt-online.org:80/
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Xenotransplants: proceed with caution

The US Public Health Service (PHS) agencies have rejected recommendations for a moratorium on clinical trials of xenotransplants, and left the door open for nonhuman primates to be donors. Your Briefing on xenotransplantation1 summarizes the important elements of this subject, and captures perfectly the split between those who want to get it right and those who want to get it right now.

In the Briefing, Jonathan Allan, a virologist on the Food and Drug Administration (FDA)'s advisory subcommittee on xenotransplantation, points out the neglect of the precautionary principle in a situation where it is most needed, given the risk of public exposure to xenozoonoses. The United States is fortunate in having bodies such as the Centers for Disease Control and Prevention, the National Institutes of Health and the FDA, which give it the confidence to halt activities “should something happen” — but containment is the wrong strategy here, and any epidemic that starts may involve countries other than the United States. https://www.nature.com/articles/32023

This happened in 1997 and see the timeline of events on xenotransplantation that follows. There was a worldwide ban on all xenotransplantation because of the risk of infecting human recipients with animal retroviruses. Imagine that! It was Harold Varmus with the help of John Coffin who helped get the ban for it use lifted. Xenotransplantation is not just transplanting animals part. It includes implanting ore using animal cells in research and biologicals.

Xenotransplantation: Science, Ethics, and Public Policy - 1996 (the mixing of human and animal cells in research and biologicals) - John Coffin and Harold Varmus helped with this and getting animal cell and parts re-implemented in 2001. The IOM committee helped make it happen. https://www.ncbi.nlm.nih.gov/books/NBK45534/
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Timeline of events

1997 – Worldwide ban on all xenotransplantation

Concerns about the risk of infecting human recipients with animal endogenous retroviruses lead to a worldwide ban or moratorium on animal to human transplants. Pig endogenous retrovirus (PERV) is of particular concern.

1997–1999 – Risk of infectious disease assessed

2000–2011 – Ban on xenotransplantation is lifted in some countries

The ban on xenotransplantation is lifted in some countries and applications for trials with xenotransplants are assessed on a case-by-case basis.

2007–2011 – Clinical trials of pig cell transplants continue

Russia, New Zealand and Argentina all approve clinical trials of pig cells for the treatment of type 1 diabetes. Find out more in the article Pig cell transplants.

https://www.sciencelearn.org.nz/resources/2125-xenotransplantation-timeline
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The first serious attempts at xenotransplantation (then called heterotransplantation) appeared in the scientific literature in 1905, when slices of rabbit kidney were transplanted into a child with renal insufficiency.[7] In the first two decades of the 20th century, several subsequent efforts attempts to use organs from lambs, pigs and primates were published.[7]

Scientific interest in xenotransplantation declined when the immunological basis of the organ rejection process was described. The next waves of studies on the topic came with the discovery of immunosuppressive drugs. Even more studies followed Dr. Joseph Murray's first successful renal transplantation in 1954 and scientists, facing the ethical questions of organ donation for the first time, accelerated their effort in looking for alternatives to human organs.[7]

In 1963, doctors at Tulane University attempted chimpanzee-to-human renal transplantations in six people who were near death; after this and several subsequent unsuccessful attempts to use primates as organ donors and the development of a working cadaver organ procuring program, interest in xenotransplantation for kidney failure dissipated.[7]

An American infant girl known as "Baby Fae" with hypoplastic left heart syndrome was the first infant recipient of a xenotransplantation, when she received a baboon heart in 1983. The procedure was performed by Leonard L. Bailey at Loma Linda University Medical Center in Loma Linda, California. Fae died 21 days later due to a humoral-based graft rejection thought to be caused mainly by an ABO blood type mismatch, considered unavoidable due to the rarity of type O baboons. The graft was meant to be temporary, but unfortunately a suitable allograft replacement could not be found in time. While the procedure itself did not advance the progress on xenotransplantation, it did shed a light on the insufficient amount of organs for infants. The story grew so big that it made such an impact that the crisis of infant organ shortage improved for that time.[8][9]

Xenotransplantation of human tumor cells into immunocompromised mice is a research technique frequently used in oncology research.[10] It is used to predict the sensitivity of the transplanted tumor to various cancer treatments; several companies offer this service, including the Jackson Laboratory.[11]

Human organs have been transplanted into animals as a powerful research technique for studying human biology without harming human patients. This technique has also been proposed as an alternative source of human organs for future transplantation into human patients.[12] For example, researchers from the Ganogen Research Institute transplanted human fetal kidneys into rats which demonstrated life supporting function and growth.[13]

https://en.wikipedia.org/wiki/Xenotransplantation#cite_note-who2005-34
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The FDA regulatory process governing clinical investigations includes requirements applicable to manufacturing processes, the study of the safety and efficacy of such cells, and the protection of human participants in such studies. If you plan to co-culture human embryos with living nonhuman animal cells for transfer into a human recipient, we can provide you with information and guidance regarding filing such an application. FDA's Xenotransplantation Action Plan website contains relevant guidance documents for the clinical use of human cells that have been exposed to animal cells. They include the following:

PHS Guideline on Infectious Disease Issues in Xenotransplantation, January 19, 2001.

Guidance for Industry: Source Animal, Product, Preclinical, and Clinical Issues Concerning the Use of Xenotransplantation Products in Humans

Draft Guidance for Industry: Precautionary Measures to Reduce the Possible Risk of Transmission of Zoonoses by Blood and Blood Products from Xenotransplantation Product Recipients and Their Intimate Contacts, February 1, 2002.

Guidance for Industry: Public Health Issues Posed by the Use of Nonhuman Primate Xenografts in Humans, April 6, 1999.

FDA's regulations on investigational new drugs, including those for the submission and review of an IND, are described in Title 21 of the Code of Federal Regulations (CFR), Parts 50, 56, and 312. The agency has discussed the applicability of these requirements to cellular and tissue-based products in many public forums and in various published documents available at http://www.fda.gov/cber/. They include the following:

A Federal Register (FR) notice describing FDA's authority over cell and gene therapy products ("Application of Current Statutory Authorities to Human Somatic Cell Therapy Products and Gene Therapy Products," October 14, 1993, 58 FR 53248).

A comprehensive regulatory program for the regulation of human cellular and tissue-based products, based on a tiered, risk-based assessment ("A Proposed Approach to the Regulation of Cellular and Tissue-Based Products," February 28, 1997).

"Human Cells, Tissues, and Cellular and Tissue-Based Products; Establishment Registration and Listing," Final Rule, January 19, 2001 (66 FR 5447). This rule establishes the criteria for regulation of human cells, tissues, and cellular and tissue based products (HCT/Ps), including reproductive cells and tissues, solely under the authority of section 361 of the Public Health Service Act. HCT/Ps that do not meet the criteria are regulated under section 351 of the Public Health Service Act and/or the Food Drug and Cosmetic Act (FDCA), as biological products, drug products, and/or medical devices.

Suitability Determination for Donors of Human Cellular and Tissue-Based Products; Proposed Rule, September 30, 1999 (64 FR 52696).

Current Good Tissue Practice for Manufacture of Human Cellular and Tissue-Based Products; Inspection and Enforcement; Proposed Rule, January 8, 2001 (66 FR 1508).

https://wayback.archive-it.org/7993/20170404183839/https://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ucm136703.htm
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Robyn Erland updated status.  (Facebook posting)

The DHHS sponsored two public workshops on xenotransplantation during 1997 and 1998. The first meeting, held in July 1997, focused on virology and documented evidence of cross species infections. Titled "Cross-Species Infectivity and Pathogenesis," the meeting addressed current knowledge about the mechanisms and consequences of infectious agent transmission across species barriers. Discussions also focused on the possibility that an infectious agent might cross from an animal donor organ or tissue to human xenotransplantation product recipients. The conference also highlighted gaps in knowledge about the emergence of new infections in humans, especially as a result of xenotransplantation. The basic consensus of the meeting was that while there were examples of animal infectious agents crossing species barriers to infect, and even cause diseases in humans, the actual likelihood of this in xenotransplantation product recipients cannot be ascertained at this time. Small adequate and well-controlled clinical trials designed to test the safety and efficacy of xenotransplantation were considered to be appropriate. One anticipated outcome of such trials would be to both minimize and better understand the risks of transmission of infectious agents. The meeting summary can be accessed at: http://www.niaid.nih.gov/dait/cross-species/default.htm

May 31, 2014, 3:51 PM
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Robyn Erland updated her status.  (Facebook posting)

This is also posted on the FDA site and it's all current information:

Xenotransplantation is any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs. The development of xenotransplantation is, in part, driven by the fact that the demand for human organs for clinical transplantation far exceeds the supply.

Currently ten patients die each day in the United States while on the waiting list to receive lifesaving vital organ transplants. Moreover, recent evidence has suggested that transplantation of cells and tissues may be therapeutic for certain diseases such as neurodegenerative disorders and diabetes, where, again human materials are not usually available.

Although the potential benefits are considerable, the use of xenotransplantation raises concerns regarding the potential infection of recipients with both recognized and unrecognized infectious agents and the possible subsequent transmission to their close contacts and into the general human population. Of public health concern is the potential for cross-species infection by retroviruses, which may be latent and lead to disease years after infection. Moreover, new infectious agents may not be readily identifiable with current techniques.

May 31, 2014, 3:39 PM
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Robyn Erland updated her status.  (This was a Facebook posting)

Current information on the FDA website for Xenotransplantation:

Viral Safety Studies in Xenotransplantation and Gene Therapy Products

Principal Investigator: Carolyn A. Wilson, PhDOffice / Division / Lab: OCTGT / DCGT / GTIB

General Overview

Gammaretroviruses are simple animal viruses that are related to HIV, the cause of AIDS.These viruses might pose risks in several regulated biologics products, both as contaminants and in their use for gene therapy, in which they act as carriers, or "vectors" to deliver genes that treat a disease by producing a therapeutic molecule.

May 31, 2014, 11:23 AM
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Robyn Erland shared a link.   (This was a Facebook posting)

Also from the same lawsuit filed against the FDA: In September 1996, the Department of Health and Human Services (HHS) issued a set of draft voluntary guidelines on xenotransplantation. Currently, xenotransplantation is "regulated" by the Food and Drug Administration (FDA); Over the last several years, FDA has approved limited clinical trials with animal tissues, cells, and organs. " CBER scientists have acknowledged that xenotransplantation presents a risk of introducing novel pathogens into the human population." http://www.crt-online.org/who.html

May 30, 2014, 9:50 PM
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Robyn Erland updated her status. (This was a Facebook posting)

From a lawsuit filed against FDA in 1996 "An animal virus residing in a xenograft recipient could become airborne, infecting scores of people, and causing a potentially deadly viral epidemic of global proportions akin to HIV or worse". "There is no way to screen for viruses that are not yet known. Proceeding with xenotransplantation could expose patients and non-patients to a host of new animal viruses which could remain dormant for months or years before being detected. Xenotransplantation could thus be viewed as a form of involuntary human experimentation which violates US laws and United Nations charters." "Xenotransplant proponents claim that they will breed "germ-free" animals, thereby diminishing the risk of viral transmission. But it is impossible to breed "germ-free" animals since no animal can remain completely free of parasites or endogenous viruses. In fact, genetically engineered animals are more susceptible to a host of diseases because of weaker immune systems." "CRT believes that HHS violated the Public Health Service Act by ignoring the scientific evidence showing that xenotransplantation is dangerous and ineffective. HHS failed to adequately consider the legal, social, ethical, and economical implications of xenotransplantation. HHS issued voluntary draft guidelines on xenotransplantation, September 23, 1996, despite scientific evidence demonstrating that the xenograft recipient will suffer significant harm. Scientists have criticized the voluntary guidelines for being weak, ineffectual, and unlikely to protect the public. HHS did not adequately consider how to protect the public from contracting novel animal viruses, how to deal with the issue of informed consent, or the large costs associated with xenotransplantation. HHS issued voluntary guidelines to regulate the technology. It is highly probable that HHS will be unable to protect the xenograft recipient or the public from being infected by an animal virus. As a result, HHS should have considered how the government would handle an infectious epidemic before the guidelines for xenotransplantation were issued." HHS has not addressed how infected individuals will be identified and how those infected will be prevented from spreading diseases. HHS has also failed to address who will pay for treatment and care for those infected. Treating and caring for individuals infected with animal viruses will most likely cost the U.S. billions of dollars. So far, HHS has not stated whether it would compensate victims who inadvertently come into contact with a lethal animal virus. However, this should be a consideration because the government has already had to respond to compensation claims filed by Persian Gulf War veterans, victims of Agent Orange, hemophiliacs infected by HIV-tainted blood, and parents of vaccine-damaged children. Although HHS identifies procedures for obtaining informed consent in the xenotransplantation guidelines, the agency failed to consider several important issues. An Institute of Medicine 1996 report on xenotransplantation indicates that "more research needs to be done on the psychological, religious, and social interpretations of xenotransplants for patients and their families." HHS should have considered that xenograft patients will most likely be very ill when they decide to take part in xenograft procedures. These patients, many in desperate situations, must understand highly complex issues, including the experimental nature of xenotransplantation and the health risks not only to themselves, but also their close personal contacts. It is unlikely that patients would fully understand the consequences of their participation in such experiments.

May 30, 2014, 9:33 PM
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Robyn Erland updated her status. (This was a Facebook status posting)

Check this out! Even though there were a lot of unknowns and still are regarding the use of animal cells in biologicals, check out this article from 1997. They were inserting mice cells into people’s brains! (and from what the article says these experiments were not helpful)

This procedure must be weighed against the potential risks of generating pathogens harmful to others. Here's the name of the article: Benefits and risks of hosting animal cells in the human brain

From the article: Mouse cell therapy for brain tumors Implantation of mouse cells releasing retrovirus vectors bearing a suicide gene has proven an effective treatment for brain tumors in experimental animals 3,42,43. In clinical trials throughout the world, hundreds of patients have now been implanted with such mouse cells 44. It is estimated that in the United States there are approximately 35,000 individuals with malignant gliomas. For these patients the prognosis is devastating. The time from diagnosis to death for glioblastoma multiforme usually ranges from a few months to a year, even with access to surgery, radiation and chemotherapy 46. Thus, an affected individual has much to gain from a few more months of life, and many of the risks to the individual undergoing this gene therapy protocol (hemorrhage and loss of cerebral function, for example) are already inherent in current treatments. However, the potential benefits of this procedure must be weighed against the potential risks of generating pathogens harmful to others.

For gene therapy protocols aimed at delivering a therapeutic gene to tumor cells on site, one of the most critical parameters is the efficiency of gene delivery. This includes both the number of tumor cells transduced per given dose and the distribution of these cells in the brain. Currently there is little information available about the efficacy of gene delivery to tumor cells in the human brain. In this therapeutic protocol, immortalized mouse cells are engineered in culture to express functional components of retrovirus virions. Genetic components of the virus, including gag, pol and env genes, are inserted into the cell genome at different sites in order to reduce the chance of generating wild-type virus by recombination between inserted and endogenous retrovirus elements47,48 (Fig. 3). These same cells are then transfected with retrovirus vector sequences consisting of long terminal repeat elements (LTRs) Sadly, studies in humans indicate that this procedure is very inefficient at gene delivery to tumor cells and has no marked therapeutic efficacy 4. The low level of gene delivery probably reflects a number of factors, including the slow rate of retrovirus release from cells; the instability of virions; However, if this is the primary means of tumor killing by this mode of therapy, there are probably more controlled ways of effecting this, rather than introducing mouse cells expressing high levels of retrovirus sequences. I would think so!!!!! http://www.nature.com/nm/web_specials/xeno/review.html

May 29, 2014, 9:58 AM
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Robyn Erland shared a link.  (Facebook posting)

http://www.nap.edu/openbook.php?record_id=5365&page=39
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This is the 1996 IOM workshop recommendation from the Institute of Medicine for: 

Infectious Disease Risk to Public Health Posed by Xenografting

Here's what it had to say: "The possibility that infections can be transmitted from animals to humans is of concern not only because of the threat to the health of the recipient, but also because such infections may be transmissible to others, creating a public health hazard. Further, such infections may be due to previously unrecognized organisms, making detection difficult if not impossible. If the time from infection to clinical symptoms is long, the risk of widespread transmission is greater, because during this time the new organism may silently spread from person to person, as happened with human immunodeficiency virus (HIV)."

Here was their recommendation: The following conclusions and recommendations are based on the IOM workshop presentations and discussions, as well as review of relevant materials and extensive discussions among the committee: The progress of basic science in the field of xenotransplantation has been rapid, and clinical trials of specific applications of xenotransplantation are under way. it is well recognized that infectious agents can be transmitted from animals to humans and that organisms benign in one species can be fatal when introduced into other species. Further, it is known that the pathogenicity of infectious organisms can change under a variety of conditions and that the effects of infection by some organisms, such as the human immunodeficiency virus, are delayed for years or even decades. Because xenotransplants involve the direct insertion of potentially infected cells, tissues, or organs into humans, there is every reason to believe that the potential for transmission of infectious agents (some of which may not even now be recognized) from animals to human transplant recipients is real. If established in the recipient, the potential for transmission to caregivers, family, and the population at large must be considered a real threat. NOW REMEMBER THIS WAS THE RECOMMENDATION IN 1996 and it has not been updated, Ready? Drum roll: The IOM committee recommends that, when the science base for specific types of xenotransplants is judged sufficient and the appropriate safeguards are in place, well-chosen human xenotransplantation trials using animal cells, tissues, and organs would be justified and should proceed.

Now they said this above, so how would they know all the safeguards in 1996 if there was and infectious agent they had no current test for? " Because xenotransplants involve the direct insertion of potentially infected cells, tissues, or organs into humans, there is every reason to believe that the potential for transmission of infectious agents (some of which may not even now be recognized) from animals to human transplant recipients is real." http://www.nap.edu/openbook.php?record_id=5365&page=39

May 28, 2014, 12:52 PM
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Robyn Erland shared a link. (Facebook posting)

In response to John Coffins (NIH/NCI contractor's) recent Twiv podcast regarding human retroviral infections: Coffin was and still is on the committee that approved the use of gammaretroviruses for cancer and other research and biologicals! At the point of this FDA document dated 2000, it was not realized that gammaretroviruses could become airborne and get into other cell lines. This was discovered as a result of recent research published in 2011. Several gammaretroviruses were found in cell lines by Dr. Adi Gazdar and others , Gazdar team warned, “Laboratories working with xenograft-derived human cultures should be aware of the risk of contamination with potentially bio-hazardous human-tropic mouse viruses and their spread to other cultures.” 

My note- Once a gammaretrovirus gets into another cell line it can recombine with another to produce an infectious exogenous retrovirus! Here is what Coffin’s subcommittee came up with on the use of these retroviral agents:

“Xenotransplantation: any procedure that involves the transplantation, implantation, infusion into a human recipient of either (a) live cells, tissues, or organs

from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs.”

Report of the FDA Subcommittee on Xenotransplantation

Meeting of January 13,200O

Food and Drug Administration

Center for Biologics Evaluation and Research

CHAIRMAN’S SUMMARY REPORT

XENOTRANSPLANTATION SUBCOMMITTEE

(Subcommittee of the Biological Response Modifiers Advisory Committee)

Subcommittee Participant: 

(One of the committee members was)

“John M. Coffin, Ph.D.”

(2) Examination of Risks Posed by Different Xenotransplantation

Products:

The Xenotransplantation Subcommittee, working with the FDA, had previously agreed on the principle that recipients of xenotransplants (my note: this would include xenograft cell lines used in research and biologicals) and their contacts should be deferred from blood donation indefinitely.

The transmission of potential zoonotic infections between humans is most likely to occur by exposure to body fluids, implying that “contacts” of xenotransplant recipients would most likely involve truly “intimate” contacts,

Who should not donate blood if they came in contact with fluids of xenograft recipient: 

Persons who are intimate contacts of xenotransplantation product recipients should be

indefinitely deferred from donating Whole Blood, blood components, including Source Plasma, and Source Leukocytes- Health care workers, including laboratory personnel, and other individuals who have -had contact with blood and body fluids from a xenotransplantation recipient, through percutaneous inoculation (such as accidental needle stick) open would, non-intact skin,

Considerations in Deferral Policy

The risks of zoonotic transmission to xenotransplant recipients, and their contacts, remain undetified.

The risks to the public health of blood or plasma becoming unavailable are immediate and significant.

Because transplantation necessitates disruption of the recipient’s usual protective physical and immunologic barriers, xenotransplantation may facilitate transmission of known or as yet unrecognized zoonotic agents to humans. (more to come on this TWIV Podcast) Here is the FDA info on xenograft products: http://www.fda.gov/ohrms/dockets/ac/00/backgrd/3603b1n.pdf

Jan 25, 2015, 1:24 PM
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Robyn Erland shared a link.  (Facebook posting)

Well isn't this interesting. They are using XMRV cloned reagents in (and these can be used for commercial use) through the NIH, NIAID AIDS Program. I hope they are all careful since we know XMRV can end up in everything. Watch out for those recombination events. Hopefully that's listed on the msds sheets too. These XMRV reagents could still be a problem though. What if they should recombine with HIV? https://www.aidsreagent.org/search_results_nav.cfm?searchStart=21&cat1=4&cat2=XMRV

Jan 1, 2015, 12:30 PM
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Robyn Erland shared a link.  (Facebook posting)

How about vaccines made from tumors? Here's the recent FDA discussions on it. Hey, they approved xenografting, and now they know that lab mice have replication competent retroviruses in them. And humans can get infected with infectious retroviruses if they graft the mice cells with human cells and then use them in humans. So, what does it matter if they throw in some tumors to go with it? Hey the cancer can just come on quicker then: http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/BloodVaccinesandOtherBiologics/VaccinesandRelatedBiologicalProductsAdvisoryCommittee/UCM319573.pdf

Dec 31, 2014, 11:00 PM
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Robyn Erland  (Facebook posting)

August 22, 2017

I know you ME/CFS patients will remember Robin Weiss. Check this out as a refresher given the new CRSPR technology to pigs and other animal retroviruses for us all. Too bad they already injected this crap into several generations. And CRSPR is not going to remove latent retroviruses in the genomes of these animals. It's all another money-making scam. Remember that old saying "If it seems too good to be true???"

Circe, Cassandra, and the Trojan Pigs: Xenotransplantation

ROBIN A. WEISS

Professor of Viral Oncology

University College London

Xenotransplantation—the transfer of animal cells, tissues, or organs into humans—poses a number of problems: ethical, physiological, immunological, and microbiological. Ideally, the source animal will be reared in specific pathogen-free conditions and should therefore be much less of an infection hazard than a “free range” human donor who might be infected by HIV or hepatitis viruses, and certainly will be carrying several kinds of herpesvirus. But certain porcine viruses, the paleontological ones, cannot be eliminated; they reside within the pigs’ DNA, but like the Greeks hidden inside the Trojan horse, they may emerge once the pig tissue or organ is taken into the human body"

My note: and John Coffin is also quoted several times: It is the fossil viruses, however, the topic of this symposium, that have created the most concern about the infection hazards of xenotransplantation. As John Coffin has described, retroviruses can be maintained in their host populations by two quite distinct modes of transmission. The first, as in all other viruses and transmissible agents, is by infection. The second is by the virus’s genes’ becoming embedded or integrated in the DNA of the host’s chromosomes (fig. 4). When the germ line—the cells destined to become eggs or sperm—integrate viral DNA, the latent virus gains a free ride to the next generation, and to countless further generations through being inherited by the host as aMendelian trait. We call these viral genomes endogenous retroviruses(Coffin 1982). This phenomenon has occurred in all vertebrate species studied; for example, thanks to the complete sequencing of the human genome we now realize that approximately 8% of our DNA represents the paleontological record of germ line infection. 

But some of the endogenous retroviruses have maintained the capacity to awake, Rip van Winkle-like, and to emerge again as infectious agents. For example, baboons inherit a retroviral genome through the germ line that produces infectious particles in the placenta. This virus transferred by cross-infection to cats and in turn entered their germ line (Benveniste and Todaro 1974) (fig. 5). And, curiously, the cat retrovirus was discovered in cats only after it appeared as an actively propagating virus in a human tumor grown in a fetal cat brain as a xenograft (Coffin 1982).

https://web.archive.org/web/20150501080814/http://www.amphilsoc.org/sites/default/files/proceedings/480303.pdf
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Robyn Erland (Facebook posting) Would xenotransplantation be safe? 

August 22, 2017
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A number of national and international ethical committees as well as individual scientists have looked at the question of xenotransplantation.3 . One of the particular foci of concern has been the issue of safety. We know that pigs carry what are called porcine endogenous retroviruses (engagingly abbreviated as 'PERVS'). In the light of BSE and AIDS it is unsurprising, and encouraging, that there is tremendous hesitancy in allowing any scientific/technological procedure to go ahead that might lead to new human infections. The current (November 1999) position in the UK is that if (and it is a big 'if') xenotransplants are allowed, the safety requirements will be stringent. In particular, there is a great deal of work going on to reduce to near-zero levels the chance of any infectious agents, such as viruses, passing as a result of transplants from pigs to humans. The United Kingdom Xenotransplantation Interim Regulatory Authority is proposing that anyone receiving a xenotransplant must agree to provide lifelong post-operative compliance with a whole set of conditions including: (a) use of barrier contraception; (b) refraining from pregnancy / fathering a child; (c) allowing the relevant Health Authorities to be notified when moving abroad. In addition, all household members and sexual partners will need to be seen pre-xenotransplantation to ensure they are informed about possible risks, how to minimise them, and to have baseline blood samples taken for indefinite archiving. Some recent research suggests that the chances of porcine endogenous retroviruses passing from pigs https://core.ac.uk/download/pdf/111612.pdf
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Robyn Erland (This was a Facebook posting) May 3, 2019 They really don't want people reading this stuff which used to be freely available. Look at the cost of the book: $1385.02 https://www.amazon.com/Animal-human.../dp/0952270129
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Robyn Erland (This was a Facebook posting) May 3, 2019 And not all of these retroviruses are endogenous. Some are infectious and can also recombine with other retroviruses and RNA viruses to produce new, never before seen versions. John Coffin knew that too when he helped Varmus get the use of the animal cells and parts reimplemented. I have the transcripts of the meetings. It even says on the FDA site that zoonosis which is what can happen when mixing human and animal parts and cells together, that it can produce new never before seen retroviruses that could go undetected just like HIV. They knew it and they did it anyway! I believe what we are seeing now are the outcomes of zoonosis for many of these viruses and retroviruses and the illnesses that came with them. They are hard to find when they are new and not listed in the GenBank as a human infection.
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The 1996 IOM report said this:

Xenotransplantation
Science, Ethics, and Public Policy

Recommendation 1

There is ample evidence for the transmission of infectious agents from animals to humans. Transmitted organisms benign in one species can be fatal when introduced into other species. Because xenotransplants involve the direct insertion of potentially infected cells, tissues, or organs into humans, there is every reason to believe that the potential for transmission of infectious agents (some of which may not even now be recognized) from animals to human transplant recipients is real. Once an infection is established in the recipient, the potential for transmission to caregivers, family, and the population at large also must be considered a real threat.

The committee concludes that, although the degree of risk cannot be quantified, it is unequivocally greater than zero. Hence, the committee recommends that guidelines for human trials of xenotransplantation address four major areas: (1) procedures to screen source animals for the presence of infectious organisms and consideration of the development of specific pathogen-free animals for use in xenotransplants; (2) continued surveillance throughout their lifetimes of patients and periodic surveillance of their contacts (families, health care workers, and others) for evidence of infectious diseases; (3) establishment of tissue banks containing tissue and blood samples from source animals and patients; and (4) establishment of national and local registries of patients receiving xenotransplants. Special efforts should be made to coordinate with international registries and databases.

Recommendation 2

The committee discussed various alternatives for oversight or regulation of clinical trials in light of the risk of transmission of infectious agents to the general population from xenotransplantation. Several committee members felt strongly that special regulation of xenotransplant research is not justified because other types of research, including allotransplantation, also involve substantial risks. Other members of the committee argued that the potential for transmission of new infections to humans is a unique risk justifying special regulations. All members of the committee agreed that some mechanism is needed to ensure attention to the risk of infectious disease transmission. The committee was aware of and commends the effort of the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) in developing the first set of guidelines, which are soon to be released but were not final before this report was complete.

Therefore, the committee recommends that adherence to specific national guidelines be required of all experimenters and institutions that undertake xenotransplantation trials in humans. Local institutional review boards (IRBs) and animal care committees, in consultation with outside experts, are appropriate vehicles for review of proposed protocols, provided that they are required to conform to the national guidelines for minimizing and for continued surveillance of infectious risks.

https://www.ncbi.nlm.nih.gov/books/NBK45528/?report=reader

Original E-mail I sent: 

Sent: Monday, June 13, 2016 9:44 PM

Diaries of Despair Report
Diaries of Despair 5 CHAPTER 1 Introduction 1.1 Controversial research Xenotransplantation is the transplantation of live organs, tissues or cells between different species. Such transplants are also referred to as xenografts. This report organises and interprets an extensive cache of leaked documents that
www.xenodiaries.org

Sat 3/16/2019 12:19 AM

NIAID was involved in this:
https://cdn.cnsnews.com/attachments/replication_of_cmv_in_the_gut_of_hiv-infected_individuals-pathogens-february_27-2017.pdf


Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction - cdn.cnsnews.com

RESEARCH ARTICLE Replication of CMV in the gut of HIV-infected individuals and epithelial barrier dysfunction Ekaterina Maidji1, Ma Somsouk2, Jose M. Rivera1, Peter W. Hunt1, Cheryl A. Stoddart1* 1 Division of Experimental Medicine, Department of Medicine, Zuckerberg San Francisco General, University of California, San Francisco, San Francisco, California, United States of America, 2 Division ...
cdn.cnsnews.com


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My story and why I became involved in the study of XMRV/MLV retroviruses and other associated areas of research

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