Xenotransplantation

[CrackSmokeRepublican]

Xenotransplantation
Search Biologics

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.
-
http://www.fda.gov/BiologicsBloodVaccin ... efault.htm

[Panoptimist]

#

    Xenotransplantation: The Next Biotech Disaster?
    Xenotransplantation: A Biotech Disaster Just Waiting to Happen by Alix
    Fano

    from the Ecologist magazine (UK) December 2000 issue
    <www.theecologist.org>



    Falsified reports, incompetence, the possible introduction of AIDS and
    other new diseases, and not one single success story. All this lies
    behind the attempts to transfer the organs of one species into
    another, yet still the biotech companies continue to experiment,
    dollar signs in their eyes. Alix Fano wonders if they'll ever get the
    message.

    On 21 September 2000, The Daily Express landed on the news stands with
    an explosive story that caught the British public - and much of the GM
    industry - on the hop. The expose' was based on leaked internal
    reports describing xenotransplantation experiments on higher
    primates - including cynomolgus monkeys and wild caught ******s -
    commissioned by Imutran, the British subsidiary of Novartis, and
    conducted by the controversial contract research laboratory, Huntingdon Life
    Sciences in Cambridgeshire.

    Now, although many people know that xenotransplantation experiments -
    the process of transplanting organs, tissues and cells between
    different species - takes place, few were aware of the horrors that
    were being perpetrated at Huntingdon in the name of science. The
    article not only highlighted extraordinary levels of animal suffering
    in the laboratories, but revealed glaring technical failures in the
    experiments conducted by the company, despite Imutran/Novartis's
    earlier claims that they were succeeding. These failures had been
    brought to the newspaper's attention by the British advocacy group,
    Uncaged Campaigns, whose 150 page report, Diaries of Despair: The
    Secret History of Pig to Primate Organ Transplant Experiments, was
    based on an extensive cache of leaked documents from an anonymous
    source.

    Imutran has taken legal measures to prevent Uncaged from disseminating
    the report. A court date was set for late November. The extent of the
    incompetence surrounding these experiments was staggering: the report
    revealed at least 520 errors and omissions in the conduct of studies,
    including organ weights not recorded, unlabelled and uncovered
    veterinary medications, inadequate surgery records, a quadruple
    overdose, the illegal reuse of animals, conflicting pathology reports,
    the accidental freezing of a kidney during transplantation surgery and
    a case of a swab being left inside a primate, which resulted in his
    death. In one particular incident, seven ******s appear to have been
    experimented upon despite a warning that they 'must not be worked on
    due to positivity for Herpes B' - a virus lethal to humans.

    READING BETWEEN THE LINES

    Was this just pure incompetence, or is there an even more serious
    charge here? The documents demonstrated that, after five years of
    research, Imutran had improved the average survival time of monkeys
    with functioning pig kidneys from two to just four weeks. The success
    rate of heart xenotransplantation is even less tangible - just 11 days
    according to the documents. As a result of these statistics, in April
    2000, Novartis had set an 18month time limit to achieve major
    improvements in survival times. Uncaged Campaigns charge that
    Imutran/Novartis greatly exaggerated the success of their pigtoprimate
    experiments in published articles, by selectively using their 'best'
    data while ignoring data on average survival times and the overall
    health of the primate recipients.

    The 'success' of Imutran's pigtoprimate experiments should now be
    called into question based on the complete picture revealed by the
    leaked documents. What is so remarkable about this information is that
    the research was being carried out in a field that is so dangerous.
    Here was a corporate sponsored, government sanctioned, laboratory
    apparently overstating its success in a branch of science that will
    have extreme repercussions for mankind. Was Imutran/Novartis really
    prepared to sanction shoddy and seemingly deceptive work in
    pigtoprimate organ transplantation - a stepping block to pigtohuman
    organ transplantation - merely to hit a deadline?

    The implications are highly disturbing, particularly as
    xenotransplantation hasn't had that great a track record. Since 1905,
    82 humans have received whole organs from chimpanzees, ******s, pigs,
    goats and other animals, and all have died from infections and
    complications related to hyperacute rejection within hours or days of
    the surgeries. Human and animal organs have evolved over the millennia
    to be able to deal with viruses, necessary immunities and other
    foibles and subtleties that each species requires. The trouble with
    xenotransplantation is that you just don't know what comes with each
    organ.

    Numerous published documents have warned of the dangers and
    unpredictability of animal viruses. The swine flu epidemic of 1918
    killed 2040 million people worldwide. During 1998 and 1999, the novel
    Malaysian 'Nipah' encephalitis virus, which originated in fruit bats,
    jumped from pigs to humans, infected 269 people, killed 117, and led
    to the mass slaughter of one million pigs. The virus, which caused
    brain damage in dozens of victims, has resurfaced this year in several
    Malaysian villages. In May 2000, a British farmer died after
    contracting a rare pig disease, streptococcus suis. It appears he
    inhaled the virus after it was breathed out by his pigs. A 1999 study
    by British scientists found that cancer causing retroviruses are
    transmitted much more frequently and easily between different species
    in the wild than previously thought, adding concerns regarding the
    xenotransplantation of pig organs to humans.

    In September 2000, scientists gathered at the Royal Society of London
    to determine whether polio vaccines made with chimp kidneys and
    contaminated with the simian form of HIV could have triggered the
    epidemic of the AIDS virus, which has stricken 53 million people, most
    of them in Africa. If this theory proves true, it increases the odds
    that a potentially lethal microbe from another species could
    accidentally be introduced into the human population via
    xenotransplantation.

    COMPOUNDING THE FOLLY

    Despite these complex and largely unforeseeable cans of worms opened
    every time an organ is transplanted from one species to another, the
    scientists won't leave xenotransplantation alone. Pigs, they say, are

#
09-17-2005 11:49 PM #29
sb11

    * View Profile
    * View Forum Posts
    * View Blog Entries
    * Visit Homepage

sb11 está offline
Super Moderator sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11's Avatar

Join Date
    Feb 2004
Location
    USA
Posts
    33,512
Blog Entries: 1

    source animals of choice because they breed quickly, have been
    extensively farmed, and have organs that are allegedly 'similar' in
    size to ours. Today, multinational biotechnology companies claim that they have bred 'germfree' pigs with human genes whose organs are less likely to be rejected by the human body. Soon, farms could be filled
    with cloned 'humanised' pigs - living factories, genetically
    engineered to meet the world's growing demand for replacement organs.
    For there's money to be made.

    According to the United Network for Organ Sharing, a quasigovernmental
    organisation that coordinates human organ and tissue donation in the
    US, approximately 4,000 Americans die each year waiting for
    transplantable organs. Compared to the number who die from heart
    disease (726,974), cancer (539,577), pneumonia/influenza (86,449),
    AIDS (16,516), and by suicide (30,535), this may not seem high. But
    with over 60,000 Americans on transplant waiting lists (180,000
    worldwide), a perceived chronic shortage of human organs and tissues,
    and a potential market in pig parts and expensive antirejection drugs
    worth $6$10 billion annually, the race to cash in on this market is
    officially on. Some researchers and biotechnology companies claim that
    putting pig organs into people may become a commercial reality within
    two years. Robert Michler, chief of transplantation at Ohio State
    University Medical Center in Columbus, believes that human trials
    should begin as soon as possible, as soon as 50 per cent of a group of
    ******s with transplanted pig hearts survive for three months - a
    target set by the US Food and Drug Administration (FDA).

    In August, scientists at BioTransplant, a Massachusetts based
    xenotransplantation company, in collaboration with Massachusetts
    General Hospital, announced that they had bred a line of miniature
    pigs that could provide a 'safer source of cells, tissues, and organs
    for xenotransplants' because they allegedly do not transmit
    potentially harmful viruses to human ells. (Patents are being filed in
    the US and abroad to protect such allegedly lucrative 'inventions'. On
    8 October 2000, The Sunday Times UK announced that BioTransplant had
    submitted an application to the European Patent Office for an
    'embryonic pighuman hybrid', the uses for which have not been defined
    by the company.)

    BioTransplant researchers theorise that generations of inbreeding
    could have weakened the viruses and taken away their ability to
    infect. However, Porcine Endogenous Retroviruses (PERVs) - a family
    of AIDS like viruses that are harmless to their hosts but potentially
    lethal when transferred to other species - are incorporated in the
    pig's genome and cannot be bred out. It has been estimated that
    hundreds of different endogenous retroviruses may be present in a
    given animal. BioTransplant admits that their minipigs still carry
    PERVs in their DNA, and thus in very organ, cell and tissue destined
    for transplantation.

    MUTATION FEARS

    Virologists like Dominic Borie and Robin Weiss have cautioned that
    endogenous retroviruses in pigs could recombine with human viruses
    and/or mutate into more infectious forms after transplant. Pigs may
    also contain other as yet unknown viruses. Daniel Salomon, a
    researcher at the Scripps Research Institute in La Jolla,
    California, has said that earlier studies, which suggested that PERVs
    have not infected people, 'may not have looked in the right places'.
    Patients injected with pig pancreatic islet cells to treat diabetes
    have had their peripheral blood lymphocytes (white blood cells) and
    blood serum tested for PERVs, and have been declared free of
    infection. But PERVs do not usually infect blood lymphocytes. They
    prefer epithelial tissues - tissues that line the inside and outside
    of organs. Only biopsies of these tissues could reveal the presence of
    the pig virus(es), and such biopsies have not been done in humans.

    ****** cytomegalovirus was, in fact, recently detected in stored
    tissue samples from a recipient of a ****** liver who died after a
    xenotransplant in 1992. A blood test will only pick up an active
    infection; but many infections (eg AIDS or 'mad cow disease') may
    remain latent in the body for years before they're ready to surface.
    So the fact that a blood test does not detect PERV in a patient's
    blood at a particular point in time, does not mean that that patient
    is not harbouring the virus. Moreover, most studies of xenotransplant
    patients have been retrospective, meaning that patients' blood was not
    sampled for PERVs periodically from the moment treatment began, as
    would be done in a controlled study. Most studies have also lacked a
    control group - a group receiving a placebo transplant.

    Peter Collignon, an infectious diseases physician at Canberra Hospital
    in Australia, observes that, without a control group, there is no way
    to determine whether the treatment really worked. Indeed, the testing
    of xenograft patients that has been done to date has not established
    the technology's safety or its efficacy. One could go so far as to say
    that tests have been designed to conceal unfavourable outcomes. Many
    other questions and concerns remain, one of the most important being
    whether animal organs will ever be able to sustain human life. Will
    pig organs continue to grow at a 'pig rate' once transplanted into
    humans; will they become susceptible to human diseases; will they be
    able to carry out functions necessary for human survival? For example,
    unlike the human organ, the pig kidney lacks a mechanism for
    controlling levels of medicines, which could have a significant impact
    on a xenotransplant patient who requires several drugs. The porcine
    kidney cannot handle the high levels of uric acid found in the human
    bloodstream, which could lead to kidney stones or kidney failure; and
    it may not respond normally to the hormone vasopressin, which is
    released from the human brain. Such discrepancies could affect blood
    pressure, hydration and fluid balance.

    Human red blood cells are larger than those of the pig and there are
    incompatibilities in bloodclotting mechanisms, so that in a grafted
    pig organ, blood clotting, organ failure and death may occur from
    blockages in the tiny blood capillaries. A pig's heart normally pumps
    smaller amounts of blood per minute than required by a human, due to
    its horizontal posture. If the output of the heart is too low,
    multiple organ failure and death would result. In Transplantation
    Proceedings (1999, Vol 31, pp9058), M E Breimer describes
    physiological incompatibilities between humans and pigs, including
    differences in anatomy, physiology (regulation of blood circulation,
    hormone systems), immunology, complement and coagulation systems,
    pharmacology and metabolism. Despite these seemingly insurmountable
    problems, pig research continues unabated. The prospect of commercial
    crossspecies transplantation has created huge financial incentives for
    multinational drug and biotechnology companies.

    Novartis (which also makes cyclosporine, the leading antirejection
    drug), Baxter Health Care and their many subsidiaries that dominate
    the field have already invested over $100 million in research. Such
    enormous capital investment has prompted research collaborations
    between different companies and medical centres in an attempt to share
    risks and costs. Novartis is also sponsoring xenotransplant research
    at several American, European, and Canadian medical centres, to save
    on contract lab and research costs. Novartis is funding pigtoprimate
    xenotransplantation experiments at the Universities of Ohio State
    (Columbus), Pennsylvania (Philadelphia), Wisconsin (Madison), Stanford
    University, Massachusetts General Hospital and, in Canada, at the
    Universities of Western Ontario, Toronto, and Guelph. The Mayo Clinic
    in Rochester, Minnesota, which opened a large xenotransplant programme
    and pigbreeding facility last year, has forged an alliance with Baxter
    Health Care/Nextran, a New Jersey based biotech company, to breed
    transgenic pigs whose organs would not be prone to rejection.
    Christopher McGregor, Mayo's director of cardiothoracic
    transplantation, has declined to say how much money Mayo has received
    from Baxter. Despite these collaborations, there is fierce competition
    between each individual company or medical centre to be the first to
    successfully transplant pig organs into humans, driven by the desire
    to reap financial rewards, to gain publicity and to pacify anxious
    investors.

    Alexion Pharmaceuticals in New Haven, Connecticut, is developing
    stronger drugs to suppress the immune system. PPL Therapeutics,
    associated with the Roslin Institute in Scotland (famous for cloning
    Dolly the sheep and filing a world patent on the cloning of all animal
    species, including humans), is trying to breed transgenic pigs whose
    organs will not provoke hyperacute rejection when transplanted into

#
09-17-2005 11:51 PM #30
sb11

    * View Profile
    * View Forum Posts
    * View Blog Entries
    * Visit Homepage

sb11 está offline
Super Moderator sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11 has much to be proud of sb11's Avatar

Join Date
    Feb 2004
Location
    USA
Posts
    33,512
Blog Entries: 1

    humans because they lack a specific sugar called alphagalactosidase.
    In March 2000, PPL announced it had cloned a litter of five female
    pigs using a double nuclear transfer technique. The company claims that pig cloning will ensure a plentiful supply of pigs for
    xenotransplantation. However, cloning pigs for transplants is an
    expensive, technically difficult and inhumane proposition. Last May, BBC News Online reported that PPL was having trouble producing cloned pigs because none of the genetically modified embryos were surviving to term in their surrogate mothers. PPL acknowledges a 50 per cent postnatal loss of cloned animals.

    Cloned animals are typically weaker than their traditionally bred
    counterparts and may be prone to congenital abnormalities, chronic organ dysfunction, premature ageing (due to changes in chromosome
    structure), high infant and juvenile mortality and cancer (see Michael
    W Fox, Beyond Evolution, Lyons Press, 1999). Moreover, cloning pigs
    will not rid the animals of the numerous viruses, bacteria, and
    parasites they carry, which may lead to dangerous infections in
    humans. Nevertheless, over the last several decades, US federal
    agencies have dispensed tens of millions of dollars to university
    researchers and private corporations for cloning and related
    xenotransplantation projects.

    The Commerce Department's Advanced Technology Program, established
    under the Bush Administration, has given multimillion dollar grants to
    corporations like Alexion Pharmaceuticals and Organogenesis Inc, and
    to PPL for their pig cloning projects. A B Cosimi, a researcher at
    Massachusetts General Hospital in Boston, received over $15 million
    from the National Institutes of Health (NIH) between 1992 and 2000 to
    study the immune response involved in xenograft rejection between pigs
    and ******s. A team of researchers at Duke University in North
    Carolina received almost $2.5 million from 1997 to 1998 to transplant
    pig hearts into monkeys and other animals in an effort to elucidate
    the 'immunological barrier to cardiac xenotransplantation'. In 1997,
    the NIH published an announcement on the Internet soliciting
    'applications [from domestic and foreign researchers] to enhance [the]
    ability to transplant organs and tissues across species barriers
    (xenotransplantation)'. The NIH even promotes xenotransplantation in
    articles designed for children on its website under the guise of
    'science education'.

    CHANGE OF OPINION?

    But not all US companies continue to be enthusiastic about
    xenotransplantation. In August, Geron BioMed, a US biotech firm,
    announced that it was cutting back funding for its Scottish
    subsidiary's xenotransplant research programme, Roslin BioMed, citing
    concerns about public health risks. Geron stated it would redirect its
    efforts to cultivating human stem cells for research and
    transplantation. Ian Wilmut, Roslin's chief scientist, said he was
    disappointed by Geron's decision but understood concerns about
    'unknown [pig] viruses being released into the human population'.
    Shortly after the Geron announcement, PPL Therapeutics, which is a
    Roslin offshoot, distributed a press release stating that it was not
    abandoning its xenotransplantation research programme, least of all
    because of virus fears, leading critics to question the motives behind
    the company's sudden retraction.

    In April 2000, the US FDA suspended cellular xenotransplant
    experiments in which foetal pig brain cells were injected into the
    brains of stroke patients. Thomas Fraser, president of the
    Charlestown, Massachusetts based company Diacrin, admitted that one
    patient developed seizures a week after a transplant and another had
    minor brain swelling and muscular fatigue. The company said it would
    try to determine whether the pig cells or the equipment used to
    deliver them to the brain are to blame for the 'side effects'. A study
    published in the British journal Nature on 17 August 2000 raised
    further questions about the safety of cellular xenotransplants.
    Salomon et al showed that when insulin making pig pancreatic islet
    cells were transplanted into mice with deficient immune systems,
    PERVs jumped the species barrier, migrated from the site of
    transplantation, and infected mouse tissues such as the spleen, liver,
    salivary gland, skin, small bowel and lung. Given this chain of
    events, the pig virus would likely be present in saliva, faeces,
    broken skin and coughed up lung secretions. Salomon and colleagues
    concluded that pigtohuman islet xenotransplantation could result in
    patients becoming exposed to infectious PERVs that might be able to
    replicate. It is unlikely, however, that Salomon's study, or any
    other, will be heeded by US regulatory officials or companies
    investing in xenotransplantation. After all, reports in 1997 and 1998,
    stating that various strains of PERV from different breeds of pigs
    infected human cells, didn't seem to raise enough of a red flag for
    anyone to actually halt xenotransplantation research.

    Andr* Jestin and his colleagues at the French Agency for Food Safety
    in Ploufragan found that the complete genomes of, amazingly, 11 types
    of PERV are expressed in pig organs, including the heart, liver,
    pancreas and kidneys. Jestin believes that controlling these viruses,
    or eliminating them via genetic engineering, will be much harder than
    anyone thought. Porcine pseudorabies virus has been detected in
    Swedish diabetes patients treated with porcine cells in 1997. And in
    August 1999, Science published the results of a Novartis sponsored
    study of 160 patients in nine countries exposed to living pig tissue
    over a 12year period. Some patients in the study reported persistent
    rashes and strange fevers. But most worrisome was the finding that 30
    patients who had their blood 'filtered' through pig spleens tested
    positive for PERV DNA; 23 patients had pig cells circulating in their
    bodies 8.5 years after teatment; and four patients, injected with pig
    cells, produced antibodies against PERVs, leading the authors to admit
    that 'PERV infection [could not] be excluded'.

    WHO WILL ACT?

    So where do we go from here? At a public meeting in January 2000, Dr
    Phil Noguchi, Director of the US FDA's Division of Cellular and Gene
    Therapies, acknowledged that xenotransplantation is 'fraught with
    danger'. FDA documents have openly stated that '[X]enotransplantation
    may facilitate the transmission of known or as yet unrecognised agents
    to humans'. New pig viruses, like 'Nipah', and strains of PERVs, are
    continually being discovered. A pig virus, contracted via
    xenotransplantation, could spread to other humans undetected, causing
    an AIDS like plague. Yet there are currently 12 FDA approved
    xenotransplant clinical trials ongoing in the US. Most, if not all,
    are industry sponsored, and involve the use of pig cells to treat
    diabetes and neurological diseases, and whole pig livers and cells to
    perfuse ('filter') the blood of patients with acute liver failure. The
    FDA (which has also sanctioned the sale of unlabelled and untested
    genetically engineered foods) has refused to enact even a temporary
    moratorium on such trials, claiming that it will monitor patients
    closely to ensure public safety. Sound familiar? In the 1980s, the FDA
    allowed thousands of people to receive HIV tainted blood and blood
    products, resulting in thousands of cases of HIV infection and the
    deaths of over 10,000 haemophiliacs. Clearly, governments have chosen
    to ignore the Precautionary Principle in the xenotransplantation
    debate. They have also completely ignored alternatives to
    xenotransplantation, including prevention of disease, use of human
    tissue for transplant and increased human organ donation.

    Each and every day in the United States, 6,000 bodies full of human
    organs are buried or burned. That's two million each year, many times
    the number of organs required for all types of transplants. In 1998,
    the General Accounting Office found that the US is doing a poor job of
    retrieving organs for transplantation. Many nations, including the
    Netherlands, Austria, Spain, Belgium and Singapore, have seen organ
    donation rates soar after the passage of 'presumed consent' laws,
    which assume that citizens will donate their organs after death unless
    they 'opt out'. Although a majority of Americans (85 per cent) support
    organ donation, the feasibility of such a law has not been considered.
    Meanwhile, in the wake of the Huntingdon scandal on 22 September 2000,
    Uncaged Campaigns called for an independent judicial inquiry into the
    information contained in the leaked documents, as well as a ban on
    animal based xenotransplantation research in the UK. On 26 September
    2000 Novartis announced it was closing down operations at Imutran.
    However, the announcement added that the company was merging with US
    based BioTransplant, perhaps hoping to leave a scandal behind and
    transfer its operations to the US, with its notoriously lax animal
    welfare and biotechnology regulations. Novartis, which had been
    collaborating with BioTransplant to breed lines of pigs with human
    genes, will own 67 per cent of the company and retain the rights to
    commercialisation of research from the new merger. In return,
    BioTransplant will receive royalty payments from Novartis sales.

    Elliot Lebowitz, BioTransplant CEO, revealed that commercialisation of
    xenotransplantation could generate 100 million dollars in annual
    revenue for his company. The work continues. Alix Fano, MA, is
    executive director of the Campaign for Responsible Transplantation
    (CRT) and author of a chapter on xenotransplantation in the book,
    Redesigning Life? The Worldwide Challenge to Genetic Engineering,CRT, an international coalition of physicians,
    scientists and 90 public interest groups, is promoting a ban on
    xenotransplantation and advocating for safer, and
    humane farming alternatives.