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The drugs don't work - vivisectors lose their TRAIL
A ‘breakthrough’ cancer drug awaiting human trials that passed
all animal tests, including in vitro animal cell tests, was found to have
devastating effects on human in vitro cell cultures. The drug, TRAIL (an
acronym for Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand),
was seen in animal experiments to destroy tumour cells by causing them
to commit suicide. It appeared that it only affected cancerous cells,
leaving normal ones unaffected. The team who conducted the cell culture
tests noted in their report that:
"In a study with non-human primates, injection of soluble human
TRAIL did not cause toxicity to tissue or organs, apparently ‘clearing
the way’ for Phase I studies in humans."
However, the research team, led by Dr. Stephen Strom at the University
of Pittsburgh in Pennsylvania, say they have found that TRAIL could also
have a devastating effect on healthy cells. Writing in Nature Medicine,
the scientists said that more than 60% of the human liver cells exposed
to TRAIL in the laboratory were wiped out within ten hours.
"Apoptosis (programmed cell suicide) and cell death in human hepatocytes
was massive and rapid," they reported. The cells shriveled and
their DNA fragmented. Tests on liver cells in rats, mice and rhesus
monkeys did not show the same response."
These results indicate that if TRAIL was used in human trials, "considerable
hepatoxicity or fulminant hepatic failure could result." Yet this
new drug had passed all animal tests, had all the usual hype that is routinely
lavished on ‘breakthrough’ anti-cancer agents, and was ready
to begin trials in human patients. This sorry story re-emphasises the
pointlessness of animal experiments given the many important and complicated
species differences. This is re-iterated throughout the report by Strom
et al:
"These results indicate that there are species differences in
sensitivity to TRAIL, and that substantial liver toxicity might result
if TRAIL were used in human cancer therapy.
"TRAIL did not induce apoptosis in parenchymal hepatocytes from
any other species other than human."
Furthermore, one has to ask why in vitro human cell culture tests were
not conducted first, thereby saving innocent animals from being subjected
to pain and death. Invasive procedures were conducted on rats, mice, and
rhesus monkeys (culminating in death) some considerable time before Strom
et al conducted five (5) in vitro cell culture experiments. The Animal
Procedures Committee is supposed to ensure and enforce the principle that
no license for animal tests will be granted if there are ‘alternative’
methods available. Strom et al conclude with what is surely a statement
of the obvious:
"Moreover, the extrapolation of data from preclinical investigations
in other species should be made with caution, and investigations with
human cells should be included in the preclinical evaluation of therapeutic
agents."
It speaks volumes about the mentality of the pharmaceutical industry
that, by May 2000, human cell tests are not included in pre-clinical investigations
already, and it takes a near disaster with a supposedly ‘magical’
drug for anyone to suggest this.
The final, frightening, word in the of this grisly farce goes to Shigekazu
Nagata, from Osaka University Medical School who, again in Nature Medicine,
said:
"It may still be possible to delay clinical trials until we have
a better understanding of why some cells but not others are resistant
to Trail." !
[Source: Nature Medicine, Vol. 6, No. 5, May 2000, p. 502-503, and p.
564-567]
Max Newton
Study holds serious implications for safety of xenotransplants
Many commentators on the danger of virus transfer posed by xenotransplantation
have pointed to the example of HIV as a virus that appears to have crossed
from animals to humans with catastrophic effect.
The precise route of transmission of HIV from chimpanzees to humans has
been shrouded in mystery. Now, a painstakingly researched book, The River
(Penguin, £25), presents a powerful case that the first polio vaccine
trials to take place in Africa - in 1957 - were responsible for the global
AIDS pandemic which has killed an estimated 15 million people. As the
evidence grows that AIDS crossed from animals to humans via a medical
product, the warning bells over xenotransplantation ring louder than ever.
In The River, author Edward Hooper produces evidence that a U.S.-based
body, the Wistar Institute of Philadelphia, used chimpanzee kidneys to
culture the polio virus that formed the basis of the vaccine. Wistar has
always denied this, claiming that Asian monkeys were used which do not
become infected with the relevant AIDS-like virus.
However, Hooper has traced eyewitnesses who recall that chimpanzees were
indeed used in research and vaccine production at an animal research facility
at Lindi, in what was then Belgian Congo. Hooper then shows the correlation
between the use of the Wistar chimpanzee-derived vaccine in central Africa
in the late 1950s and the first confirmed cases of HIV infection in the
same region at the same time.
Chimpanzee kidneys are an effective medium for growing polio virus and
would have been an obvious first choice for scientists. Significantly,
the name of the primate species used to develop the vaccine was not published
at the time by the leader of the project, Dr Hilary Koprowski.
The Wistar has always been very sensitive to suggestions that it was
responsible for the creation of AIDS. However, it’s main argument
against the polio vaccine theory was recently demolished. A British sailor,
David Carr, who had returned from Africa shortly before the trials began,
was thought to have been the first documented victim of HIV infection,
thereby exonerating the vaccine from responsibility. But in 1995 it was
revealed that Carr had not travelled to Africa, and he had not been infected
with HIV.
One of the best ways to test Hooper’s theory would be to analyse
samples of the polio vaccine used in the trials to see if they contain
the progentor of HIV, the simian immunodeficiency virus (SIV). However,
there are serious practical difficulties with conducting a relevant study.
Wistar claims that the old vials of vaccine may not be exactly the same
as the ones used in the trials. Furthermore, the forty-two year time period
that has elapsed since the production of the vaccine means that there
may not be enough of the virus present to yield meaningful results.
Despite these difficulties, the publication of The River will increase
the pressure on Wistar to find an independent research team to test the
old vaccine samples. Although negative results would not rule out Hooper’s
theory, positive results would confirm it.
The parallels with xenotransplantation are clear. Hooper’s convincing
theory demonstrates how a virus that has existed for millenia in its natural
host can suddenly become modernity’s most lethal infectious disease.
Misguided and cruel exploitation of animals may well have created the
AIDS pandemic. Incredibly, we are now on the threshold of embarking on
another hazardous medical experiment: the implantation of animal organs
and tissue into humans.The most important lesson to be learned is the
utter folly of the whole concept of xenotransplantation.
Dan Lyons
(19/08/99)
Imutran / Novartis study brings false sense of security
- risk of epidemic from animal organ transplants remains
The following statement is issued by Uncaged Campaigns in response to
the publication in this week’s edition of the journal Science (20.8.99)
of a study of 160 patients who had received live pig tissue. Some reports
claim that the study provides evidence to support the case that animal
organs will not pose a risk to public health as a result of virus transmission
from pigs to humans.
Dan Lyons, spokesperson for Uncaged Campaigns, says:
"The findings of this study are not a reliable guide to the risk
of virus transfer in the event of xenotransplantation taking place.
There are numerous problems with the design of the study:
- It is too small - in statistical, public health terms, 160 people
is a very small sample.
- The tests employed are, it is generally accepted, not powerful enough
to guarantee that any PERVs present will be definitely detected. The
collection and analysis methods used could also impact the results.
- It is universally acknowledged that there will be unknown pig viruses
present which cannot be tested for reliably.
- The numbers of cells (and therefore viruses) transplanted was much
less than would be the case in the event of whole organ xenotransplantation.
- None of the patients had received transgenic pig tissue. Imutran/Novartis’s
xenografts would be transgenic. Virologists such as Robin Weiss have
warned that the transgenic xenografts could increase the chances of
a pig virus infecting a recipient and then the wider population.
- The explanation given for the presence of PERV DNA in some patients,
that pig cells have survived for up to eight and a half years in the
bloodstream, is not reassuring. Retroviral infections can remain latent
for many years before causing ill-effects. These kind of infections
can then transmit undetected through the human population for many years,
as the tragic example of HIV demonstrates.
Laboratory studies have already demonstrated that PERVs can infect human
cells. Furthermore, there are several examples of diseases crossing from
animals to humans with catastrophic effect . For example, the Spanish
influenza epidemic of 1918 that killed between 20 million and 40 million
people is thought to have been transmitted by pigs. Most new human diseases
originate in animals, and xenotransplantation provides a uniquely efficient
way of transmitting a new disease.
We fear that the results of this inconclusive study will be used by Imutran/Novartis
in a desperate attempt to protect their multi-million pound investment
in xenotransplantation, despite the abundant evidence already available
which demonstrates the intrinsic dangers of the technology.
We hope that the UK Government and regulators around the world will resist
ill-founded and irresponsible calls for clinical trials to commence. Their
first duty must be to protect public health, not promote the commercial
interests of the biotechnology industry. That means banning xenotransplantation."
For more information and interviews, please contact
Dan Lyons on 0114 2530020 or 07990 584158.
-ends-
Notes for editors
- Uncaged Campaigns are the leading opponents of xenotransplantation
in the UK. Through our public education work we have submitted 125,000
signatures to the Government calling for a ban on xenotransplantation,
and the Health Secretary has received 20,000 postcards from members
of the general public expressing opposition to xenotransplantation on
public health and animal welfare/rights grounds.
- Dan Lyons is a PhD researcher into the ethics of xenotransplantation,
as well as directing Uncaged Campaigns project, Xenotransplantation
Concern.
- Uncaged Campaigns latest action against xenotransplantation took place
in Cambridge, the home of Imutran, on 24 July this year. 400 concerned
people from around the country joined together in a massive ring-a-roses
(see 'A'Tissue!' story below). Ring-a-roses is a medieval children’s
rhyme commemorating the devastating effects of the Great Plague. The
aim of the event was to highlight the danger of creating a modern epidemic
posed by xenotransplantation.
16/02/99
Uncaged Campaigns hold protests outside xenotransplantation
companies
Outrage at "Frankenstein" animal experiments
A demonstration took place outside the troubled animal-testing firm Huntingdon
Life Sciences (HLS), at 12 noon Monday 15th February, in response to the
revelation that the company has provided facilities for controversial
experiments where transgenic pig hearts and kidneys have been transplanted
into primates, including baboons captured from the wild. This new information
has been uncovered by a BBC Radio 5 Live documentary, 'Ed Hall Investigates...',
broadcast 12 noon on Sunday 14th February.
HLS has also been exposed as a hiding place for the herd of unique pigs
containing human genes. The pigs are owned by IMUTRAN LTD, a Cambridge-based
subsidiary of NOVARTIS. The location of these pigs has been a closely-guarded
secret until now.
Dan Lyons, spokesperson for pressure group UNCAGED CAMPAIGNS, organisers
of the demonstration, explains:
"This research programme involves perhaps some of the cruellest
experiments currently taking place in Britain. Humanised pigs are kept
in unnatural, sterile conditions - condemned by the RSPCA - that frustrate
the natural desires and instincts of these highly intelligent animals.
Some primate recipients of pig organs have suffered and died because
of the poisonous effects of high doses of immunosuppressant drugs that
have been tested on them. Other primates have died because of infections
that have arisen because their immune systems have been so damaged.
The misery inflicted on these animals at HLS should not be allowed in
a civilised society."
HLS has been in financial difficulties since employees of the company
were filmed cruelly treating beagle dogs in the Channel Four documentary
"It's a dog's life" in March 1997. With HLS's involvement in
more controversial research now exposed, it's future looks even more uncertain.
"This could be the final nail in HLS's coffin", remarks Dan
Lyons.
Imutran - "Global dealers in death"
A further demonstration took place at 3.00pm, Monday 15th February 1999,
outside the offices of Imutran Ltd, Douglas House, Trumpington Road, Cambridge
(by junction with Bentley Road).
Imutran are the Cambridge-based biotechnology company researching animal-to-human
organ transplants. Campaigners are angry that Imutran have exported 95
transgenic pigs to countries all over the world. This information has
come to light in a BBC Radio 5 Live documentary to be broadcast on Sunday
14 February, 12.00 noon.
Until now, press reports and Government Dept of Health answers, have
indicated that only two pigs had been exported, in May 1998, to the Netherlands.
Imutran, who are owned by the multinational drug company Novartis, have
exported pigs for research and breeding purposes to the Netherlands, Canada,
the USA, Japan, Spain and Italy. The transgenic pigs contain human DNA
so that the pigs' organs may be suitable for transplant into humans, Imutran
claim.
By exporting the transgenic pigs from the UK, Imutran are avoiding relatively
strict British regulations on animal experiments and human trials.
In animal experiments in the UK, welfare regulations have forced Imutran
to euthanase suffering primates who have received transgenic pig organs.
Thus, Imutran have lost the opportunity to gain more knowledge about
how the pig organs are rejected by the primates. Back in 1995, Imutran
claimed that they were ready to start trials of pig hearts in humans by
the end of 1996.
However, the UK Government has consistently refused permission for human
trials because of the fear of transferring a new viral disease into the
human population as a result of such experiments, among other reasons.
Similar sentiments caused the parliamentary assembly of the Council of
Europe to vote on the 29 Jan for an on-going ban of human trials.
Dan Lyons, spokesperson for UNCAGED CAMPAIGNS, organisers of the demonstration,
comments:
"Given that Novartis, owners of Imutran, are a global company,
it is not surprising that they have taken the pigs to wherever they
can conduct their experiments as quickly as possible. Imutran claim
that they are concerned about safety and animal welfare, but their behaviour
clearly demonstrates that they are prepared to sidestep safeguards in
their haste to try to develop this technology. At the same time, Imutran/Novartis
are inflicting immense suffering on intelligent, sensitive animals,
while threatening to expose the public to the potentially lethal risk
of new viruses."
References
1 John Wallwork, "Current status of xenotransplantation", International
Journal of Cardiology 62 Suppl. 1 (1997) S38.
2 David Dickson, "Pig heart transplant 'breakthrough' stirs debate
over timing of trials", Nature, 377, 21 September 1995: 185.
International Week of Action Against Xenotransplantation
22nd February to 28th February 1999
An international week of action against xenotransplantation (animal-to-human
transplants), running from 22 February 1999 to 28 February 1999, has been
initiated by Sheffield-based pressure group Uncaged Campaigns, one of
the UKs leading opponents of the technology.
A BBC Radio 5 Live documentary broadcast on Sunday 14th February 1999
uncovered an international trade in genetically engineered pigs. The transgenic
pigs were bred by Imutran, a Cambridge-based biotechnology company owned
by the multinational drug company Novartis. Ninety-five pigs have been
exported to the USA, Canada, Japan, Italy, Spain and the Netherlands for
both breeding and research purposes. Imutran claim that they have now
bred two thousand transgenic pigs, most of whom are probably in the UK.
By exporting the transgenic pigs from the UK, Imutran are avoiding relatively
strict British regulations on animal experiments and human trials. In
animal experiments in the UK, welfare regulations have forced Imutran
to euthanase suffering primates who have received transgenic pig organs.1
Thus Imutran have lost the opportunity to gain more knowledge about how
the pig organs are rejected by the primates. Back in 1995, Imutran claimed
that they were ready to start trials of pig hearts in humans by the end
of 1996.2 However, the UK Government has consistently refused permission
for human trials because of the fear of transferring a new viral disease
into the human population as a result of such experiments, among other
reasons. Similar sentiments caused the parliamentary assembly of the Council
of Europe to vote on the 29 Jan for an on-going ban of human trials.
Given that Novartis, owners of Imutran, are a global company, it is not
surprising that they have taken the pigs to wherever they can conduct
their experiments as quickly as possible. Imutran claim that they are
concerned about safety and animal welfare, but their behaviour clearly
demonstrates that they are prepared to sidestep safeguards in their haste
to try to develop this technology. At the same time, Imutran/Novartis
are inflicting immense suffering on intelligent, sensitive animals, while
threatening to expose the public to the potentially lethal risk of new
viruses. Uncaged Campaigns contacted scores of animal protection organisations
in several countries to ask them to participate in the week of action.
Particular attention has been paid to groups in countries where xenotransplantation
research is taking place, such as those countries that have imported Novartis
transgenic pigs.
One of Canada's largest animal protection groups, Animal Alliance of
Canada, are particularly worried about their domestic situation because
trials involving the hooking up of patients to pig livers outside the
body appear to be imminent. However the Canadian Government has failed
to draw up any guidelines to regulate xenotransplantation, and public
debate has been virtually non-existent. Canadian bioethicists fear that
these experiments may go-ahead before the Canadian public has even had
an opportunity to contribute to the debate. Uncaged Campaigns are organising
a letter to be submitted to the Canadian High Commission in London, respectfully
requesting that the Canadian Federal Government consider our case for
a complete ban on research into xenotransplantation.
Much of the UK activity has been focussed on Cambridge, home of Imutran.
Events have taken place in Cambridge on every day of the week of action,
instigated by a local organisation, Animal Rights Cambridge. Wednesday
24th February was the date for the largest action in the UK. A crack team
of bio-troubleshooters successfully sealed off Imutrans offices on Trumpington
Road, Cambridge, to symbolise our efforts to protect the public from the
risk of viruses passing into the human population as a result of Imutrans
activities. There were between 30 and 40 of such intredpid bio-troubleshooters
- all dressed in blue boiler-suit style uniforms replete with biohazard
symbols and face-masks. The day, and indeed the whole week, was a great
success in bringing to the public's attention the immense dangers that
could be unleashed upon the human population for the next millenium, as
well as the abominable experiments being carried out on pigs and primates
in the pursuit of this 'science' in Britain and around the world today.
This was all despite the rather bizarre presence of some sort of private
investigator who attended all the events and even followed people home!
In addition to the Cambridge actions, Uncaged Campaigns will be touring
towns and cities across the UK during the next week to distribute thousands
of organ donor cards and registration forms (see Alternatives to Xenotransplantation),
and to alert the public to the dangers of xenotransplantation.
References:
John Wallwork, Current status of xenotransplantation,
International Journal of Cardiology 62 Suppl. 1 (1997) S38.
David Dickson, 'Pig heart transplant ' breakthrough
stirs debate over timing of trials, Nature, 377, 21 September 1995: 185.
Dan Lyons
(22/01/99)
Uncaged Campaigns discover first application to conduct
trials of pig-human transplants has been received by UK Department of
Health
Yesterday (Thursday 21st January 1999), the UK Department of Health revealed
that the United Kingdom Xenotransplantation Interim Regulatory Authority
(UKXIRA) has received its first-ever application to conduct a trial of
pig-to-human transplants. The application was received just before Christmas.
No such trials have yet been permitted in the UK. The historic information
emerged in answer to an inquiry made to the Authority today by Dan Lyons
from the pressure group Uncaged Campaigns, who have been lobbying against
xenotransplantation for the past two and a half years.
The Government has so far prevented human trials of xenotransplantation,
mainly because of the risk of viruses transferring from pigs to humans
and creating new disease in the general population. Test tube research
has discovered that pig retroviruses can infect human cells. The genetic
engineering of the pigs to try to prevent rejection, ironically, could
make it easier for viruses to infect a recipient of pig tissue and then
infect contacts of the patient.
An all party Commons Motion will be tabled calling for a brake on xenotransplantation
trials until legislation is put before Parliament to discuss whether,
and how, xenotransplantation should be regulated. Patients who receive
pig tissue would have to be monitored for the rest of their lives for
signs of viral infection, according to UKXIRA guidelines. However, such
surveillance regimes are currently impossible to enforce - the necessary
legislation simply doesn't exist at the moment.
Dan Lyons comments: "To permit trials of this hazardous procedure
without even being able to minimise the risk of viruses spreading is to
multiply the danger to public health. I cannot believe that the Government
would give permission for any trial before the issue is debated in Parliament."
-ends-
For more information and interviews, please contact Dan Lyons on 0114
2530020 or 0421 056014.
Notes for Editors
- The final decision on whether to permit human trials of xenotransplantation
procedures rests with the Secretary of State for Health, Frank Dobson,
after UKXIRA have made their recommendation as to whether the trial
should be permitted or not.
- When guidelines for applications for clinical trials were published
by the Government on 30 July 1998, Imutran Ltd, the leading UK researchers
into xenotransplantation, announced their intention to conduct a trial
involving filtering the blood of human patients through a pig liver
housed externally to the patient in a matter of "months to years".
Imutran then intend to move towards transplanting pig kidneys directly
into humans. The Department of Health have refused to reveal any information
about the nature of the application for reasons of protecting "commercial
confidentiality". Imutran have denied that they have submitted
the application. Imutran are owned by the multibillion pound pharmaceutical
firm Novartis.
- The main signatories on the House of Commons Early Day Motion are
Norman Baker MP, Tom Brake MP (both Lib Dem), Maria Eagle MP, Paul Flynn
MP (both Lab), David Amess (Con).
- Uncaged Campaigns have formed and lead a network of organisations
perturbed by xenotransplantation, called Xenotransplantation Concern
(XtC). Other participants in XtC include Animal Aid, the British Union
for the Abolition of Vivisection (BUAV), the National Anti-Vivisection
Society, Compassion in World Farming (CIWF), Genetic Engineering Network
and the Green Party.
- Uncaged Campaigns have submitted 125,000 signatures to the Government
calling for a ban on research and trials of xenotransplantation on animal
rights/welfare, medical and safety grounds. As a result of another Uncaged
Campaigns initiative, the Department of Health has so far received approx.
17,000 postcards from members of the public expressing opposition to
xenotransplantation on ethical and medical grounds. A Teletext opinion
poll on 1st August 1998 discovered 79% opposition to animal-to-human
organ transplants. A poll conducted for the BUAV and CIWF by NOP found
54% of respondents disagree with transgenic research into xenotransplantation.
- Text of EDM:
- That this House notes the recent submission of an application to the
United Kingdom Xenotransplantation Interim Regulatory Authority (UKXIRA)
to conduct a clinical trial of xenotransplantation procedures on humans;
notes that, despite the theoretical benefits to transplant patients,
there are major scientific obstacles and hazards to public health (in
particular, the potential of introducing a new viral pathogen into the
wider population) which remain to be addressed; observes that the required
legal sanctions to enforce the UKXIRA-recommended surveillance regimes
for any recipients of animal tissue are currently absent; recognises
serious ethical and animal welfare concerns generated by the practice;
acknowledges the existence of widespread public unease regarding xenotransplantation,
as evidenced by opinion polls and petitions; and, in the light of these
gaps in scientific knowledge, regulatory powers and the absence of informed
public consent, calls upon the Government to withhold permission for
human xenotransplantation trials pending unequivocal evidence of the
microbiological safety and clinical effectiveness of xenotransplantation,
and categorical public consent for the commencement of human trials
and, subsequent to these conditions being satisfied, the introduction
of the necessary legislation to ensure public health.
(22/03/99)
UKXIRA Open Meeting Report
Monday 7th December 1998
UKXIRA (United Kingdom Xenotransplantation Interim Regulatory Authority)
was created in March 1997 following the publication of the report, Animal
Tissue into Humans, two months earlier. Its terms of reference are as
follows:
To advise the Secretaries of State of the UK Health Departments on the
action necessary to regulate xenotransplantation, taking into account
the principles outlined in Animal Tissue into Humans, and worldwide developments
in xenotransplantation. In particular to advise:
a. on safety, efficacy and considerations of animal welfare and any
other pre-conditions for xenotransplantation for human use, and whether
these have been met.
b. on research required to assess safety and efficacy factors in xenotransplantation
procedures;
c. on the acceptability of specific applications to proceed with xenotransplantation
in humans; and
d. to provide a focal point on xenotransplantation issues within government.
UKXIRA held its first open meeting on Monday 7th December 1998 at the
Queen Elizabeth II Conference Centre, Westminster, to launch its first
Annual Report and provide an opportunity for interested parties to discuss
issues with the panel of UKXIRA members. Alistair Currie and Dan Lyons
from Uncaged Campaigns were amongst an invited audience that included
scientists, representatives from xenotransplantation company Imutran/Novartis
, and other animal welfare and animal rights campaigners such as Joyce
D' Silva (Compassion in World Farming) and Dr Gill Langley.
Presentations were given by various UKXIRA members through the afternoon,
and the main issues to surface from the meeting are summarised here:
Impossible to measure risk
Professor Sheila McLean, Professor of Law and Ethics in Medicine, Glasgow
University gave an articulate and well-organised presentation explaining
the criteria by which applications for clinical trials will be assessed.
Although those criteria included an assessment of the safety/risk of the
procedure to both the patient and the wider population, Professor McLean
admitted that there is currently "insufficient information to undertake
microbiological risk assessment." In other words, there is no way
of accurately assessing the risk of a new viral disease emerging via xenotransplantation
procedures: this is the major issue worrying scientists and regulatory
bodies across the world.
Professor McLean revealed that each application to undertake a clinical
trial will be scrutinised by several "independent" assessors,
selected by UKXIRA for their expertise in relevant areas. However, upon
further questioning, Professor McLean confirmed that none of the "independent"
assessors had expertise or a particular interest in safeguarding animal
welfare, despite the requirement to consider issues of animal welfare
when regulating xenotransplantation contained in the terms of reference
of UKXIRA. Already, we sensed that the minimal commitment to consider
animal welfare was more rhetorical that real.
Viral transfer issues remain unanswered
Next on the podium was Professor Herb Sewell, Professor of Immunology
at Nottingham University. Professor Sewell reported to the meeting the
findings of the Workshop on Retroviruses convened by UKXIRA in August.
Professor Sewell outlined the evidence obtained from in vitro tests which
established that two known pig retroviruses (PERVs) do indeed infect human
cells in culture, albeit relatively slowly. Another PERV, closely related
to viruses that cause certain cancers in human beings, may infect human
cells. As yet, there is no evidence to confirm that these viruses can
either cause disease in humans, or be transmitted from human-to-human.
Pig-to-monkey experiments cannot provide any answers to these burning
questions because, unlike humans, the monkeys subjected to these experiments
do not have the kind of receptors on their cells that allow these viruses
to infect and replicate.
Studies of previous recipients of pig tissue are currently being undertaken.
However, once more these procedures do not offer any kind of reliable
guidance as to the safety of whole organ xenotransplantation because they
have involved:
- relatively small numbers of cells
- very short term ex vivo perfusion of patients blood with pig organs
- non-genetically-modified pig tissue
- most patients have not been immunosuppressed
- the overall number of patients being studied is small in statistical
terms - approximately 160.
These factors make the transfer of pig viruses into these patients far
less likely to occur than in the case of full-scale xenotransplantation,
especially should the procedure become an established procedure with many
xenografts taking place.
The first three events in a sequence of seven, which would result in
a new virus transferring from pigs to humans, have been fulfilled. Professor
Sewell announced that there are "no clear answers on the safety of
pigs as tissue donor sources," and said that decisions on whether
the risk of viral xenozoonosis were low enough to permit the commencement
of human trials should be taken by "industry, clinicians, scientists
and the public." One of those decisions could be to "abandon
xenotransplantation."
Surveillance cannot be guaranteed
After a short break, Professor George Griffin, Professor of Infectious
Disease at St George's Hospital discussed the work of the newly-formed
Surveillance Working Group. Professor Griffin outlined various measures
designed to monitor patients for the emergence of a new viral disease.
Professor Griffin admitted that the kind of intensive, life-long surveillance
regimes required to monitor recipients of pig tissue that offer the best
hope of containing any pig virus are, it appears, not strictly enforceable:
the legislation to ensure compliance with these strict regimes simply
does not exist at present, apparently. This seems to reveal a gaping hole
in UKXIRA and the Government's plans to regulate xenotransplantation and
protect public health.
Open discussion
The meeting ended with an open discussion of the Authority's work and
xenotransplantation. The discussion was dominated by questions regarding
the animal welfare remit of UKXIRA. It was this discussion which reinforced
the impression that animal welfare was not taken seriously by UKXIRA.
Joyce D'Silva asked the panel a direct question regarding the relevant
difference between pigs and primates which justified the exploitation
of pigs, but not primates, for source tissue, as outlined in Animal Tissue
into Humans. The members of the Authority had great difficulty addressing
this issue. Professor Griffin even went so far as to deny that Animal
Tissue into Humans had ruled out the use of primates on ethical grounds.
This is quite disturbing as UKXIRA is supposed to base its considerations
on that report, which concluded:
" ... it would be ethically unacceptable to use primates as source
animals for xenotransplantation, not least because they would be exposed
to too much suffering." [para. 7 and 4.28].
Professor Griffin also revealed a rather cavalier attitude to the whole
question of animal welfare and primate use. Another member of the Authority,
Mr John Dark, Consultant Cardiothoracic Surgeon at the Freeman Hospital,
Newcastle appeared openly hostile to the animal welfare viewpoint.
Another area of concern surrounds the issue of how the public were integrated
into the consultation process. When addressing this question, the Chair
of UKXIRA, Lord Habgood of Calverton, expressed scepticism as to whether
the House of Commons was a fit body to be discussing such complicated
matters. Though, to be fair to Lord Habgood, his comment was made rather
tongue-in-cheek, the issue of democratic scrutiny is a very important
one, and once again UKXIRA seem to be paying lip service to the notion
of public involvement, without seriously incorporating it into their deliberations.
The overall impression of UKXIRA that I and others received is of a body
which although it is working within a framework that could allow for a
relatively fair and balanced consideration of xenotransplantation issues,
is composed of members of rather mixed ability and attitudes, and is failing
to meet some of the complex demands required of it, particular in the
area of animal welfare. Too little attention is being paid to the precautionary
principle, and far too much faith is being placed in the ability of science
and technology to assess and control risks which are not understood and
are literally beyond the limits of scientific knowledge. The inevitable
presence of unknown viruses was not mentioned once during the meeting.
Given the immense repercussions of xenotransplantation, any shortcomings
in UKXIRA are a cause for great concern.
Dan Lyons
(29/09/98)
Xenotransplantation research "in breach"
of RSPCA policy
Correspondence with Dr Maggy Jennings, Head of Research Animals at the
RSPCA, has revealed that substantial elements of Imutran's research programme
are incompatible with RSPCA policy. The RSPCA is opposed to all experiments
which cause pain, suffering or distress; is opposed in principle to manipulating
animals' genetic constitution; is opposed to the use of wild-caught animals;
is opposed to the import and export of laboratory animals; and is opposed
to all forms of farming that deprive animals of the opportunity to indulge
in their natural behaviour. Of the last of these, Dr Jennings writes:
The RSPCA has always expressed serious concern at the welfare implications
of keeping pigs in SPF/QPF conditions [Specific Pathogen-Free/Qualified
Pathogen-Free]. Part of Imutran's herd is kept in QPF conditions. We believe
that this seriously limits their ability to express their normal behavioral
repertoire and therefore seriously curtails one of the Five Freedoms widely
recognized as important for farm animals.
Imutran's research, genetic manipulation and breeding programme on pigs,
its export of a transgenic pig to Holland and its transplantation experiments
on primates including wild-caught baboons contravene these policies.
Max Newton
(20/08/98)
Govt prepare the way for xenotransplantation trials
At the end of July Frank Dobson announced the Department of Health's
guidelines on applications for clinical trials in xenotransplantation.
Immediately before the Government announcement Imutran announced their
intention to make an application under the guidelines to use pig liver
tissue in a supportive role outside the body, although they did not specify
when they would be ready to do this.
The Guidelines contained nothing very surprising to close observers of
the issue. The Government's basic position is that the organ donor shortage
is unlikely to be solved by other means (which is true if they continue
to be unwilling to consider changes in current donation policy and laws)
and that they are, therefore, unwilling to stand in the way of a potential
solution to that problem if they can be convinced of its safety. Mr Dobson
re-iterated the line the government has already taken in Parliamentary
Questions and other statements that:
"Trials in xenotransplantation involving humans will only be allowed
to take place if and when we are fully satisfied that the risks associated
with such procedures are acceptable taking account of all the available
evidence at the time."
Applications for trials will be considered by the United Kingdom Xenotransplantation
Interim Regulatory Authority (UKXIRA) and the final decisions rest with
ministers. Steps have been taken to ensure that all NHS hospitals and
ethics committees comply with these regulations, which are non-statutory.
The Government states it is willing to introduce legislation but has no
timetable at all for doing so at present. Other details include the inclusion
of a specific animal welfare role for UKXIRA, preparation of guidelines
on source animal welfare by the Home Office and preparation of surveillance
procedures (ie testing for evidence of infection or virus transfer) for
organ recipients.
(20/08/98)
Virus transfer symposium takes place beind closed
doors
A Government-sponsored meeting of experts to discuss virus transfer took
place at the beginning of August. Unfortunately details of what was discussed
have not been made public, despite the obvious implications for public
health. Speculative reports in the scientific press suggest that the message
on risk was mixed. Apparently studies of previous xenograft (i.e. tissue
such as skin or pancreatic cells) recipients show no evidence of virus
transfer so far, although these patients were not generally immunosuppressed
and, of course, did not receive tissue containing human genetic material.
There is also evidence that a third kind of endogenous virus (i.e., a
virus "inbuilt" into pig DNA) carried by pigs can infect human
tissue in the laboratory. Two other endogenous viruses have already been
shown to do this.
Public announcement of the results of Imutran's study of 160 previous
xenograft recipients is still pending, as are the results of Prof Robin
Weiss' research into the implications of the introduction of genetic material
which may make it possible for viruses to "disguise" themselves
as human tissue.
(29.4.98)
MPs calls for urgent Commons Debate on pig-to-human
transplants
Following a press briefing held by Imutran, the Cambridge biotechnology
comapny researching pig-to-human transplants (xenotransplantation), outlining
their intended path to clinical trials of the procedure, an Early Day
Motion (No.1255) has been tabled by Paul Flynn MP for Newport West (Lab.)
and Norman Baker MP for Lewes (LibDem) calling for a Parliamentary debate
to discuss the far-reaching public health and animal welfare implications
of xenotransplantation.
Virologists have warned of the potentially devastating consequences of
a pig virus contaminating the human population, following research demonstrating
that pig viruses can infect human cells.
"Should xenotransplantation trials go-ahead, the entire population
of Britain will be the subject of a dangerous and unnecessary experiment",
commented Dan Lyons of pressure group Xenotransplantation Concern (XtC).
Over 100,000 signatures opposing xenotransplantation research and clinical
trials were handed in to the Government last month. The Department of
Health has received in excess of 15,000 postcards from members of the
general public registering opposition to xenotransplantation.
"Our experience clearly shows that the public are very concerned
about xenotransplantation from both a public health and an animal welfare
viewpoint. The very least they deserve is that a technology with such
massive implications receives democratic scrutiny", says Dan Lyons.
So far, Government policy on this issue has been determined behind closed
doors.
Early Day Motion 1255 Xenotransplantation. Tabled 28th April 1998
That this House notes the public health risks associated with pig-to-human
transplants, including the introduction of novel infectious and dangerous
microorganisms into the human population and the immunological, anatomical,
and biochemical discrepancies between pigs and humans; recognises the
potential for substantial cost implications for the National Health Service
should the risk of infection or other medical complications materialise;
notes the considerable suffering endured by pigs and primates in the course
of xenotransplantation experiments and the prospect of an increase in
the level of suffering endured by pigs should xenotransplantation become
a routine clinical practice; and, in the light of these profound implications
for public health and animal welfare, calls upon the Government to preserve
the moratorium on clinical trials, to initiate as a matter of urgency
a full and wide-ranging Parliamentary debate on xenotransplantation to
facilitate the democratic scrutiny that xenotransplantation demands, and
to ensure that the precautionary principle applies to xenotransplantation
whereby one of the conditions to be fulfilled before clinical trials are
considered is that the safety of the procedure is guaranteed.
(23/04/98)
Xenotransplantation clinical trials imminent?
It was recently reported that an Israeli surgeon has expressed his desire
to perform a pig-to-human heart transplant using genetically-modified
pigs obtained from Imutran in the UK, and the reports implied that a clinical
trial was imminent in the UK. The Department of Health were caught on
the hop by these reports and when we contacted them they had only just
managed to confirm that clinical trials were not imminent by phoning Papworth
Hospital. This suggests that either regulation of possible clinical trials
may not be nearly as tight as it should be, or that internal communication
within the Dept of Health is imperfect.
There has been a "moratorium" on human clinical trials of xenotransplantation
since January 1997 but as there is no legislation governing xenotransplantation
the Government is not in a position to directly ban it, especially if
it were to take place in a non-NHS hospital. A British hospital ethics
committee would be unlikely to approve a clinical trial without Government
approval but it remains theoretically possible for one to take place.
In fact, the Dept of Health is willing to consider human trials if it
can be satisfied that all risks, including the risk of virus transfer
or other infection, could be adequately controlled - in effect the "moratorium"
is moribund. The United Kingdom Xenotransplantation Interim Regulatory
Authority receives applications for clinical trials and is responsible
for advising ministers, but this process takes place entirely behind closed
doors - all we know of UKXIRA's work is its remit and the names of its
members. We do know that they are in close contact with Imutran, and while
this is clearly appropriate given their role, it gives Imutran - who through
their parent company, Novartis, have resources beyond your wildest dreams
- lobbying opportunities denied to groups such as ourselves.
Xenotransplantation Concern remains committed to the complete prohibition
of xenotransplantation and we believe that a better informed public and
political community will promote that end. We also believe that the risks
involved in this procedure render it unacceptable for decision-making
to take place behind closed doors. We are currently working to promote
greater open-ness in this process through our political contacts and will
provide more details of this component of our campaign soon.
(01/04/98)
100 000 say NO to Xenotransplantation
Xenotransplantation Concern presented a 100 000 signature petition to
10 Downing St on 31st March 1998, calling for an immediate end to xenotransplantation
research and a ban on clinical trials. Norman Baker MP formally presented
the petition to the House of Commons on the same day.
The petition was originally launched by Uncaged Campaigns in 1996, but
now forms part of the broad-based campaign against xenotransplantation
being co-ordinated by XtC. It calls for an immediate cessation of xenotransplantation
research on the grounds of microbiological risk, the danger to human recipients,
the neglect of policies to increase human organ donation and ethical objections
to the use of animals in this way.
Alistair Currie of Xenotransplantation Concern said:
"Opposition to xenotransplantation is not confined to a minority
of activists and pressure groups, as some may like to believe. This
petition is clear evidence of the strength of public concern over xenotransplantation,
concern that is strongly justified by the risks associated with this
procedure. The introduction of living animal tissues and the viruses
they contain into living human bodies is a potential biological time
bomb. Any progression to human clinical trials would not only be dangerous
to the patients involved but to the community as a whole and would represent
a contemptuous disregard for the concerns of the public. Once the first
xenotransplant has taken place it will be too late to decide the risk
is unacceptable. This might be our last chance."
(29/05/98)
Imutran still promising jam tomorrow
Leading xenotransplantation researchers Imutran held a press briefing
in April to discuss their plans for the future. The briefing, which included
a contribution from Prof Robin Weiss, an immunologist who has warned of
the dangers of virus transfer, painted a picture of prudence. They are
currently undertaking a retrospective study of patients who have received
pig tissues, such as skin grafts, to look for evidence of infection in
humans by porcine viruses. If this should produce no evidence of infection
they hope to commence a trial involving pig liver cells outside the body,
similar to those which have been undertaken in the USA. They also hope
to undertake kidney transplantation, but were noncommittal about the timing,
finally suggesting five years down the line when pressed by journalists.
In 1995 Imutran claimed they were ready to proceed to human trials in
early 1996. In October of last year, Alistair Currie of Xenotransplantation
Concern attended a meeting at which one of the surgeons involved in the
research said they could proceed to trials "next week" if the
government would permit them. From the point of view of human welfare
their new found caution is welcome: unfortunately it is likely to lead
to much more animal suffering in the course of pursuing the increasingly
unlikely possibility that xenotransplantation will ever provide an effective
therapy.
(26/06/98)
Transgenic pig imported to Holland
It has come to light that Imutran, the UK's leading xenotransplantation
researcher, has been conducting research in a controversial animal laboratory
in Holland, and that it recently exported a transgenic pig to the laboratory
where its organs have been harvested and transplanted into monkeys.
The work being conducted at the Biomedical Research Centre (BPRC) appears
to involve the testing of immunosuppressant regimes, and has been conducted
since at least November 1997 using non-transgenic pigs and macaques. A
transgenic pig (accompanied by a companion animal, slaughtered on arrival)
was flown to Amsterdam in early May, both of its kidneys being removed
after slaughter and transplanted into two macaques whose own kidneys had
been removed.
It appears that Imutran are attempting to circumvent the relatively tough
regulation that applies to their experimental procedures in the United
Kingdom - why else would they undertake such an expensive exercise for
procedures that appear to be the same as those conducted in this country?
The Animal Procedures Committee has explicitly stated that it is willing
to delay the progress of research on animal welfare grounds and a representative
of Imutran admitted in 1997 that British regulations have sometimes prevented
them from concluding experiments as they would wish - ie they have not
been permitted to keep animals alive indefinitely who are suffering substantially.
BPRC has, incidentally, been criticised by groups such as the RSPCA for
the condition in which its primates are kept. This latest development
serves to emphasise how low a priority animal welfare actually takes in
this research.
(04/06/98)
Wild-caught baboons used in xenotransplantation
The answer to a parliamentary question put by Norman Baker MP has revealed
that wild-caught baboons have been used in xenotransplantation research.
A previous answer by George Howarth of the Home Office, had admitted that
wild-caught baboons were still being used in experiments despite the need
for "exceptional and specific justifications" for their use.
Baboons are the most advanced primate permitted to be used for research
in the UK. Pursuing this answer, Norman Baker asked what these justifications
were. The answer, to Written Question no 176, asserted that baboons had
to be used as no other permitted primate was large enough, and sufficient
quantities of captive-bred baboons were not available, despite "extensive
efforts" by the research team to obtain them from captive sources.
The baboons appear to have been used in heart transplant surgery, as
part of the xenotransplantation research programme, presumably by Imutran,
who are the only researchers undertaking this kind of work in the UK at
present. The suffering of these animals is profound, as they undergo major
surgery and then the consequences of trasnsplant. Imutran's published
research suggests that their experimental subjects tend to survive periods
of weeks following surgery, before, presumably, dying of complications
related to the transplant.
That such suffering should be permitted to be inflicted on any animals
for so speculative a prospect as xenotransplantation is an indictment
of the 1986 Act. That it should be inflicted on animals on top of the
distress of being caught in the wild and transported to this country is
profoundly shocking.
(01/04/98)
Another new virus
As recently as 26th of February a new pig virus was reported to have
infected two workers in Sydney, Australia. Causing deformities and stillbirths
among pigs and severe flu-like symptoms in the two workers, the virus
was traced back to a colony of fruit bats near the piggery.
One of the most frightening potential consequences of xenotransplantation
(animal-to-human tissue transplants) is the transfer of viruses carried
by donor animals into the human population. Pigs are considered to be
"safer" donors, microbiologically-speaking, than primates as
the infections from which they suffer are less likely to cause human disease
than those of primates, but it has already been shown in the test tube
that their viruses can infect human tissue. Xenotransplantation's advocates
have claimed that screening could eliminate viruses but we have no mechanism
to detect unknown viruses. As Australian virologist Peter Kirkland told
a meeting in Sydney "you can't screen for disease agents that you
don't know about." The discovery of this new virus, and the fact
that it transferred from bat to pig to human being through a far less
direct route than the implantation of living tissue inside the body, is
yet another reminder of the level of our ignorance in this area, and the
potential risks of this procedure.
(28/01/98)
Scientists call for moratorium on xenotransplantation
Seven specialists with an interest in xenotransplantation, led by Fritz
Bach of Harvard Medical School have called for a moratorium on human trials
in the USA until an informed public debate on the issue has taken place.
In a letter to Nature, published 22nd January, they note the risk of infectious
agents crossing from pigs to human beings and write:
"given the potential risk to the public, the issue is first and
foremost an ethical one..an informed public debate is needed so that
the public can decide whether it wishes to consent to clinical xenotransplantation
at all and, if so, under what conditions."
Nature's editorial counselled caution, and another editorial in The Economist
on 24th Jan wrote "to allow any further xenotransplants without a
far clearer idea of the potential risks - and a strong, international
system in place for monitoring recipients - would be folly indeed."
The risk of transfer of pathogens and the potential for a transferring
virus to cause an epidemic has been highlighted by the recent outbreak
of flu originating in chickens in Hong Kong - HIV 2 is also known to have
originated in monkeys. In October 1997 British scientists announced the
discovery of viruses carried by pigs' own DNA which can infect human tissue
and which, according to one researcher may be impossible to eradicate
prior to transplant (New Scientist 18/10/97). Screening for unknown viruses
is an even greater challenge.
As Bach writes, the risk of infection in the general population renders
the issue one of concern to everyone; in effect any human trial constitutes
an experiment on the entire population. For a critically-ill individual
patient offered a xenotransplant in the absence of a human organ, the
risk of infection may appear to be worth taking; the possible consequences
of that decision have far wider ramifications however. It is essential
therefore that an informed public debate precedes any progression to clinical
trials. This is particularly important at present as the UK government's
decision on human trials is expected to be announced within a month.
Of course, many scientists and others consider the unknowns surrounding
xenotransplantation an indication for more animal research. The fact is,
of course, that no animal experiment can prove the safety of animal organs
which, theoretically, could last twenty years in a human being. Even the
smallest immunological difference between humans and experimental animals
could become the gateway for a pathogen. The moral and prudent solutions
to the shortage of organs are prevention of conditions that may lead to
the need for a transplant, improving the supply of usable human organs
and improving the long term success of human transplants.
It is interesting to note that opinion polls have shown some divergence
in attitudes to xenotransplantation between the USA and the European Union.
In the US 75% of people would consider an animal organ for a loved one
if no human organ was available. In the EU only 36% thought the practice
morally acceptable. Most interestingly, the US study found opposition
to xenotransplants strongest among those people with the highest level
of knowledge about it.
No big surprise?
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