9 February 2002
PROFESSIONAL PROSTITUTION/PATENTS/GE WEAPONS
"the New England Journal of Medicine published a negative review of a widely hailed book linking chemical pollution to cancer but failed to disclose that the review was written by the medical director of a major polluter. In another case, the journal Neurobiology of Aging published a panel report endorsing a proprietary blood test for Alzheimer's disease but did not disclose that one of the panelists held a patent on the test and another was a co-founder of the company that planned to market the test. Nonetheless, most scientific journals still do not disclose authors' conflicts of interest..." (item 1)
"Not only does the patent appear to have inhibited use of the genetic test and study of the gene, it is beginning to look as if the gene was not the right one, anyway." (item 2)
"Pandora's box is well and truly open and the time has come for the worldwide community of biological scientists... to sit up and pay attention.' (item 3)
"It may well be that 50% of the articles on drugs in the major journals across all areas of medicine are [ghostwritten by industry].. This raises the question of whether the eminent scientists whose names were on the papers ever saw the raw data from the trials" (item 5)
1. Scientists Call for Disclosure of Conflicts of Interest
2. Doctors hindered by company's gene patent
3. GE Smallpox: Weapon of the Future?
4. Europe grants Geron animal cloning patent
5. Scandal of scientists who take money for papers written by industry
1. Scientists Call on Journals to Disclose Authors' Conflicts of Interest
Today, more than two dozen prominent scientists, including two former editors of the New England Journal of Medicine and a former editor of the Journal of the American Medical Association, sent a letter to editors of Science, Proceedings of the National Academy of Sciences, and 200 other scientific journals, urging them to strengthen their policies concerning disclosure of conflicts of interest.
The letter reflects increasing concern about financial and other conflicts of interest that may jeopardize the integrity of scientific research. Such conflicts, many of which are associated with the rise of industry-funded science, have already attracted scrutiny from Congress, a number of specialty societies, and several leading medical journals.
"Whether the issue is clinical research, cancer clusters, or global warming, corporate interests can hide behind the credibility of peer-reviewed journals", says Virginia A. Sharpe, Ph.D., a bioethicist and Director of CSPI's Integrity in Science project which coordinated the initiative. "A presumption in favor of routine disclosure will convey a clear message that journals want to affirm the value of transparency and the reader's need for information to assess possible bias."
The scientists are urging journals to publish alongside studies, editorials, and other items:
*authors' sources of funding;
*financial interests of authors and their immediate families in the last 5 years in companies that may be affected by the published article;
*the specific contribution of each author of the published paper.
In the last few years, a number of spectacular failures of disclosure and editorial oversight have come to light. In one case that resulted in a revision of the journal's policy, the New England Journal of Medicine published a negative review of a widely hailed book linking chemical pollution to cancer but failed to disclose that the review was written by the medical director of a major polluter. In another case, the journal Neurobiology of Aging published a panel report endorsing a proprietary blood test for Alzheimer's disease but did not disclose that one of the panelists held a patent on the test and another was a co-founder of the company that planned to market the test. Nonetheless, most scientific journals still do not disclose authors' conflicts of interest, and for those that do, there is very little uniformity in the requirements or consistency in the application of the policies.
"With the amount of industry money pouring into scientific research," says Dr. Orrin Pilkey, Director of Duke University's Program for the Study of Developed Shorelines and a co-signer of the letter, "there is a risk that more research will just become 'client science' where truth is determined according to your clients' needs. At the very least, journal editors and the public should be informed of the financial interests behind a study."
Some of the letter's cosigners include: Marcia Angell, M.D., Harvard Medical School; Lisa Bero, Ph.D., University of California, San Francisco; Thomas Bodenheimer, M.D., University of California, San Francisco; Bruce C. Coull, Ph.D., University of South Carolina, School of the Environment; Sheldon Krimsky, Ph.D., Tufts University; George Lundberg, M.D., Medscape General Medicine; Herbert Needleman, M.D., University of Pittsburgh School of Medicine; Marion Nestle, Ph.D., M.P.H., New York University; Edmund Pellegrino, M.D., Georgetown University Medical Center; Arnold Relman, M.D., Harvard Medical School; Sandra Steingraber, Ph.D., Cornell University; and David Suzuki, Ph.D., University of British Columbia.
Letter to Editors of Scientific Journals:
2. Doctors hindered by company's gene patent
The Guardian (London), February 7, 2002
Doctors' ability to diagnose and study a debilitating disease caused by iron overload in the body is being hampered by the patenting of a key gene. The disease, called haemochromatosis, affects up to 20,000 Britons and two common mutations in the gene known as HFE are thought to be responsible for 80- 85% of cases of the illness. The patent, given in 1998 to the Californian company Mercator, which discovered the gene, passed through various hands, ending up with the company Bio-Rad. The patent gives a monopoly on testing for the mutations in patients suspected to have haemochromatosis. According to a study published in today's edition of Nature, the enforced monopoly on testing, by successive companies, has led to 30% fewer labs offering the test than would have been the case had the gene not been patented. Haemochromatosis, which affects disproportionately those of north European descent, causes the body to absorb too much iron from food, which in turn leads to liver damage, heart disorders, lower sex drive, and bronzed skin. It is easily treated, by bloodletting, but often misdiagnosed at the early stage. The researchers behind the Nature study found that about a third of 128 laboratories they contacted in the US had either stopped carrying out genetic tests for the HFE mutation or had never bothered to introduce them because of the restrictions imposed by the patent holders. "A lot of clinical study is needed to validate and extend the discovery of a disease gene," said the researchers, led by Jon Merz, a bioethicist at the University of Pennsylvania.
"Our results give us reason to fear that limiting clinical testing will inhibit further discovery as well as the understanding that emerges naturally from broad medical adoption (of genetic diagnosis)."
The haemochromatosis experience offers an argument against human gene patenting. Not only does the patent appear to have inhibited use of the genetic test and study of the gene, it is beginning to look as if the gene was not the right one, anyway. In a vivid example of the way the right to exploit human genes now passes from hand to hand, Mercator, the firm that patented the gene, merged with another firm, Progenitor, which then licensed the patents to SmithKline Beecham Clinical Labs. The patents were then sold on to Bio-Rad. However, specialists in haemochromatosis now say it is doubtful whether the HFE gene mutations were ever a reliable indicator of whether a person would become seriously ill with the disease. Studies suggest only 1% of people with two copies of the gene are in danger. A meeting of the European Haemochromatosis Consortium concluded the illness was not caused by a single gene, but a multitude of factors. Special report on genetics at dian.co.uk/gene
3. Smallpox: Scourge of the Past, Weapon of the Future?
By Professor Christopher J. Davis OBE and Dr Wendy Orent
Doctors and scientists worried about the threat of bioterrorism fear no disease more than smallpox. It is disfiguring, highly contagious (transmissible from person to person), and often fatal, killing at least one in three victims. Naturally occurring smallpox was effectively controlled and then eradicated by vaccination. But, what if 'bioweaponeers' were able to produce a strain of the smallpox virus that could overcome the vaccine's protective effects? The entire world would once again be vulnerable to one of humankind's worst scourges.
A deadly discovery
The prospect of vaccine-resistant smallpox is more than just science fiction. Australian scientists have been investigating the use of viruses in their pursuit of a novel method of birth control based on the vaccination principle. What they discovered in the course of this work surprised them, and horrified the scientific community.
Working with Mousepox, a virus related to smallpox causing a disease of mice, they showed that the addition of a single gene - one that produces IL4 [interleukin 4], a chemical messenger controlling the immune system - could enable the virus to overcome both natural and vaccine-induced immunity. IL4 had the effect of shutting down cell-mediated immunity, the part of the immune system our bodies use to fight smallpox. In these experiments 60% of the supposedly immune mice died.
No one knows whether a similar effect could occur with smallpox; no one has tried the experiment.
No one in the West, that is....
Bioweapons research during the Cold War
Accounts from Russian 'bioweaponeers', who left the former Soviet Union to settle in the West, suggest that Russian scientists were very close to producing genetically-modified smallpox, and that they may have actually done so.
Making diseases more dangerous
There were at least two large, highly classified Russian bioweapons research programmes, code-named 'Factor' and 'Hunter', working in this direction:
'Hunter' focused on combining genes from two viruses together, such as smallpox and Ebola, or smallpox and Venezuelan Equine Encephalomyelitis, in order to produce a new microorganism with the characteristics of both, sometimes referred to as a chimaera.
'Factor' involved the use of genetic engineering to make bacteria and viruses produce toxins and other foreign proteins
Initially, according to Sergei Popov, who ran part of the programme at the vast Vector Research Complex at Koltsovo near Novosibirsk, in Siberia, 'Factor' was devised "just" to make viruses and bacteria more pathogenic or better able to cause disease and death in humans. Eventually, the programme transformed and "became much broader"
'Factor' scientists looked for ways not only to increase pathogenicity by inserting genes for foreign toxins into viruses and bacteria but also to create novel strains with completely new properties, such as the ability to degrade the immune response of the human target or modify human behaviour or physiology. They synthesized DNA, coding for the production of toxins and human proteins such as IL4, and then inserted this artificial DNA directly into Vaccinia, the vaccine virus, used as a substitute for smallpox in experiments.
Changing smallpox for the worse
Popov claims his team succeeded in placing genes for toxins into Vaccinia, including conotoxin, a lethal shellfish poison and anaphylatoxin, which produces shock. Popov had intended to extend his work to cover all the interleukins, but he left Vector in 1987 to work at another Soviet bioweapons laboratory.
Other reports indicate that the scientists at Vector did synthesize the IL4 gene, among others, but whether they were successful in inserting it into the Vaccinia or smallpox virus is anyone's guess. Nor do we know whether they had discovered that adding IL4 might yield vaccine-resistant smallpox.
When asked about the Australian experiment recently, Dr. Lev Sandakchiev, long-time Director of the Vector Research Complex and a veteran of the Soviet bioweapons programme only remarked, "Of course this is not a surprise."
In fact Sandakchiev and his team had developed the technology for creating vaccine-resistant smallpox as early as 1991, when Vector was still under the control of Biopreparat, the civilian "front organization" for the former Soviet biological weapons programme. We do not know if they actually created such a strain.
Now we know, thanks to the Australian experiment, that the approach works. The thinking and experiments behind much of this Soviet/Russian work is already 10-15 years old and what is outlined here represents only a fraction of their overall research programme. Much that was attempted and for all we know successfully accomplished remains to be uncovered.
Pandora's box is well and truly open and the time has come for the worldwide community of biological scientists, from physicians to ecologists, to sit up and pay attention. The science of biology has come of age and in the same way that the community of physicists had to face up to the use of its knowledge and talent to create nuclear weapons over half a century ago, so now must the community of biomedical scientists do the same, before it is too late - if it isn't already!
Professor Chris Davis spent 17 years in the Royal Navy where he specialised in nuclear, biological and chemical defence. While on the Defence Intelligence Staff, he was responsible for the collation and assessment of intelligence on biological weapons. In the early 1990s he took a leading role in the team of US and UK weapons inspectors, which, after the defections and subsequent revelations of two Soviet officials, for the first time assessed the full extent of the Soviet biological weapons capability. For this he was awarded an OBE.
Professor Davis currently lives in the US where he is Chief Scientist at Veridian, involved in commercial biodefence programmes, and is Visiting Professor on the Medical Faculty at the Center for Civilian Biodefense Studies at Johns Hopkins University. He is a contributor to the drama documentary Smallpox 2002: Silent Weapon, a Wall to Wall production for BBC Two.
Dr Wendy Orent is a science writer with a special interest in infectious diseases who is currently writing a book about plague.
4. Europe grants Geron animal cloning patent
RTf 02/06 1657 UPDATE 1-
(Adds details, background, stock price, paragraphs 2, 5, 7-9)
LOS ANGELES, Feb 6 (Reuters) - Geron Corp.
Geron which owns the technology that cloned Dolly the sheep, on Wednesday said the European Patent Office granted it a patent on aspects of nuclear transfer technology in the cloning of nonhumans. Nuclear transfer is a cloning method in which researchers take a normal egg, remove the nucleus, which contains most of the genetic information, and replace it with the nucleus from the cell being cloned.
"The claims of this European patent cover the cloning of animals, including cattle, sheep, pigs, goats and birds," said David Earp, Geron vice president of intellectual property. Geron said its nuclear transfer patent portfolio now includes two issued U.S. patents, 19 patents that have been granted or accepted in other countries and over 60 pending patent applications worldwide for cloning technology. The Menlo Park, California-based company in 1999 purchased from Scotland's Roslin Institute the technology that in 1997 produced the world's first cloned animal, Dolly. Geron has since licensed the animal cloning technology to several livestock breeding companies. "This is significant given the commercial opportunities in cloning various species for agriculture, industrial applications, xenotransplantation (animal-to-human organ transplants) and biopharmaceutical production," Earp said.
Geron is currently in a patent battle with Advanced Cell Technology Inc., the company claiming to be the first to clone human embryos, over an animal cloning patent licensed to ACT by the University of Massachusetts. Geron claims the Roslin cloning breakthrough came before the university's patent, which should be voided. Geron last week said the U.S. Patent and Trade Office has ruled that in order to keep its patent, the University of Massachusetts must prove it invented the cloning technology before the Roslin Institute. Geron's shares were down 39 cents, or 4.5 percent, at $8.26 on Nasdaq.
5. Scandal of scientists who take money for papers ghostwritten by drug companies
Doctors named as authors may not have seen raw data
Sarah Boseley, health editor
Thursday February 7, 2002
Scientists are accepting large sums of money from drug companies to put their names to articles endorsing new medicines that they have not written - a growing practice that some fear is putting scientific integrity in jeopardy.
Ghostwriting has become widespread in such areas of medicine as cardiology and psychiatry, where drugs play a major role in treatment. Senior doctors, inevitably very busy, have become willing to "author" papers written for them by ghostwriters paid by drug companies.
Originally, ghostwriting was confined to medical journal supplements sponsored by the industry, but it can now be found in all the major journals in relevant fields. In some cases, it is alleged, the scientists named as authors will not have seen the raw data they are writing about - just tables compiled by company employees.
The doctors, who may also give a talk based on the paper to an audience of other doctors at a drug company-sponsored symposium, receive substantial sums of money. Fuller Torrey, executive director of the Stanley Foundation Research Programmes in Bethesda, Maryland, found in a survey that British psychiatrists were being paid around $2,000 (£1,400) a time for symposium talks, plus airfares and hotel accommodation, while Americans got about $3,000. Some payments ran as high as $5,000 or $10,000.
"Some of us believe that the present system is approaching a high-class form of professional prostitution," he said.
Robin Murray, head of the division of psychological medicine at the Institute of Psychiatry in London, is one of those who has become increasingly concerned. "It is clear that we have a situation where, when an audience is listening to a well-known British psychiatrist, you recognise the stage where the audience is uncertain as to whether the psychiatrist really believes this or is saying it because they them selves or their department is getting some financial reward," he said.
"I can think of a well-known British psychiatrist I met and I said, 'How are you?' He said, 'What day is it? I'm just working out what drug I'm supporting today.'"
Marcia Angell, former editor of the New England Journal of Medicine, wrote a year ago that when she ran a paper on antidepressant drug treatment, the authors' financial ties to the manufacturers - which the journal requires all contributors to declare - were so extensive that she had to run them on the website. She decided to commission an editorial about it and spoke to research psychiatrists, but "we found very few who did not have financial ties to drug companies that make antidepressants."
She wrote: "Researchers serve as consultants to companies whose products they are studying, join advisory boards and speakers' bureaus, enter into patent and royalty arrangements, agree to be the listed authors of articles ghostwritten by interested companies, promote drugs and devices at company-sponsored symposiums, and allow themselves to be plied with expensive gifts and trips to luxurious settings. Many also have equity interest in the companies."
In September her journal joined the Lancet and 11 others in denouncing the drug companies for imposing restrictions on the data to which scientists are given access in the clinical trials they fund. Some of the journals propose to demand a signed declaration that the papers scientists submit are their own.
The success of Prozac, the antidepressant which became a cult "happy" drug in the 1990s, substantially raised the stakes in psychiatry. Its promotion coincided with the decline of state funding for research, leaving scientists in all areas of medicine dependent on pharmaceutical companies to fund or commission their work. That in turn gave the industry unprecedented control over data and ended with research papers increasingly being drafted by company employees or commercial agencies.
The responsibility of scientists for the content of their papers takes on serious significance in the context of court cases in the US, where relatives of people who killed themselves and murdered others while on SSRIs (selective serotonin reuptake inhibitors) - the class of drug to which Prozac belongs - claimed the drugs were responsible. According to David Healy, a north Wales-based psychopharmacologist who has given evidence for the families, the companies have relied on articles apparently authored by scientists who may in fact have not seen the raw data.
Dr Healy, who had unprecedented access to the data that the companies keep in their archives, said: "It may well be that 50% of the articles on drugs in the major journals across all areas of medicine are not written in a way that the average person in the street expects them to be authored."
He cites the case brought last year against the former SmithKline Beecham (now GlaxoSmithKline) by relatives of Donald Schell. The court found that the company's best-selling antidepressant, an SSRI called Seroxat, had caused Schell to murder his wife, daughter and granddaughter and commit suicide.
The company's defence was based on scientific papers which analysed the results of trials comparing Seroxat with a placebo and found there was no increased risk of suicide for depressed people on Seroxat. But the raw data probably does not support that, argues Dr Healy. Some of the placebo suicides took place while patients were withdrawing from an older drug. When the figures are readjusted without these, he says, they show there is substantially increased risk of suicide on Seroxat.
This raises the question of whether the eminent scientists whose names were on the papers ever saw the raw data from the trials - or saw only tables compiled by company employees, he says. David Dunner, a professor at the University of Washington, who co-authored one of the papers in 1995, admits he did not see the raw data. "I don't know who saw it. I did not," he said. "My role in the paper was that the data were presented to us and we analysed it and wrote it up and wrote references."
His co-author Stuart Montgomery, then of St Mary's hospital medical school in London, declined to answer calls and emails from the Guardian. The third name on the paper is that of Geoff Dunbar, a company employee.
The World Health Organisation has expressed concern about the ties between industry and researchers. Jonathan Quick, director of essential drugs and medicines policy, wrote in the latest WHO Bulletin: "If clinical trials become a commercial venture in which self-interest overrules public interest and desire overrules science, then the social contract which allows research on human subjects in return for medical advances is broken."
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