INQUEST: HOW DID ALIEN GENES KILL
JESSE GELSINGER?

Irwin D. Bross, Ph.D.

President

Biomedical Metatechnology Inc.

1. Purpose of this Inquest

A young man named Jesse Gelsinger died on September 17, 1999 as a direct result of the gene therapy that he was given at a University of Pennsylvania medical center. As in nearly all gene therapy, the genes that he had been given were alien genes--they were not his own genes. The rationale for gene therapy is this: When a person's genes are defective they can be replaced by alien genes that do not have the defect. The death occurred so soon after the gene therapy was given-- and the autopsy was so striking--that it was undeniable that the death was caused by the gene therapy.

The autopsy revealed that several of Gelsinger's internal organs were massively damaged and the lung damage was considered the immediate cause of death. This damage was caused by the complex interactions between Gelsinger's host defense systems and the therapy he had received (the alien genes and to the cold virus vector used to transport them). Therefore, this fact was also unquestionable: The alien genes were involved in his death.

The main question, then, is how did the alien genes kill Jesse Gelsinger? What special circumstances and major factors led to Gelsinger's death?

Other patients had survived similar gene therapy; what was different in Gelsinger's case?

The purpose of this inquest is to answer these and other important questions that have been raised by Gelsinger's death. The public has the right to get honest answers. If the American public understands the circumstances that increase the risk of death and illness from gene therapy, they or their loved ones would be in a better position for informed consent. In other words, they will be better able to judge whether they should accept (or encourage loved ones to accept) gene therapy. Honest answers about who and what caused Gelsinger's death are needed so that the public can protect its own health and safety when issues involving human experimentation arise.

So far there have been few straight answers to the key questions.

In Gelsinger's case, the treatment proved to be far worse than the disease. Unfortunately, this is an increasingly common situation nowadays. One major reason why this problem is getting worse is the advent of powerful and aggressive Biotechnology drug companies. They are expert at manipulating the mass media-and especially the Nightly TV News to get free publicity for ineffective or outright hazardous treatments. If the public ever hears the grim truth about these conterproductive therapies, it come much too late to do much good.

2. Why is an Independent Inquest Needed?

Although citizens have a right to get straight answers to questions about the risks and benefits of gene therapy, one point is clear: They are certainly not going to get straight answers from the principals in the Gelsinger case.

The doctor in charge, James Wilson has discussed the death on television. He has insisted that he and his team are "comfortable" with what they did-- including deliberate non-compliance with the reporting requirements of the U.S.National Institutes of Health (NIH). The University of Pennsylvania held a closed official inquiry which apparently produced no action on the non- compliance. This is "par for the course" when the members of a "jury" are involved in the misbehavior .

The Biotechnology drug corporation, Schering-Plough, a major player in the death of Gelsinger, has actively and constantly lobbied the NIH and demanded that the information on deaths and illnesses from gene therapy be kept from the public in the name of "confidentiality". This biotech company seems to have strong supporters within NIH and within the Food and Drug Administration (FDA). It has been a consistent policy of Biotech industries to infiltrate government agencies in the United States, Britain, Canada and other countries. This provides what businesses sometimes call "inside salesmen".

Monsanto and Schering-Plough are Biotech companies that have been especially successful in turning civil servants into their servants. Inside salesmen in top level policy making civil service jobs have managed to replace long-standing policies that protect the public interest with new policies that favor Biotechnology interests. The Gelsinger case provides good examples of this.

3. Why Isn't there a Government Inquest?

For a short time it appeared as if NIH might investigate this unexpected death in a human experiment under NIH control. Indeed, at first, NIH reacted positively: It proposing a revision in the rules which required that all illnesses and deaths in gene therapy human experiments be reported. This would eliminate the most common excuse for not reporting the deaths in gene therapy experiments (i.e., the doctor was uncertain about what to report).

From both a scientific and a public policy standpoint, doctors who are in an acute conflict of interest situation should not be the ones to decide what should or should not be reported. However, NIH has indefinitely postponed this revision. According to some NCI officials this was because Schering-Plough complained (in its comments on the revision) that this would add too much work for NIH officials!

A more plausible reason for this waffling is this: Neither the drug companies nor NIH wanted an open database. With modern computers systems, an open database would be a simple and inexpensive way to handle the deaths and illnesses and the best way to protect the patients. There would be little or no extra work for NIH officials. Although public access to information on the illness and deaths in gene experiments would make it easier for activists and lawyers to actually protect the patients in human experiments, none of the principals want to have the public looking over their shoulders.

The public has the right to an independent inquest on the death of Jesse Gelsinger since it could provide it with important information it could use to protect its own health and safety. However there is little chance that there will be any public inquest on this death by federal agencies. This is why I have volunteered to do this conduct this inquest. With over half a century of experience in biostatistics, medical research, and public health and with more first hand experience running controlled clinical trials than almost any other living person, I am one of the few scientists who is qualified to do the job.

4. Background Factors: Gene Therapy and the Media

The death of a young man, Jesse Gelsinger, from his gene therapy was reported in the mass media and on the TV Nightly News for a few days. As is usual with the mass media, it has been quickly forgotten--replaced in the limelight by other news stories. However, even in its short airing on the TV Nightly News, the Gelsinger story produced a furor that for the first time raised serious questions about the highly publicized medical treatment, gene therapy.

Americans were surprised to hear--for the first time--that most of what they had previously told about gene therapy was hype from public relations departments of the big Biotechnology drug companies. The media presented it as if it were scientific fact. A very few moderately successful results had been blown up out completely out of proportion by the Biotech drug companies and the doctors who work for (or with) them. The U.S. mass media had presented the claims of Biotech public relations departments as "science" and the sales talks of doctors as "medical science". One lesson the public and the media could learn from this inquest is this: Hype can be hazardous to your health.

One of the results of the media hype was that many patients--including Gelsinger--were lured into the gene therapy human experiments under false pretenses. They were led to expect that they would be cured; they were never told that there was little or no scientific evidence to support their expectations.

5. Background Factors: Research Risks in Gene Therapy

Patients in the gene therapy experiments were deliberately misled about the research risks of this therapy. According to the Biotechnology drug company mantra, gene therapy had remarkably few side effects and the alien genes used in gene therapy were "harmless". This was the gene therapy version of the mantra of the Biotechnology food companies that the alien genes in the food products were "harmless".

What was true was this: Much of the time, neither the public nor the government agencies nominally in charge of the experiments had heard much about the adverse side effects. As has emerged during the media furor, numerous illnesses and deaths had occurred but they had been covered up. It was the consistent policy of the aggressive Biotech companies and the doctors connected with them to conceal the illnesses and deaths from gene therapy from the public and from the medical and scientific community. This cover up was often done in the name of "Confidentiality".

The Biotech companies had an additional reason to cover up the facts in the Gelsinger case. Despite Biotech safety claims, alien genes are not harmless to humans. The death of Gelsinger provided indisputable scientific proof that alien genes can kill human beings.

One of the most basic principles of human experimentation is "informed consent". To some doctors "informed consent" merely means getting the patient's signature on a piece of paper as a protection to the doctor. In this narrow sense, there was informed consent in the gene therapy experiments. However, the real purpose of informed consent is to protect the patient--to inform the patient about the benefits and risks of the treatment so that the patient can make a sensible decision about whether or not to take the treatment. As noted above, the patients were given dishonest sales talks because the actual success rates are so poor; the Biotechnology policy of cover-up of the illnesses and deaths in gene therapy experiments insured that the patients could not be given valid scientific information on the research risks.

In sum, the basic protection of informed consent was deliberated denied to the patients in the gene therapy experiments. This factor increases research risks in human experiments and played a major role in Gelsinger's death.

6. Background Factors: Human Experimentation

More than 50 years ago the world was shocked by the human experiments of the Nazi doctors on Jews and other helpless captives of the German Nazis. The public outcry against such experiments led over the years to the evolution of rules for human experiments were that were intended to protect patients in human experiments in the United States. The death of young Gelsinger clearly shows that the current rules are not working.

As will be shown here, the death of Gelsinger would have been prevented if the U.S. rules and regulations for human experimentation (which have been in place for years) had been obeyed. In government agencies such as the Office of Protection again Research Risks (OPRR), failure to follow these rules is call "non-compliance". The nominal mission of OPRR is to stop such non-compliance. It has the power to punish non-compliance by debarring the principals involved from human experiments. However, although the Gelsinger case is flagrant example of non- compliance, OPRR has not used its powers. There were two clear warning signals-red lights-that should have stopped the Gelsinger experiment before it killed the young man. Hence, in a technical sense it was non-compliance with these rules that killed Gelsinger.

A critical factor here is that non-compliance with national laws and with government regulations seems to be habitual behavior in Biotechnology. The ethics of Biotechnology food and drug companies seem similar to the elitist ethics of the Nazi doctors in World War II. Biotechnologists seem to feel that they are a master race--that they have the right to abuse any other human beings on the planet if this might add to their glory, increase their profits, or double their stock prices.

Result: The protection of the subjects of human experiments has been set back 50 years.

7. Dangerous Circumstances: Running A Red Light

Gelsinger died because James Wilson and his team at Penn ran through two red lights-agreed upon warning signals in the protocol of the experiment. If either one of the red lights had been obeyed, the death would have been prevented. A "protocol" in this context is simply a way of spelling out the detailed application of the "rules of the game" for human experimentation.

Gelsinger was the last patient in a series of 18 patients at Penn who were to be given gene therapy. The previous patients had failed to show any remarkable benefits from their therapy. According to the Food and Drug Administration, FDA, two of the earlier patients had significantly elevated liver enzyme levels--a warning signal that the dosage levels in this gene therapy series were causing potentially serious damage to vital organs. While one report might only turn on a caution light, when a second patient confirmed this damage this was a clear red light. The protocol said STOP but James Wilson did not stop.

Why didn't he stop? I suspect that Wilson was getting desperate: Gelsinger was his last chance to score the spectacular success that would advance his career, delight his sponsor, Schering-Plough, and please its stockholders. Wilson's use of what doctors call an "heroic" therapeutic strategy (higher than ordinary doses) is the strategy of a gambler.

Why didn't the FDA, who was supposedly monitoring this study step in and put a stop Wilson's gamble? The FDA could not do this because Wilson has decided not to report these liver enzyme levels to the FDA. This defiant non-compliance endangered Gelsinger's life.

8. Dangerous Circumstances: Running A Second Red Light

A second STOP sign occurred in the 18^th experiment itself. The FDA has said that Gelsinger's ammonia levels were higher than the Penn researchers and the FDA agreed would be allowed. The ammonia level is not so important in itself; rather it is a warning signal that a patient's body systems are becoming unstable. Gelsinger's underlying medical problem was that his body systems were maintaining a delicate balance--they were in equilibrium but the balance was fragile. Any sign of instability was a clear warning: STOP.

James Wilson has said publicly that he and his team felt "comfortable" going through the red light because the ammonia levels had gone down. However, the ammonia level is just a warning signal. While it is a good sign when it goes down, this does not necessarily mean that the body systems are back in balance. It is often a serious mistake to assume that, when a warning light goes out, this is an assurance that all danger is gone. It is certainly not a justification for non-compliance with a protocol which had been set up to protect the patients in a risky human experiment.

Running the second red light was not a "human error" was deliberate act. Worse yet, this non-compliance was part of a repeated pattern of non- compliance. Biotechnology bioethics seem to encourage non-compliance and lying to conceal non-compliance.

For example, when the news story of Gelsinger's death first broke, a spokesman for Biotechnology was quoted as saying, mournfully, that no such deaths had occurred in the animal experiments. Later, it turned out that when this kind of gene therapy was given to monkeys, it killed two of them. This was an even earlier red light--it might have saved Gelsinger's life. As usual, however, these animal deaths were not reported to the FDA.

9. What is the Root Cause of Gelsinger's Death?

The root cause of Gelsinger's death (and also the consistent failure of gene therapy to produce the promised benefits) can be expressed in one word: Hubris.

The hubris of Biotechnology is the combination of pride, arrogance, and ignorance that underlies the non-compliance. The most dangerous condition may be ignorance: The principals in the Gelsinger case literally did not know what they were doing.

The scientific situation in this case was one where three components of a complex system were interacting; the principals lacked genuine scientific knowledge of the components or their interactions in the system. The first component was Gelsinger's host defense systems; at the start these systems were in an unstable equilibrium that was adequate to keep him alive. The second component was a virus of the common cold which was the vector. The third component was the alien genes.

While Gelsinger's host defense systems were less stable than those of most human beings, there is a large proportion of the population who have serious problems with their host defense systems. Such people are vulnerable to foreign substances such as alien genes. There is a lot of jargon and mumbo jumbo that scientists may use to pretend that they understand the operation of human host defense systems. >From a scientific standpoint, however, no one can accurately measure the instabilities in human host systems; no one can predict what will happen when there is an external stress such as alien genes.

When doctors or scientists involve with Biotechnology give the public the false impression that they know what they are doing (when they really know very little), this is hubris that can kill people. In particular, it killed Gelsinger.

While somewhat more is known about the other two components, viruses and alien genes, no one can reliably predict their interactions with the human host defense systems. Gene therapy is therefore not medical science. In the centuries prior to genuine medical science, doctors who give treatments blindly, hoping for the best, were once called "rude empirics".

Biotechnology advocates often point out that the foods and drugs are extensively tested in animal--but this argument only shows their incredible arrogance and ignorance. Any good biologist knows that the human host defense system is unique. Interactions involving this component of the triple system cannot possibly be tested in animals (which have completely different host defense systems). Since animal tests are the basis for the safety assurances that are given for Biotechnology food and drug products, from a scientific standpoint none of these assurances have any scientific value. The aggressive Biotechnology sales strategies that force untested products on helpless customers endanger the health and safety of everyone on the planet.

10. Why We are All at Risk

All three of the components of the system involved in the death of Gelsinger, an impaired host defense system, a cold virus, and alien genes are circumstances that are quite common in human populations nowadays. What happened to Gelsinger in a human experiment could happen to other persons when there is the wrong combination of these circumstances. the refusal to honestly label Biotechnology products makes it impossible for any American to avoid exposure to alien genes has led to massive de facto human experiments in the U.S. While it may not be very likely that you will be killed by alien genes, it could happen. We are all at risk.

What, then, is the main lesson that the public should learn from this inquest?

It is this: Like any technology, Biotechnology is not inherently an evil science. Biotechnology becomes a menace to the public health and safety when it is used for evil purposes. The deadly combination of pride, arrogance, and ignorance of the Nazi doctors in World War II was what made their human experimentation evil. This same combination in Biotechnology is the root cause of Gelsingers death. Gelsinger's death should have been prevented but a deadly combination of circumstances made it inevitable.

As director of the University of Pennsylvania Institute for Human Gene Therapy, James M. Wilson was under very heavy pressures. He has admitted on camera that he ran the final red light that would have avoid Gelsinger's death. Wilson was using a very dangerous research strategy, the strategy of increasing dosage beyond the usual levels when a treatment isn't working. Doctors call this an "heroic" strategy. In ordinary English usage, it is not considered heroic to take chances with someone else's life.

Putting all the blame on James Wilson, however, is not going to prevent abuse or exploitation of the patients in human experiments in the future. As long as gene therapy research continues to be done in this kind of "pressure cooker", there will be more deaths and serious illnesses from gene therapy. Until there is genuine scientific knowledge about the interactions of therapies with the human host defense systems, gene therapy can, at best, benefit only a very small proportion of the patients.

James Wilson was one man who failed to resist the heavy pressures to go through the red lights, the pressures of his medical environment. His colleagues are working in the same pressure cooker. Biotechnology has added extremely heavy pressures--especially the pressure to make money out of research. It may not be possible to predict who will kill the next gene therapy patient; however until stoplights that work are installed, there will be many more deaths and severe illnesses that could have been prevented.

11. Who can be Held Responsible for Gelsinger's Death?

From the standpoint of prevention, this inquest finds that individual human failure is not as important a factor here as the failure of the various organizations that should have prevented Gelsinger's death.

On Nightly TV News, there were representatives of most of the major players that have created an environment for human experimentation where genuine scientific research was almost impossible. There was the elite university, the University of Pennsylvania where the Gelsinger experiment was carried out. There were at least two major federal health agencies, FDA and NIH, with direct oversight responsibility. There was a powerful Biotech drug company, Schering-Plough with numerous "inside salemen" in the two agencies. Despite the death this drug company continued to demand rules changes to protect its interests. Finally, some of the key players in the U.S. medical establishment were shown on the Nightly TV News at an NIH committee meeting considering the Gelsinger case.

All of these powerful institutions, organizations, and corporations must bear some responsibility for the death of Jesse Gelsinger. All of them, separately and combined failed to protect the life of this one young man (although almost any one of them, acting alone, could have done this job. Worse yet, this complex of organizations is failing to protect the lives of all patients in human experimentation--not only in gene therapy but in cancer research and other areas.

A key lesson for the public is: The people and organizations that are supposed to protect your health and safety are simply not doing their job.

Probably the main reason for this is that they are far more concerned with protecting their own self-interests than with protecting the public interest. The fatality in the Gelsinger case was unusual; however the underlying factors s that led to this fatality are likely to be present in any American human experiment. In sum, as long as these organizations (or their counterparts) control U.S. biomedical research, we will all remain at risk.

12. What Can We Do About It?

Righteous indignation may be a natural response to the unnecessary death of Jesse Gelsinger but it cannot prevent more unnecessary deaths in the future. How can this be done?

There is another very old lesson that the public needs to relearn: The gods help those who help themselves.

The complex of organizations that is responsible for the Gelsinger death tried to protect their own images but did nothing to prevent another such death. The public cannot rely on elite universities, federal agencies, or the U.S. medical establishment to protect the patients in human experiments. However, you can protect yourself. Simply refuse to be lured into any human experiment; advise relatives and friends to avoid gene therapy and other experimental treatments run under the FDA, NIH, or the National Cancer Institute. It is almost certain that they will do more harm than good.

There is also a very new lesson that the public needs to learn: Thanks to modern technology and internet in particular, there will be better ways for the public to protect itself in the 21^st century.

The opening shots in the battle for a global democracy were fired in the Battle of Seattle. A precipitating factor in the Battle of Seattle which, in effect, shut down the WTO and gave the Clinton Administration a "black eye" was the use of WTO to promote the genetically modified (GM) food products.

GM foods, as this name implies, are contaminated with alien genes. As this inquest has shown, alien genes can cause human illness and deaths in certain circumstances. When President Bill Clinton repeated the false assurances of the safety of GM foods in Seattle; he got these from federal agencies such as FDA. The inside salemen in these agencies. in turn, got them from the public relations department of the Biotech multinational, Monsanto. U.S. trade agencies (under heavy pressure from Biotechnology companies transmitted) this pressure to WTO. WTO then imposed a billion dollar penalty against European Union (EU) food products in an attempt to compel the EU to import GM foods (mainly Monsanto hormonal meat and milk products). These foods had been barred because EU scientific committees had warned Monsanto's products might cause breast and prostate cancer.

This outrageous behavior of Biotech companies, trying to force the EU to endanger the health and safety of its citizens, was one of the sparks that ignited the Battle for Seattle.

In the Gelsinger case as well as for GM foods Biotechnology has played the role of a "predator" that regarded ordinary people around the globe as helpless "prey". A key lesson of the Battle of Seattle is the "prey" can sometimes take advantage of modern technologies, such as the Internet, to protect themselves against global "predators". The "prey" has put the "predators", Biotechnology and the WTO, on the defensive for a while. Can what happened to GM foods also happen to gene therapy? Stay tuned.