BIOETHICS - by Anna KrohnNews Weekly
Are commercial interests blinding gene researchers?
, December 18, 1999
In early December a team of medical scientists at the University of Pennsylvania released their findings into the death of an 18-year old clinical trial volunteer Jesse Gelsinger. The University's Institute for Human Gene Therapy had conducted a new type of trial in which a modified and 'disarmed' virus (an adenovirus, commonly associated with infections like the common cold) was used to transport genes. It was hoped the procedure would correct a congenital disorder, into the liver of the young patient.
Gelsinger, who died in September this year, had been introduced to the gene therapy treatment in 1997 and had been receiving progressively larger doses of the corrective gene preparation. It was found that 'the injection of the vector triggered the sequence of events that led to Mr Gelsinger's death'.1
The young man's immune-system reacted violently to the gene therapy, causing the massive coagulation of his blood, damage to the liver and finally to oxygen deprivation caused by severe lung dysfunction and fatal coma. The researchers also found, but could not explain that the patient appeared to have been affected by a malfunction of those bone marrow cells which are responsible for the production of red blood cells.
Gelsinger was the 18th participant in the Pennsylvania University trials, suffered from a mild form of a sometimes life threatening genetic disease called ornithine transcarbamylase (OTC) which causes a malfunction of the liver. Prior to the trial Gelsinger appears to have led a fairly healthy life, his disease being adequately controlled by conventional drugs and by a special diet.
In theory, gene therapy and the appropriately conducted trials using gene therapy, hold out the prospect of genuine therapeutic progress for a range of debilitating and potentially fatal illnesses. It is also true that any form of medical treatment carries a degree of risk and the unpredictable and tragic result can and does occur.
However there are some very troubling questions about certain aspects of this trial which are still to be answered.
The first is that although Gelsinger was a 'volunteer', it appears that this research project recruited its subjects using a direct appeal to people via a patient advocacy Web page; a method, some US health officials feared might be wrongly interpreted or subtlely coercive.
The researchers had assured the NIH that they would obtain subjects via the mediation of physicians, this was not done.
Secondly, there is a question of misrepresentation of the risks of the trial. The internet publicity suggested that 'low doses' were to be used, but in fact the project involved escalating doses of adenoviruses to relatively high levels. More serious was the fact that the original consent form passed by the US National Institute for Health included the fact that monkeys in earlier trials has died on related treatment, but the patient's version omitted that information.
Thirdly, although traditional research ethics, permit patients in dire situations for whom no conventional cure is known, to consent to trials which carry a certain degree of uncertainty and risk, since the intention is that such research may chance upon a cure, and will not worsen his or her situation,
Jesse Gelsinger was not dying or seriously ill. Berlin researchers who had conducted adenovirus research and who had noted the acute toxic reactions in rabbits, concluded that adenoviruses should be used 'only in dire circumstances'.
Overarching these concerns has been the enormous commercial stakes in the race to achieve the first successful liver related gene delivery.
The team head in this case had financial interests in his own private company. Another company, Biogen Inc. had invested $37 million in the researchers company to have rights in the marketing of this type of therapy.
The research team head, convinced the National Institute of Health's regulatory body to allow the trials. He argued that their list of reservations were groundless and that 'you should let people be heroes if they want to be'.2
Many researchers urged on by corporate pressures and competitive career prospects are pushing for a loosening of the provisions of the Helsinki Declaration on Human Research.
It seems that this tragic research result might force the scientific establishment and government regulators to appreciate that Declaration's protective and moral force.
1 Press Release. Institute for Human Gene Therapy, Pennsylvania University Homepage http:www.med.upenn.edu/~ihgt. December 2nd, 1999.
2 The Washington Post. November 21, 1999. p. AO1.