Asking for participation where trust in research has eroded
Trust in research may have been eroded by bad research in the past, and misinformation has eroded trust in science and medicine. Asking for participation where trust has eroded means facing two problems: trust in science and medicine, and how to encourage participation without crossing from informed consent into overreaching or coercion. The death of a volunteer in a gene therapy trial, who should never have been enrolled and whose investigator and institution had financial conflicts of interest, shows how far one case can set back a field, and who kept encouraging its research afterwards.
Two problems in asking for participation
Encouraging participation ethically where bad research may have eroded trust in research, without crossing the line between informed consent and overreaching or coercion, raises two separate problems.
Trust in science and medicine
The first problem is trust in science and medicine. A great deal of unfiltered, unadjudicated and un-peer-reviewed information is available, and people believe what they want to believe. Over a decade that took in the COVID-19 pandemic, institutions were eroded radically, perhaps nowhere more than in the United States, where people took hydroxychloroquine, drank bleach and took other things that were in no way going to be safe and effective against COVID-19. Scientists who make a statement based on empirical data are immediately shouted down as tools of the state or as paid off by the pharmaceutical industry. How to reverse this is not known. Society has no known way to impose effective filters on misinformation while the platforms that carry it are unwilling to, short of a draconian governmental imposition on free speech and expression. So a great deal of misinformation stays available, and it will harm people, because they follow their own wishful thinking. Faith, confidence and trust in science are something civilisation will have to confront, with no known way to reverse the alarming trend.
Encouraging participation without coercion
The second problem, encouraging participation without coercing it, is best met by fair balance. An application to a regulatory authority shows what fair balance means: the sponsor is obliged to present both the data that support its hypothesis and the data that conflict with it. Information presented that fairly, without suppression, lets the individual make a more unbiased choice. They can weigh the pluses and the minuses and decide what is best in their own situation, understanding that the outcome is not predictable and the risks and benefits are not known, because it is research.
The Gelsinger gene therapy case
Jesse Gelsinger, a young man with the inborn error of metabolism ornithine transcarbamylase deficiency, volunteered for a gene therapy procedure although more than fifty pills a day controlled his condition. Ornithine transcarbamylase deficiency is an X-linked genetic disease of the liver, characterised by an inability to metabolise ammonia. In the experiment, a corrective gene sequence, a normal gene carried in an adenovirus vector, was injected into his liver.
Gelsinger died four days after the injection, presumably from a massive immune response to the vector, and was the first person to die while enrolled in a genetic trial. On 29 September 1999 a Washington Post headline reported that a teenager had died undergoing experimental gene therapy. A firestorm of questions about ethics, improprieties and informed consent followed and ended in sanctions and apologies, and a shadow was cast that threatened the progress of gene therapy.
Investigation made clear that Gelsinger fell outside the study's inclusion parameters and should never have been enrolled. The institution and the principal investigator had financial conflicts of interest around the corrective gene, which may have impaired their judgment. The principal investigator had a financial conflict of interest in the development of the vector: had it worked, he could have made a lot of money by using it to treat people or by selling it to other researchers, and the conflict may have influenced the treatment decisions he made as he continued his experiments.
Many gene therapy trials before Gelsinger's had been acclaimed. His case was a severe setback for scientists working in genetics. After his death, parents who had hope for gene therapy kept encouraging research, raising money and forming support groups.