If you find yourself living on a frontier where very different views of life contend, it’s hard to avoid consistent confusion. Professor Sawyier’s illness brought her to just such a frontier. Malignant pleural mesothelioma introduced her to therapeutic nihilists, who seemed not to realize that patients can become research subjects, and to experimental enthusiasts, who seemed not to realize that research subjects needn’t stop being patients. It was left up to Professor Sawyer to sort out the difference between being a patient and being a research subject and to intuit what it means to be both at once. No one seems to have tried to explain the frontier to her. Perhaps no one could.

The Magic 50%
Professor Sawyier says her tale gets morally interesting about half way through, but that’s too modest; it’s morally interesting right from the start. Consider the surgeons who diagnosed her disease. Their ignorance (or, just possibly, inability to communicate) is remarkable. They failed to convey to their patient that her own grim sort of cancer was the target of a research group in their very own institution. When, by way of a New York City detour, Professor Sawyier did find her way to that meso-clinic back in Chicago, she was eagerly welcomed into the trial. Yet, all she recalls of her preliminary discussions with the re-searchers is that she chose (with understandable enthusiasm) MTA, an agent advertised as having few of chemotherapy’s characteristically nasty side effects. Nothing about what would make her use of MTA part of an experiment rather than part of a therapeutic regimen seems to have stuck in her memory. Perhaps nothing was said. About the signing of the form attesting to her fully informed and voluntary consent to become a research subject, she relates only that it was an annoyingly empty ritual. The hollowness of the procedure didn’t keep her from signing, of course-consider, as she says, her alternative. What was the chance that she would say anything other than an enthusiastic yes?

The signing of that subsequently fugitive form seems thickly insulated from anything else in her story. For example, neither the discussion of various chemotherapeutic possibilities that took place before the signature ceremony, nor the weekly ‘test’ that had to be ‘passed’ afterwards, seems to have had anything to do with what Professor Sawyier took herself to be about as she inked the consent form. When she finds that she has ’failed’ the test - that despite the shrinkage of her tumor and the remission of her symptoms, she is no longer to have access to the life-saving drug she is astonished. It is only then that she asks what could possibly generate such a protocol, concluding that the re-quirement that at least half of the tumor have vanished must be to show that the drug saves as many as it kills.

This conclusion seems to me both unlikely and enlightening. A 50% shrinkage rate as a cut-off for continued inclusion in the trial seems to have no interesting relationship to a 50% mortality rate attributable to the drug. My suspicion is that the cut-off was motivated by the desire to demonstrate a result robust enough statistically so that Lilly could claim that, for at least a subgroup of those who took MTA, tumor degradation could be decisively attributable to the drug and nothing else. Professor Sawyier’s interpretation makes it plain, though, that she had not yet thought about the possibility of her exclusion from the trial on any grounds other than her own health. (Was that perhaps what she took the weekly tests to be determin-ing?) When she did come to realize just where she was - smack in the middle of a research protocol - her effort to make sense of things assumes that the side-effect-less drug she had been taking was a very dangerous, potentially lethal agent.

The Therapeutic Misconception
What’s enlightening about her response, I think, is that it shows the depth of the “therapeutic misconception.” What goes awry is that the ill subject does not grasp that what she has volunteered for really is research; it can be enormously hard to shake the erroneous belief that the intervention is designed to make the volunteer better, rather than contribute to anything as faceless as the medical welfare of future patients. Professor Sawyier’s reaction to being dropped from the trial shows how tenacious the misconception can be even for the most intelligent, well-educated, intellectually and socially confident people in our society, as well as how relatively deranging it can be when that misconception is shown to be what it is, a misconception.

At the time of her writing, Professor Sawyier was once again receiving MTA; she looked forward to doing so as long as it continues to help her. I hope that is a very long time indeed. She remains confused about why the protocol was structured as it was -- where was the magic in that 50% figure -- and about the fairness of a system that demands extraordinary amounts of personal status and social power to secure what’s needed to continue a life that remains richly rewarding, both to her and to those with whom she shares it. It is indeed hard to understand why no one has explained to her the scientific justification for the 50% figure; you would think that the research physicians, to say nothing of Lilly itself, would have been anxious to offer that justification, if only to keep her good will.

Professor Sawyier’s question about the influence of power and status on access to the things that may keep us alive is tougher - no one seems to have a definitive answer - but the research-therapy boundary is not the only morally puzzling frontier on which we sometime find ourselves.

Some Related Questions
The question that I find myself left with here is whether there is any practical way to forestall the therapeutic misconception? How can we reliably get decent informed consent - decent enough to make research on very ill human beings morally defensible? It seems clear to me that whatever effort was made to help Professor Sawyier see just what she was getting into failed miserably, and such a failure, with such a person, does not auger well for research with seriously ill people in general. I also find myself wondering, not whether it is fair that only the rich and powerful can gain access to such scarce and precious goods, but whether it is fair that even the rich and powerful can. What’s the character of the contract between society, science, and the sick here?

We have a practice of withholding even promising pharmceuticals from general availability until they’ve passed some pretty tough tests. In consequence, the stand- dard formulary consists of agentswhose benefits, and whose risks, are fairly well understood -- an enormous benefit to us all. Yet the consequence is also that some potentially very useful drugs are available only in research protocols and, within those protocols, only to those who satisfy research-driven criteria. Those who cannot gain access to the protocols, or who get randomized into ‘control groups,’ don’t get the chance to benefit (or to run the risk of being harmed) by the intervention in question. Is gaining reliability at the cost of access thus constricted unfair?

Time to Muddy the Waters?
Of course, Professor Sawyier’s chance of benefit from MTA was hardly hypothetical. Perhaps what her case shows is that we need to consider a modification of that contract between society, science, and the sick. We now end trials prematurely if an experimental intervention causes a subject to die. We also end the trials if the subjects receiving the active intervention are clearly responding much better than are the subjects in the control group. Why, then, should we not, as a matter of course, change the protocol if an experimental intervention seems to be saving a particular subject’s life? Such subjects could well be removed from the trial if the interaction of drug and disease does not meet protocol targets, but continue to receive the treatment as long as they seem to benefit.

If the therapeutic misconception was a problem before, would not adopting this sort of proposal make the problem worse? On the contrary, fusing research and therapy may be just what’s needed. If we recognize that protection from risks is not the only goal of ethical medical research, that there is nothing unethical or otherwise improper about research benefitting specific research subjects, the best response to the therapeutic ‘misconception’ may not be trying to get people to understand that they are not to benefit from their involvement. The best response might be to acknowledge, from the start, that it is possible that some subjects might benefit from their involvement -- and even to shift procedures so that it is more likely that they will. Sometimes, the best way to live on a frontier is to make it a little more like home.