This year I spent a whole week down in DC soaking in the latest and greatest in neuroscience. My week started at the Dynamical Neurosciences pre-meeting, where a who’s who of deep brain stimulation experts presented their latest findings. This was everything a conference should be: an inspiring, supportive, contentious, zeitgeist-summarizing orgy of scientific progress. There were videos of dystonic children suddenly disentangling their limbs and walking as if born to run, of depressives suddenly feeling joy, of minimally conscious subjects suddenly becoming more conscious, all because of electrical stimulation from a well-placed electrode deep in the brain. It was palpable in that room: stuff was getting done.
And yet, at the same time, there were the arguments that have long made scientific meetings great: Joe Fins, the medical ethicist from my research group at Weill Cornell, got into it with Ben Greenberg of Brown University, the OCD DBS expert, about whether his use of a humanitarian device exemption was legit, or was simply bad science. The HDE is a way for researchers who study very small populations to get around the rigors of the FDA approval process since it is difficult to get approved without a big trial, and a big trial is impossible without a big population.
The HDE, Fins argued (and has argued in print), relieves those involved of the responsibility of conducting a trial that would allow for scientific discovery of negative outcomes and mechanisms of action, so that they might statistically demonstrate efficacy and iteratively improve the approach. Further, it rests on a fundamental misconception: that the safety standards previously met by the same device (in this case, a Medtronic DBS electrode) can be transferred to the new population without fear of introducing new side effects. Fins argued that this is ridiculous: stimulating different parts of the brain obviously changes the potential for serious side effects. Perhaps most troubling, participation in the HDE trial for patients was neither enrollment in an official clinical trial nor a clear clinical therapy, but rather represented a practical and existential grey zone. They might get better because of the research protocol, but it was not a clinical promise. And the research protocol was underpowered to prove the effect was real to the larger scientific community. They were neither true research subjects nor patients. And, of course, underlying all of this is financial motivation: corporations like Medtronic, when granted an HDE, suddenly find themselves with a much cheaper avenue to device approval for a new indication.
Fins, in his talk, called the approach an “ethical cul-de-sac” (snap!). Ben Greenberg just shook his head. Throughout the two days, they argued this point semi-publicly from their seats in the front of the room. They did not use their inside voices.
What made this argument all the more compelling was that Greenberg’s work was some of the more incredible work we saw. Greenberg showed one patient who had a form of OCD that made her believe everything that came into her home was covered in blood. When people came over to her house, they carefully wrapped everything that crossed the threshold. She did not sit on other people’s furniture. She was, for all intents and purposes, incapable of living in public. What’s more, she understood her OCD was ridiculous, and her inability to get over it clearly depressed her. After DBS implantation, as we saw via video, she was happy, and her symptoms were gone. She could look back and wonder, “what was I thinking?” Suddenly statistical power seemed ready to yield to the emotional power of The Cure.
These conflicts–between progress and propriety, the right way versus the expeditious way–are everywhere in science. There is more to “doing it right” than forsaking the forgery and fakery we see in the newspaper. Never have I seen that murky ethical swampland more clearly than at the DBS meeting, and I was forced to ask myself: “if I were Greenberg, what would I do?” I find the question impossible to answer. It was, in sum, an awesome meeting.