The People and Serendipity of the EyesOnALZ project

The People and Serendipity of the EyesOnALZ project Pietro Michelucci Timing is everything. It was during the pre-Web, Internet period of the late 80s that I was using so-called “connectionist models” (now known as “artificial neural networks”) to see how well they could explain human behavior. At the time, I was struck by the parallel between neurons in the brain and people connected to the Internet. To me, they both seemed like examples of computational nodes joined by a network, with the potential to produce a collective output greater than the sum of its parts. I could only wonder about the potential capabilities of systems that somehow combined the thinking of thousands or millions of networked humans. At that time, my academic mentor espoused a contrarian view about knowledge representation in the brain: that two very different kinds of information processing are necessary to account for human behavior. I eventually realized that one of these types—symbolic reasoning—seemed better suited to machines than humans. This suggested the value of creating partnerships between humans and machines. I might have predicted those formative experiences would lead to a life-long pursuit of human computation—an emerging field that leverages the complementary abilities of networked humans and machines to solve real-world problems. There is no way I would have guessed the first such problem I tackled using human computation would be Alzheimer’s disease, which turned out to be [End Page 29] coincidentally appropriate, as it employs human minds en masse to save human minds en masse. Janis Dickinson, a professor of natural resources, happened to meet Chris Schaffer at a Cornell University faculty dinner. Schaffer, a professor of biomedical engineering, described his Alzheimer’s disease research to Janis who, realizing there might be an opportunity to apply human computation, made an introduction. The mere prospect of addressing a disease like Alzheimer’s, which has no effective treatment or cure, compelled me to follow up immediately. What happened next can only be described as an alignment of the stars. I met with Chris at his Cornell office. He offered me a laboratory-grade espresso and then we sat down as he began to describe his research. They were studying Alzheimer’s by inserting the human gene for the disease into mice and then comparing outcomes to the “wild type” mice without the disease. He went on to describe a new imaging technique they had invented that allows them to see blood flow in the brains of these mice. This enabled a key finding—that the Alzheimer’s mice exhibited a relatively high rate of stalled brain capillaries, meaning that many of the tiny vessels were plugged and had no blood flowing through them. Chris and his colleagues conducted a follow-up study showing that, due to downstream effects, these capillary stalls were responsible for an overall reduction of 30% of blood flow in the mouse brains, which is the same reduction observed in humans with the disease. Chris explained that although we’ve long known that human Alzheimer’s patients have reduced brain blood flow, we’ve never understood why. The new imagining technique created the opportunity to investigate this phenomenon in Alzheimer’s mice exhibiting the reduced blood flow. This enabled a serendipitous discovery. Victorine “Torie” Muse joined the Shaffer-Nishimura Lab as an undergraduate research assistant. In one of her first assignments, she was instructed to use an antibody as a marker to help identify stalled blood vessels in the mice being studied. At first, Torie was discouraged when she didn’t find any stalled vessels, thinking that perhaps she had made a methodological error. Despite feeling embarrassed, Torie brought her negative findings to Chris, who realized the antibody intended to help visualize the stalled vessels was actually interfering with the stalling mechanism, suggesting an immunological aspect to the reduced blood flow. Thus, Torie’s accidental finding led to the first understanding ever of the mechanisms underlying reduced brain blood flow in Alzheimer’s disease. Based on this key finding, additional mouse studies showed that unclogging these capillaries restored brain blood flow to normal levels and reversed cognitive symptoms such as memory loss. The problem was...