It was late 1972, and Michael Wigler, then a 25-year-old medical student at Columbia University, was feeling downcast. Wigler had begun his medical training two years earlier after graduating from Princeton University with a degree in mathematics, renouncing what he thought would be the socially withdrawn life of a mathematician for a career that was more "socially useful."But medicine, too, was giving him little satisfaction.Wigler lives by a handful of axioms: an apple falls when you drop it; every human is equally "weird;" and nearly every human opinion is flat-out wrong.But doctors make life-or-death decisions based on other people's research, which is often ambivalent or inconclusive."There's a small set of things that I have good evidence to believe are true, and I base everything on them. You can't do that and be a doctor," he says. "I just couldn't live like that."Wigler dropped out of medical school in 1973 and turned his analytical mind to biological research. As a graduate student in microbiology, he crafted a method for transferring genes into animal cells using a simple virus. By 1981, he was running his own lab at Cold Spring Harbor Laboratory in New York, where he used the technique to isolate the first human cancer genes.Over the following decade, his lab created a powerful genetic screening technology to study tumor genomes — making him a big fish in a crowded pond.That didn't suit him. In a packed field, "You can't tell your ideas from other people's ideas," he says. "Since what basically interests me is the ideas, I'd much rather work sort of in isolation."Partly because of that, a few years ago he turned to autism, at the time a relatively little-studied condition. Wigler suspected that, like cancer, autism stems from tiny, spontaneous changes in the genome.In April 2007, Wigler rocked the autism field when he discovered that large deletions or duplications in DNA, dubbed copy number variations (CNVs), are much more common in people with autism than in the general population.Seeking a logical explanation for autism's complexity, he brought together his genetic findings with what's known about the condition's epidemiology to propose a 'unified theory of autism' — a simple genetic model that accounts for some of the seemingly inexplicable features of the condition, including why it's more common in boys than in girls."Michael's brain is different than most others': he tends to make connections between observations and facts that other people don't make," says Richard Axel, professor of biochemistry at Columbia, who worked closely with Wigler on the gene transfer technique. "As a consequence, [Wigler] is full of outlandish ideas, many of which are wrong. But those that are right are often extremely creative."Read more at...SFARI, September 2009.