Riding Life's Twists and Turns

When Michael Heller was 11 years old, his mother bought him a copy of life magazine. The picture on the cover shaped the course of his career. It showed the elegant DNA double helix that James Watson and Francis Crick had discovered two years earlier. "I remember telling my mom, 'When I get older, I'd like to work on that kind of thing,' " Heller says.

He did that—and much more. Combining his interests in biochemistry and electronics, Heller got in on the ground floor of the biotechnology revolution and helped establish the technology behind DNA microarrays. These dime-sized devices are used to quickly analyze hundreds of DNA samples at a time, to detect genetic diseases and mutations.

Microarrays are typically made by placing tiny spots of DNA tagged with a fluorescing molecule onto a glass plate. When a biological sample is washed over the microarray, messenger molecules that carry instructions from different genes in the sample bind with corresponding DNA spots, causing the spots to fluoresce. By using an optoelectronic scanner to see which spots are glowing, a researcher can tell which genes are active in the sample.

But Heller pushed the technology further. Using silicon for his substrate instead of ordinary glass, he developed a version that lets researchers move DNA molecules around electronically (most biological molecules carry a slight positive or negative electric charge). Concentrating molecules in different microarray locations in this way increases the speed and improves the efficiency of the analyses, allowing different types of genetic tests to be integrated on the same chip. To commercialize his work, Heller cofounded Nanogen Inc., in San Diego, now one of the top makers of DNA microarrays in the world.

Nearly five decades after that pivotal Life cover, Heller is a professor in the electrical and computer engineering and the bioengineering departments at the University of California, San Diego. His 30-year career has been as full of twists and turns as the DNA molecule, but his innovator's spirit is still apparent, as is his modesty. "I'm 60 years old and still excited every day when I go in, hoping I'll come up with something," he says. "I'm really lucky to have seen science and technology from so many perspectives....Other people out there are much smarter than I am."

Although Heller'S Parents were factory workers, they encouraged his interest in science. He had a microscope and a homemade telescope when he was very young. "I was nerdy about those things," he recalls. He received a Bachelor's degree in biology from the University of Connecticut. In graduate school at Colorado State University in Fort Collins, Heller used nuclear magnetic resonance to study nucleic acid structure, which was "pretty forward-looking stuff at the time." He then did postdoctoral research in synthetic chemistry at Northwestern University, in Evanston, Ill.

In 1976, after finishing his postdoc, he began working for a branch of Standard Oil Co., in Naperville, Ill., which was starting to diversify into biotechnology. Heller led the company's new DNA Technology Group, working on the chemistry of DNA assay, or testing, systems. About this time, artificial DNA and genetic cloning had sparked a flurry of activity in the fields of molecular biology and genetics. Researchers needed faster and easier ways to manipulate DNA molecules, and automation was the answer. This led to a swarm of start-up companies doing research on automatic DNA synthesizers and analyzers.

Riding the biotech wave, Heller went to San Diego in 1984 to work at a start-up called Molecular Biosystems Inc. There he got involved in developing optoelectronic tools for detecting mutated genes. Soon after, he left MBI and cofounded a company called Integrated DNA Technologies Inc., in Skokie, Ill., to develop similar diagnostic methods.

By The Late 1980s, people were thinking of ways to integrate an entire DNA diagnostics lab into a single device. Heller's diverse research interests drew him to this area, and in 1991, working on his own and using his retirement money, he started experimenting with the idea of an electronic DNA microarray. "My wife said I could do this on two conditions," he recalls. "She said, 'You've got two years to put something together...and if this doesn't work, I don't want to hear you complain, plus you have to work until you die.'" Fortunately, Heller's idea did work, and in 1993 he cofounded Nanogen.

Heller joined the UC-San Diego faculty in 2001, but he still consults for Nanogen and remains active in the company's new nanotechnology efforts. His current research goal, he says, is to use the electronic arrays to move nanoscale particles around and assemble them into tiny electronic circuits or biosensing devices. In the future, attaching DNA molecules to these nanoparticle components could allow devices to assemble themselves, similar to the way in which the DNA helix replicates itself.

Like his research interests, Heller's hobbies are varied. He enjoys golfing and skiing, and he visits Alaska periodically to go fishing. Lately, he says, he has been enjoying oil painting and has converted his home office into a small studio. "When I come home now, instead of watching TV, I put a little paint on the canvas," he says. But his love for the outdoors reflects his adventurous philosophy toward his research. "Sometimes," he says, "I like to wander in the desert and see what's over the next hill."