Untamed Genius

Kary Mullis

Tech graduate Kary Mullis is inventor of one of biotechnology's most important--and hottest--new techniques

By John Morkes
Photography by Tim Davis

Kary Mullis is an untamed genius, a free spirit with a hyperactive mind and a curiosity that quickly leads him to distraction.

Despite these attributes, or perhaps because of them, Mullis--a 1964 chemistry graduate of Georgia Tech--invented one of today's hottest techniques in biotechnology: the polymerase chain reaction (PCR). In recognition of this achievement, Mullis was named R&D Magazine's 1991 Scientist of the Year.

From a single sequence of DNA, PCR can reproduce the sequence in huge quantities much more cheaply and faster than other techniques. The process works exponentially, yielding a two-fold amplification of genetic material for each cycle of use. Producing 100 billion similar molecules in one afternoon is no problem with PCR, which has no size limitations. "It can make DNA in vats if you want," Mullis says.

PCR can be used to find toxic genes in bacteria and to help police track murderers and rapists. The technique also plays a role in genetic research and is helping scientists study viruses and cancer.

The idea for PCR came to Mullis in 1983 while he was driving his Honda Civic on a moonlit mountain road in Northern California. "I do my best thinking while driving," he says. "Driving puts me where I can't be distracted--I can't get up and do something else, which is my tendency if I'm stationary for very long."

That night Mullis knew he was onto something significant. "It was difficult for me to sleep with deoxyribonuclear bombs exploding in my brain," he later wrote.

Mullis developed the process while working for Cetus Corp., Emeryville, Calif. Cetus fended off a legal challenge by DuPont Co., which claimed PCR had been described almost 20 years ago in papers by MIT Professor H.G. Khorana.

"When I searched the literature to see if there was anything remotely resembling PCR, I found nothing," Mullis said. "The U.S. Patent Office did a search too, and they didn't find anything. I knew that if somebody had invented it, I would have heard about it. The technique is not the kind of thing anybody would hide because it's so eminently useful."

Today Mullis works as a consultant, free to jump from project to project, which is the way he thinks, quickly jumping from one idea to the next. Ideas come so fast that they often collide, forcing Mullis to interrupt himself when he is speaking.

And he constantly fidgets. "I really don't like the idea of Monday through Friday being work week," he says, bending an arm behind his back. "I like to come and go."

The 46-year-old scientist has married and divorced three times, which has been good for science, because he feels more creative when he's romantically involved. "The juices that flow when I'm in a romantic relationship sometimes really cause things to go on in my life," he says. He has three children, not counting those he fathered as a donor to an artificial insemination program.

"Kary is eccentric, very excitable, and exciting to work with," says Fred Faloona, Mullis's friend and technician when PCR was being developed. "He has a real knack for solving complex problems.

"He's a very young person at heart. He relates to everyone very well. They think he's nuts in some ways, but they really love his energy and openness."

When Mullis is not working in his car, he works in clients' labs, or in his La Jolla, Calif., apartment, which overlooks the ocean. The entrance is guarded by a jungle of potted plants and toy dinosaurs.

He has planned for a while to set up a lab on his 30 acres of land in Mendocino County, where he's building a house. But there's just too much other work, too many ideas racing through his head.

"It's been a project forever," he says of the property he bought in 1975. So far he's managed to build some ponds and stock them with fish. He also installed his own windmill invention, that drags a piece of metal across a pipe, making an unpleasant noise that keeps gophers and moles from digging in the ground.

But Mullis always had an itch for science, even as a young boy growing up with three brothers in Columbia, S.C. At an early age he started playing with electricity. "I shut down power in the house quite often," he says.

Says his mother, Bernice Frederick, "He was a very active little boy. He was mixing things all the time. When he was 3, he beat up eggs into a paint and painted the house yellow. Frequently I found jars of bugs and worms that he had collected. I thought he was wild. He was into everything. I realize now that his brain was overactive."

His first serious invention was a fuel for toy rockets developed when he was 17. It was made by heating potassium nitrate and sugar. "We had some mishaps, but no one got hurt," Mullis says. "One time about a pound of fuel went off at once. It made a huge flame, scared the hell out of my mother, and filled the neighborhood with smoke. Fortunately, it smelled sweet."

Mullis used his fuel and a four-foot rocket to send a frog a mile and a half into space. Incidentally, the frog was recovered alive.

In high school, Mullis was vice president of the student council, a National Merit Scholar, president of the Forensic Club, a member of the German Club, and a writer of published poetry and essays. But he always knew his career would be in science. "I never really thought of any other possibilities," he says.

After earning his Tech degree, Mullis received a doctorate in biochemistry from the University of California, Berkeley, where he studied from 1966 to 1972.

In 1968, Nature published one of Mullis's papers, "The Cosmological Significance of Time Reversal," in which he suggested that exactly half the universe is hidden inside black holes that consist of antimatter running backward in time.

After spending several years doing post-doctorate work, Mullis joined Cetus, where he developed PCR. From 1986 to 1988 he was director of molecular biology at Xytronyx Inc. in San Diego, where he developed an ultraviolet sensitive plastic that changes color in response to sunlight. He started working as a consultant in 1987.

His continued success as a consultant seems guaranteed, as new uses for PCR multiply.

For one company, Specialty Laboratories, Santa Monica, Calif., he's developing a method to rapidly remove DNA from blood in order to screen the blood for various viruses.

PCR is an excellent way to find out which viruses are present in organs destined for transplant, Mullis says, though researchers are still trying to find out at which levels the viruses are dangerous. Inoculation may help transplant patients avoid problems in the future.

In addition, the technique could help in the development of DNA for use as a drug, Mullis says. "You could try to wipe out specific organisms by targeting their genes, by inhibiting biological processes by hitting them with DNA."

The method is also a quick way to find out if a fetus has sickle-cell anemia, and could be used to diagnose other genetic diseases.

PCR is ideally suited to detect cancer, Mullis says. "We're gathering the data now on cancer, which could help us look for early warnings in the future. Researchers are working so one day we can isolate cells and say, 'These are the earliest forms of this type of cancer. This is a definite indication that you need therapy.' We need to find the mechanism to look six months into the future."

One issue this work raises, Mullis points out, is how much people want to know about their own futures. "If we can tell you all kinds of diseases that you're going to be susceptible to and can draw that out in more and more agonizing detail, and we can say what strengths and weaknesses you're going to have, down to whether or not you'll be a chronic liar, do you want to have that written on your birth certificate?

"Right now I wouldn't wane to know all that about myself because in my culture and upbringing, it's been assumed that I wouldn't know it. Perhaps 500 years from now, it may not seem as scary to us."

Mullis is starting a company that will use PCR to make DNA from famous people to sell as relics. "If we could get a sample of Elvis Presley's hair, we could make his DNA," Mullis says. "I know that would sell. Of course, we'd have to get permission, and we're going to try to do it in a respectful kind of way."

He's also developing a new technique "that could dwarf PCR in terms of applications," he says. It's an analytical system involving scanning probe microscopy that will identify the concentration of hundreds of compounds in a blood sample.

"I want to make a dedicated instrument for $2,000 for that purpose," Mullis says. "Then I can say, 'Company A, do you want it or do you want to die? Company B? Who wants it? Whoever gets it wins all of clinical chemistry."'

Mullis has many projects under way but has a hard time finishing them. Once he starts a project, he's often tempted to stop and do something else. "I'm not attached to the act of doing things," he says. "In fact I much prefer to not do anything. It's a lot more fun to lay out on my pond and watch my fish and drink sangria. I don't like to do things that are hard. That's the important part of being an inventor--trying to figure out an easy way to do something."

Mullis has broad interests. He enjoys writing and has published some fiction. "I really would like to write more," he says. "I've got a lot of stories in my head."

Photography is another hobby. Sometimes he generates fractal patterns on his computer and projects them as slides onto friends posing for the camera.

Mullis also plays the keyboards "Recently I started exploring the potential of playing my Casio keyboards with the frogs," he says.

"Those keyboards make froglike noises. Sometimes I get the feeling that, by God, these frogs are gradually accepting the fact that I can honk like them, and they respond in some way. I don't think I fool many into thinking I'm one of them, but I'm getting to know them more."

Now Mullis is looking for "time and space" to put down on paper a lot of the ideas that have been colliding in his head.

"I really want to take a slower pace and transfer my life up to Mendocino," he says. "Eventually that place will overlap with my life completely. Then I'll escape from the world and maybe I'll write."

If only there weren't so many distractions.