CAUTION: REPLICATING THE LIFESTYLE OF DNA GURU KARY MULLIS MAY BE HAZARDOUS

Kary Mullis rubs his stubby fingers together and stares ahead with a
shaman's wide eyes as he ponders the awesome power of his big invention,
the one that got him the Nobel Prize.

"I mean, sequencing DNA now is one of the easiest jobs you could have
besides sloppin' burgers," Mullis says in a South Carolina drawl barely
softened by 20-odd years in California.

Once a precious commodity, microscopic DNA samples can be made as plentiful
as ground beef thanks to polymerase chain reaction, or PCR, a chemical
process Mullis dreamed up in the early 1980s for concocting practically
limitless copies of genetic material.

Mullis, 53, has a claim to fame that most chemists would die for -and a
reputation as a free-living hippie that makes many of them gnash their
mortars and pestles in disgust.

He swears by astrology. He surfs. A recovering ladies' man and three times
divorced, he once showed homemade slides of nude women at a scientific
conference. He talks freely about the pharmacy full of mind-altering drugs
he has sampled.

Imagine Austin Powers as a biochemist instead of a spy.

In town recently to promote his new book, "Dancing Naked in the Mind Field"
(Pantheon), Mullis showed that he may have toned down his act a bit, but
the irreverence that fuels his creativity and his rogue behavior survives.

"Most scientists are just clogging up the works," Mullis said while dining
alongside his latest wife, Nancy, at a Near North Side restaurant. "True
innovation has little to do with having scientists in the world."

One might expect that Mullis' genius could be teased apart from his
stranger thoughts and deeds, that the much-abused body hides a pristine
mind somewhere down deep. Alas, no. In the tie-dyed tapestry of his life's
work, each flawed, funky thread is inseparable from the rest.

Take AIDS, for example. Mullis may have indirectly saved thousands of lives
through a PCR-based test for HIV levels that is more accurate than anything
before it. The same PCR advances have allowed researchers to study the AIDS
virus and its constant mutations in unprecedented detail.

Problem is, Mullis doesn't believe HIV causes AIDS.

"No research has ever been performed that proved it, or made it probable to
an informed skeptic that it's true," Mullis says.

Such disdain for the establishment makes Mullis a pariah in some quarters,
according to Steve Doughty, a genetic oncologist at Washington University
in St. Louis who consulted for Mullis as a graduate student.

"He feeds a lot of negative feelings that he's a scientific comic rather
than a real scientist," Doughty said. "He's purposely doing that. He's got
a Nobel Prize, he can do whatever he wants.

"For the record," Doughty hastens to add, "HIV causes AIDS."

Rock Star Status

Among his admirers, Mullis enjoys rock-star status. He has autographed
countless PCR machines around the world.

That star quality got a boost during the O.J. Simpson murder trial.
Retained by the defense as an expert on PCR-based techniques of DNA
fingerprinting, Mullis was set to undermine yet another of his invention's
applications.

Instead, he spent a few days ogling Marcia Clark and frequenting Los
Angeles strip clubs before being dropped from the witness list at the last
minute.

"If I had gotten to testify, it might have turned into a circus," Mullis said.

Turned into?

"Well, yeah, it was already big enough," Mullis reflects. "To put me up
there and take a chance that the jury would have gotten confused about the
LSD issue and stuff like that was too much, I guess."

Yet Mullis' fame grew from his mere presence at the trial. As Simpson
lawyer F. Lee Bailey writes: "He was -- even more than Simpson himself --
the most important witness we never had a chance to call."

Even as a kid growing up in Columbia, S. C., Mullis expressed his love for
science in odd ways. He and his friends used their chemistry sets to fuel
rockets designed "to see how high into the sky we could send a frog and
bring it back alive."

He pursued chemistry at Georgia Tech, but soon felt something was missing.
Intricate as the known rules of chemistry and physics were, they left him
with a gnawing sense that the universe consisted of much more.

"Most of my engineering friends felt that the world is pretty simple, and
there's not a lot here that we don't have a grip on already," Mullis said.
"My creativity was saying, I don't think that's true. There are things in
my life that I cannot explain."

So for graduate school, Mullis chose a place where the climate in 1966 was
altogether different -- the University of California at Berkeley.

Off to Berkeley

"I thought, something's happening out there that sounds to me like these
people are looking for answers in different places," Mullis said.

"And the first thing I started looking for was somebody who could get me
LSD. I'd been reading about it in Time and Life, and in those magazines at
the time they weren't down on it at all, they were actually sponsoring it.
And Berkeley was the place to get it."

Few graduate students at Berkeley during that era could avoid the blooming
drug culture. But the new experiences changed Mullis utterly and
permanently, in ways that he says affected his entire approach to science.

The person who emerged sounds at times more like a grilled cheese vendor at
a Grateful Dead concert than a scientist.

"The altered states of consciousness that LSD and various other drugs led
me into were saying, `You were right,' " Mullis said. "(The world) is a lot
more complicated than you think. It's much more than you think. It's
basically infinite, and you are always looking at just a little piece of
the iceberg.

"How can you know who you are if you're always looking out the same two
holes? You need to have that rotated around about 90 degrees until you see
yourself from the side. I think there's no better way than taking a drug
that will derange your mind for a little while."

When he wasn't synthesizing psychedelic substances, Mullis rounded out his
graduate education with heavy doses of physics and cosmology. The result
was his first and only paper published in the premier journal Nature, a
partly drug-inspired effort titled "The Cosmological Significance of Time
Reversal."

That paper, containing a second-year graduate student's musings that half
the universe is constantly traveling backward in time, received worldwide
media attention. Fifteen years later, Mullis couldn't even get Nature to
publish his paper on his groundbreaking new process, PCR.

"That's a funny take on the system," Mullis said. "If you invent a thing
that's really novel, you should expect to run into barriers."

In the 1970s, Mullis dabbled in fiction writing, went through three wives,
sired three children, and branched out into new drugs. He got frostbite on
his tongue and lips one night after passing out while inhaling nitrous
oxide from a tank.

"I don't recommend anesthetizing yourself in a general way," Mullis says
after a moment's reflection. "It's best to have somebody watching you
anytime you're taking a serious mind-altering drug. Just like it's good to
have a designated driver."

Even at San Diego-based Cetus Corp., where he thought up the idea for PCR,
Mullis surrounded himself with a merry prankster's parody of a laboratory.

Instead of using well-marked drawers for test tubes and pipettes, as most
chemists do, Mullis used labels that read, "Love," "Regret," "Remorse,"
"Happiness" and "Sunshine."

The once-in-a-lifetime flash of insight came as Mullis on a Northern
California highway late one night, a young lovely asleep in the passenger
seat.

All at once, Mullis saw how he could use existing chemical techniques to
amplify selected stretches of DNA. It involved using heat to unzip the
double helix's twin strands and enzymes to reassemble the two parts, then
repeating the process to yield billions of copies.

Steve Doughty first met Mullis during a conference at Cold Spring Harbor
Laboratories in 1986, when Mullis introduced PCR to some of the world's
biggest names in molecular biology, including James Watson, the
co-discoverer of the structure of the DNA molecule.

"It just blew the audience away," Doughty said. "You could drop a pin,
because everyone was waiting on the next word he said."

The other crazy idea being floated for the first time at the conference,
that of sequencing the entire human genome, suddenly seemed within reach.

In contrast to the haze that surrounds some parts of his life, Mullis is
utterly clear-headed when discussing the importance of his scientific baby.

He need not embellish. PCR has made possible not only the human genome
sequencing project and the use of DNA samples to solve crimes, but the
growing ability to cure disease genetically, to trace human and animal
evolution from the fossil record and even to identify the bodies of the
Russian royal family.

"PCR is the word processor for DNA," he said. "Think of all the things you
can do with a word processor -- you can search for some text, you can make
copies of it, append something to it, delete something from it. You can do
all those things with PCR and DNA. And you do it with a little drop of
water at the bottom of a conical tube, in a few hours.

"Yeah," he says, "I'm proud as hell of it!"

He's also serious about Nancy Cosgrove, a painter whom he met through a
childhood friend and married in March. He felt so strongly that he attached
an epilogue about Nancy on reprints of his 1993 Nobel speech; the pair
rarely walk together without holding hands.

Cosgrove, by far the more practical one, says the stories about Mullis'
more licentious days sound like a different person than the one she knows.

"It did get out of control," she said. "Kary had a wild nature to him. He
did some things I wouldn't have wanted to put up with. But they seem to be
out of his system now."

"Wild," Mullis points out, "is a relative term."

"Well, but wild for me," Cosgrove replies.

"Wild for you," Mullis nods, smiling. "As far as I'm concerned, my life has
been fairly sedate and normal."

Professionally, Mullis has turned his talents to writing and consulting on
a variety of pharmaceutical projects. At Vyrex Inc., where researchers are
developing a drug for spinal cord injuries, president Shelly Hendler
describes Mullis' job as "official gadfly."

"He'll try to find fault in everything you've thought about," Hendler said.
"It makes a lot of scientists upset, but for me that's always been Kary's
most important role."

Many of Mullis' beliefs don't sound like those of a hardened skeptic.

He talks enthusiastically about a recent study showing that successful
medical school applicants tend to be born in certain months, and states
that the data would be cleaner if the researchers had used astrological
months.

Then there's the woman who convinced Mullis that she visited him through
the astral plane as he lay knocked flat by nitrous oxide. And the glowing
raccoon that Mullis encountered in the forest, a raccoon that he thinks may
have been an alien abductor, since he has no memory of the hours
immediately following his sighting.

So what gives? How does a guy who applies radical doubt to an accepted
theory like the mechanism for AIDS turn around and blithely spout such
seeming nonsense?

"You just have to trust me on these," Mullis said. "I can't make the
raccoon glow again."

"There are just some things no one has figured out how to get a handle on."

Like Kary Mullis.

Far Out A List Of Some Of Kary Mullis' Ideas And Adventures

Mullis believes he may have been abducted by aliens in the form of glowing
racoons.

He appeared on the confiscated hit list of Unabomber Theodore Kaczynski.

He is not convinced that AIDS is caused by the virus known as HIV.

He surfs every morning to wake up.

He says drugs may have given him heightened creative and paranormal abilities.

He once got frost bite on his lips and tongue after passing out while
getting high from a tube of nitrous oxide (which he claims was
providentially removed by a woman travelling on the astral plane).