To understand the kind of person Dr. Antonín Holý is, consider this: During his 40-year-career, the renowned chemist at the Czech Academy of Science's Institute for Organic Chemistry and Biochemistry (ÚOCHB) has published some 200 scholarly papers in the journal Collection of Czechoslovak Chemical Communication, including some of his most significant, groundbreaking work with anti-viral research.

By all accounts, these papers are excellent, even vital, in the field of biochemistry — and destined to yellow in obscurity. For Collection rejoices in being one of the least-read, most ignored scientific journals in the world; a publication, as one chemist bluntly puts it, "with almost no impact."

"It's Tony's favorite journal," this chemist says.

Holý, 69, has helped AIDS patients throughout the world. His work with chemical compounds has resulted in AIDS medications that millions take today to improve their quality of life. One compound in particular attacks the disease with such effectiveness that Gilead Sciences, a pharmaceutical company in California, has turned it into Truvada, the world's first single-dose pill.

Holý has more than 60 Czech and international patents for his compounds, and his work has enough potential for other diseases, like Hepatitis B and cancer, that this summer Gilead announced it was opening its own research institute at the ÚOCHB and tapped Holý to run it. The company will pay $5.5 million (120.8 million Kč) during the next five years, $1 million of which will finance's Holý's research.

His work is worth millions to any drug company's portfolio, but Holý has lived, with his wife of 42 years, in the same modest house on Prague's outskirts since the 1970s, and takes public transportation to his lab in Dejvice, where he usually puts in 13-hour days.

"I have never really cared what the drugs are against as long as they work and can be used for treatment," he told a reporter in 2004.

Věra Nováková, 70, a classmate of Holý who still works in his lab, says of his success, "It hasn't changed him. He's so modest. Too modest, I would say."

Slow body, keen mind

On a recent morning, Holý is in his narrow office at the back of the institute, surrounded by a clutter of stacked papers, files and books that weighs down shelves along one wall. Two Japanese prints hang on another.

He is small and has sunken eyes and thin hair. He wears thick glasses. His hands are deeply grooved, his fingernails uneven. When he speaks, his voice is a church whisper.

"Chemistry, for me, is an experimental science," he says. "I like to work with my hands."

Holý spends most of his days, from 7 a.m. to as late as 8 p.m., among the confusion of beakers and burners that is his small lab, Room 149, where he oversees a team of eight scientists and 10 students.

He says he never had any other calling than being a scientist. Born in Prague in 1936, Holý came across a book of chemistry and physics from the time of the Austrian monarchy when he was 6, and became fascinated with the intricate sketches of things the human eye can't see.

That was enough to encourage his studies in the physical sciences. When he was older he began to see "how chemistry is behind everything." As a Ph.D. student at the ÚOCHB in 1960, he decided to focus on nucleic acid chemistry, working with the building blocks of molecules.

Time has slowed Holý physically. He doesn't spark a Bunsen burner as quickly as he used to, and his colleagues often have to repeat things directly into his ear, but his mind remains sharp, they say.

You see mind and body battling as he walks down the hall in a steady shuffle, carrying a beaker, leaning forward with his head leading the way.

"Isn't it time to slow down at your age?" a visitor asks.

"You must have met my wife. That's what she always says."

Holý turns 70 Sept. 1. When will he hang it up?

"When my hands are so shaky that I cannot work with them. Then I'll have to admit that I can't continue," he says.

Breaking it down

If a molecule is a puzzle piece, then a compound is what you get when you find two or more that happen to fit together. Finding those fits — synthesizing them — is what lab work is all about. And when you create one, all you usually have is something with a lot of potential.

"It's a very long journey from the beaker to an anti-viral compound," says Michal Česnek, another chemist in Holý's lab, "15 years in some cases."

To find out what a compound can do, a chemist needs a microbiologist, someone to set the compound free against strands of living things: a cancer cell, for instance, or a virus. If the compound kills or attacks what it comes into contact with, it's active.

For Holý, that's where Erik De Clercq, a medical doctor and biologist from Belgium, comes in.

In his office, Holý picks up a small vial containing what looks like sea salt, a compound he says he created a few days before. "This is going into a package that I will send [to De Clercq]. I know what it is, but I don't know what it can do."

A productive partnership

Holý and De Clercq have worked together for 30 years.

They met in Germany in 1976 at a chemistry symposium, De Clercq there as a "chemist at heart," he says, but not in training.

"The chemists tolerated me," De Clercq recalls. "Especially this young chemist, from Prague, and he somehow got my attention. And he trusted me. Normally, Tony Holý is reserved. Before he will trust you, you need to show you're worth being trusted."

A month later, Holý sent De Clercq his first batch of compounds.

They have published more than 60 papers together, including a groundbreaking 1986 report in Nature detailing a new group of compounds that were highly effective against viruses.

AIDS and HIV were just starting to get attention at that time, and almost immediately Holý and De Clercq began applying these anti-viral compounds to AIDS-related viruses.

U.S. pharmaceutical companies took notice, seeing the possibility in packaging these compounds as drugs. First came Bristol Myers, then later Gilead, which has worked with Holý for almost 20 years now.

Holý and De Clercq patented three compounds applicable to AIDS. Cidofovir, on the market as the drug Vistide, is active against many of the viruses that result from the onset of AIDS. Adefovir, on the market as Hepsere, is used primarily by Hepatitis B patients, though it can also fight AIDS.

Holý's most valued compound is Tenofovir, marketed by Gilead as Viread. It's so effective against AIDS that after five years patients have no traceable HIV in their blood.

In 2001, Gilead combined Tenofovir with another compound to create the drug Truvada, a single pill that ends the so-called drug cocktails AIDS patients had to endure. The U.S. Food and Drug Administration approved it in 2004, and its European counterpart is expected to follow suit this year.

That same year, Gilead announced it would distribute Truvada to 68 developing countries around the world at cost.

Both Holý and De Clercq waived all royalties from that deal.

The happy accident

Holý says AIDS no longer interests him. He is not callous. He says it has become a disease that is manageable, unlike cancer. Of course, he has a lot to do with that fact.

He shrugs. It was all an accident, he says.

"I didn't know anything about viruses when I started," he says.

Money from Gilead will allow Holý to update his equipment, patent more compounds and welcome visiting experts, all in an effort to reach new areas of anti-viral treatment. Even now, some of his newer compounds have been found to fight certain viruses that cause some cancers.

"This collaboration today will lead to many, many things, but it will probably be decades before we'll know about it," John Milligan, Gilead's vice president, told reporters last month.

Holý keeps notebooks dating to the 1960s on the shelf in his office, their spines frayed. On the right-hand pages of each there is a single compound drawn out like a map.

There are almost 4,000 such drawings.

Much of this work, of course, took place during the communist regime. Holý says he was not persecuted — on the contrary, he received support and funding. The physical sciences were an important endeavor during Soviet times, unlike today, when funding can be difficult, he says.

De Clercq says their work generates $20 million in annual royalties, half of which goes to De Clercq's institution, half to the Czech Academy of Sciences. But Holý doesn't seem to see much of that. Why isn't he cashing in on his discoveries?

"I have what I need," he says. "What I would do with so much money, I can't imagine."

He pauses, thinks. "If that would buy 20 years of life back, then I would gladly do it."