Two Teams Reached Key Discovery : Friendly Rivals: Scientists Race for Answer to AIDS

Scientist Mandy Fisher always feels a little insecure when she thinks she’s got something. She never lets herself get too excited, just in case she is wrong.

So on a sultry day in August, her reaction was predictable when she peered through a high-powered electron microscope to examine the results of an experiment involving the genetic material of the AIDS virus.

“I’ve made some kind of mistake,” thought the 27-year-old English scientist.

Then she looked again.

It was no mistake.

Fisher and her co-workers at the National Cancer Institute here--under the direction of Robert C. Gallo, the American credited with discovering the AIDS virus--had at last found a way to cripple the virus and prevent it from growing--a potentially major contribution toward the development of new drugs or a vaccine to fight the usually fatal acquired immune deficiency syndrome.

But the government researchers were not alone in their exaltation, as they quickly learned.

At about the same time, scientists in the Boston laboratory of William Haseltine, a Harvard University professor, were making the very same finding on their own--a breakthrough that prompted Haseltine’s group to uncork yet another bottle of champagne. They, too, had been fiddling increasingly with the various genes in the mysterious virus.

The latest development, announced by the two teams Friday, also illuminates the delicate balance that highly driven scientists must maintain between the desire to be first and the professional obligation to share knowledge with one another, a balance that is usually hidden from public view.

A Complicated Task

“Most viruses are like a cowboy’s coffee pot--simple. But this one is like an Italian espresso machine,” said Haseltine, referring to the HTLV-III virus. “It has lots of doodads on it that we can mess up.”

Both research teams--which regard each other as friendly rivals--spent much of those summer days “messing up” the same “doodad”--a critical gene known as the transactivator, or TAT.

The gene was already known to greatly accelerate the production of virus by an infected cell. But no one knew for sure what would happen if TAT were removed, said Flossie Wong-Staal, the NCI’S lead researcher on the project, although both groups suspected that the virus would continue growing after TAT was removed.

Thus, when Fisher looked into her microscope that August day, she had fully expected to see some particles of AIDS virus--meaning that the removal of TAT had slowed the viral growth.

Growth Stopped Cold

Instead, she saw nothing. That meant the growth of the virus had been stopped cold.

“What makes a scientist happy is to discover something which is of universal importance--something which starts a whole new field,” Haseltine said, recalling his own elation.

“The discovery of how the TAT gene works opens a new door to biological investigation,” he added in an interview in his cramped office at the Dana-Farber Cancer Institute in Boston that is lined with dozens of empty champagne bottles.

This latest chapter in the war against AIDS began last summer.

It was in mid-August at the National Cancer Institute that Fisher began the final phase of the experiment. Co-worker Steven Josephs brought her several frozen samples of DNA from the AIDS virus--called “constructs”--in tiny bullet-shaped plastic tubes.

Fisher, an expert in cell biology, thawed the vials and mixed each sample of the milky colored substance with a group of human cells.

Basis for Comparison

One group received viral DNA in which Josephs had snipped out the TAT gene. A second “control” group, to be used as a comparison, received DNA whose genes were intact.

Fisher waited a week and then looked.

First she examined the control group. She could see the characteristic round particles of viral protein. That meant the virus was growing like crazy--exactly what it was supposed to do.

Then Fisher looked at the second group--the cells that had been treated with altered DNA. She expected to see some particles of virus, but fewer than the control group--meaning that the removal of TAT had slowed the viral growth. But she saw nothing.

“I couldn’t believe it could be such a clear-cut thing,” she recalled. “I thought maybe I should have waited a little longer, or maybe I failed to get the DNA into the cells--even though the controls were positive. I thought: I’ve got to repeat it.”

Checking It Twice

She performed additional tests to be sure. Finally, she was.

“I walked over to Flossie’s office and told her what had happened.” she said. “We thought: We’d better make sure this stuff is right--and get it out fast. To be honest, we were hearing that Haseltine was onto the same thing.”

They had heard right. In fact, they had heard it from Haseltine himself. The Harvard researcher had been discussing his own experiments with Gallo--research that paralleled that of the government lab.

Haseltine, 41, had been studying TAT for more than two years.

“We’re interested in where the weak spots are in the virus,” Haseltine said. “TAT is one of them. We learn as much about the virus as we can and then predict where the weaknesses are so that either we or others can attack them.

“We’re doing a systematic analysis of the virus, knocking out bits and pieces and then plugging the holes in order to get a detailed picture of how the virus goes about its business,” Haseltine added.

Goal of Research

“The virus is like the backside of the moon, something we recently glimpsed through the use of high technology. The goal is to understand enough about the virus so that we can design a rational approach based on deep understanding of drugs to stop the disease,” he said. “Drugs we hope will be useful for treatment and protection from infection.”

Late Friday afternoon, the Haseltine team emptied its 51st champagne bottle, marking the team’s latest achievement.

In 1983, they found the TAT gene and its products in viruses that are related to HTLV-III, the virus that causes AIDS. That same year, he and his co-workers conducted important studies of transactivator genes in related viruses, HTLV-I and HTLV-II, which cause leukemia in humans.

In 1984, the Harvard scientists worked with Gallo and his co-workers on studies that determined the DNA sequence of HTLV-III. Much of the theoretical work on how the genetic material of the virus uses the infected cell to multiply was done in Haseltine’s lab.

Groundwork for Progress

And in 1985 came the finding by Haseltine that laid the groundwork for last week’s announcement--discovery of the TAT gene in HTLV-III and the protein it manufactures.

“We collaborate on some things and we compete on other things,” said Wong-Staal, speaking from Gallo’s office last week. “These are important enough problems that they need to be verified by another group. We’re all after the same answers.”

Still, competition is competition.

“Once, with pointed shoes, Flossie went as hard as she could on Bill’s (Haseltine’s) bare foot by the side of a swimming pool,” during a break at a recent AIDS conference in Martinique, recalled Gallo, a highly respected scientist known for his occasional irreverence.

“It’s true that she kicked me--but it had nothing to do with scientific competition,” Haseltine said.

Then he turned serious.

“I couldn’t begin to do what I do without the cooperation of other labs around the world,” he said.

“It’s far from the idea that many people have--that scientists are competitive and out for their own good. For every one thing I give Gallo, he gives me ten.”

Marlene Cimons reported from Bethesda and Harry Nelson from Boston.