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22 Aug 2003

Source: Los Angeles Times, August 28, 2002.


In the Lab, Suspicion Spreads

Since Sept. 11 and the anthrax scare, biologist who ponder pond slime as well as deadly spores have found themselves under the microscope.

By Rosie Mestel

Tomas Foral, a 26-year-old graduate student at the University of Connecticut, was moving biological specimens from a broken lab freezer last fall when he came upon some samples collected nearly 35 years ago from an anthrax-infected cow.

Foral moved two samples to a working freezer in the building and promptly forgot about the matter. Now, he is paying for this seemingly innocent and mundane act.

In July, Foral became the first person to be charged under the USA Patriot Act of 2001 with possessing a biological agent with no "reasonably justified" purpose—a crime that carries a penalty of up to 10 years in prison. He was investigated by the FBI and now faces an investigation by his university. His name was added to a computerized government watch list along with fugitives, drug smugglers and immigration violators.

"I think this is going a little bit too far," protested Foral, a soft-spoken researcher who lives in Hartford, Conn. "I saved many other tissues that day. This is one of the samples that I saved. That's all that happened."

Foral's tale is giving other scientists chills because of what it says about the blizzard of change overtaking the once-quiet world of microbiologists—a motley group dedicated to the study of bacteria, fungi and viruses. These are the aficionados of everything from smelly pond slime and cheese-making bacteria to dangerous microbes on the "select agents" list—a litany of noxious germs including anthrax, smallpox, Ebola and lesser-known scourges, such as Crimean-Congo hemorrhagic fever.

Overnight, obscure scientists who had spent years happily nurturing odd microbes in petri dishes became the center of attention, hounded by reporters and interviewed by federal investigators.

Anthrax laboratories are bristling with new security cameras, electronic locks and alarms, and there are rumblings about censoring biology in the name of national security. Scientists are grappling with the prospect that one of their own—maybe someone they know -- is a killer.

The fears -- and the wave of new laws -- have unleashed an unsettling timidity, as universities and scientists rush to destroy samples of anthrax and other disease-causing microbes that they once would have kept, or sent to their colleagues for study. Some scientists have even requested that key facts be omitted from articles they publish, lest they inadvertently supply dangerous information.

Zero Tolerance

These are zero-tolerance days, with the government and universities guaranteed to come down hard on anyone mishandling a biological sample -- even unintentionally.

"It's a clear warning," said Ronald Atlas, bioterrorism expert at the University of Louisville in Kentucky and president of the 42,000-member American Society for Microbiology. "The scientific community has been put on notice that we have to watch what we do."

Their world wasn't always this way. Labs were more relaxed in the days of yore, and it was common enough for freezers to harbor many a long-forgotten sample. Money for microbiology was tight—in fact, some microbiology departments closed because their discipline was viewed as losing relevance.

"In the past, I don't think the glamour was there," said Samuel Kaplan, chairman of the microbiology and molecular genetics department at the University of Texas Health Science Center at Houston. Students were drawn more to glitzy genome and stem-cell work than to a life studying germs.

Today, microbiologists had better know what's in their deep freeze, and anthrax labs have been turned into little Ft. Knoxes.

Students are flocking afresh to microbiology classes, and money for studying dangerous germs is flowing like water. At the National Institutes of Health, funding for bioterrorism has increased from $52.8 million last fiscal year to a projected $1.7 billion in 2003.

The changes have been all the more jarring because of the speed with which they arrived. Sept. 11 happened, then the anthrax attacks, and actions that would have barely raised an eyebrow during the summer became deeply suspicious in the fall.

It was bad luck for Foral that the freezer he was helping to clean up broke in October, at the height of the anthrax attacks.

Some time during the next few weeks, somebody saw the dead cow samples sitting in freezer space used by Foral to store samples of West Nile virus, the subject of his graduate studies. In November, that person tipped off the FBI, just around the time a 94-year-old Connecticut woman died after inhaling anthrax spores.

The FBI started an investigation. The university closed the building containing the samples that Foral had saved, and it tested the facility for anthrax contamination. Foral retained a lawyer and continued his research -- and then came July, when the Czech-born U.S. citizen was charged under the Patriot Act.

The act, hurried into law after Sept. 11, made it a crime to possess "any biological agent, toxin or delivery system" that is not reasonably justified by "bona fide research or other peaceful purpose."

There is fuzziness to the story: University authorities say the department chair had decreed that the samples be destroyed, and some tubes were indeed sterilized. But there were many students carrying tubes to and fro that day, and Foral maintains that he never received that instruction.

"I am convinced that the student had no ill intent and thought he was doing what we teach all grad students to do -- keep specimens," said Kirklyn Kerr, dean of the college where Foral studies.

Foral cooperated fully with the FBI and agreed to community work and some restrictions on his activities to avoid prosecution.

But he remains bitter at how far the investigation went, and he worries that the affair will cast shadows on his future. Several weeks ago, he was reentering the country after overseas National Guard training, and he was detained by authorities because his name had been placed in the Interagency Border Inspection System, a computerized database that lists suspicious people.

Foral said he wishes the anonymous tipster -- he still doesn't know who it is -- had acted differently.

"The reasonable course of action would have been to inform me, and the department head, and resolve this issue internally. But no, this person runs to the FBI," he said. "Whoever did it needs to think about it for five or 10 minutes --'What am I trying to do? What is the purpose of it?' "

Biologists understand that times, and laws, have changed and that they must by necessity amend the way they do business. But they say that some of the responses by university administrators and authorities -- who are not, after all, microbiologists -- have been driven by an inflated fear of the bacterium itself. The reaction, some scientists say, has been far out of proportion to the actual risk of storing and working with anthrax, which until recently was an obscure microbe studied mostly in veterinary schools.

"People hear the word 'anthrax' and almost go into a panic," said Ronald Welsh, veterinary microbiologist at Oklahoma State University in Stillwater.

At Brandeis University in Waltham, Mass., research scientist Daniel Perlman ran into trouble with university authorities after conducting experiments specifically intended to help in the fight against bioterrorism.

Shortly after the anthrax attacks, he'd been asked by a company to devise a diagnostic tool to detect anthrax contamination.

He and a microbiologist colleague revived an old sample of anthrax from a decades-old strain collection and within weeks created a nutrient on which pretty much only anthrax would thrive.

Upon hearing of the scientists' study, Brandeis' administration became alarmed that anthrax had been grown without university approval. It called in authorities, and it shut the biology building for a week to test for spores.

Neither Perlman nor colleague Inga Mahler -- both of whom were interviewed by the FBI -- would comment on their experiences, but others familiar with the case said the university placed Perlman on leave for nearly a month and set into motion a formal inquiry into possible scientific misconduct. Both were cleared in May, but Perlman must now get permission from his department chair for every experiment he conducts.

The university is pursuing a patent for his invention.

Few scientists have had encounters with the FBI as intimate as those of Foral and Perlman, but even the cheese makers and pond scum enthusiasts have had a modicum of contact. In January, the FBI sent a letter to the microbiology society's entire U.S. membership, requesting help in catching the anthrax killer.

"It is a horrible feeling to think that it could be someone I know, that the perpetrator is a microbiologist among us," said Theresa Koehler, anthrax geneticist at the University of Texas Health Science Center at Houston.

It is horrible to be a suspect as well -- or merely a "person of interest." Steven J. Hatfill, the most frequently named scientist in connection with the anthrax mailings, has never been identified as a suspect. Yet he has been the focus of numerous news articles, often including quotes from unnamed investigators, and he has been placed on administrative leave with pay from his job at Louisiana State University. In a news conference this month, he accused the media and FBI of making "a wasteland" of his life.

A Fundamental Change

Most microbiologists have adapted to the changes, in part because most have little contact with the exotic and dangerous world of deadly pathogens. But even researchers in the most benign corners of microbiology can sense that something fundamental has changed beneath their feet.

Microbiology has assumed a kind of split personality. One side is dedicated to manipulating tiny critters for human good. The other is a potentially dark enterprise that has now put the world on high alert.

At the American Society for Microbiology's annual meeting in May, 10,000 microbiologists invaded Salt Lake City, thronging the convention center and local cafes. Much of their chatter was oceans away from the world of bioterrorism: microbes that grow in sauerkraut fermentation vats, bacteria that chomp up pollutants, genes of ulcer bacteria and the antimicrobial actions of garlic. Session after session dealt with one of the field's hottest topics: antibiotic-resistant bacteria.

But clearly, bioterrorism was center stage. Extra-eager scientists consumed sweet rolls and coffee at a sunrise special on the nuts and bolts of identifying biowarfare agents. The conference was peppered with sessions on the anthrax attacks, agricultural bioterrorism and biological privacy.

At one packed symposium, the audience was giggling one moment at a silly, germ-themed cartoon ("Be a virus, see the world") and aghast the next as a speaker described a bioterrorism cookbook that has been legally sold at gun shows.

One speaker ruffled feathers by questioning the ability of the government to respond efficiently to a bioterrorist threat, illustrating her point with a numbingly complex flowchart of all the government agencies involved. An angry microbiologist stood up and attacked the speaker for challenging the dedication and patriotism of government scientists.

The evident tension has also touched one of the fundamental tenets of scientific research—the open exchange of information through the hundreds of scientific journals.

It's easy to understand the concern. Some scientific papers would seem to fit perfectly into Bioterrorism 101 primers: fine details of the anthrax genome, how to render a virus more resistant to the mammalian immune system, and the existence of antibiotic-resistant anthrax strains.

One study in July showed how scientists could build the polio virus from scratch in a test tube -- unsettling some critics who thought it gave terrorists another recipe for mayhem.

Yet it is very difficult to figure out reasonable limits to experiments or access to biological information, said John D. Steinbruner, director of the Center for International and Security Studies at the University of Maryland.

"It's easy to invent schemes that would do more harm than good," he said. In much of modern biology, the potential for good and evil are closely intertwined.

What could be more benign than an experiment to create a new mouse contraceptive for pest control? Ingeniously, a team of scientists engineered a mousepox virus (closely related to the smallpox virus) to trigger an immune attack against mouse reproductive cells. The engineered virus, however, shocked them with its virulence: It was able to kill even immunized mice.

The implications for a would-be bioterrorist were obvious -- and the study caused a furor among scientists when it was published.

Today, discussions set in motion even before Sept. 11 are being pursued with fresh vigor, as scientists, ethicists, and policy and bioterrorism experts convene in a variety of panels to hash out what, if any, restrictions should be placed on the free flow of biological information.

Holding Firm

For now, the American Society for Microbiology is holding firm on the principle of publishing enough details of an experiment to allow other scientists to try to repeat the work. It reiterated its policy after several scientists submitting papers to the society's journals asked that fine details of their experiments be left unpublished for fear that they could be misused.

"This is going to grow into a major debate in the scientific community," predicted Atlas of the microbiology society. "If restrictions are reasonable and responsible, they're just fine. If they get too draconian, they'll chill science."

In many ways, the chilling process has already begun. It is driven in part by the scientists themselves, who have found that it may be wiser in these less innocent times to destroy samples and restrict themselves rather than risk a bureaucratic or legal nightmare.

In the aftermath of the anthrax attacks, universities in Iowa and Texas destroyed collections of hundreds of anthrax strains that had been amassed over decades.

"That is worse than a book-burning," said Glenn Songer, veterinary microbiologist at the University of Arizona in Tucson. "With a book-burning, some copies of a book will survive, but these organisms are gone."

Scientists who would once store or mail isolates of anthrax or other select-agent bacteria to their colleagues when they showed up in specimens being diagnosed are immediately destroying the samples instead.

"We've seen this time and time again—field samples that normally we would see have been destroyed because people got nervous," said Martin Hugh-Jones, anthrax researcher at Louisiana State University and holder of an extensive collection of strains of Bacillus anthracis. "It slows up research immensely."

Even less dangerous bacteria are getting dumped instead of shared, scientists say, because the paperwork involved in mailing bacteria and viruses has become too tedious.

"I think there's some composting needed to work out what is really needed, what is realistic and what is just a fuss," Hugh-Jones said. "We're going through a maturation episode, and hopefully when we come out on the other side we'll be better off."

In the meantime, the wise scientist plays it safe.

Not long after September, Okalahoma State's Ronald Welsh was repeatedly hauled in front of university administrators for having the harmless Sterne strain of anthrax in his lab. Sterne is used as an animal vaccine and can be bought over the counter.

"Joe Bloggs can have it to vaccinate his cattle, but this guy is being reprimanded for having it," said Songer.

After hearing of Welsh's travails, Songer took no chances when a sample of Sterne arrived at his own lab. He knew if he kept it there before the university understood what it was, it could end up confiscated and steamed into oblivion in the autoclave -- and he could end up with some explaining to do.

So, while he waited for official clearance from the university, he popped it into a double-walled container, took it home and stored it in the family freezer.

"I knew it was legal there," he said.

There it sat for weeks on end -- near the frozen beef, peas and carrots and the chocolate fudge ice cream.