No Time to Lose: A Life in Pursuit of Deadly Viruses (2 page)

That’s why, when I graduated, I applied for a job as a junior researcher in Pattyn’s lab with the aim to obtain a doctorate. His attitude to all new arrivals was that you began in the kitchen. In those days, there was almost no plastic in a scientific laboratory: plastic was expensive. All the equipment was glass and was recycled, even the pipettes. And all the bacteriological and virological media, which today any self-respecting lab would order from a catalogue, were prepared in-house, by hand. So for the first three months I sterilized pipettes and prepared gels and broths. It was very much like starting out in a restaurant kitchen by working as a sous-chef, chopping onions; or like learning to become a medieval artist by first grinding pigments as an apprentice. If the basic media are not properly prepared the entire experiment is invalidated, and so I needed to understand all the ingredients and all the processes of microbiology, from the ground up.

I liked it. I had always liked doing things with my hands. I started learning how to identify bacteria—a shigella, a salmonella—under a microscope and using biochemical tests. My first real assignment was to grow
Mycobacterium leprae
, the cause of leprosy, in mice footpads. This was part of clinical trials to test the effectiveness of a combination therapy that would ultimately cure the disease, as demonstrated by several research groups. Pattyn’s microbiology lab was located at the Institute of Tropical Medicine, but he worked with the University Hospital and also, incidentally, with the Antwerp zoo. When someone (or some animal) fell ill, a sample of stool, or urine, or blood, or a throat swab, came to us for analysis. I cultivated it and then stared at it—not focusing intently but trying to detect something unusual, something striking.

It took about a year to master that routine work. Our techniques would be considered laughably ancient today. For salmonella, you took the person’s stool, diluted it, put it on a plate spread with agar and a culture medium, and placed it in an incubator. You waited and watched what grew. You needed an eye to pick out which colony of bacteria looked like a possibility. Ah,
this
one might be a candidate. You picked it up, put it on another plate, grew that, so there’d be a sizable amount, and then you began doing biochemical tests, checking perhaps five or six different chemical combinations. Then you knew it was salmonella. But which serotype? A
typhi
bacteria, which causes typhoid, or something banal that merely gives you the runs?

I found a lot of weird anomalies staring down the familiar funnel of the microscope in Pattyn’s lab. I isolated a number of bacteria for the first time—specific subtypes of salmonella, things like that—from people, seals, elephants, flamingos, and shrimp. These weren’t world-class discoveries, but they validated my feeling that I was where I needed to be—that I had that particular, slightly obsessional, very meticulous skill that microbiology requires, an approach that crucially involves
not
throwing away things that don’t fit into your preconceived scheme of ideas.

After about a year, Pattyn let me begin working on viruses. In the days before PCRs and DNA probes, the viral detection techniques were very difficult and precise. As we say in Dutch, you had to be even more of an ant-fucker than with parasites or bacteria—really obsessed with detail. First you had to isolate the virus—say, polio. You took the patient’s stool, diluted it, and then, instead of placing it on agar you injected it onto cells. Most of these cell lines, such as VERO, were derived from cancer cells, because they replicated easily; but in those days you couldn’t just buy them, you had to prepare them. You placed a sample of the stool on them, and then twice a day you observed the cells under a microscope. Certain viruses kill the cells; they detach from the side of the glass container, creating a pattern of holes as they fall away. When you saw that, you took a sample and put it on another cell layer to be certain that it stemmed from an infectious virus. And then to identify herpes virus, for example, you brought it in contact with antiserum treated with a fluorescent dye or looked at it under an electron microscope, where you could really see the virus.

It was a tiny, detailed job, and it wasn’t exotic, and it didn’t involve traveling. But I was content, even thrilled, to do it. I knew I needed to arm myself with this knowledge and these skills before I could go to Africa and work there, to discover new diseases and new solutions that would save lives.

ON SEPTEMBER 30,
the Flemish nun who was the source of the original blood samples died in Dr. Courteille’s clinic in Kinshasa. He sent us some fragments of her liver to us for pathologic examination. (Again, the samples were flown to Belgium on a
passenger
aircraft.) To add to the diagnostic confusion, microscopic examination of the samples showed swollen “Councilman bodies”—lesions considered typical of yellow fever. However, as Pattyn knew, they may also feature in Lassa virus, an African hemorrhagic fever whose transmission is mainly from rodents shedding virus in their urine and feces. So although Pattyn’s hypothesis that the samples from Kinshasa contained a hemorrhagic virus was not confirmed, it was not disproven either.

By this point for him to keep us working on those samples was sheer folly; he knew we were not equipped to do the work in safety. In 1974 there were only three labs outside the Soviet Union that could handle hemorrhagic viruses: Fort Detrick, a military lab in Maryland that did high-security work on anthrax and other highly lethal diseases; the Army High Security Laboratory in Porton Down, in England; and the so-called hot lab at the Centers for Disease Control, in Atlanta.

Nonetheless, we continued to bustle around like amateurs in our cotton lab coats and latex gloves, checking our VERO cell lines. The cells began detaching from the glass sides of their containers: it was either a toxic effect or an infection, but either way, cytotoxicity had kicked in. That meant we might be close to isolating a virus, and we began extracting cells to cultivate them in a second line of VERO cells. And Pattyn had been told we should expect more samples from Zaire in the next few days.

But just as we were beginning to cultivate the second VERO cell line, Pattyn intervened. He had received instructions from the World Health Organization’s Viral Diseases Unit to ship all samples and biological material from the new mystery epidemic to Porton Down in Britain. (In fact, a few days later Porton Down sent them on to the Center for Disease Control in Atlanta, which was the world’s reference lab for hemorrhagic viruses.)

Pattyn was furious, and I too was upset. It looked as though our outbreak investigation was over before it had even begun. Glumly, we prepared to pack everything in tightly sealed containers: the patient serum, the inoculated cell lines, and the autopsied mouse brains and samples. But then Pattyn told us to keep some of the material back. He claimed that we needed a few more days to ready it for transport. So we kept a few tubes of VERO cells, as well as some of the newborn mice, which were dying. Perhaps it was a stubborn rebellion against the whole Belgian history of constantly being forced to grovel to greater powers. That material was just too valuable, too glorious to let it go. It was new, it was exciting—just too exciting to hand it over to the Brits or, in particular, to the Americans.

Pattyn was a colorful character, with a razor-sharp brain. He didn’t have the smug, colonial attitude of so many men of his generation; he wore funky eyeglasses and collected contemporary art. And although he could be contemptuous I never felt his scorn was connected to skin color or social class—only to stupidity. But he certainly had an outsized ego.

There was a rack of secondary tubes in the lab, which we had inoculated after the first VERO cell line was killed. We knew there was something in there—something that was trouble—but still, we had taken out the rack so we could examine the tubes under the microscope. Doing that kind of work wasn’t Pattyn’s job. He was a micromanager but he wasn’t a technician, and in fact he could be rather clumsy. But impulsively he reached for one of the precious tubes, to check it out himself under the scope, and as he did so it slipped from his hand and crashed on the floor.

Little René Delgadillo was the one who got his shoes splashed. They were good, solid leather shoes but René bleated, “Madre de Dios” (Mother of God!) while Pattyn swore, “Godverdomme” (Goddamn!)—and there was a moment, just a beat, of blank fear. Immediately we whisked into action: the floor was disinfected and the shoes removed. It was just a small incident. But it struck me only then how lethal this thing really might be and the huge risks we had been taking in handling it so cavalierly.

ON OCTOBER 12,
our semiclandestine secondary cell line was ready for analysis. Guido took a sample and treated it so an ultrathin slice could be examined under an electron microscope. Then we took it over to Pattyn’s friend Wim Jacob, who handled electron microscopy in the university hospital lab. A few hours later he came over to our lab with the photographs.

“What the hell is this?” said Pattyn.

There was a long pause as he glared at the photographs, at us, at the walls of the corridor. I peered over his shoulder and saw what were by virus standards very large, long, wormlike structures: nothing like yellow fever. Pattyn’s excitement, or irritation, was rising.

“This looks like Marburg!” he exploded.

I didn’t know much about Marburg.

Everyone else in the lab seemed to know about Marburg, and today of course all you’d need to do to find out would be to check the Internet. But back then I needed an atlas of infectious diseases. So I went to the institute’s library and sure enough our virus
did
look like Marburg.

In those days Marburg was the only known virus that was this long—up to 14,000 nanometers, or 0.000014 millimeters. Huge. (In comparison, polio is up to 50 nanometers.) It had been identified just nine years before, in Germany, when a number of pharmaceutical workers became infected by a batch of monkeys imported from Uganda. It appeared to be extremely virulent and swiftly lethal. Seven of the 25 people infected by direct contact with the monkeys died with hemorrhagic fever, and six more individuals fell ill following contact with those primary infections.

Marburg was clearly a very scary illness, and as we did not have Marburg virus–specific antibodies, we could not definitely conclude whether our isolate was Marburg. Perhaps it was a different virus with similar morphology.

Pattyn was not suicidal. Once he had established that “our” virus was—at the very least—closely related to the terrifying Marburg, he had the sense to shelve all further work on it and sent the remaining samples directly to the high-security lab at the CDC.

I was still very excited. It felt as though my childhood fantasy of exploration was almost within my reach. I kept arguing that we had to follow up our work, go to Zaire and check out the epidemic. I felt strongly that we shouldn’t hand this world-class discovery over to some other team.
We
had identified this virus, after all, so
we
should be the ones to establish its lethality and its real effects on the ground.

Pattyn was not immune to this line of argument himself, but our lab had no budget to pay for anything so bold and unscripted as an expedition to Zaire. He went to the Ministerial Department for Development Aid, and was told they funded programs to help poor people, not programs to assist medical research. It was my first encounter with the sobering reality of fund-raising: how crucial it is and how difficult it can be to raise money when you wait until the crisis arises. It was also the first of a long series of confrontations with bureaucracies, a major lifelong source of irritation.

Even if safety demanded that all the research had to be done in an expensively equipped, high-security lab, why
should
we leave it to the Americans and WHO to do the epidemiological work on the ground, where the epidemic was certainly still underway? How often does a small research institute in Belgium have the opportunity to make medical history? It’s not often that a twenty-seven-year-old comes within reach of the discovery of a new virus, and it looked as though the virus we cultivated had a fighting chance of being just that.

On Thursday October 14, the answer came by telex: it was indeed a new virus. Karl Johnson, chief of Special Pathogens at the CDC, reported that his team had isolated a similar virus from other samples of blood from the same Flemish nun in Kinshasa. Pushing our information one step further, he added that this virus did not react with Marburg antibodies. Therefore it was different from Marburg, though we did not know how different it was.

I learned two things. One was that my institute (and indeed my country) had very limited means. The other was that there was a worldwide network of scientists who could solve almost any problem in no time. Back then we didn’t even have fax machines—only the phone and the telex—but this network seemed all-knowing, and most of it was implanted in America. That’s when I began to tell myself that I wanted to go to America, to plug into that network and learn how we could become world class too.

As for my impossible dream of taking our outbreak investigation to Zaire, I figured it was over. It was time to go back to looking for salmonella in the stool samples of patients with a nonspecific bellyache. I was crestfallen.

But Pattyn was not a bad guy. I think he saw how despondent I was, and on Friday, October 15, he sent me to Paris for the weekend with my then wife, Greta Kimzeke. (We met when I was in medical school and she was a psychology student. At this point we’d been married for just six months.) Pattyn had been invited to a conference organized by Beecham, the pharmaceutical company, about some new antibiotic they were bringing out. He hated that stuff, and he was kind enough to let his young assistants make trips that pharmaceutical companies constantly offered him.