Part one A virologists tale of Africas first encounter with Ebola

first_imgPeter Piot grew up in Belgium dreaming of exotic adventures and helping the poor. He saw medicine as the passport to both goals. But at one point in his medical education, Piot recalls in his 2012 memoir No Time to Lose, a professor offered a bit of advice:“There’s no future in infectious diseases,” he stated flatly, in a tone that bore no argument. “They’ve all been solved.” But I wanted to go to Africa. I wanted to help save the world. And it seemed to me that infectious disease might be just the ticket and full of unresolved scientific questions. So I ignored him.Piot would become one of the world’s most respected epidemiologists because of his work on the viruses that cause AIDS and Ebola—he is a former under secretary-general of the United Nations, former president of the International AIDS Society, and now director of the London School of Hygiene & Tropical Medicine. In part one of this edited excerpt from his memoir, Piot describes how he and colleagues, with what now seem crude and risky methods, became co-discoverers of the deadly virus now on the rampage again.A Blue Flask of VirusesAll this work was done with no more precautions than if we had been handling a routine case of salmonella or tuberculosis. It never occurred to us that something far more rare and much more powerful might have just entered our lives.On the last Tuesday in September 1976 my boss at the microbiology lab was alerted that a special package was on its way to us from Zaire. It was flying in from Kinshasa: samples of blood from an unusual epidemic that seemed to be stirring in the distant Équateur region, along the river Congo. Sign up for our daily newsletter Get more great content like this delivered right to you! Country Country * Afghanistan Aland Islands Albania Algeria Andorra Angola Anguilla Antarctica Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia, Plurinational State of Bonaire, Sint Eustatius and Saba Bosnia and Herzegovina Botswana Bouvet Island Brazil British Indian Ocean Territory Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon Canada Cape Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo Congo, the Democratic Republic of the Cook Islands Costa Rica Cote d’Ivoire Croatia Cuba Curaçao Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Falkland Islands (Malvinas) Faroe Islands Fiji Finland France French Guiana French Polynesia French Southern Territories Gabon Gambia Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guatemala Guernsey Guinea Guinea-Bissau Guyana Haiti Heard Island and McDonald Islands Holy See (Vatican City State) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jersey Jordan Kazakhstan Kenya Kiribati Korea, Democratic People’s Republic of Korea, Republic of Kuwait Kyrgyzstan Lao People’s Democratic Republic Latvia Lebanon Lesotho Liberia Libyan Arab Jamahiriya Liechtenstein Lithuania Luxembourg Macao Macedonia, the former Yugoslav Republic of Madagascar Malawi Malaysia Maldives Mali Malta Martinique Mauritania Mauritius Mayotte Mexico Moldova, Republic of Monaco Mongolia Montenegro Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands New Caledonia New Zealand Nicaragua Niger Nigeria Niue Norfolk Island Norway Oman Pakistan Palestine Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Qatar Reunion Romania Russian Federation Rwanda Saint Barthélemy Saint Helena, Ascension and Tristan da Cunha Saint Kitts and Nevis Saint Lucia Saint Martin (French part) Saint Pierre and Miquelon Saint Vincent and the Grenadines Samoa San Marino Sao Tome and Principe Saudi Arabia Senegal Serbia Seychelles Sierra Leone Singapore Sint Maarten (Dutch part) Slovakia Slovenia Solomon Islands Somalia South Africa South Georgia and the South Sandwich Islands South Sudan Spain Sri Lanka Sudan Suriname Svalbard and Jan Mayen Swaziland Sweden Switzerland Syrian Arab Republic Taiwan Tajikistan Tanzania, United Republic of Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States Uruguay Uzbekistan Vanuatu Venezuela, Bolivarian Republic of Vietnam Virgin Islands, British Wallis and Futuna Western Sahara Yemen Zambia Zimbabwe Nothing quite like this had happened in the two years I had so far been working in a junior position at a lab at the Prince Leopold Institute of Tropical Medicine in Antwerp, Belgium. But I knew it was part of the job. We sometimes took in strange samples of bodily fluids and tried to work out what they were. Our lab was certified to diagnose all kinds of diseases, including arbovirus infections like yellow fever, and the working hypothesis for this epidemic was reported to be “yellow fever with hemorrhagic manifestations.”I never actually worked with any suspected yellow fever. It wasn’t every day we received samples from as far away as equatorial Zaire. And it was clear this was an unusual sample, and that something pretty curious had occurred, because several Belgian nuns apparently died of the disease even though their vaccinations were completely up to date.The next day—September 29—the package arrived: a cheap plastic thermos flask, shiny and blue. I settled down with Guido Van DerGroen—a shy, funny, fellow Belgian aged about thirty, a few years older than I—and René Delgadillo, a Bolivian postdoc student, to open it up on the lab bench. Nowadays it makes me wince just to think of it. Sure, we were wearing latex gloves—our boss insisted on gloves in the lab but we used no other precautions, no suits or masks of any kind.We didn’t even imagine the risk we were taking. Indeed, shipping those blood samples in a simple thermos, without any kind of precautions, was an incredibly perilous act. Maybe the world was a simpler, more innocent place in those days, or maybe it was just a lot more reckless.Unscrewing the thermos, we found a soup of half-melted ice: it was clear that subzero temperatures had not been constantly maintained. And the thermos itself had taken a few knocks, too. One of the test tubes was intact, but there were pieces of a broken tube—its lethal content now mixed up with the ice water—as well as a handwritten note, whose ink had partially bled away into the icy wet.It was from Dr. Jacques Courteille, a Belgian physician who worked at the Clinique Ngaliema in Kinshasa. He described the thermos’s contents as two vials, each containing 5 milliliters of clotted blood from a Flemish nun who was too ill to be evacuated out of Zaire. (Once a Belgian colony known as the Belgian Congo, the country was named Zaire in 1971, before being renamed the “Democratic Republic of Congo” in 1997.) She was suffering from a mysterious epidemic that had so far evaded identification, possibly yellow fever.I was still trying to find my way in the labyrinth of infectious diseases research, and this kind of thing made my heart beat faster. Guido and René picked out the one remaining test tube of blood from the thermos and set to work. We needed to look for antibodies against the yellow fever virus, and other causes of hemorrhagic or epidemic fever such as typhoid. To isolate any virus material, we injected small amounts of the blood samples into VERO cells, an easily replicable cell lineage that is used a lot in labs. We also injected some into the brains of adult mice and newborn baby mice. (I never liked this aspect of the work. Sometimes we needed to inject patient tissue into the testicles of rats, to isolate Mycobacterium ulcerans, the cause of Buruli ulcers, and it made me cringe.)All this work was done with no more precautions than if we had been handling a routine case of salmonella or tuberculosis. It never occurred to us that something far more rare and much more powerful might have just entered our lives.In the next few days, the antibody tests for yellow fever, Lassa fever, and several other candidates all came up negative, and it seemed likely that the samples had been fatally damaged by their transportation at a semi-thawed temperature. We bustled nervously around the mice and checked our cell cultures four times a day instead of two. On the weekend, each of us popped in to check the samples. All of us,I think, were hoping something would grow.Then it happened. On Monday morning, October 4, we found that several adult mice had died. Three days later all the baby mice had also died—a sign that a pathogenic virus was probably present in the blood samples that we had used to inoculate them.By this time our boss, Professor Stefaan Pattyn, had also gleaned a little more information about the epidemic in Zaire. It seemed to be centered on a village called Yambuku, where there was a mission outpost run by Flemish nuns—the Sisters of the Sacred Heart of Our Lady of s’Gravenwezel. (S’Gravenwezel is a small town north of Antwerp.) The epidemic had been raging for three weeks, since September 5, and at least 200 people had died. Although two Zairean doctors who had been to the region had diagnosed the malady yellow fever, the patients suffered violent hemorrhagic symptoms, including extensive bleeding from the anal passage, nose, and mouth as well as high fever, headache, and vomiting.Hemorrhagic manifestations are quite unusual in yellow fever. Although Pattyn could be a bit of a bully, he was hardworking and knew his stuff. He had worked in Zaire for six or seven years, and exotic viral illnesses were right up his alley, though his specialty was mycobacteria—tuberculosis and leprosy. I recall him telling us that this had to be that strange and lethal phenomenon: a hemorrhagic fever.I was just a recently graduated physician; none of the rare hemorrhagic fevers had ever crossed my path. Nor had they featured at all during my medical training. So I made a quick run to the institute’s library to try to absorb as much as I could. It was a small but diverse group of viruses, from mosquito-borne dengue to exotic, recently discovered rodent-borne South American viruses with names like Junin and Machupo. All, by definition, caused high fevers and massive bleeding, and their fatality rate was often in excess of 30 percent.Previously I had been excited about the work we were doing; now I was inflamed. If we were hunting for signs of a hemorrhagic virus, this was outbreak investigation of the most stirring variety. I truly loved the detective thrill of working in infectious disease. You came in and figured out what the problem was. And if you managed to figure it out quickly enough—before the patient died, basically—then you could almost always solve it, because, just like my medical school professor of social medicine had said, solutions had by this time been found for almost every kind of infectious illness.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 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 by rats is either gastrointestinal or respiratory. 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 bioterrorism 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 (CDC), 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 Viral Diseases Unit of the World Health Organization (WHO) 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 Centers 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 micro-manager 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.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 to a conference organized by Beecham, the pharmaceutical company, about some new antibiotic they were bringing out. However, when I walked into the conference room at the Hotel Nikko on that Friday afternoon, my name was on a screen, with a message: I should urgently contact a phone number in Brussels. What the heck?Before doing anything, I called Pattyn, who was still at the lab. He said the Department for Development Aid and the Ministry for Foreign Affairs had been ringing his phone off the hook: we had to get to Kinshasa. The Americans were going there to take a look at the epidemic, and there was some kind of French delegation already in place; even a South African was on his way. Also, Belgian expatriates in Kinshasa had begun panicking, sending their children to Europe because of the epidemic.“The Belgian government is under pressure to do something,” he told me. I thought, surely that “something” can’t be just me, a recent graduate from medical school? But I kept my mouth shut.“This is now a political priority!” Pattyn continued, and I thought: So, that’s how it goes. Unless something is a political priority, figuring out how to save lives is not a big issue.“It’s our Congo, you know,” he said, and I had no idea whether he meant it ironically or straight up, no ice.So I phoned a Dr. Kivits at the Department of Development Aid. There was minimal discussion. He said I should leave the next day on a 10-day mission. I asked if it would it be OK if I waited untilSunday, and Dr. Kivits said fine. So I said yes. I didn’t think about it for a second but asked my then-wife Greta, who was three months’ pregnant and immediately agreed.In a sense, it would be a voyage of self-discovery as much as discovery. In that classic way of the Grand Tour, I was leaving my home, at the age of twenty-seven, to discover myself. Leaving the plain, hard-headed Flemish world of no bullshit—head down, nose clean, hard work, low profile—and heading to a place of big, apocalyptic emotions: despair and exuberance and tragedy and fear. A place that was really coming apart at the seams; a slow-moving disaster scene that had just once again hit a new catastrophe. It was my dream: I was going to the heart of Africa—Zaire—to explore the outbreak of a new virus.Next, part two: ZaireI examined her blood, and it was a catastrophe. The platelet count was terrifyingly low. As green and unimaginative as I was, the real lethality of this virus began to sink in, and my hands shook a little as I handled her blood. Who knew how this virus was transmitted—by insects, or body fluids, or dust … .Adapted from No Time to Lose: A Life in Pursuit of Deadly Viruses by Peter Piot. Copyright © 2012 by Peter Piot. With permission of the publisher, W. W. Norton & Company Inc. 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