NEWS FEATURES Downloaded from http://science.sciencemag.org/

on May 1, 2020

THE CORONAVIRUS CZAR The COVID-19 pandemic has made German virologist Christian Drosten an unlikely cult figure

By Kai Kupferschmidt, in Berlin PHOTO: VOLKER LANNERT VOLKER PHOTO:

462 1 MAY 2020 • VOL 368 ISSUE 6490 sciencemag.org SCIENCE

Published by AAAS NEWS

but now one of those pathogens was killing virus he has spent most of his life studying. patients in a hospital a few blocks away. “If this were influenza, for instance, I would And instead of teaching virology to a few not be doing this,” he says. hundred students, Drosten now addresses hundreds of thousands of anxious Germans. DROSTEN’S CORONAVIRUS CAREER effectively Twice a week around 10 a.m., he sets a blue began on Saturday, 15 March 2003, when a microphone on his desk, puts on head- 32-year-old doctor from Singapore named phones, and waits for a science journalist Leong Hoe Nam was taken off a plane in from German radio station NDR Info to call Frankfurt, Germany, and taken to the city’s him. For the next 40 minutes, he answers university clinic. Leong had treated patients questions about vaccines, respiratory drop- in Singapore before attending an infectious lets, school closures, or masks. The podcast, diseases course in New York City, and had de- simply titled Coronavirus Update, has made veloped symptoms consistent with an alarm- Drosten the face, or rather the voice, of the ing new respiratory disease that was rapidly pandemic in Germany. More than 1 million people regularly download what has become the country’s most popular podcast. Drosten is one of the world’s foremost ex- “Many people may not perts on coronaviruses; his career has closely understand everything tracked their emergence as a global threat.

Now, he is also a popular—if nerdy—hero. he says. But it is Downloaded from In one widely shared meme, his face, with a pair of horn-rimmed glasses photoshopped comforting to listen on it, sits next to three movie stills of actor to someone explaining Jeff Goldblum, to whom he bears a passing resemblance. “He has fought dinosaurs, body what is going on.”

snatchers, and aliens,” the caption reads, “so http://science.sciencemag.org/ Holger Wormer, I’ll trust him with this virus too.” Drosten’s Technical University of Dortmund cult status reminds Holger Wormer, a jour- nalism professor at the Technical University of Dortmund, of Stephen Hawking’s: “Many spreading in Asia. That same day, the World people may not understand everything he Health Organization (WHO) had christened says. But it is comforting to listen to some- the new disease “severe acute respiratory one explaining what is going on.” syndrome,” or SARS. His calm, considered communication has At the time, Drosten was building up a earned Drosten widespread appreciation. lab for molecular diagnostics at the Bern- “It’s a stroke of luck that we have someone hard Nocht Institute for Tropical Medicine

here in Germany who is recognized world- in Hamburg, Germany. The Frankfurt viro- on May 1, 2020 wide as an expert on coronaviruses and who logists sent Leong’s blood and other sam- is willing and able to communicate so well,” ples to Drosten, hoping he could help iden- says Volker Stollorz, head of the German tify what was believed to be a new virus. But Christian Drosten admits Science Media Center. On 20 April, the Ger- tests for everything from adenoviruses to the pandemic surprised him, man Research Foundation announced it was paramyxoviruses came back negative. despite having worked on awarding Drosten a one-off prize for “out- About 1 week later, however, when coronaviruses for 17 years. standing science communication during the Drosten was in Frankfurt to defend his doc- COVID-19 pandemic.” toral thesis, the same virologists told him Drosten also explains coronaviruses to they had managed to grow the virus in a politicians. He has advised German Chancel- petri dish. Drosten realized this would allow n a recent Monday morning, lor Angela Merkel—they chatted by phone him to use a new catch-all method he had Christian Drosten said goodbye to for about an hour recently, he says—and developed for identifying unknown viruses, his wife and 2-year-old son in front Minister of Health Jens Spahn. He has been which amplified viral genetic material so it of his apartment block and got on called Germany’s “coronavirus-explainer-in- could be sequenced and checked against on- his bicycle for his daily commute to chief” and “the coronavirus pope,” the Ger- line databases. Drosten picked up a sample, Charité University Hospital here. man equivalent of a “coronavirus czar.” then drove the 5 hours back to Hamburg in It looked like a scene from Yet colleagues describe Drosten, 47, as his old Opel and went straight to his lab. Af- normal daily life. But of course an unlikely character for his new role. “He ter a few days with little sleep, he had a small it wasn’t. His wife was going for is not someone who seeks out this kind of part of the new virus’ genome. The closest a walk with their child instead of bringing attention,” says Isabella Eckerle, a match was a cattle coronavirus Ohim to the day care center, which was closed. former lab member who now runs that doesn’t infect people. “My first The Berlin streets Drosten traversed were a laboratory for emerging viral dis- Science’s thought was, maybe it is some kind eerily quiet, most shops were closed, and eases at the University of Geneva. COVID-19 of contamination from the FCS,” the coverage some people on the sidewalks wore masks. Drosten says he wouldn’t have is supported fetal calf serum used to grow cells in Charité’s Institute of Virology, which Drosten stepped into the limelight if SARS- by the the lab, Drosten recalls. heads, was studying exotic viruses, as always, CoV-2 weren’t exactly the kind of Pulitzer Center. But he and his colleague Stephan

SCIENCE sciencemag.org 1 MAY 2020 • VOL 368 ISSUE 6490 463

Published by AAAS NEWS | FEATURES

Microbes and man Christian Drosten’s career paralleled the emergence of coronaviruses as a serious human threat. He worked on severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) and in January, his lab developed the first test for SARS-CoV-2, the new pandemic virus.

1966 1967 1968 1975 2002 2003 2004 2005 2012 2019 2020 229E OC43 Name Family of SARS SARS-CoV NL63 HKU1 MERS-CoV COVID-19 SARS-CoV-2 (cold virus) (cold virus) “coronavirus” coronaviruses outbreak discovered (cold virus) (cold virus) discovered pandemic discovered discovered discovered coined established begins in discovered discovered begins China in China Coronaviruses

1960 1965 1970 1975 1995 2000 2005 2010 2015 2020

Christian Drosten

1972 1994 2003 2007 2013 2017 2018 2020 Born in Starts Develops Becomes Work with Becomes Also becomes Lab Lingen, studying frst test head of the Marion head of Charité research develops Germany medicine in for SARS University Koopmans University director of frst test Frankfurt, of Bonn’s shows Hospital’s Charité Global for SARS- Germany Institute of camels carry Institute of Health, CoV-2 Virology MERS-CoV Virology a new center Downloaded from

Günther quickly realized they were seeing caused by a paramyxovirus, had jumped to too, originated in camels. It was a warning a deadly new member of the family. “At the humans from bats. They also showed that sign, Drosten said at the time, that MERS time, medical students learned hardly any- Nipah, another bat-borne virus, originated could follow the same course as SARS,

thing about coronaviruses,” Drosten says. in Africa, even though it was discovered which had originated in bats, and evolve http://science.sciencemag.org/ The only two known to cause disease in in Malaysia after hundreds of pig farmers to become a true human disease. Animal humans, named OC43 and 229E, accounted there developed encephalitis in 1999. coronaviruses, it seemed, posed a particular for a small percentage of human colds ev- Scientists discovered two new corona- threat of sparking a pandemic. ery winter. This new virus was a very dif- viruses in the years after the SARS outbreak, ferent beast. SARS killed 10% of the almost both of which caused the common cold. Then WHEN ANOTHER severe respiratory syn- 8000 people it infected in nearly 30 coun- in 2012, researchers isolated a new corona- drome emerged this year, Drosten—who tries before it was contained. virus that spelled greater danger. It came moved to the prestigious Charité University Researchers at the U.S. Centers for Disease from a 60-year-old man in Saudi Arabia Hospital in 2017—was prepared. After see- Control and Prevention and the University of who had developed pneumonia. Intrigued, ing the first rumors about a coronavirus in Hong Kong realized the culprit was a corona- Drosten geared his research to the new China online, Victor Corman, who leads the virus around the same time. But Drosten was agent, which was soon called the Middle East lab’s virus diagnostics group, began to scour on May 1, 2020 the first to develop a diagnostic test, and he respiratory syndrome (MERS) virus. In 2013, existing sequences of SARS-related corona- distributed the protocol freely on the inter- he reported on a wealthy 73-year-old patient viruses, isolated from bats, for regions that net. It earned him international recogni- from Abu Dhabi, United Arab Emirates, who were the same across different viruses. He tion as well as the Federal Cross of Merit, an was treated for MERS in Germany and died. was trying to guess what parts of a new important German award. (Leong survived Relatives said the patient had cared for a sick SARS-like coronavirus might look like, in his bout with SARS and is now treating racing camel before falling ill—the first sign order to create a test. Based on those se- COVID-19 patients himself. He says he has that camels might be involved. quences, he designed and ordered 20 pairs not met Drosten, but reads every paper Saudi Arabia, which had the most MERS of so-called primers, little snippets of DNA, coming from his lab. “Truly, he is an incred- cases and a multimillion-dollar camel rac- that pair with a pathogen’s genome, so that ible scientist, with out-of-the-box thinking,” ing industry, initially scoffed at the link. it can be amplified and detected. Leong wrote in an email.) “We don’t think camels are involved,” When Chinese researchers finally pub- then–Deputy Minister of Health Ziad lished the genome of the new virus from Wu- DROSTEN GREW UP on a pig farm in northern Memish said. But work from Drosten’s han on 10 January, Corman used the primers Germany. He studied medicine in Frankfurt, group and others soon confirmed the sus- that best matched the viral sequence and the first person in his family to go to univer- picion. Memish and Drosten teamed up to prepared the diagnostic test almost imme- sity, and rose quickly in German academia. study the new disease, and Drosten’s Bonn diately. WHO posted Corman’s protocol on After his stint in Hamburg, he became a lab became a leading MERS hub. It devel- its website on 13 January, allowing countries full professor at the University of Bonn oped a test to detect the virus’ RNA and around the world to produce a test them- and, at 35, head of the Institute of Virology. then an antibody assay that helped show selves and detect imported cases of the new His research interests were ideal prepara- the virus had likely been infecting people in virus. Drosten predicted the test would also tion for COVID-19. He established a system the region for decades. help scientists understand whether the virus for probing the function of the SARS virus’ The research yielded some unexpected was able to spread from human to human. SCIENCE genes and started to study viral evolution, insights. While looking for coronaviruses It was. looking for close relatives of human viruses in camels, the scientists found pathogens Three and a half months later, SARS-CoV-2, in animals. In one such study, his team dis- closely related to 229E, one of the common as it is now known, has traveled to all corners

covered that mumps, which like measles is cold coronaviruses, suggesting that virus, of the world, infecting millions of people and DESAI/ N. GRAPHIC:

464 1 MAY 2020 • VOL 368 ISSUE 6490 sciencemag.org SCIENCE

Published by AAAS killing well over 200,000. It has forced coun- He chided political journalists who asked treat tapeworms and other parasites. In a tries from Austria to Zambia to shut down whether important soccer matches and paper posted on the preprint server bioRxiv their economies and societies, causing im- Germany’s sacred Oktoberfest would need this month, Drosten’s colleague Marcel mense suffering and igniting heated debates to be canceled, saying that was not his ex- Müller showed that SARS-CoV-2 interferes about the right way to deal with the threat. pertise. He bristles at stories describing his with the cellular recycling process called Drosten concedes it has surprised him, de- “sensual lips” and tousled hair. “I talk about autophagy. It’s unclear how exactly that spite his 17 years of work on coronaviruses science,” he says. “I don’t want to read about benefits the virus, but niclosamide counters and his knowledge of the threat they pose. “I my haircut.” Wormer says Drosten is doing the interference. Treatment with the com- didn’t think that SARS would come back like a great job talking about the science, but is pound reduced SARS-CoV-2’s growth in cell this,” he says—as a virus that is both deadly a tad naïve about what interests the media. culture by 70%, the authors write. Drosten and much more transmissible. It is adept at “For some people going to the stadium is hopes to start to enroll patients soon in a infecting cells of the upper respiratory tract, important and you just have to accept that,” trial to test a combination of the two drugs. from which a cough can expel it, and unlike he says. For a public figure, a bit of mockery For the moment, Drosten is learning what SARS—but like the flu—it can spread before comes with the territory as well, he says. he can from sequencing virus samples and symptoms emerge. “That’s pretty astonish- Drosten has balked at suggestions that probing the pathogen in the biosafety level ing,” Drosten says. he has become a political player. He seemed 3 lab in the institute’s basement. He is also Drosten says a key reason for SARS-CoV- genuinely angry after a spate of stories sug- interested in how SARS-CoV-2 made its way 2’s success may be a tiny part of the “spike,” gesting virologists had taken the reins of Ger- from animals to humans. He’s fascinated by the protein that sits on the virus’ surface man government. “If that doesn’t change, we the role livestock appear to play as a bridge and makes it look like a crown between bats, which are corona-

when seen through a microscope. viruses’ natural hosts, and hu- Downloaded from The spike protein attaches to a mans. 229E and MERS came from receptor on human cells called camels, OC43 from cattle. SARS angiotensin-converting enzyme infected civets and also raccoon 2. Before the virus can enter the dogs, raised by the millions in cell, however, a part of the pro- China’s fur industry. SARS-CoV-

tein has to be cleaved. The SARS- 2’s origin is unclear, but Drosten http://science.sciencemag.org/ CoV-2 spike protein cleaves more wonders whether raccoon dogs readily than equivalent proteins could be an intermediate host. “I in other coronaviruses, because would love to take samples from it has evolved something called 20 of these farms,” he says. a polybasic cleavage site, which Drosten likens to the perforations FOUR MONTHS after the emer- on a notepad that make it easier gence of the pandemic, Ger- to rip off a page. That feature may many is widely seen as a explain the virus’ rapid spread Christian Drosten (center) at a March press conference with German Minister of success story in Europe. The from cell to cell, he says. Health Jens Spahn (right) and Petra Gastmeier, director of the Charité Institute country tests widely for the

Drosten started to warn of of Hygiene and Environmental Medicine (left). virus—thanks in part to on May 1, 2020 the new virus’ potential in TV that first assay, developed in interviews in January, but quickly grew are reaching the point where science has to Drosten’s lab—and has managed to keep exasperated. After long interviews, journal- start an orderly retreat,” he said on the pod- case numbers low. Now, as in many coun- ists often used one short quote that failed cast. His role as a political adviser is small, tries, pressure is building to reopen shop- to convey the immense threat, he says. “I he told Science. “It’s not like I’m in and out of ping malls, bars, and restaurants. Drosten actually called up some of them afterwards ministries all day.” When a German newspa- is worried some German states are moving and told them: ‘You are missing the boat on per ran his photo under the headline “Is this too fast, which could lead to an explosive this.’” So when a producer from NDR asked our new chancellor?” he bristled at the idea. resurgence of the virus. Drosten in February whether he was will- That concern has led him to depart from ing to answer a few questions every day, DROSTEN FEELS most at home concentrat- his science-only strategy. “In this situation, his answer was swift: “Traveling at the mo- ing on his research. Virologist Marion for once, I have to express my opinion a ment, like the idea, we can start Monday.” Koopmans of Erasmus Medical Center in little bit here in this podcast,” he said on

S (Drosten recently reduced the frequency to the Netherlands recalls seeing him during 22 April. Discussing press reports of shop- G E twice a week.) a technical planning meeting of a large re- ping malls full of people, he said, “It’s sad I MA The show’s conversation is easygoing, search consortium, huddled at the back of to see that we may be in the process here in

G E T TY and Drosten occasionally offers advice. the room with two or three others. “Prob- Germany of completely gambling away the

V I A In March, he told listeners to avoid beer ably writing a Nature paper,” she says. “He advantage we have had.” O T from the tap, because glasses might not be doesn’t like the blah blah blah.” With COVID-19 drugs and vaccines un- cleaned thoroughly. “When I go to a bar, I But Drosten wants his research to save available, such words may be the most pow- always order beer in a bottle, for many years lives. Large cardboard boxes in his office erful tool to curb the spread of the virus.

ON TI N I / U R P H O now,” he said. If Drosten is himself emotion- hold supplies of two medicines waiting to be And whether or not he likes it, Drosten’s ally shaken by the pandemic and the way it tried in the clinic. One is camostat mesylate, podcast has given him real influence, says is changing the world, he doesn’t show it. a pancreatitis drug approved in Japan that Marcel Fratzscher, head of DIW Berlin, an Drosten also seems unfazed by his new- Drosten and others found can prevent both economic research institute. “At this point, O : E M A N U L C

T found fame, but he gets annoyed when SARS-CoV and SARS-CoV-2 from entering if Drosten says it is too early, that carries as

PH O the focus drifts away from the science. cells. The other drug is niclosamide, used to much weight as Merkel saying it.” j

SCIENCE sciencemag.org 1 MAY 2020 • VOL 368 ISSUE 6490 465

Published by AAAS The coronavirus czar Kai Kupferschmidt

Science 368 (6490), 462-465. DOI: 10.1126/science.368.6490.462 Downloaded from

ARTICLE TOOLS http://science.sciencemag.org/content/368/6490/462

RELATED http://stm.sciencemag.org/content/scitransmed/12/541/eabb5883.full CONTENT

http://stm.sciencemag.org/content/scitransmed/12/534/eabb1469.full http://science.sciencemag.org/ http://stm.sciencemag.org/content/scitransmed/11/499/eaat0360.full http://stm.sciencemag.org/content/scitransmed/9/396/eaal3653.full

PERMISSIONS http://www.sciencemag.org/help/reprints-and-permissions

on May 1, 2020

Use of this article is subject to the Terms of Service

Science (print ISSN 0036-8075; online ISSN 1095-9203) is published by the American Association for the Advancement of Science, 1200 New York Avenue NW, Washington, DC 20005. The title Science is a registered trademark of AAAS. Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works