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Adrian Hill Is the Brilliant but Widely Loathed Scientist Behind the AstraZeneca Vaccine

It was 2019 and Adrian Hill was still waiting for his success.

The 61-year-old British molecular geneticist had spent nearly three decades working with a colleague, Sarah Gilbert, on a malaria vaccine. Historically, most vaccines used killed or weakened versions of a virus to teach the immune system to fend off a pathogen. Hill and Gilbert favored a more controversial approach—they used a chimpanzee virus to shepherd a malaria gene into the body’s cells.

Using a virus—derived from chimp poop, no less—to ferry genetic code into human bodies might seem strange, or even dangerous. The approach was based on sound logic, however. Chimpanzees are humans’ closest living relatives, so a virus that infected these mammals seemed likely to spread in humans as well. That means it was capable of doing a good job chauffeuring a piece of the malaria parasite into the body. And there was no danger to using the chimp virus because Hill and Gilbert had tweaked it so the virus would infect human cells, but be incapable of spreading within the body.

Hill, an Irish vaccinologist at the University of Oxford, had been fascinated with malaria since the early 1980s. As a medical student in Dublin, he had spent his vacations visiting an uncle who worked as a priest in a hospital in Rhodesia, which later became the nation of Zimbabwe. Hill saw how malaria absolutely hounded the region. But pharmaceutical companies weren’t eager to tackle the disease, partly because it’s endemic in developing nations and has minimal profit potential.

Hill dedicated himself becoming the one to develop protective shots, work that went on for years. By late 2019, Hill was still working with Gilbert to produce a malaria vaccine. They also worked on shots to fend off influenza, HIV, and other viruses and diseases. At that point, though, the Oxford team hadn’t gained approval for a single vaccine.

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Professor Adrian Hill holds the Ebola vaccine at Oxford in 2014.

Steve Parsons/Reuters

Limited success had hardly humbled Hill, though. In fact, he had emerged as one of the most controversial and disliked men in the world of science, notorious for his sharp critiques of fellow researchers and caustic, even offensive, behavior. At scientific meetings, Hill was usually the first to jump to his feet, grab a microphone, and challenge a point being made in a presentation. He often did it in degrading or insulting language. Here are snippets of quotes from Hill over the years, as related by various scientists in his field:

“That’s a really dumb idea.”

“Your data sucks.”

“That’s the most ignorant thing I’ve ever heard.”

Researchers came to these meetings girded for Hill’s blunt, even vicious, verbal lashings. If Hill merely cleared his throat, it likely meant some kind of savagery was on its way. Some peers learned to appreciate the remarks, realizing that Hill’s punches were often packed with trenchant points that enabled researchers to perfect their methods. But younger or unprepared scientists were sometimes startled by the comments, which they viewed as unnecessarily personal.

At times, the criticisms were made with such vehemence and intensity that Hill’s face turned bright red, nearly matching his hair color. Hill’s derisive comments hit hard because the self-worth of some researchers, not to mention their career prospects, were tied up in their scientific data and conclusions.

What bothered Hill’s peers most was that he seemed more critical of the work of others than he was of his own research. It seemed that almost every year, the BBC, CNN, or another media outlet profiled the progress he and Gilbert were making against some disease or other. Rivals thought he overstated his group’s chances of success. Yet there was Hill, at one more medical conference, lecturing another scientist about why her approach was doomed. Gilbert was a quiet, restrained presence at the meetings, but Hill eagerly shared his critiques.

Once, at an annual meeting of experts in infectious tropical diseases, an academic named Chris Plowe corrected an answer Hill had given to the crowd during a presentation. Plowe referenced work by Joana Carneiro da Silva, a younger colleague at the University of Maryland. Hearing her work mentioned, Silva approached a microphone in the audience to share her data and explain the mistake Hill had made. Hill quickly waved off Silva’s critique, exhibiting a disdain that researchers in the room had come to expect.

Silva was new to the field, though, and she didn’t appreciate being publicly disrespected. To the shock of the scientists in the room, Silva walked right back to the microphone, her voice slightly trembling, to correct Hill, once again, proving detailed evidence to bolster her cause. Hill wouldn’t back down from his points.

Silva wasn’t willing to give in. She stood up to challenge Hill, this time even more forcefully, as the group privately cheered her on. It was like the new kid in school fighting back against a bully accustomed to getting his way while watching his victims quiver.

“He was banking on his reputation to have his argument prevail, and that was infuriatingly abrasive,” she says.

Hill’s behavior over the years was too much, even for his fans.

“Adrian is a superb scientist, he truly believes in helping mankind and I like him,” says Hildegund Ertl, a senior scientist. “But a truly great scientist knows they don’t know it all and are humble. Humble and Adrian Hill don’t go together.”

Behind his back, peers gave Hill nicknames, most of which poked fun at his perceived arrogance.

It didn’t help Hill that he appeared a near-picture-perfect caricature of one of the most disliked of all British archetypes: the self-important Oxbridge academic. Hill was pompous, he had spent nearly four decades at Oxford, and he had floppy, unkempt hair. Hill loved tweed coats, and while he didn’t wear bright red trousers, he probably had them at home, scientists joked, pressed and hanging in a closet. Behind his back, peers gave Hill nicknames, most of which poked fun at his perceived arrogance. Some called Hill, whose full name is Adrian Vivian Sinton Hill, “Lord Adrian VS Hill of Hillington,” while others went with “Lord Adrian.”

Over a pint or dinner, Hill was much more likable. Scientists who didn’t directly compete with Hill said he treated them with respect and deference. And Hill was supportive and helpful to younger Oxford scientists, earning their loyalty. These junior researchers often had more problems with Hill’s scientific partner, Gilbert, viewing her as cold and difficult to deal with. To outsiders, though, Hill remained a lighting-rod.

“Adrian has a Marmite personality,” says a colleague, referring to the odorous, brownish, vegetable spread beloved in the U.K but detested most everywhere else. “You love him or hate him.”

Hill’s friends sometimes stepped up to lend him support.

“No other person has run so many phase one trials,” Rino Rappuoli, a senior immunologist.

Saying someone is really good at running phase 1 trials, though, is a bit like complimenting a soccer player for how many shots she’s taken on goal. At some point, you have to score. Hill had never come close to an approved vaccine or drug.

In November 2019, Hill flew to National Harbor, Maryland, just south of Washington, D.C., for a meeting of global infectious-disease experts. Hill was cocksure, as usual, weighing in on various pathogens and ideal vaccine approaches. He didn’t realize it, but as he spoke, the threat of his lifetime was emerging thousands of miles away.

Early in 2020, Hill and Gilbert paid little heed to the new pathogen emerging in Wuhan, China. Hill traveled to Senegal, New York, and elsewhere, busy with his malaria research. Gilbert began building a potential COVID-19 vaccine. But she hoped clinical trials of her vaccine might begin in July or so. There didn’t seem a need to rush. Emerging pathogens always get people scared but peter out on their own, don’t they?

A rivalry emerged between Hill and Gilbert over who could exhibit more certainty, or even arrogance, about their vaccine.

A younger Oxford scientist was growing anxious, however. Sandy Douglas read disturbing articles about the virus and the underlying data pointed to trouble. He called and texted Hill, trying to engage him in the developing crisis. He didn’t get anywhere. A 37-year-old physician, Douglas had first-hand experience with Britain’s tightly funded National Health Service. He knew the health service could become overwhelmed in a crisis. Douglas’ father, who had cancer and was on chemotherapy treatments, went on a trip to Rome, even as the virus was rapidly spreading in Italy, stirring Douglas’ fears. With each news article and fresh data point, Douglas became more agitated.

“I was going nuts,” he says.

Slowly, though, Hill began shifting his focus to the emerging virus, thanks in part to Douglas’ entreaties. In February, Hill told colleagues they needed to go superfast and that their vaccine needed to be ready for testing as soon as April.

“No later,” he said.

Gilbert initially resisted the idea of rushing to test and introduce a vaccine. Soon, though, she also got on board. By the end of March, she and her colleagues had lined up more than enough backing from U.K. bodies and others to push ahead.

The Oxford scientists received early evidence their jabs might work. Researchers at the National Institutes of Health’s Rocky Mountain Laboratories in Montana inoculated six rhesus macaque monkeys with single doses of the Oxford vaccine. Then, the researchers exposed the monkeys to a huge amount of the coronavirus—28 days later, the monkeys were all healthy.

Hill, confident as always, let out a cheer.

“It wasn’t promising—it was fantastic,” Hill said a bit later.

Soon, Hill and his colleagues had raced past all their competitors, making plans to start large human trials for their vaccine. In late April, they forged an agreement with AstraZeneca, a British drug giant based in Cambridge, U.K., to help test, manufacture, and distribute the shots.

By then, the new coronavirus had reached almost every corner of the world, overwhelming the health-care systems of many countries. Health authorities in the U.S., U.K., and elsewhere saw Oxford’s jabs as the most likely means for the world to escape the virus’s grip. A rivalry emerged between Hill and Gilbert over who could exhibit more certainty, or even arrogance, about their vaccine. In May 2020, Hill told Reuters that the Oxford/AstraZeneca shots were “almost certainly the best single dose rapid-response vaccine,” while dismissing the mRNA vaccine approach.

By late summer of 2021, the Oxford vaccine still hadn’t been authorized in the U.S. It’s not clear it ever will be.

“Why would you take a vaccine technology that is new, unproven, maybe quick to manufacture, but expensive to manufacture and has never been scaled up—and has never been shown to protect against anything in humans, and prioritize that in a global emergency?” Hill asked.

In July he said, “We know the adverse event profile and we know the dose to use, because we’ve done this so many times before… Obviously we’re doing safety testing, but we’re not concerned.”

When a friend called asking Hill about his team’s progress, Hill sounded optimistic, even relieved. After decades of work, he seemed to have a winner.

In May 2020, Operation Warp Speed gave the Oxford/AstraZeneca effort $1.2 billion to test and manufacture their coronavirus vaccine in exchange for 300 million doses. Final efficacy data and regulatory approvals were expected by September. At Oxford, spirits were high. Soon, though, U.S. officials became concerned. The Oxford researchers didn’t seem to communicate well with AstraZeneca’s scientists. American authorities sometimes waited weeks for important trial data—such as details about various vaccine batches—that other vaccine companies delivered overnight. By early summer, AstraZeneca had enrolled far fewer people in its trials in Britain and Brazil than U.S. authorities were requesting. Delays were growing. Hill and Gilbert’s effort had lost its front-runner status.

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Brazilian doctor Monica Levi was one of the volunteers in a Phase 3 trial of the Oxford/Astrazeneca vaccine.

Nelson Almeida/Getty

In late November, the Oxford team counted down to their vaccine’s phase 3 clinical-trial result, a clear chance for the group to move past its troubles. Over the weekend of November 22, Oxford and AstraZeneca executives received the results. Their vaccine had an efficacy of 62 percent for the largest group of trial participants, nearly nine thousand volunteers, who had received two full-strength doses several weeks apart. The figure paled in comparison with those of Pfizer/BioNTech and Moderna days earlier.

As they analyzed the data, though, the Oxford team found a reason to celebrate. A smaller number of volunteers, 2,741 in total, who had been given an initial, half-strength dose of the vaccine before receiving a second, full dose twelve weeks later. For these people, the vaccine had been 90 percent effective, exciting the researchers.

On the morning of November 23, Oxford and AstraZeneca announced the results. Oxford called the results a “breakthrough,” while AstraZeneca in a separate release said that “the vaccine was highly effective in preventing COVID-19.” The very first figure AstraZeneca cited was the efficacy figure of 90 percent. After sharing the lower, 62 percent efficacy figure, AstraZeneca said that combining the two dosages had “resulted in an average efficacy of 70 percent.”

Almost immediately, the Oxford/AstraZeneca team faced a barrage of criticism. The higher-efficacy figure had resulted from a small subset of their overall study. Some accused the researchers of cherry-picking their data. They couldn’t even explain why a half dose had provided such strong protection, nor even how it had resulted.

“We stumbled upon doing half dose–full dose,” Mene Pangalos, head of AstraZeneca’s non-oncology research and development, told Reuters. “Yes, it was a mistake.”

But his boss, Pascal Soriot, said, “It was not a mistake,” something both Gilbert and Hill were adamant about.

Critics piled on. “The world bet on this vaccine,” said Eric Topol, a clinical trial expert at the Scripps Research Institute in San Diego. “What a disappointment… If they just were upfront on safety, on efficacy, on dosing, on everything, from the get- go, they’d be in such a better position.”

AstraZeneca announced plans to deliver up to three billion doses by the end of 2021, including hundreds of millions for people in poor and middle-income countries.

Hill had spent his career dishing criticism. Now, scientists and others were ripping into him and his colleagues. He was livid. Gilbert and Hill built their shots to be inexpensive and easy to manufacture, store, and transport. Yes, his group could have improved their communication and analysis, he told people, but they had acted swiftly to help stop a pandemic. Their vaccine might not be perfect, or even the best of the lot, but it worked and it was saving lives. Why couldn’t people see that?!

When a fellow scientist called him late in 2020, Hill vented his frustrations.

“Nobody knows what the hell they’re talking about,” he said, referring to scientists, the media, and pretty much everyone else criticizing the Oxford/AstraZeneca effort.

Hill’s voice rose as his defense continued.

“We got a vaccine out the door,” he said. “This virus is killing people!”

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Prime Minister Boris Johnson receives his second jab of the Oxford/AstraZeneca vaccine in June.

Matt Dunham/Getty

On December 30, 2020, the Oxford/AstraZeneca vaccine was authorized for use by the U.K. Doses were immediately distributed, helping the country fend off a new surge of COVID-19 cases. In late January, the shots were authorized in Europe as well. After decades of work, Hill finally had a vaccine going into arms.

New and serious concerns soon arose, though. The Oxford/AstraZeneca effort experienced production shortfalls. They also confronted questions about the vaccine’s effectiveness for the elderly and worries about its ability to handle new strains of the coronavirus. When blood clots arose in a small number of previously healthy women, the worries and criticisms grew, even among U.S. government officials.

It was all too much for Hill. He couldn’t believe official bodies were undermining his group’s vaccine, even as the virus killed thousands a day and too many people were finding reasons to resist inoculation.

“Talk about efforts to maintain confidence in vaccines,” Hill emailed a Washington Post reporter after a monitoring board leveled public criticism. “What is going on?!”

By late summer of 2021, the Oxford vaccine still hadn’t been authorized in the U.S. It’s not clear it ever will be. Still, the shots were being used more than 70 countries, the most widely used shots in many parts of the world. The jabs were among the cheapest and easiest to transport and store, lasting more than six months at normal refrigeration. AstraZeneca announced plans to deliver up to three billion doses by the end of 2021, including hundreds of millions for people in poor and middle-income countries.

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The Royal Box stands and applauds University of Oxford Professor Sarah Gilbert (seated in red, bottom right) ahead of the opening match of Wimbledon 2021.

AELTC/Joe Toth/Getty

By then, Hill and Gilbert were mostly past the mockery and mistakes. Speaking with friends and others, the scientists shared frustrations regarding the criticisms. But they also expressed pride about how they had helped develop a safe and effective vaccine that was protecting so many people around the world.

Hill had already returned to his original passion: fighting malaria. A malaria vaccine he had developed had begun a phase 3 trial. It had showed efficacy of 77 percent. Hill and his colleagues hoped their low-priced jabs would be in arms by 2023, combatting a disease that takes 400,000 lives each year, most of them children in sub-Saharan Africa.

One day in the summer of 2021, Hill received an honorary knighthood from Queen Elizabeth, while Gilbert was made a Dame, career-capping honors for both scientists. That evening, Hill attended a barbeque in Oxford with colleagues and friends. He received a round of applause and a champagne toast. Hill, who had just returned from a trip to Gibraltar, where he had remarried, was jovial, optimistic, and proud.

Excerpted and adapted from A SHOT TO SAVE THE WORLD: The Inside Story of the Life-or-Death Race for a COVID-19 Vaccine by Gregory Zuckerman, now on sale from Portfolio/Penguin.

https://www.thedailybeast.com/adrian-hill-is-the-brilliant-but-widely-loathed-scientist-behind-the-astra-zeneca-vaccine?source=articles&via=rss Adrian Hill Is the Brilliant but Widely Loathed Scientist Behind the AstraZeneca Vaccine

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