Operation Warp Speed: The Untold Story of the COVID-19 Vaccine
How an unlikely group of scientists, generals, and government officials supercharged the effort to get us back to some kind of normal. Moncef Slaoui, the retired head of the vaccine department at the pharmaceutical giant GlaxoSmithKline, was called to answer a call from a former Republican congressman from Pennsylvania asking if a vaccine against the COVID-19 pandemic could be widely available by the end of the year. Sl aoui was an unlikely recipient of such a call, but he quickly realized that vaccines held out more promise to help people than politics ever could. He helped develop vaccines against genital herpes, human papillomavirus, rotavirus and pneumococcal bacteria, malaria, H1N1, Ebola, and more. When the Ebola virus hit West Africa in 2014, SlaOUi's division put everything else aside to make a vaccine quickly. GSK took a hit in the stock market and GSK agreed to help create a nonprofit division to design vaccines that could prevent pandemics and prevent diseases.
Yayınlanan : 2 yıl önce ile By Chris Whipple, By Joe Nocera and Bethany McLean, Condé Nast, By Julie Miller, By Philip Bump, By Nate Freeman içinde Health
On a chilly day in mid-April 2020, Moncef Slaoui, the retired head of the vaccine department at the pharmaceutical giant GlaxoSmithKline, was sitting by his unopened pool in Gladwyne, Pennsylvania, when his phone rang. The hopeful hint of spring in the air belied the dark desperation that suffused the world as the COVID-19 pandemic raged and the world’s wealthiest country struggled to figure out a way forward. The caller was Jim Greenwood, a former Republican congressman from Pennsylvania who, since 2005, had served as the CEO of the trade association BIO, short for the Biotechnology Innovation Organization. Greenwood was reaching out after getting a call from Secretary of Health and Human Services Alex Azar. He had an urgent question for Slaoui: “Do you think that if you had unlimited resources, money, and people that we could have a vaccine against COVID-19 widely available by the end of the year?” On one level, Slaoui was an unlikely recipient of such a call. He was no fan of Donald Trump, and of course Trump had no use for anyone who didn’t support him. Slaoui had never even been a Republican. He was an immigrant from Morocco, one of four siblings, all of whom got either their PhD or their MD, even though neither parent had gone to college. His childhood was a time of rampant repression; Slaoui’s memories of high school in Casablanca included frequent student strikes followed by army clampdowns. When he headed to the Free University of Brussels, he became part of the Moroccan Student Union, a Marxist group that wanted to make Morocco a more populist and democratic country. Slaoui, who is fluent in English, French, and Arabic, speaks in a measured and cosmopolitan manner that can mask strong passions. At that time, his passion was politics. For several years, he did little academic work, spending his time instead on activism. After finishing his PhD in 1983, he spent two years as a postdoctoral fellow at Harvard and Tufts University. In 1985, he made his way back to Belgium when his first wife, an immunologist, was recruited by Glaxo Wellcome, which was trying to develop an HIV vaccine. Slaoui was still enough of a socialist to view the pharmaceutical industry with disdain. But as he watched his wife’s work, he began to realize how world changing vaccines could be. To Slaoui, vaccines held out more promise to help people than politics ever could. He’d often tell people that vaccines had saved more lives than any other tool in history. In 1988, Slaoui began to work for what would eventually become GlaxoSmithKline. (Today, the company is called GSK.) Over the ensuing decades, he helped develop vaccines against genital herpes, human papillomavirus, rotavirus, pneumococcal bacteria, malaria, H1N1, Ebola, and more. In all, he supervised seven vaccines through development, an unrivaled accomplishment. When the Ebola virus hit West Africa in 2014, Slaoui’s division put everything else aside to make a vaccine quickly. It took only seven months to have the vaccine ready for a phase one trial, in which the drug is tested for safety in otherwise healthy people. (This is the first of three phases needed to get a drug approved by the FDA.) But while the Ebola outbreak killed more than 11,000 Africans, it had largely subsided by the time GSK’s vaccine was developed. Dr. Slaoui at home by his swimming pool where he first received the call from Secretary of Health and Human Services Alex Azar. Left with little demand, GSK took a hit in the stock market. And the government officials who had been so adamant about the need to develop the vaccine suddenly had more important things to do. “Everybody who was talking to us every day, all the governments who were saying, ‘Where are you? How can we help you?’ just turned around and looked the other way,” Slaoui says. Slaoui realized that the world needed a way to support the development and manufacture of vaccines that didn’t depend on publicly traded companies trying to maximize shareholder value.
So Slaoui got GSK to agree to help create a nonprofit division called the Biopreparedness Organization, or BPO. Its purpose was to design vaccines that could prevent pandemics and, just as important, to build a strong vaccine manufacturing capacity. Vaccine manufacturing is incredibly complex, particularly when done at large scale. To that end, Slaoui even persuaded GSK to buy an empty plant in Maryland. “Unfortunately, one of these days, one of these agents is going to be global and very lethal. It’s going to be catastrophic,” Slaoui told CNBC in 2016. “So we have to have a longer-term commitment and solutions that governments and a long-term institution should drive and fund.” GSK had always assumed that the government would help fund the BPO. But it turned out that the Obama administration wasn’t interested. The Bill & Melinda Gates Foundation also passed. It never went anywhere. When Slaoui retired from GSK, he started dabbling as a venture capitalist while also joining a number of company boards. One of those boards was Moderna’s. What Slaoui calls his “aha moment” came in the fall of 2019, when Moderna reported the results of a phase one clinical trial for a vaccine against cytomegalovirus, a common virus that can cause severe problems for people with weakened immune systems. After the phase one trial, he knew mRNA would work. By the time Greenwood asked Slaoui whether a coronavirus vaccine could be produced by the end of the year, he was convinced that mRNA might make it possible. A few weeks after Greenwood’s call, Slaoui got an email from Robert Kadlec, the assistant secretary of HHS who was trying to help manage the Trump administration’s early response to the pandemic. Kadlec invited Slaoui to come for an interview. When Slaoui had his job interview on May 11, he minced no words. “All I want to do is make a vaccine that helps our country and the world,” he said. “I’m not going to be afraid to break things. I have no political ambition.” If he had to hold meetings just to placate people, he was out. And if there was any political interference, he would resign on the spot. The other five candidates all expressed doubt about having a vaccine by the end of 2020. Slaoui alone said he could do it. He got the job. He resigned from Moderna’s board and sold all his stock in the company, knowing that he was likely forfeiting a fortune. He also decided he wouldn’t take a paycheck for overseeing the project. Three days later, when Trump unveiled Operation Warp Speed in the Rose Garden, Slaoui thought to himself, There’s nowhere to hide. WARP SPEED WAS CARRIED OUT, FOR THE MOST PART, BY PEOPLE WHO THOUGHT THE MISSION WAS SO IMPORTANT THEY PUT ASIDE THEIR DISTASTE FOR THE PRESIDENT. “I THINK 99 PERCENT OF US VOTED DEMOCRATIC.” Greenwood’s call to Slaoui marked a pivotal moment in the US effort to subdue the pandemic. After months of government and industry being at odds, with Trump even tweeting out criticism of companies like General Motors and 3M that were trying to help, the two forces finally joined together. Pharmaceutical and biotech companies raced to develop a COVID-19 vaccine. The companies that developed vaccines were aided by the federal initiative Slaoui would soon head. Without the government’s involvement, some companies would no doubt have succeeded in developing COVID-19 vaccines. But it would likely have taken years. “I think history will remember this as an all-of-government and all-of-America approach to solving a societal problem,” says a former FDA civil servant. “We were able to cut through a lot of barriers, including bureaucratic barriers. It will be remembered as proof of concept that we can break down silos.” Carlo de Notaristefani, a longtime pharmaceutical executive who joined Warp Speed to run manufacturing, says, “For me, the number one learning is that government alone cannot resolve a pandemic, and industry alone cannot. You need to bring the two together.” Trump announced the formation of Operation Warp Speed on May 15, 2020, laying out a goal of making 100 million vaccine doses available by November and 300 million by January 2021. He was flanked by Slaoui and General Gustave Perna, the former head of the Army’s Materiel Command, who would serve as the chief operating officer. Although most scientists remained doubtful that a safe vaccine could be produced that quickly, Slaoui said that he had seen some early trial data that gave him a measure of confidence. “We will do the best we can,” he said. That May 15 press conference marked one of the few times Trump had any significant involvement in Operation Warp Speed. That may help explain why it was the administration’s one true COVID-19 success story—and ironically enough, as one person involved argues, that may also explain why Warp Speed could only have worked under Trump. Few other presidents would have been so hands-off. Warp Speed was devised by people who had been marginalized by the White House, and it was carried out, for the most part, by people like Slaoui, who thought the mission was so important they put aside their distaste for the president. “I think 99 percent of us voted Democratic,” says one person who was involved.
The only vaccine candidate that wasn’t fully Slaoui’s choice was AstraZeneca’s. Oxford University, which had a crack vaccine team at its Jenner Institute for Vaccine Research, had already begun a clinical trial for a vaccine it was developing; AstraZeneca was its distribution and manufacturing partner. And the press was already calling the Oxford-AstraZeneca vaccine a winner. That made Azar think about Birx’s demand for a non-mRNA vaccine, so he put Kadlec and Marks in charge of negotiating a deal. On May 21, Operation Warp Speed gave AstraZeneca $1.2 billion in exchange for 300 million doses, so long as its vaccine got FDA approval. That came out to about $4 a dose. (The company insisted that it would not make a profit from the vaccine.) When Azar called Trump to tell him about the deal, Trump was furious. “Boris Johnson is going to kill me,” he said, according to someone who was in the room. A few days earlier, Moderna announced that its vaccine had generated neutralizing antibodies in eight volunteers. It was a tiny sample, and there was still plenty of skepticism. Nevertheless, Moderna’s stock, which had sold for less than $30 a share back in April, shot up to $80. That evening, the company announced another stock sale. This time, it was able to raise more than $1.3 billion to help jump-start its manufacturing capabilities. In total, Moderna received about $10 billion from the federal government. Each company got its own bespoke deal from Slaoui. Sanofi, which was collaborating with GSK, got $2.1 billion for 100 million doses. Johnson & Johnson got $1 billion for 100 million doses. As for Pfizer, with 2019 revenue of nearly $52 billion, it didn’t need or want to be part of Warp Speed. It feared that partnering with the government would slow it down. Inside Pfizer, the quest to develop a vaccine with its partner BioNTech was labeled Project Light Speed. “You can have any resources you need, but you need to succeed,” the company’s CEO, Albert Bourla, told his vaccine team. “And by the way,” he added, “my expectations on timeline are far faster than anything you think is actually possible, and you have no excuse not to deliver, because any resource you ask for, you’re going to get.” But there was one thing Pfizer needed that only Warp Speed could supply: a guaranteed market. Even mighty Pfizer couldn’t risk shareholders’ wrath by making a huge investment that didn’t pay off. Slaoui took care of that in July, making a deal to pay the company $1.95 billion for 100 million doses. Although Pfizer insists it was not thinking about profits when it began its vaccine work, this deal nonetheless set the price of a dose at close to $20. Moderna’s US price ended up being set around $16. Where was Warp Speed’s money coming from? Lacking their own congressionally mandated funds, the team had to scramble. They pulled $10 billion from the CARES Act, which was there thanks to Treasury Secretary Steven Mnuchin, who had added extra money to the Strategic National Stockpile in order to create a slush fund. They also pulled money from the hospital fund established by the CARES Act. “Thank God for Steven,” Azar told a colleague. By late May, Slaoui held a virtual meeting with the companies to discuss the next step: the phase three clinical trials. “We are preparing to run what may turn out to be the largest and fastest field efficacy trials…in history,” Slaoui wrote in the invitation to the meeting. The trials would require finding, preparing, vaccinating, and monitoring 120,000 people over six months—or more if Novavax and Sanofi got through their phase two trials. It was important that the group be diverse, given the disproportionate effect of COVID-19 on communities of color. In normal circumstances, phase three trials take years. Slaoui wanted them done in a matter of months. In addition to dramatically speeding up the process, Operation Warp Speed had to find and equip all the clinical trial sites with hard-to-obtain personal protective equipment so that everyone involved in the trials would be safe. “We basically have to go from an early adolescent company to a full adult company, skipping all of late adolescence,” Moderna’s Juan Andres later told Harvard Business School. Every minute mattered. “I think it would be very difficult to claim that the vaccines would have been developed in this time frame without not just the money but the coordinating role that Warp Speed played,” says Noubar Afeyan, the CEO of Flagship Pioneering, which helped found Moderna. “General Perna and Moncef Slaoui brought a level of expertise and experience and logistical capability and, I’d say, a soft hard touch. A velvet stick, such that people had to behave.”
Because this was the first time mRNA had ever been used in a drug with full FDA approval, Warp Speed and the companies had to figure out how the manufacturing process would work. “All of it started from zero,” says Afeyan. The logistical complexity was astounding. For every vaccine, de Notaristefani says, there can be as many as 2,000 components and hundreds of suppliers. “These are not things that you buy off the shelves,” he says. “So you need to negotiate with multiple suppliers so that you can receive enough materials every week for years to keep the factories going.” It didn’t help that the pandemic, in addition to causing shortages of PPE, caused shortages of manufacturing components. As with so many other products, a lot of the key components were made in China. “Everything was missing or in short supply, from the plastic bags that would hold a finished vaccine before it was put into a vial to the vials themselves,” says Paul Mango, Azar’s then deputy chief of staff. “This is an industrial mobilization story, not a vaccine development story.” To get the necessary supplies, Operation Warp Speed began using the Defense Production Act, a law enacted during the Korean War that gives the government the power to order any company located in the United States to prioritize certain orders going to certain customers. In this case, it was used to get components to vaccine manufacturers. The glassmaker Corning, for instance, dedicated all its existing equipment to making the glass vials that would contain the vaccine. “The lead time for plastic bags was 48 weeks,” says de Notaristefani, in what he says is just one of many examples. “We needed them in 12 weeks. So, the expert from the Department of Defense goes into the supplier and looks at the manufacturing plant and, basically, orders the supplier to reprioritize their manufacturing and move the deliveries to the rated order ahead.” Because these were all products used in the manufacture of drugs, this also involved another layer of coordination with the FDA to make sure that Operation Warp Speed didn’t inadvertently cause shortages of other medications. Perna’s team of Army logistics experts, meanwhile, worked hand in hand with pharmaceutical experts. De Notaristefani had set up small teams of people, usually led by Army majors, inside most plants, to provide real-time information. “There was always some crisis somewhere, some material that was late, and that would risk delaying manufacturing at some of the factories,” he says. “The Army was calling FedEx and UPS and saying, ‘Hey, this piece of machinery in Germany or Asia or wherever is going to take four weeks by boat,’ ” says de Notaristefani. “ ‘Can you get it on a plane and get it to us in 48 hours?’ At that time, it could take three months to get a slot on a cargo plane. There was no capacity anywhere. So they were dispatching military cargo planes around the world to pick up transportable equipment.”
The team adopted the routines and lingo of the Army. “Battle-ready” meant adherence to the calendar, including a daily meeting at 8 a.m. “We would go through all the new issues and the things that needed to be done to make sure nothing was overlooked,” Slaoui says. “It created a discipline of execution. You can’t have a meeting on Monday and say ‘I’ll do this’ and the next day say you haven’t done it. It makes it impossible for you to drop the ball because you’re going to be held accountable the next morning.” There was more. “NSTR,” for instance, means “nothing significant to report.” “I had a cheat sheet with all of the acronyms and terms the Army uses, some of which are incredibly effective,” says de Notaristefani. “We all struggle with teleconferences where you have 20 people on the line and people tend to talk over each other, right? But when you put 20 people from the Army on, that never happens, because they communicate the same way they do on radios. So if I’m talking, I say ‘break’ if I pause, but I’m going to continue talking, so don’t interrupt me. Only at the end do I say ‘over,’ so someone else can talk. It’s simple, strange, and very effective.” He continues, “If I ask someone to do something, that person will always answer, ‘Acknowledged.’ ” That way, everyone knew the task had been assigned and the assignment had been accepted. For those who came from the private sector, working with the Army was a revelation. “It was honestly my best work experience,” says Slaoui. De Notaristefani, for his part, says he plans to use some of the lessons he learned in his private sector work. Not everything was so battle-ready and acknowledged. Trump’s erratic press conferences were a distraction. Trump’s complaint, which he voiced often, that the FDA was purposely delaying the approval of vaccines until after Election Day was an even bigger problem. In early August, Trump told Geraldo Rivera that a vaccine might be available before Election Day, which would help his chances. It was the worst thing he could possibly have said. If it were to appear that the pharmaceutical companies were rushing their vaccine development for political reasons, it would do enormous damage. People wouldn’t trust the very medicine that was supposed to immunize them from the coronavirus. In response, the CEOs of the vaccine manufacturers drafted a joint statement in early September: They would apply for FDA authorization of a vaccine only if it demonstrated safety and efficacy in a phase three clinical trial. “We believe this pledge will help ensure public confidence in the rigorous scientific and regulatory process,” the pledge read. Slaoui told Science magazine that he would quit if anyone in the administration pressured him to rush a vaccine to market before its efficacy was proven. The FDA, for its part, increased the time it wanted to wait after the phase three volunteers were given their second shot to at least 60 days. That made it clear the FDA would not be in a position to authorize a vaccine until after the election. The delay appeared to be an effort to prove to the public that the vaccine process was not going to be influenced by politics. (In fact, even after the vaccines were available, many anti-vaxxers claimed they couldn’t be trusted because they had been rushed.) Through all of this, Warp Speed itself remained remarkably immune from political pressure. “I was surprised that we didn’t get a lot of political interference,” says de Notaristefani. “That was my major concern. So frankly, it was good for me that we were left alone and almost forgotten to a certain extent.” He adds, “I think it was mostly Alex [Azar] acting as a shield for the organization.” Slaoui says that he would get calls from people pushing vaccines and therapeutics that they “knew” were going to work. “Jared would say please listen to them, so I’d listen to them and call him and say, crap no,” he says. “And that would be the end of it.” About Kushner, he says, “The guy is fact-based and straightforward. He’d say, ‘If this is what the science says, what the data says, then that’s what we’re going to do.’ He gained my respect.”
The markets reacted joyously. The S&P had its best November since 1928. Both Pfizer’s and Moderna’s stocks soared. “I’m an ornery cynic,” says one Wall Street trader who had previously bet against Moderna’s stock. “But thank God for the believers, the people who are willing to fund companies like this.” Alas, it wasn’t long before people were fighting over the vaccine. The earliest fights were over which groups should get the first doses. In those early days, vaccine availability was limited. Progressives wanted people of color to be first in line because they had suffered disproportionately from the pandemic. Public school teachers believed they should go first; if teachers weren’t vaccinated, they would continue to teach remotely, said many union leaders. The CDC recommended that health care workers and the elderly get priority, which for the most part they did. There were, of course, some failures and setbacks. Both Johnson & Johnson and AstraZeneca had to pause their clinical trials; several participants came down with rare blood-clotting disorders. While both vaccines were eventually approved, the news about blood clots steered most people away from those two companies. As for Novavax and Sanofi, scientific glitches outside Warp Speed’s control caused the companies to delay their request for emergency use authorization until 2022. For the most part, their vaccines are being used abroad. The initial distribution of the vaccine went less smoothly than its production had. Part of the problem was that Operation Warp Speed decided it had to delegate distribution to the states. After all, the Warp Speed officials weren’t supposed to be involved in the fraught decisions about who should get vaccinated first. There was also an unusual glitch by Perna’s team when more than 10 states discovered that their allocation of Pfizer’s vaccine was much lower than they had been led to believe. Perna didn’t duck. “It was a planning error,” he said. “I am responsible.” Slaoui faced a reckoning of his own. In March 2021, soon after leaving his government post, he was fired as chairman of the board of Galvani Bioelectronics over sexual harassment allegations brought by a woman with whom he’d worked years before at GSK, which co-owns Galvani. Slaoui did not deny the allegations and issued an apology. There was also criticism of the fact that Warp Speed didn’t meet its goal of delivering 100 million doses by year’s end. Its leaders say that it was more aspirational than anything else. Azar, borrowing from the management experts Jim Collins and Jerry Porras, called it a BHAG—“a big hairy audacious goal” meant to motivate people. “How do you define success?” says one of Warp Speed’s senior leaders. “I knew we would never be able to get all the doses we wanted, but I was absolutely convinced that we would have enough doses for everyone in the US by mid-2021.” Which they did.
Konular: Coronavirus