Can a Vaccine for Covid-19 Be Developed in Record Time? In the history of medicine, rarely has a vaccine been developed in less than five years. ......... Antiviral drugs, too, have generally taken decades to develop; effective combinations of them take even longer. The first cases of AIDS were described in the early 1980s; it took more than a decade to develop and validate the highly effective triple drug cocktails that are now the mainstay of therapy. We are still continuing to develop new classes of medicines against H.I.V., and notably, there is no vaccine for that disease. And yet the oft-cited target for creating a vaccine against SARS-CoV-2, the virus that causes Covid-19, is 12 months, 18 at the outside. ........... the maddening complexity of the challenge and the extraordinary collaboration it has already inspired ......... successfully inventing and developing any new drug or vaccine is quantifiably among the hardest things that human beings try to do ............ the vast majority of efforts fail ........... each of the rare success stories usually occurs over many years, often a decade or two. ......... The hope is that it will be within a year, but that is not in any way guaranteed. That projection will be refined as time goes on — and a year assumes that everything goes smoothly from this point forward. That’s never been done before. And safety cannot be compromised. ................ The goal of a vaccine is to raise an immune response against a virus or a bacterium. Later, when a vaccinated person is exposed to the actual virus or bacterium, the immune system will then block or rapidly control the pathogen so that the person doesn’t get sick. ........... All coronaviruses have a so-called spike protein, which is what gives the virus its corona-like morphology, the “crownlike shape,” as can be visualized in an electron microscope. ............ This spike protein represents a particularly attractive candidate for a vaccine, because it is a protein that most prominently sticks outside of the surface of the virus, and so it’s the part of the virus that is most visible to the immune system. ................. the inactivated polio vaccine and the inactivated flu vaccine. .......... Gene-based vaccines, such as DNA vaccines and RNA vaccines, do not consist of the entire virus particle. Rather, these vaccines use just a small fraction — sometimes even just one gene — from the virus. .............. In Moderna’s case, it involves using RNA as the inoculum. ........ Currently there are no approved DNA vaccines or RNA vaccines. ............ With Covid-19, there’s currently a hamster model that looks like it works pretty well to mimic the disease and also some promising research with mice, ferrets and also nonhuman primates. ........... For H.I.V., for instance, there is no natural protective immunity, and that’s part of the reason that H.I.V. vaccines have been so hard to develop. ......... The full-length spike protein appeared to work the best. .............. both natural immunity and vaccine-induced immunity can exist in primates ......... DNA encoding the full-length spike protein has been stitched into the common-cold virus vector as a more efficient way of transporting the spike-protein DNA into cells. That’s the basis of the vaccine we are developing with J.& J. ............. The Oxford vaccine is based on a chimpanzee common-cold virus, and it also encodes the spike protein. ......... Several vaccines are also in clinical trials in China, including Sinovac’s inactivated-virus vaccine and another vaccine based on a human common-cold virus. ........... The process includes small-scale manufacturing; Phase 1, Phase 2 and Phase 3 clinical trials; and then regulatory approval and large-scale manufacturing. For SARS-CoV-2, the goal is to compress these timelines considerably without compromising safety ............... we can’t abandon the rigor of the science. And we certainly can’t abandon the ethics of how we do studies either. But what we can do is, frankly, ask developers to take more risks themselves. Vaccine development can be costly and success uncertain. As compared to a drug that someone may take every day, the return on investment versus risk of failed development is pretty high for vaccines. Because vaccines are often viewed as a public good, protecting both people and communities, there can be considerable pressure on companies to restrict price on vaccines, so a company rarely has a “blockbuster” vaccine the way that a cancer treatment, ulcer drug or cholesterol-lowering drug can be. Also, there are liability issues because you are giving a vaccine to a healthy person to protect them from disease rather than treating an existing problem. ................. For Covid-19, developers are talking about performing as many steps in parallel as possible, as opposed to sequentially. For example, multiple vaccine manufacturers are willing to take enormous financial risks — planning for large-scale manufacturing up front, even before knowing whether the vaccine works or not. .............. There are questions about safety, efficacy, manufacturability and scalability that must be tackled. ........... we don’t just need a vaccine that works; we need one that can be reliably scaled up to manufacture in very large volumes ......... For certain pathogens, it has been considered ethical to perform human-challenge studies but typically only for pathogens for which there is a highly effective treatment. ........ The dilemma for Covid-19 is that there currently is no curative therapy. .............. challenge trials are too dangerous. Young people can get quite sick and die from Covid-19. ........... There’s been a whole history — extremely fraught — where minorities were used as experimental subjects without their understanding or consent. ............ working with the communities where these large-scale Phase 3 studies will be done. Some will be done in the U.S., but others will be done in other places around the world — lower-resourced places that may not have the kind of clinical-research infrastructure that we have here, whether it’s having enough trained researchers or the sophisticated health care services they need, like lab and diagnostic tools and basic things like refrigeration and cold storage. ................ There are two timelines that matter. One is the infrastructure and timeline needed to manufacture massive numbers of doses of the vaccine, and a separate, potentially different timeline to actually deploy the vaccine. ........... the manufacturing process for an RNA vaccine is entirely different than for an adenovirus vector-based vaccine. For rapid deployment of a vaccine after clinical efficacy is shown, large-scale manufacturing of multiple vaccine candidates has to begin before there is demonstration of vaccine efficacy. ............ Once a vaccine is approved, it is not going be available the next day for whoever wants it. ............ Manufacturing has to be done in a high-quality and consistent way. There are materials that are needed that can be in limited supply, like the vials and the stoppers that you need for packaging. And then there are chains for distribution, and sometimes vaccines have to be kept frozen at very low temperatures. So you have to have all of those important systems for manufacturing, packaging and delivery and distribution up and running and the supply chains flowing in order to actually get what might now be an approved vaccine actually into the bodies of the individuals who need it. ........... there’s going to be a huge nationalistic push for countries to try to get hold of as much vaccine as they can for use within their own borders, yet ultimately the safety of any country or community depends on addressing and protecting against this virus all over the world. ............. If we don’t have a safe and effective vaccine for one to two years, or even longer, we need to develop other treatments as a bridge to a vaccine — to allow society to have a path toward reopening and functioning, while we await a vaccine. .............. How can we move from where we are — isolate, quarantine, mask, distance — toward a therapy that will bridge us to the vaccine? ............. The world has gotten interested in the drug remdesivir, which inhibits the process of RNA replication ........ Until there’s a vaccine, I don’t think there’s going to be one magic bullet for treating this thing, and we’re certainly not going to find that magic-bullet drug treatment in a repurposed drug pulled off the shelf. ........... And there’s an apparent association of this novel coronavirus with a very serious hyperimmune syndrome in children, the so-called Kawasaki-like syndrome. ........... You can almost think of it as a temporary vaccine. Instead of waiting for a vaccine that will make the body make its own antibodies against the virus, we can make exactly those kinds of antibodies and inject them into people........... In virtually every infectious disease, the use of antibacterials or antivirals or even antibodies against a virus early in the course of disease is better. In terms of remdesivir, it’s possible that the drug is much more likely to be efficacious when used early than late, and in fact, the published trial from the N.I.H. has a hint of that. .................. Patients given early remdesivir recover and do not progress to the fulminant lung disease. ............... Yes, just because a compound inhibits the virus in a petri dish, doesn’t mean that it can immediately become an antiviral drug for human use. The compound might be toxic to humans. It might be degraded into an inactive substance by the body. Its dose might be so high that it’s impossible to administer. But I do think while we’re waiting for the antibodies and the vaccines, it seems reasonable to proceed with testing thousands of drugs against the virus — called “drug screening” — so that if something does come up, we might find a drug to combine with remdesivir or with antibodies, making an anti-viral cocktail. .................... I’ve never seen this before, either. Our C.D.C. permit to receive the virus, which is classified as a biosafety Level 3 agent, was approved in less than two days. We received at least two material-transfer agreements, which have to be signed by a number of institutional officials and sometimes lawyers, in a matter of hours. Both of those processes have taken much longer, sometimes weeks, in the past. This is just one sign of administrators and scientists collaborating with each other and acting extra efficiently to facilitate the science. .................. From a research perspective, I have never seen such collaborative spirit, such open sharing of materials, data, protocols, thoughts and ideas among academic groups, industry groups, government groups and the clinicians on the front lines. .............. we are all coming together, and things are happening at unprecedented rates because we realize that we have a common enemy
What If Working From Home Goes on … Forever? Miserable as it can often be, remote work is surprisingly productive — leading many employers to wonder if they’ll ever go back to the office. ........... a foot of carpet can hold up to a pound of dirt .......... Harcus was stuck sitting on the gray couch in his small San Francisco apartment, trying to figure out a new challenge: How do you sell a robot to people who can’t touch it? ............. After discovering that executives were easy to reach — “They’re bored,” he says, “because they’re used to being in the field, cleaning” — Harcus began making five or six sales calls a day over Zoom, the videoconferencing app. .......... studied webcam technique to get his lighting right. (“We call it the ‘witness-protection-program look’ that you’re trying to avoid, where you look superdark,” he says.) And he came up with new patter. Talk about the weather was out, while commiserating over at-home child care was in: “I have a lot of screenshots running of babies crawling on people I’ve met.” .............. It worked; clients kept signing contracts. The day before we spoke in early May, Harcus said, he closed deals with six hotels. ......... had been worried that employees would slack off if they weren’t in the office. Instead, they all began working so nervously, even neurotically, that productivity rose ............. The hours that employees previously spent commuting were now poured into sales or into training customers online. ............. how time-intensive sales used to be. “We spent all this time, we flew robots out — we flew out,” he says. Yet usually the face-to-face demo was astonishingly brief. “Hours! Hours and days of prep! Just for a 10-minute discussion.” ...................... what’s crazier: being forced to work from home, peering into a webcam all day? Or the way they used to work? ................. half of those who were employed before the pandemic were now working remotely. ......... (In 2018, a U.S. Census Bureau survey found that just 5.3 percent of Americans worked from home full time.) ........... The coronavirus crisis is forcing white-collar America to reconsider nearly every aspect of office life. Some practices now seem to be wastes of time, happily discarded; others seem to be unexpectedly crucial, and impossible to replicate online. For workers wondering right now if they’re ever going back to the office, the most honest answer is this: Even if they do, the office might never be the same. ................ even though they had lost the easy rapport of face-to-face office contact, productivity didn’t sink. It went up, when measured by several metrics — developer productivity, for example. “If you, six months ago, had said, ‘We’re going to give you a few weeks’ notice, and then you’re going to have your whole work force working from home,’ I would have said: ‘You’re insane. There’s no way it’s possible.’” ................ Many workers who live alone are experiencing enforced isolation as an emotional grind. Among those with young children, many are finding it exhausting to juggle child care, home schooling and their jobs. A senior communications specialist at TD Ameritrade, Ruby Gu, told me that she and her husband, a quality-assurance engineer, were taking turns hunkered down in their basement while the other looked after their 21-month-old and 4-year-old in the living room above (“two small children running around over my head right now”). ................ A marketing director and parent of two toddlers told me her new hours were “9 to 4,” by which she meant 9 p.m. to 4 a.m., the only quiet hours she could find to work. ......... It’s a messy moment, further blurring a line between home and office that has already been heavily eroded by phones and computers. Nearly every parent I spoke to had their fingers crossed that schools and day care would reopen in the fall — at which point remote work might become an option they could choose, as opposed to one they were forced to endure. .............. Research conducted before the pandemic found that remote work offers significant positive effects for both employee and employer. ............. Output often rises when people work remotely. ............ the boost in productivity derived from employees’ being able to work more efficiently, without interruptions from their colleagues. ........... People also worked more hours: There was no commute to make them late for their shifts, and even their tea breaks were briefer. ......... a powerful correlation between telecommuting and job satisfaction ......... People tend to prize the greater flexibility in setting their work hours, the additional time with family members, the reduced distractions. Even with the onslaught of online messages confronting teleworkers, “no one’s stopping by your cubicle standing over you saying, ‘Hey, I need this,’ or ‘I need your help right now’” ..................... for the U.S. Patent Office, “real estate savings were immense” — fully $38 million .......... talented employees who can’t afford or don’t want to relocate to exorbitantly expensive coastal cities ............... Many will hesitate at the idea of riding a crowded, unventilated elevator to an open office where people are crowded together. ............ companies are figuring out how to “virtualize” every part of work — every meeting, every employee check-in — so that it could potentially be done remotely. “It has accelerated three years of digital cultural adaptation to three months” ........... help people collaborate while scattered to the winds. But fully 95 percent of Slack’s 2,000-plus employees work in one of the company’s offices. After the pandemic hit, they were sent home, which is where they were when the latest all-hands meeting rolled around. ............ your kids are going to creep into the video, and that’s OK. ......... Staff members rated this all-hands event higher than any previous one. .......... Meetings, of course, have long been a lightning rod in corporate life. Many are crucial for coordination; others seem pointless. But as executives know, it can be hard to tell the difference. Because communication is generally essential to every company’s mission, most meetings that are proposed take place, and then are scheduled again and again until they build up on employee calendars like plaque. ............... employees pine for fewer meetings ....... surveyed 182 senior managers; 71 percent found too many of their meetings “unproductive and inefficient”, and nearly two-thirds thought they came “at the expense of deep thinking.” ............ Meetings became smaller and less frequent. ......... They were, everyone agreed, just as productive as ever, maybe more so. They had reduced the frequency of their formal meetings, yet the communication felt nonstop — a flurry of Slack messages and emails too. ........... the value of small talk, those seemingly casual interchanges that keep information flowing ............ You can feel removed from colleagues even while drowning in digital messages from them. ........... She added that she looked forward to the day when the lockdown was over and she could have a waiter place a meal in front of her and then take the dirty dishes away. “I feel like I’m cooking 250 meals a day.” ............. “Zoom fatigue.” ......... When we’re hanging out together, we’re constantly exchanging glances — but only brief ones. Long stares, research shows, seem quite threatening. ............. experimental subjects were asked to look at a video of a face that turned to stare directly at them. People found the gaze enjoyable, but only for about three seconds. After that, it became unsettling. ............. videoconferencing is characterized by remarkably poor design, because we’re expected to face the camera and stare ...... The polite thing also winds up being the creepy thing. ........ when you’re in a “Brady Bunch” meeting with a dozen people arrayed in a grid, they’re all staring straight at you. No halfway normal meeting of humans behaves like that. ......... It’s possible that we’re still in an awkward adolescent phase with video calling, that protocols for how to behave correctly haven’t yet emerged. (In the telephone’s early days, some users debated whether saying “Hello” at the outset of a call sounded friendly or barbaric.) ......... standing back from your camera can reduce creepiness. ............. having a bigger view helped them achieve synchrony and bond with their opposite number. These days, when Nguyen video-chats, he sits a few feet away from his keyboard, so his upper body is visible. He also speaks more emotively. “Ramp up the words that you’re saying,” he notes, “and then exaggerate the way you say it.” ............ (“We always say that people kind o f smell with their eyes.”) .......... office work is more than just straightforward productivity — briskly ticking off to-do items. It also consists of the chemistry and workplace culture that comes from employees’ interacting all day, in ways that are unexpected and often inefficient, like the stray conversations that take place while people are procrastinating or bumping into one another on the way to lunch. ................. “Strong ties” are people in your life you talk to frequently, even daily. “Weak ties” are the people with whom you rarely communicate, perhaps 15 minutes a week or less. ......... strong ties were becoming stronger. Ordinarily, 45 percent of the time someone spent communicating with colleagues — online or face to face — was with their five strongest ties. In the first weeks of lockdown, that figure exceeded 60 percent. That makes sense: “You’re stressed about work, and these are the people you know really well, so you’ll probably talk to them more,” Waber told me. That’s partly why productivity has stayed so high. .......... it’s those weak ties that create new ideas......... Waber predicts that companies will continue to hit their marks and be productive while remaining partly — or heavily — remote. The real damage will sneak up a year or two later, as the quality of new ideas becomes less bold, less electrifying. He also suspects that the overall cohesion of employees, how well they know one another, might suffer. “I think we’re going to see just this general degradation of the health of organizations” ......... Groups that connected solely online (the experiment used email rather than video) did not collaborate very well. But when they were allowed to meet for brief periods face to face, their rates of cooperation rose dramatically. ......... If employees are able to meet in person some of the time, it can help build the bonds that make remote collaboration richer. ........ staggered office hours: Employees generally work remotely, but individual teams or groups of colleagues show up a day or two each week to work together. ........ workers’ happiness grew in correlation with the number of hours they worked remotely — up to 15 hours a week, at which point, he told me, “it plateaued.” ........... spending two days a week remotely could let a worker gain all the benefits before a “sense of isolation,” or perhaps “some increased difficulty communicating,” begins to eat into the gains. ............. as newfangled as remote work may seem, it relies on a set of tools that are by now quite old: video calls, discussion boards, chat, shared online documents........ the audio.... is the most pleasant mode for casual back and forth .......... ....... Hanging out with the avatars was a curious sensation — somewhat like when I interact with other players inside an online video game like Animal Crossing........... “I could be present at this meeting, but I don’t have to stare at the screen the whole time. It’s very liberating” ........ as much as our offices can be inefficient, productivity-killing spreaders of infectious disease, a lot of people are desperate to get back to them
