‘Warp speed’ is too slow for scientists testing COVID-19 vaccine on themselves

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In late March, officials in the United States were still talking about the coronavirus lockdown in terms of weeks instead of months. People were wiping down their groceries with disinfectant spray and basically scared to step outside.

It was then that biologist Preston Estep sat alone in a Boston lab with a coronavirus vaccine his team had developed over just a few weeks.

“I took a small dose first,” he said. “You know, I usually do this even with pharmaceutical therapeutics, I always take a small dose first just in case there was some sort of negative reaction.”

Estep took maybe a tenth of the total dose, waited a few hours, and then took the rest.

“I just felt really good, really positive about taking that first step, taking that first shot of vaccine,” he said. “And when I say shot, I mean a nasal spritz up the nose. So less dramatic than sticking a needle in oneself.”

What drove Estep here, sniffing his home-made vaccine?

It was the way people were dying. He was devastated by the thought of people dying alone.

“Basically, older people were being quarantined away from their families, and they were being left to die alone in sealed rooms,” Estep said.

Couple that with the rosiest vaccine estimates coming from the government at the time: If everything went right, we’d have a vaccine, and a way out of this, in 12 to 18 months.

“These were people suffering and dying alone, hundreds, and then thousands of them. And I just couldn’t stand the idea that we were gonna wait a year and a half while these sorts of scenarios played out,” he said.

Estep is a geneticist by training, not an infectious-disease specialist. But he’s Harvard-trained and highly connected in scientific circles. A world renowned geneticist, George Church, was one of the first to take a version of his vaccine.

“I had studied with some of the smartest and most capable and amazing scientists in the world, and I’d seen people do some pretty amazing things,” he said. “I’ve been up close and personal to some radical breakthroughs and important scientific work that’s happened very quickly.”

The way he explained it, it’s not so much that he was convinced he could do something about the coronavirus. More like, he just wasn’t convinced he would be totally useless.

He assembled the Rapid Deployment Vaccine Collaborative, RadVac, essentially a posse of scientists that he’d known from previous work. Estep said they weren’t only brilliant, they had a healthy conception of risk calculation. He needed risk takers because, in his mind, self-experimentation was the only way to move faster than the virus.

“I knew that we were on uncharted territory. This was previously only sort of a theoretical challenge that was going to hit civilization at some point — that there would be a worldwide pandemic,” he said. “But I knew that my colleagues that I originally reached out to had thought about these kinds of things.”

Estep found it wasn’t all that hard to get the band back together. Scientists — like many of the rest of us — had their careers upended by March of this year. A lot of them were out of work or at least cut off from whatever they were researching at the time, thanks to coronavirus restrictions. One of his collaborators had a lab space.

“So we had a fully stocked professional biotech lab basically ready to go, that had sufficient equipment,” he said.

And they were off.

Design, test, improve

Look into vaccine development in general and you discover that it’s not all that hard to create one from a technical standpoint. It’s not of the same engineering order as, say, making a nuclear reactor.

Estep found there was already decades-old technology that had been tested in humans that he could use to deliver the vaccine in a nasal spray.

“You can form gel nanoparticles that are about the size of a virus that cross the mucous membrane because of both the size and the chemical properties,” he said. “And it acts as an ideal intranasal delivery vehicle.”

There are basically five ingredients to form those particles that are readily available. To elicit an immune response, Estep’s team used little bits of artificially synthesized protein that mimic bits of the coronavirus.

“It basically all came together very quickly within a week or two,” he said. “I had a basic design that used these synthetic pieces, these little tiny non-infectious pieces of the virus, that I could order, you know, online.”

So if creating a vaccine is the easy part, it’s testing it that gets tricky. You have to figure out if it’s safe and effective before distributing it to literally every living human being on the planet.

The only ethical test subject, he figured, was himself.

Since taking that first dose in March, Estep and his collaborators have developed seven more versions of the vaccine, and have tried them all.

“So we volunteered ourselves as the designers of the vaccine,” Estep said. “We decided that the only way to create that rapid feedback loop of design iterations and testing was to use it on ourselves.”

Design, test, look for the immune response, improve, design and then repeat. Estep said this model makes him more nimble than the big pharmaceutical groups, able to incorporate more of what is learned about the virus into designs in real time instead of being locked into a vaccine that’s months old and that has to go through months-long regulatory and safety hurdles.

How fast is ‘warp speed’?

What the world calls warp speed — the way pharmaceutical giants and governments are working together to create a vaccine in 18 months rather than the usual span of several years — to Estep is slow motion.

“I think we do need to get a vaccine out as quickly as possible,” said Paul Offit, vaccine researcher and director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “That said, we need to make sure that the vaccine works and that it’s safe.”

Offit said much of today’s vaccine regulation architecture stems from a 1955 disaster known as the Cutter Incident.

“Jonas Salk made his polio vaccine in 1955 by taking the virus and inactivating it with a chemical, [and] five companies stepped forward to make it. One company made it badly, Cutter Laboratories of Berkeley, California,” he said. “They had failed to fully inactivate the polio virus that was in that vaccine. As a consequence, about 120,000 children were inoculated with live, fully virulent polio virus,” Offit said. Investigations later showed that the contaminated vaccine had caused about 40,000 cases of polio, in which, about 200 children were paralyzed and 10 children were killed. “I think it was probably the worst biological disaster in this country’s history.”

Offit said it’s an unfortunate part of cutting-edge medicine, especially medicine distributed to hundreds of millions of people.

“The history of, frankly, medical breakthroughs is littered with those kinds of stories,” he said.

The Cutter Incident harmed far more people than others, but Offit mentioned another vaccine from the ’60s that looked like a real winner initially. It was from the National Institutes of Health and had great results in animal models, with good initial data all around.

“[But] when they put it into a phase 3 [trial], they found the children who got that vaccine were more likely to develop pneumonia, more likely to be hospitalized and, in the case of two children, more likely to die than children who didn’t get that vaccine,” he said.

All this serves to explain why the safety protocols exist in the first place, Offit said, adding that “warp speed” doesn’t really touch the safety and efficacy hurdles that slow down vaccine development.

Instead, it simply removes much of the financial risk facing vaccine makers.

“They’ve said, ‘Look, we’ll pay for the phase 3 trials, which cost hundreds of millions of dollars; we’ll pay for the mass production, even not knowing whether or not the vaccine is safe, not knowing whether the vaccine is effective. We’ll take the risk for that,” he said, with “we” meaning the federal government. “We’ll make hundreds of millions of doses not knowing whether this vaccine works and is safe, and if it doesn’t work and isn’t safe, then we’ll just throw those millions of doses away. No pharmaceutical company would ever do that,” Offit said.

Estep, though, isn’t trying to turn a profit. All of his group’s research is open source, and he wants any scientist or anyone with access to a lab and enough know-how to be able to mix up the vaccine to have the recipe.

And unlike in the disasters Offit mentioned, the RadVac vaccine doesn’t use any actual virus —  inactive or otherwise. That may make it far safer, but to Offit there’s another risk with vaccines even if they don’t hurt anyone: They could simply not work.

“If you put a vaccine out there that is ineffective, you will lose or shake what is already kind of a fragile vaccine confidence in the United States, he said. “You will shake vaccine confidence and make it much more difficult to get that second or third vaccine out there, and we need vaccines. So you can’t lose the trust of the American public.”

Desperate times call for desperate measures

Estep, for his part, makes clear that his group’s vaccine recipes are experimental, that there’s no guarantee they’re safe and effective. Still, there are two things he thinks the rest of the scientific establishment is missing in the COVID-19 moment.

One is the idea that desperate times call for desperate measures.

“The Hippocratic oath is ‘first, do no harm,’ but when we’re talking about public health-scale measures, ‘do no harm’ is not an option — and doing nothing is doing harm,” he said.

The second idea is that his desperate measures aren’t actually all that desperate.

“A lot of people have been critical of Russia and China for rolling out vaccines to populations — that it’s too early, that these vaccines are untested,” Estep said.

Those vaccines, at least in China’s case, mostly went to soldiers and government workers first, but increasingly they’re going to everyday citizens — hundreds of thousands of people. Late last month, the governor of São Paulo, Brazil, signed a $90 million contract to buy 46 million doses of the Chinese vaccines.

“And I think that people are overweighting the risks of the vaccines, and they’re underweighting the risks of the virus. I don’t think that even the vaccines that have the least of the safety features that might cross the finish line into commercial availability,” he said. “I can’t even imagine that they would cause even one-tenth of the harm that the virus is causing right now.”

In mid-October, after Estep made those remarks,Johnson & Johnson halted its massive trial of an experimental vaccine after just one participant fell ill. It was the second Big Pharma company to press pause: AstraZeneca halted its trial in September after at least one participant had unexplained neurological symptoms.

The way Estep sees it, there’s this hyper-focus on vaccine safety slowing the rollout that ignores the real devastation the virus is causing right now, every day that passes without a vaccine.

“There’s no such thing as a vaccine that’s going to kill thousands of people a day, but that’s exactly what the coronavirus is doing,” he said. “There’s this acceptance of the harm that the virus is doing because we don’t have the power to just turn it off.”

No one company or government is solely or essentially responsible for the virus, it comes from nature. And many epidemiologists say a pandemic of this kind was more a “when,” not an “if.”

A vaccine is different. Somebody — some organization, company or government — has to create it and make the decision to distribute it, and if it hurts people, it becomes really easy to cast really specific blame. In short, it’s risky. And Estep said the problem is we humans are bad at understanding risk.

“We are living through a time where people are failing, governments are failing, every organization is failing an experiment on risk balancing,” he said.

It’s easy to forget that the world is going through something that it’s never been through before. We are all living through an experiment, and even the experts are amateurs in a way.

In the meantime, Estep said, his group still doesn’t know how robust the immune protection is from its vaccine or how long it lasts, which is going to be a challenge for the mainstream vaccine producers as well.

In early November, Pfizer announced that preliminary data shows its vaccine is 90 percent effective in preventing COVID-19 and that the company plans to apply for emergency approval to use the vaccine later this month. However, it’s still unknown how long immunity may last and there are many logistical challenges ahead for distributing a vaccine.

So these days, even after eight doses of his coronavirus vaccine, Estep still masks up, still social distances. Anything less, he said, wouldn’t be worth the risk.

Editor’s note: This story has been updated on Nov. 10 to reflect Pfizer’s announcement on early findings in its COVID-19 vaccine trial.