Vaccine Heroes
I was rowing on my Concept 2 erg Saturday morning when a minivan pulled into the driveway. A woman hopped out, came though our little wooden gate, and headed for the porch outside our kitchen, where we had left some of the mail we still get sometimes, after she and her family had rented the house during our Cleveland years. This is the wife of a Food and Drug Administration scientist who works at their nearby headquarters. Only hours before, late on Friday evening, the FDA had issued an Emergency Use Authorization for the Pfizer corporation’s COVID-19 vaccine.
As I heaved back and forth, I said, “Tell the gang at FDA, ‘Well done.’”
‘Thank you. I will.’
‘Did you guys celebrate?’
‘Oh, yes,’ she assured me. ‘There was much celebrating.’
‘Moderna next week, right?’
‘I think so.’
‘Well, let’s do it again. Work late every night, and slay it the same way. They can take Christmas week off.’
‘That’s the plan.’
‘Tell everybody we’re much obliged.’
Awesome people do awesome things everyday, refining the skills and strengths that come into play when suddenly somebody needs a miracle. We’ve seen this with cave divers, for example, as well as Army Rangers, deep sea fishermen, a center for the Steelers, dogsled drivers, a Treasury Secretary, codebreakers, and even an iconic cafe owner in Morocco. As strength athletes, we can relate to the daily grind of trial and error, patience, and high expectations. Even so, we’re amazed that things actually turn out as well as they do in the worst crises. So many things could have gone wrong, but whether it was those divers extracting the kids from deep in that cave, the Rangers pushing 30 miles behind enemy lines, or those Irish fishermen calculating set and drift on paper and then executing those turns out on a gray and rainy ocean, these folks just stayed cool, did their thing, and it all worked out. Was that purely luck? Maybe the real mistake is all the fear and doubt, and reality is far more Zen than we know.
Today’s heroes are the scientists who brought us the first two COVID-19 vaccines. As told in the WASHINGTON POST and elsewhere, their storyline is familiar: a theory - or a hope - takes shape, followed by the first crude experiments and a long, slow grind of halting progress. Then come a few opportunities to prove the concept in practice - which actually work, prompting a moment of unsure reckoning. ‘Is that it? Are we ready?’ the scientists ask one another, when out of the blue, the phone rings.
The theory behind these seemingly ‘rapidly developed’ vaccines dates back as far as 1961, when scientists came to understand that Messenger Ribonucleic Acid (mRNA) takes instructions inscribed in the building blocks of DNA - Deoxyribonucleic Acid - and delivers them to the parts of the cell that form new proteins. Scientists surmised - or dreamed, really, at this early stage - that this basic function could be manipulated for medicinal purposes. It wasn’t until 1990 that a University of Wisconsin team demonstrated that they could inject snippets of mRNA into mice and turn their muscle cells into factories that created proteins on demand.
This was groundbreaking. Holy Cow, a new generation realized. We can ‘encode fragments of virus to teach the immune system to fight against pathogens.’ We can ‘create whole proteins that are missing or damaged in people with devastating genetic diseases, such as cystic fibrosis.’
mRNA presented two problems: the molecule was almost too fragile to work with, and when it did stay in one piece, it created massive, often fatal, inflammation in the mice. In 2005, a pair of researchers, one of them a former member of Dr. Anthony Fauci’s laboratory at the National Institute of Health, discovered how to tweak a single component of the RNA code to eliminate the inflammatory response. This particular accomplishment deserves a Nobel Prize, say those in the field.
In 2016, researchers developed a nanoparticle to deliver messenger RNA to a special cell type that could turn the code into an immune system provoking protein. This was direct and efficient on an unprecedented level, enabling a vaccine to work using only a tiny amount of material. ‘Each dose of mRNA vaccine relies on an amount that’s about a fifth the weight of a penny to stimulate a powerful immune response.’
Some Americans are wary of a vaccine that appears to have been spun up quickly to the point of recklessly. The truth is that countless tiny improvements over decades transformed an idea into a working technology. “It’s new to you,” a scientist said in an interview. “But for basic researchers, it’s been long enough. . . . Even before covid, everyone was talking: RNA, RNA, RNA.”
Old fashioned vaccines work by injecting some amount of dead or weakened virus to stimulate the immune system. These newer vaccines use bits of viral surface proteins to make the necessary imprint. The trick, of course, is knowing which bit to use, but there turned out to be another problem: viral proteins change shape when they do their voodoo. They change their ‘conformation,’ say scientists - using a very interesting term that goes back to the old days of horse racing, as breeders and trainers used to talk about the bone lengths and leverages that made for champions. My old Olympic lifting coach, Joe Mills, used the term the same way in assessing whether an athlete should catch their lifts in a squat or a split.
A coronavirus particle bent on mischief, once it finds the right cell receptor, changes its spike protein to a more advantageous conformation to inject its RNA code into a cell. Beforehand, it’s sort of a squat, globular, roughly conical arrowhead - put your thumb and fingertips together. When it extends, turning inside out, it makes a longer funnel shape, acting like a hypodermic needle.
In 2013, a scientist by the name of Barney Graham - part of the gang at Fauci’s joint at NIH - discovered it was vital that a vaccine mimics the pre-fusion structure, or the arrowhead. (It makes no sense to attack the funnel after it’s already done its damage. Teaching the body to recognize the wrong structure would blow the entire scheme.) The problem with the experimental vaccines was that the arrowheads were unstable and popped into funnels too easily. Graham and colleagues, using computers to model the structures of these spikes, identified a protein in the arrowhead that was like a spring bent double. It was when this snapped open that the funnel shape was formed. Graham pioneered the ‘2P mutation,’ taking two prolines, the most rigid of 20 amino acids, and clamping the spring shut.
An immune system that knows what proteins to look for intercepts the arrowheads and caps them off before they can find receptors and morph into funnels.
Graham was among the scientists making what findings they could as the first Severe Acute Respiratory Syndrome emerged in 2003, followed by the Middle East Respiratory Syndrome in 2012. These things are going to make the leap into humans every decade, they realized. The phone rang for real in January, 2020. Chinese scientists had just posted the genetic sequence of a troubling new coronavirus. ‘All right,’ colleagues across government, academia, and industry said to one another. ‘We have some ideas.’
According to the Post, the phone rang again in Barney Graham’s house some time last month. It was the director of the NIH, calling with a heads-up. ‘News is going to break tomorrow morning. The numbers are in on Pfizer.’
‘Yeah?’
’90 percent effective.’
In spite of himself, when Graham put down the phone, he let fly a sob so loud that his son and grandchildren ran into the room. That had to be strange for the kids, aged 13 and 5, to see him cry.
I can only hope that Dad pulled them close and whispered, ‘Always remember tonight. This is when Grandpa found out he helped save the world.’
