Tagged mutants

Sarsie Rides Again

            “We are not driving this tiger, we are riding it… We are the one country in the world that’s opening up faster than ice melting in a sauna. It’s crazy… Vaccine’s coming. But it isn’t coming fast enough. It’s not. We’re not going to see a big expansion of vaccine availability for at least weeks yet. We will. Eventually we will. And I think this summer is going to be a really wonderful time that way. But we’re a ways off. B.1.1.7 is here, those numbers are beginning to rise, and I feel like it’s a déja-vu-all-over-again moment.” Michael Osterholm podcast, March 23, 2021  

            “When I first started at CDC about two months ago I made a promise to you: I would tell you the truth even if it was not the news we wanted to hear. Now is one of those times when I have to share the truth, and I have to hope and trust you will listen. I’m going to pause here, I’m going to lose the script, and I’m going to reflect on the recurring feeling I have of impending doom. We have so much to look forward to, so much promise and potential of where we are and so much reason for hope, but right now I’m scared.” Rochelle Walensky, CDC Director, March 29, 2021

            “I’m telling you right now…we are just beginning this surge, and denying it is not going to help us. We are walking into the mouth of this virus monster as if somehow we don’t know it’s here. And it is here. Now’s the time to do all the things we must do to slow down transmission, not open up, and we’ve got to get more vaccine out to more people.” Michael Osterholm on CNN, April 1, 2021

            “We’re not driving this tiger, remember, we’re riding it  … No other country in the world is loosening everything up—pretending the virus doesn’t exist any more. Nobody’s doing that… We are creating the perfect storm. We’ve got a bad, bad virus. We’ve got a lot of people yet who can still be infected despite the fact that vaccines are rising. And we’re opening up as if we’re done with the virus. It’s like dismissing gravity. ‘I don’t want to deal with gravity any more today. I’m done with it.’ It doesn’t work that way.” Michael Osterholm podcast, April 1, 2021

Dear Students,

Some of you may remember my exclusive interview with the SARS-CoV-2 virus (“Sarsie”), way back in early June. He talked a lot about his relationship with Uncle Charlie—who he said was advising him on how to evolve. I didn’t think Darwin would do that deliberately, but Sarsie clearly obeys the old man’s laws.

Actually, he wasn’t interested in being interviewed.

“Professor, shut up and press the record button. I don’t need your questions. I can talk to the students directly, and anyway they’re bored stiff with your doom and gloom. I’ll give it to them, like the new Prez says, straight from the shoulder. Okay, I don’t have a shoulder. Straight from the spike then.

“When I spoke to you back in June I was gearing up, had notched a few wins on the evolutionary scene, and was getting ready for my real triumphs. This column is the half-time show in my superspreader superbowl.

“What’s that? You don’t like the half-time show idea? How about top of the fifth inning? Okay, bottom of the fifth. The home team, your species, is scoring some runs with vaccines. In June they were barely a wisp of a hope. Nine months later, they’ve been born, quadruplets, and they’re starting to grow up.

“I know, you think it’s the seventh-inning stretch at least, or even the end-game. You think you’re about to start hitting them out of the park. Dream on. I’m looking at half the game ahead, not counting overtime. And I’m so confident, I’m about to give you my playbook. Only fair. Homo dumbellus needs a handicap.

“Let’s review the basics as Uncle Charlie set them out: Variation, adaptation, duplication, reproductive success. If you remember two words, make them the last two. You don’t even need the words, really, if you can’t spare the space in your Homo dumbellus brain. Just the letters.

      “RS.

      “It’s Darwin’s own version of Newton’s Law of Gravity. If Variant B reproduces faster than Variant A did, B rocks. If Variant C does even better, it’s Bye-Bye Baby B. And so on. Insanely simple. Not like the rocket science you need to escape gravity. Even a dumbellus can understand Uncle Charlie’s law. Heck, even a virus can.

      “In June I reviewed my early life. Years in the bat-cave spinning my wheels, then a variant that let me jump to you. Nice shot, but more of a bunt than a home run. Then a variant that let me jump from you to you, and I took off like, well, a bat out of Wuhan.

“Mutation, mutation, mutation. I love those little bloopers. Most do nothing. Some knock off the adventurous virus that blooped them. But every once in a while, and don’t forget I’m reproducing zillions of times a day—that’s an approximation—I get one of those happy typos that makes my day, week, month, or year.

“Mutation. Variation. Variants. Variants of Concern.

“My first big VoC after my breakout from Wuhan was one you didn’t even know about at the time. It was the D614G. Let me clue you in how to read that gobbledygook. The spike protein is a string of amino acids (aa’s), and this means a change in the 614th one from aspartate to glycine. Just a blooper in duplication.

“Now that wasn’t so painful was it?

“The explanation wasn’t, but the reality was. It made me much more infectious. G614 outcompeted D614 by binding better to the ACE2 receptor that folds me into your cells. I had greater fitness; that is, greater RS.

“Remember Italy and Spain in early 2020? Wildfire there, then all Europe, then New York—the Big Apple. With D614G I gave my regards to Broadway, and after that the world. Wuhan was just a memory. By June, when I last spoke to you, my darling G614 had swept the globe.

“Big spring surge, then a rest, a bigger summer surge, and after a little vacation in early fall, you took a deep breath and I got set for my giant winter surge. It went well for me. How did it go for you? Oh yeah, I remember. Homo dumbellus. Thick skulls, stupid habits, stupid leaders.

“Wow, did I take off in January. The graph itself looked like a rocket ship.

“But I didn’t rest on my laurels. Uncle Charlie wouldn’t have liked that, and I always want him to be proud of me. Turns out there were plenty of dumbelluses in England, so I fixed my fitness lens on Trafalgar Square. You know. The UK variant. B.1.1.7.

“If I squinted, I could see old Charlie nodding in his photo. He must have also liked that you started naming strains according to their evolutionary history. Couldn’t very well have named it according to one mutation. It had 23! 23 differences from the Wuhan original.

“Eight were in the spike protein, and three of those are a big deal: N501Y, (a blooper changing asparagine to tyrosine), P681H (proline to histidine), and two aa deletions at positions 69-70. The tyrosine at 501 made my spikes even better at binding ACE2, my key to your cell’s locks. The other two changes probably helped me fold myself through your cell membranes.

“You can see why I thought I saw Charlie swell with pride. I was mixin’ & matchin’! I was upping my game several ways at the same time. God I love evolution. My UK variant soon proved up to 70 percent more infectious, and the Brits, who had gotten D614G from their Southern European cousins, returned the favor as a Christmas present, sending the new B.1.1.7 back to Europe and now the world.

“Let’s take a break from the gobbledygook and note that this variant is the one you dumbelluses need to worry about right now. It’s dominant in Europe and soon will be in the US and much of the world; the only thing that will contain it other than vaccines, which work but are not moving fast enough to beat it, will be other souped-up versions of me that hold it to a standoff.

“By the way, the B.1.1.7 is also more lethal. Don’t think for a minute that I like that. Billions of my bros go into a hole in the ground every time they kill one of you—if you were still infectious when you died. Heck, what happens as soon as one of you stops breathing? No breathing, no aerosols, no RS.

“That’s why I evolved to be less virulent—less lethal—than my cousins MERS and SARS-1. I out-evolved them to put it mildly. Dumb as your species is, it gives me no pleasure to kill you. I want infections with few or no symptoms, especially in young people, whose restlessness and appetites whisk me around the world.

“Speaking of which, the world is welcoming me in more variants than one. The South African one, B.1.351, also has the N501Y blooper, but in combination with other changes in my recipe—K417T (lysine to threonine) and E484K (glutamate to lysine)—that make me resistant to your vaccines, even if Africans can get them. Africa is to me a vast unconquered world, an evolutionary opening of collossal proportions.

“Then of course Brazil, where the so-called leaders are as bad as yours, and they’re welcoming me to a banquet. My P.1 variant has 17 unique bloopers, including three that affect our binding to your receptors: K417T, E484K, and N501Y. The P.1 came out of the Amazon—famous for its diverse life forms, including me—and swept the country. But you don’t think my boys are going to stop at the Brazilian border, do you?

E484K, aka the “Eeek” mutant, may be my jiu-jitsu trick to duck your immune systems and even vaccines. You can bet I’m going to make good use of the Eeek in the future. I’ve already popped up with it in Oregon independently, meaning—Uncle Charlie rocks—parallel evolution. If I can evolve that one pretty much anywhere, and it does turn out to nix your vaccines, well, Katie bar the door.

“Meanwhile, there’s a new New York variant, the B.1.526, which affects young people more, and a new two-form California variant, the B.1.427/B.1.429, with three spike protein mutations, including the novel L452R (leucine to arginine), that make it more contagious.

“Understand: most of your species hasn’t seen any version of me yet. I’m just getting started with them. See what I mean about half time? Bottom of the fifth? I still have to get to the majority of the species, and I will keep spreading faster than vaccines. I will also keep evolving. So you Americans beat the versions you have with the vaccines you have. But wait, you already have the Eeek!

“And something else: Do you think the bottom half of the world won’t be sending evolved versions of me back to you next year? The year after?

“Eventually you’ll fight me to a standoff with evolving vaccines. The smartest strains of your dumbellus species—the scientists—move fast enough to do that. But eradicate me? Forget it. Boosters for waning immunity, annual shots like my bro the flu, we can make a deal.

“A guy like me has a career trajectory. I could evolve toward even less virulence, become more like the common cold than the flu. Just bubbling up, year after year, not much damage but spreading just fine, bubbling and bubbling forever.

“So now you have my playbook and my retirement plan. We’ll get along eventually—after the pandemic game, my species against yours, is over. Which it isn’t even close to being yet. Like the man said, don’t dismiss Newton’s Laws, or Darwin’s. If it’s the bottom of the fifth, you, the home team, are up. Are you going to continue to let me strike you out? Or do you finally hit one out of the park?”

Maybe I should ask Sarsie to say what he really thinks.

He claims he doesn’t like to kill us, but he’s killed 550,000 of us in a year. We’re losing over a thousand a day and that is not declining; cases and hospitalizations are rising, and deaths will rise too.

It’s a fierce evolutionary process that can do that for one, two, three, and soon four American surges. Some biologists say that viruses aren’t really alive. Sarsie said last time, rather annoyed, “I’m alive and I’m eating you alive.”

Either way, his biological evolution has been amazing; cultural evolution is supposed to be faster, but our cultural evolution in response to him continues to lag way behind.

Stay safe,

Dr. K

PS: Please don’t just rely on me. The most important addition I have since my last update is Dr. Michael Osterholm’s weekly podcast from CIDRAP, the Center for Infectious Disease Research and Policy of the University of Minnesota; it drops on Thursdays. He combines realistic assessments and warnings with uplifting stories about how people are finding light and small victories in the pandemic. The best resource on what is happening specifically in the state of Georgia is Dr. Amber Schmidtke’s Daily Digest. More generally, I recommend the following: The Bill & Melinda Gates Foundation COVID-19 Update, aka The Optimist; for the science of viruses, especially the new coronavirus, This Week in Virology (TWiV) podcast; Dr. Sanjay Gupta’s podcast, Coronavirus: Fact vs. Fiction; COVID-19 UpToDate for medical professionals; and for the current numbers: Johns Hopkins University (JHU); Institute for Health Metrics and Evaluation (IHME); Our World in Data (OWiD); The New York Times Coronavirus Resource Center (NYT). For uncannily accurate warnings, follow @Laurie_Garrett on Twitter. I also recommend this COVID-19 Forecast Hub, which aggregates the data from dozens of mathematical models, and this integrative model based on machine learning. For an antidote to my gloom, check out the updates of Dr. Lucy McBride, who doesn’t see different facts but accentuates the positive.