Tagged Darwinian fitness

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.

 

 

New Sheriff, New Bad Guys

      “We shall fight on the beaches, we shall fight on the landing grounds, we shall fight in the fields and in the streets, we shall fight in the hills; we shall never surrender.” Prime Minister Winston Churchill, House of Commons, June 4, 1940

     “C’mon man, gimme a break!” President Joe Biden, January 21, 2021, answering a reporter who asked if a million vaccinations a day was enough

Dear Students,

Don’t get me wrong. I love Joe Biden. I supported him when most of my family and friends supported Elizabeth Warren—who by the way was the smartest person running for president, and had policy views most similar to mine—or Bernie, or others. Also, I didn’t think anyone as old as me should be president again. Yet I supported Biden because I was fairly sure that he had the best chance of winning, and because I was completely sure that he is an exceptionally good man. Although I did not say this to many people, I thought that he might be a great president.

Also, he is off to a good start. The new sheriff is laying down the law—on racism, LGBTQ rights, economic rescue, environmental protection, masking, social distancing, and vaccinations. But as far as the virus goes, he does not get a break from me, and no, it is not nearly enough.

Dr. Peter Hotez, a distinguished physician-virologist who is probably the most knowledgeable person about the pandemic after Dr. Fauci—but who can speak more freely than Fauci even now—wrote an op-ed piece in the Washington Post on January 26th in which he described the new variants of the virus as a “looming catastrophe” that will bring us to 600,000 deaths by May. We need to deliver 500 million doses of vaccines—into Americans’ arms—to end community transmission. Do we want to wait 500 days? By that time the new variants will have run all over us. We need to do it by summer. Which is why Dr. Hotez is calling for 3 million vaccinations a day.

This means that we need more than two vaccines; a vast and rapid (warp-speed?) expansion of vaccination centers beyond those already planned; unprecedented invocation of the Defense Production Act; imaginative use of the armed forces, even beyond the National Guard; and innovative use of syringes and other equipment to minimize vaccine waste. A good account of the current vaccine development situation in terms of science is here, but we need more than science, we need wartime logistics.

We also need a new level of seriousness about masks, social distancing, and handwashing. If we don’t ramp up our use of these measures, we will surely face more lockdowns, with all the associated economic, social, family, educational, and psychological pain.

If you have studied with me, you recognize that we are in an evolutionary arms race with this virus. All infectious agents adapt and evolve. They evade our defenses—both vaccines and treatments. That’s why after almost four decades we don’t have a vaccine against HIV, which evolves even within one person. That’s why we need a new flu vaccine every year. That’s why every year, thousands die of TB and malaria because they are infected by strains that resist all known treatments.

If we don’t (culturally) adapt and evolve in the face of this new virus—or should I say these new viruses?—we will lose, and as always, black, brown, and Native American people will lose most. We will not win this arms race, this by far most deadly of all our wars, by asking for “a break.” We will only win by fighting the virus every hour of every day, in every place, in every way.

Good News

  1. The new sheriff is really, really different from the old one. His deputies can shoot straight and they know how to round up bad guys—bad viruses. The heads of the CDC, FDA, HHS and many other agencies responsible for fighting disease are superb people, not third-raters and sycophants like their predecessors; they are already speaking directly and frequently to the American people, without fear of censorship for delivering scientific truth. For the first time there is a national plan, and it is a fairly good plan. With it, we are building a shield against the virus that we never had before.
  2. There has been a significant decline in the past couple of weeks in the number of US cases and hospitalizations but not yet deaths, probably related to the end of the big holiday surge.
  3. The Pfizer and Moderna mRNA vaccines are working safely, and pretty soon a few million Americans will have approximately 95 percent protection (two weeks or so after their second dose). Preliminary data suggest that protection levels could be even higher in the community than they were in clinical trials.
  4. The Janssen/Johnson & Johnson (J&J) vaccine will likely be approved (like the first two) for emergency use in the U.S., within a couple of weeks. Despite being less protective than its predecessors, it is more effective than the seasonal flu vaccine and easily passes the threshold of 50 percent protection set by health authorities. It hides the DNA—the gene—of a SARS-CoV-2 spike protein inside the Trojan horse of a cold virus disabled from reproducing. It has tremendous advantages: first, it only requires one shot; second, it does not require any specialized freezing or cooling equipment (DNA being much more stable than mRNA). These advantages will make it literally a lifesaver in rural America and in the developing world.
  5. The Oxford/AstraZeneca vaccine, despite some stumbles in the Phase III trials, is being used in the UK and was just approved by the European Union. It requires two doses but no special freezers, and will probably be added to the US vaccine arsenal in April. It is similar in principle to the J&J but uses a non-reproducing chimp adenovirus (instead of a human one) as the Trojan horse. The DNA is stable at higher temperatures, but it is still being worked out what the ideal doses would be.
  6. A monoclonal antibody drug (bamlanivimab, Eli Lilly) has shown 80 percent effectiveness in preventing infection in a randomized controlled trial in nursing home patients, and even greater effectiveness against deaths. This would have been tremendously important a few months ago, before we had vaccines, but now that we do, it’s not clear how the antibodies will be used—especially since they may interfere with vaccine effects.

Bad News

  1. The big bad news, and it is really bad, is that the virus has evolved new variants—new bad guys that will make the new sheriff’s job much harder. Of course, it has been evolving all along. A new paper, “Emergence of a Highly Fit SARS-CoV-2 Variant,” traces the first big leap the virus took last spring. As you know, “highly fit” in this context means spreading faster for more reproductive success. That first mutation was a single base change known as D614G that emerged in Southern Europe and by June was the dominant strain in the world.
  2. Viral evolution continued. In December a new “variant of concern” (B.1.1.7) was found in Southern England that contained multiple mutations and was determined to spread much faster and cause more severe disease. The mutations make it easier for a spike protein on the virus to combine with ACE2 receptors on human cells to gain entry. Hospitalizations doubled in the UK as the new variant became dominant there. More replication, more fitness, more dominance. It has been found in several US states and is predicted to be the dominant strain here by March. Fortunately, it does not evade already existing vaccines.
  3. A new South African variant (B.1.351) with different mutations of the spike protein—one of the mutations is on the presenting tip of the spike protein—is spreading rapidly and may soon threaten my old friends in Botswana. Two cases were found in South Carolina. Dr. Brannon Traxler, Interim Public Health director for the state, announced that they are independent of each other and have no travel history. She added cogently, “We know that viruses mutate to live and live to mutate.” Another independent case was found in Maryland. Given that we only sequence half of one percent of the virus samples taken in this country, it may already be everywhere. Like the English variant, it is more contagious and produces more severe cases, but unlike the English one, it also appears to be less responsive to existing vaccines.
  4. A new Brazilian variant (P.1) is worrying scientists. It is spreading explosively there and has been found in Minnesota. It may infect people who have had the disease before. It may or may not turn out to be implicated in the newly announced tragic COVID-19 deaths of nine children in the remote Amazonian villages of the indigenous Yanomami.
  5. There is no chance that one million vaccinations a day in the United States will stay ahead of the coming invasion of these new viral variants. The best, if not the only chance, is a great intensification of other preventive measures, the same that have been recommended all along. Unfortunately the behavioral trends seem to be going in the opposite direction.

On “Meet the Press” yesterday, top epidemiologist Michael Osterholm said, “The surge that is likely to occur with this new variant from England, is going to happen in the next 6 to 14 weeks. And if we see that happen—which my 45 years in the trenches tell us we will—we are going to see something like we have not seen yet in this country… Imagine where we are, Chuck, right now. You and I are sitting on this beach where it’s seventy degrees, perfectly blue skies, gentle breeze, but I see that hurricane, Category 5 or higher, 450 miles offshore. And telling people to evacuate on that nice blue-sky day is going to be hard. But I can also tell you that hurricane’s coming.”

Dr. Nahib Bhadelia of Boston University’s School of Medicine, asked to comment on Osterholm’s metaphor, said we are in  “the eye of the storm,” not sitting on the beach with the storm hundreds of miles out. She means that the worst part of the storm so far—December and January—is deceptively slacking off. As the hurricane moves over us, the lull of the eye passes, and we get slammed with another monstrous storm surge in March and April.

Dr. Osterholm went on to say that we need “an audible”—American-footballese for a last-minute yell on the field that changes the plan. He thinks we need to get as many people as possible vaccinated once right now, and forget about the second dose until later. There is controversy about this, but Osterholm is really smart.

Recall what Dr. Traxler, South Carolina surgeon-turned-health official, said when she became the first American to announce the South African strain: “We know that viruses mutate to live and live to mutate.” She continued, ““That’s why it’s critical that we all continue to do our part by taking small actions that make a big difference. These include wearing our masks, staying at least six feet apart from others, avoiding large crowds, washing our hands, getting tested often, and when we can, getting vaccinated. These are the best tools for preventing the spread of the virus, no matter the strain.”

On December 15th, when I posted “Double Down or Double Deaths,” we had just crossed 300,000, but we were having the first vaccinations and hope was in the air. I said we could go to 600,000 if we don’t change our behavior. The IHME model now projects 582 thousand by May , 600 thousand taking the new variants into account. That’s the doubling. Considering we’re at 440,000 today, it’s not a stretch.  Depending on what we do and what the variants do, we could be anywhere between 600 and 2,400 daily deaths in May. The difference would be the equivalent of two 9-11’s every two days. And of course May will not be the end.

The new shield we got on January 20th is not nearly big enough or thick enough. And the new variants teach us that unless we think about protecting the developing world, protecting the whole world, which is the virus’s continuous playground, our shield will be full of holes.

Are you tired of the precautions? I am too. I want to hug my children and grandchildren so bad it hurts (and I don’t care that it’s ungrammatical). I want to see live theater. I want to eat out with my wife in any sort of restaurant, even McDonalds. I want to smile at people and see them smile back. I am tired of restricting myself for the benefit of myself, my community, and my country. I am, to use an  expression my mother might use, bone-tired. But I am not yet dead-tired. I will be dead-tired if and when the virus kills me.

And oh, by the way. In case you get to whisper in President Biden’s ear, give him this message from me: Mr. President, Sir, with all due respect, the next time a reporter asks you if a million vaccines a day is enough, do what you always said you would do: Level with us. Don’t say, ‘Gimme a break man.’ Say, ‘No, it’s not enough. We need three million a day at least, and  I promise you I will not rest until we have that. We are at war. We will fight this virus in the clinics and in the stadiums, we will fight in the pharmacies and supermarkets, we will fight on street corners and parking lots, we will fight in convention centers and on fair grounds, we will fight in the poor dense cities and in the bucolic countryside, we will fight with syringes and tests and masks and distancing; we will never surrender.’

Stay safe,

Dr. K