Where did SARS-CoV-2 come from?

I’ve been seeing some wild speculation that this pandemic is the product of genetic engineering — that it’s a biowarfare weapon that escaped from a lab somewhere. This is nonsense. I’ll refer you to an article in Nature Medicine, The proximal origin of SARS-CoV-2, which discusses a systematic analysis of the structure of SARS-CoV-2 in comparison to other coronaviruses.

It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus. As noted above, the RBD of SARS-CoV-2 is optimized for binding to human ACE2 with an efficient solution different from those previously predicted. Furthermore, if genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used. However, the genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone. Instead, we propose two scenarios that can plausibly explain the origin of SARS-CoV-2: (i) natural selection in an animal host before zoonotic transfer; and (ii) natural selection in humans following zoonotic transfer. We also discuss whether selection during passage could have given rise to SARS-CoV-2.

A little translation: the virus has a spike protein that binds to an enzyme on the surfaces of cells, called angiotensin converting enzyme, or ACE. This enzyme is important in regulating blood pressure, and is expressed by cells in lung capillaries (fun fact: your lungs play an endocrine role in sending out signals that maintain blood pressure). This is one reason the virus has such a dangerous respiratory effect — the lungs are the primary targets, where it can use the spike protein to bind to cells that express ACE and drill into them.

The RBD is the Receptor Binding Domain of the viral spike, and is the most variable part of the virus. This makes sense: the RBD is the key the virus uses to get access to your cells, and it varies because it confers target specificity. So there are all these different varieties of coronavirus, most of which don’t bother humans because they lack the human key — they are adapted to invade other animals’ cells. SARS-CoV-2 has acquired a spike with a human unlock code. Could some cunning super-villain have modified the spike?

Not likely, for several reasons. The virus has other similarities to coronaviruses in other animals; it’s not a de novo construct, but is a member of a large family of viruses. The modification to the spike protein is unusual. It works, but it’s not one that scientific experts would have used — they would have used something that would have been previously modeled. Then also bioengineers have lots of clever tools that could be used to stuff a desired sequence into a virus, but they all leave tool marks, little scraps of the molecule used to do the replacement. Those marks aren’t there. The best explanation is that we’re just seeing natural selection amplifying random variations in the spike.

While the analyses above suggest that SARS-CoV-2 may bind human ACE2 with high affinity, computational analyses predict that the interaction is not ideal and that the RBD sequence is different from those shown in SARS-CoV to be optimal for receptor binding. Thus, the high-affinity binding of the SARS-CoV-2 spike protein to human ACE2 is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise. This is strong evidence that SARS-CoV-2 is not the product of purposeful manipulation.

Yeah, see, if I were a nefarious super-villain, we already have an even better RBD we could yank out of other viruses, and I would have used that to build a deadly virus. But instead, the SARS-CoV-2 RBD is some clunky variation that came out of nowhere, by accident, without any other signs of intentional manipulation.

They also consider the possibility that this was an accidental variation acquired in a lab — if you pass a virus through a lot of host cells in a cell culture system, it will continue to evolve, and you might imagine the RBD might acquire a random variation that allows it to thrive in those cells, and then it accidentally escapes the lab. This is also unlikely, because it shares a lot of similarities with the pangolin coronaviruses. It’s more likely to have arisen from an existing pool of related viruses in the wild, then either acquired its novel binding site there, or after infecting humans and experiencing selection for better binding to human cells.

The best strategy is to look for intermediates in animals, or in the sequences of humans who were infected early in the pandemic.

The identification of a potential intermediate host of SARS-CoV-2, as well as sequencing of the virus from very early cases, would similarly be highly informative. Irrespective of the exact mechanisms by which SARS-CoV-2 originated via natural selection, the ongoing surveillance of pneumonia in humans and other animals is clearly of utmost importance.

Sorry, conspiracy theorists. The best explanation is evolution and natural selection, not Evil Intelligent Design.

The viral spike protein. The RBD is in green.

It’s Saturday?

I guess it is. I have to say it doesn’t seem to matter much anymore — It’s astounding, Time is fleeting, Madness takes its toll — since I’m just stuck at home, seeing no one, coming unmoored from everything, but I do have a thought which makes me feel slightly better.

Which would you rather?

A. Have a job that lets you work from home, even if it means you’re in isolation.
B. Be isolated at home without a job.
C. Not be isolated because your boss forces you to work in some mindless service job.
D. Not be isolated because you have an essential job, like health care, that exposes you to a high likelihood of getting COVID-19.
E. Have the disease.

There, that puts it all in perspective. I’m an A. I am so lucky. Which one are you?

Anyway, today my plan is to churn out a video lecture for intro bio — the historical battle between biometricians and saltationists, which was basically resolved by everyone realizing that genetics was so much more complex than Mendel thought, followed by a lot of non-Mendelian examples — and get that ready to post by Monday.

Sunday is going to be spent churning out a video lecture on linkage mapping for genetics. There are always students who get lost on this stuff, so I expect to spend some Zoom time going over it next week. Then I have to finish grading some lab reports.

I am going absolutely nowhere. Spiders were fed the other day, so I’m not going to set foot in the lab this weekend. I have everything I need to live on in my house, so no trips to the store. I might step out onto the deck to my fenced back yard and remind myself what the sun looks like, but otherwise, I am definitely an A.

Friday Cephalopod: Blinking lights! Wings! It’s an alien spacecraft!

I still dream about cephalopods, even if the arachnids are snaring most of my attention.

The University of Rochester gets stomped hard for sexual harassment, deservedly

Contemptible Skidmark, Ph.D.

Back in 2017, I wrote about this awful sexual harassment case at the University of Rochester that involved in particular, one professor, T. Florian Jaeger, who was egregiously out of line with students, but also involved an entire university administration that was outrageous in how it supported Jaeger against all reason. There was a lawsuit. There was a countersuit. It dragged on for years, but now, at last, there has been a settlement, in favor of the victims.

I feel for them, having just gone through a lesser suit that dragged us through the courts for an absurdly long time, and was finally settled just recently. There seems to be no such thing as a speedy trial in these civil suits.

One big difference, though, is that the University of Rochester settled for the amount of $9.4 million. We’re still struggling to pay off our legal debt.

One similarity is that we also retained the right to tell our story, and that does make a difference. UR has really taken a major and deserved hit here, and the whole sordid story is available online. It’s horrifying reading: Jaeger was worse than I imagined, the University was complicit, and the university president did everything he could to enable Jaeger and punish his victims.

Plaintiffs were surprised at the University’s tight embrace and protection of Jaeger and the intense retaliation campaign against them. They could not figure out why UR was so determined to support a serial sexual predator who had caused misery to students and colleagues.

Over time, however, it has become clear that the University’s approach to Jaeger and Plaintiffs fits into a broader pattern of University behavior. UR is a major force in Rochester, the largest private employer in upstate New York, and used to getting its way. Its president is a powerful figure, and after 12 years in office, Seligman has restructured the University to his liking. Faculty and administrators describe him as thin skinned, “someone who always thinks he’s the smartest person in the room,” and, as his tenure has extended, increasingly imperious. He has expanded the ranks of administrators and appointed people to top positions (many times without a search process) who, according to many faculty, will no longer stand up to him or tell him when he is making a mistake.

The settlement wouldn’t have been so large if the University of Rochester hadn’t opened itself up to guilt with it’s horrible behavior.

Jaeger’s behavior created a working environment that was severe, pervasive, intimidating, hostile, and offensive to Cantlon and other female employees in the department.

Through its failures and treatment of Cantlon and others who complained about sexual harassment and discrimination as adversaries, UR contributed to and exacerbated the hostile working environment for female employees. It gave license to its employees, including DeAngelis and other faculty, to treat Cantlon and other female employees, or employees associated with this group via their complaints, with hostility and disdain.

The hostile environment based on sex created a hostile and intimidating work environment for Cantlon and interfered with her ability to do her job to the point that she began to look for other work

There’s more. A lot more. This statement by the court is satisfactorily scathing, and also explains why this decision was so important.

The false statements made by UR, Seligman and Clark seriously call into question the Plaintiffs’ fitness for their profession. As academics and research scientists, the Plaintiffs must be seen to have integrity and to be utterly trustworthy. Honest and integrity are crucial characteristics in their profession for at least the following reasons:

a. Research scientists rely heavily on grants to fund their work. An applicant’s scientific integrity, a concept inextricably tied to honesty, must be beyond question. If a grant-making body thought that a researcher was capable of making up evidence – as UR has accused the Plaintiffs of doing – the grant-making body would never support that researcher.

b. Similarly, the scientific community and publishers must be able to trust in the integrity of the researcher’s work. If the researcher’s scientific integrity or honest is questionable, publishers are unlikely to select their work for publication and institutions are unlikely to invite that researcher to give talks or present at conferences. Publishing and presenting work are both essential components of any academic career.

c. Labs need high quality Ph.D. students and post-docs to contribute to faculty members’ research. Choosing a lab is a big decision for these students and post-docs – where they work and who they work for can have a profound effect on their own careers. They are unlikely to work in the lab of someone who is considered to be dishonest or to have a history of bullying others.

d. Serving on committees or in other leadership roles in departments or throughout the University is another key part of an academic career. These opportunities are key to obtaining leadership positions and building a good reputation. Failing to do any service for one’s department or university reflects poorly on an academic’s reputation and suitability for the profession. The Plaintiffs have been accused of dishonesty, bullying, and manipulation. They have been barred from serving on committees or as ombudspersons because they are not trusted to be honest and unbiased.

As academics and research scientists, honesty and integrity are essential to Plaintiffs’ professional success. Provost Clark, President Seligman, and UR knew this when each false statement referenced was made.

Despite winning the case (strictly speaking, they settled, the UR has not admitted guilt), this was not a happy outcome. The plaintiff’s careers were hurt, they had to leave and put down roots elsewhere, it had to have been agony having this hang over their heads for so long. They sacrificed to get this result.

The University of Rochester is going to have to cough up $9.4 million dollars. On top of that, who knows how many grants they’ve lost because of this action? They’ve definitely lost much of their prestige, their cognitive science program was climbing the rankings as one of the best in the nation. If one of my students was planning to apply there, I’d strongly urge them to consider any place other than UR.

T. Florian Jaeger is still employed at the university, and wasn’t targeted by the lawsuit at all. The piece of shit sailed through the whole thing without getting stepped on.

I don’t understand that at all.

It’s time to shut down The Federalist

The Federalist is coming down hard on fake news and quack remedies, and they can’t even be consistent about it. On the one hand, the coronavirus is a fake epidemic; on the other, the “specter of euthanasia” is raising it’s head, it’s a world-wide threat, it’s the world’s “biggest stress test since WWII”. On the third hand, it’s also full of puff pieces about how American free enterprise will beat it, and “How Grandmother’s Gargling Remedy Could Help Abate The Wuhan Flu”. (Yeah, they always call it the “Wuhan Flu”, because it wouldn’t be The Federalist without implicit racism.) It’s a disinformation site.

It’s as bad as Alex Jones, and deserves the same fate, scorn and contempt.

I’d never heard of Ralph Drollinger before

Can I please go back to my state of innocence?

Drollinger is a minister of some sort who gets together with Trump’s cabinet every week to lead them in the path of righteousness through prayer. Like Trump’s “spiritual advisor”, Paula White, he seems to be a huckster and a grifter who’s there to influence powerful but stupid people.

The Drollinger-led Bible study meets every Wednesday morning with members of Trump’s cabinet, including Secretary of State Mike Pompeo, Housing and Urban Development Secretary Ben Carson, Education Secretary Betsy DeVos, and Health Secretary Alex Azar. Carson and Azar, notably, are members of the coronavirus task force guiding the federal government response to the pandemic.

Vice President Mike Pence, a member of the task force and a listed host of Capitol Ministries, is also tied to the Bible study. Emails obtained by Gizmodo show administration officials coordinating with Drollinger’s group to schedule a session of the Bible study, including the possibility of hosting the weekly event in Pence’s West Wing office.

What could he be telling them, you wonder. It’s all predictable right wing bullshit. The pandemic is all the fault of China, homosexuals, and environmentalists.

“Relative to the coronavirus pandemic crisis, this is not God’s abandonment wrath nor His cataclysmic wrath, rather it is sowing and reaping wrath,” wrote Drollinger. “A biblically astute evaluation of the situation strongly suggests that America and other countries of the world are reaping what China has sown due to their leaders’ recklessness and lack of candor and transparency.”

Neither does he miss a chance to condemn those who worship the “religion of environmentalism” and express a “proclivity toward lesbianism and homosexuality.” These individuals, Drollinger argues in “Is God Judging America Today?”, one of the minister’s posts about coronavirus pandemic, have infiltrated “high positions in our government, our educational system, our media and our entertainment industry” and “are largely responsible for God’s consequential wrath on our nation.”

How many of these loons are influencing our country? Do they think Rasputin was a good influence on Russia, too? I sure hope we can get a president who can grab these scoundrels by the ear and kick their asses out the door.

Let it be known

If someday soon my body is found lying on the floor of my house, it isn’t the coronavirus that killed me, it’s this damned cat. I am her sole obsession. Every day she sits and stares at me, and when I get up for any reason, she follows me. No, “follows” is the wrong word; she anticipates my every footfall and makes sure to place herself exactly where it’s most inconvenient for me. Just going to the bathroom has become an epic journey, where I’m forced to walk at half-speed through the vibrating quanta of Cat. I may have to get a machete so I can hack my way through this Cat Jungle. I know it’s just one cat, but she has the ability to plane-shift and and seems to have mastered the power of simultaneity.

I think so far she’s only toying with me, but if this isolation goes on much longer I know she sees me as a backup food source, and is practicing how she’s going to break my neck. I’m afraid.

If I suddenly drop off the internet and later my body is discovered, tell the police to investigate the cat. She can’t be allowed to get away with murder.