The Evidence that Omicron Was Made in a Lab

Dr. Danny Altmann, Professor of Immunology at Imperial College London, has admitted that the emergence of the highly immune-evasive SARS-CoV-2 variant Omicron came as a surprise to most experts in the field. He writes in the Guardian:

The onslaught of highly immune-evasive variants was, for most of us in immunology and virology, unforeseen. We’d come to think of the coronavirus family as being rather more stable – less error-prone in terms of mutations – than many viruses… Omicron and the subvariant BA.2 have managed to mutate almost every amino acid residue targeted by protective antibodies, escaping protection.

He doesn’t mention the possibility, but this unexpected nature of Omicron is clearly compatible with the hypothesis that the variant is not of natural origin. Earlier in the year, Noah Carl looked at the evidence that the variant might have leaked from a lab. I recently came across the website of biochemist Dr. Valentin Bruttel, which sets out the evidence for this lab origin in detail (though be aware it has been translated from German, so the text contains a few language mistakes).

The first piece of evidence is Omicron’s evolutionary history – its most recent common ancestor was a strain extinct in the wild and last seen around April 2020.

Normal SARS2 variants emerge when a few mutations (around two to six of those in the spike protein) accumulate in currently circulating virus. Omicron (red line below) emerged from a most recent common ancestor (MRCA) virus that was last seen around April 2020, and accumulated more than 25 new spike mutations in complete isolation. That means Omicron was evolving at a never before seen speed (3.3 times faster) and without infecting others.

The second piece of evidence is the very high number of sequential non-synonymous mutations (mutations which alter the amino acid sequence) that Omicron has accrued.

Many Omicron non-synonymous mutations reduce viral fitness. And in the pre-outbreak Omicron spike protein, there are 26 non-synonymous mutations in a row, without a single synonymous mutation in between. That many non-synonymous mutations in a row has never before seen in natural SARS-like coronaviruses, but a few times in synthetic ones.

The third piece of evidence is that almost all of Omicron’s non-synonymous mutations appeared in scientific publications before they appeared in Omicron, an event which has been calculated to be statistically impossible.

SARS2 variants usually inherit a few mutations from the parental strain and then evolve a few new ones themselves… Instead of inheriting only parental mutations, Omicron ‘copied’ almost all of its spike mutations from other variants (many of them which appeared after its most recent common ancestor) or from scientific publications. That’s a bit like directly inheriting genes not only from your father, but also from six younger cousins and five classmates you first met when you were seven. Almost all of Omicron’s non-synonymous mutations were already known about half a year before Omicron emerged. Those not from variants were mostly known to confer resistance towards vaccines, or from vaccine-associated publications.

The fourth piece of evidence is that we know Omicron-like variants were being created by scientists – and indeed that Omicron’s most recent common ancestor virus, though extinct in the wild for over a year, had been stored and cultured in Durban, South Africa, not far from where Omicron was first spotted.

We know that publicly-known lab leaks happen about twice a year. We also know that scientists selectively made vaccine-resistant SARS2 viruses in labs by culturing them with diluted sera from vaccinated donors. Others made ‘greatest hits’ synthetic polymutant SARS2 spike proteins that contain 20 non-synonymous mutations known to enable vaccine escape or from other variants. The latter experiment was done in a lab with a pseudovirus, but those can also escape and their spike protein can then be copied into SARS2 by a process called template switching. We also know that this lab’s partner lab in Durban collected, froze and later cultured exactly the SARS2 variant which is not circulating anymore out there and from which Omicron evolved. And it did patient sera virus culturing experiments. Such a lab leak would explain the extinct most recent common ancestor virus, isolated ‘evolution’ and precise inclusion of only published non-synonymous spike mutations.

The fifth piece of evidence is that pharmaceutical companies were trying to create a pan-variant vaccine based on a spike protein like Omicron’s which incorporated many key mutations from circulating variants. One such vaccine was being tested in HIV patients in southern Africa, where Omicron was first spotted.

I wonder what Professor Altmann makes of this evidence, and whether it would solve for him the mystery of the unexpected highly immune-evasive variant.

To my mind the evidence is compelling, though I admit I haven’t seen the counterarguments set out. It reinforces that this kind of research is dangerous, and is likely to do more harm than good. While some might say that Omicron has brought benefits in being a milder variant that has given many countries the confidence to reopen, the fact is we don’t know what would have happened had it not appeared. The Delta wave in a number of countries appeared to be declining before Omicron showed up (see below), despite it being December when respiratory viruses normally take off – though it’s fair to say we don’t know what other variant might have appeared in Omicron’s absence.