I shall begin by repeating what I said the other day about the Boston University “study” that spliced Omicron spike proteins onto original Wuhan SARS-CoV-2 virus and proceeded to kill 8 out of 10 mice:

Playing God with viruses teaches us nothing about how these viruses evolve in the wild. Making new viruses yields no insight into viruses that exist naturally in the wild.

What the Boston University researchers did was not and will never be legitimate scientific research. It is morally and scientifically indefensible.

Naturally, there was an op-ed in Science magazine attempting to defend it. All good Faucists must stick together, apparently.

Backdrop: What The BU Team Actually Did

To understand exactly why the BU research is beyond the pale, we must first understand exactly what they did

Their research involved comparing several naturally-occurring

The recently identified, globally predominant SARS-CoV-2 Omicron variant (BA.1) is highly transmissible, even in fully vaccinated individuals, and causes attenuated disease compared with other major viral variants recognized to date1–7. The Omicron spike (S) protein, with an unusually large number of mutations, is considered the major driver of these phenotypes3,8. We generated chimeric recombinant SARS-CoV-2 encoding the S gene of Omicron in the backbone of an ancestral SARS-CoV-2 isolate and compared this virus with the naturally circulating Omicron variant. The Omicron S-bearing virus robustly escapes vaccine-induced humoral immunity, mainly due to mutations in the receptor-binding motif (RBM), yet unlike naturally occurring Omicron, efficiently replicates in cell lines and primary-like distal lung cells. In K18-hACE2 mice, while Omicron causes mild, non-fatal infection, the Omicron S-carrying virus inflicts severe disease with a mortality rate of 80%. This indicates that while the vaccine escape of Omicron is defined by mutations in S, major determinants of viral pathogenicity reside outside of S.

After creating the chimeric virus, they then cultured a series of cell cultures with the original Wuhan strain, Omicron, and their chimeric “Omi-S” manufactured strain.

We first compared the infection efficiency of Omi-S with an ancestral virus and Omicron in cell culture (Fig. 2a). For this, we infected ACE2/TMPRSS2/Caco-233 and Vero E6 cells with Omi-S, a recombinant D614G-bearing ancestral virus (GISAID EPI_ISL_2732373)30, and a clinical Omicron isolate (USA-lh01/2021) at a multiplicity of infection (MOI) of 0.01 and monitored viral propagation by flow cytometry and the plaque assay. The ancestral virus [hereinafter referred to as wild-type (WT)] and Omi-S spread fast in ACE2/TMPRSS2/Caco-2 cells, yielding 89% and 80% infected cells, respectively, at 24 hours post-infection (hpi) (Fig. 2b). In contrast, Omicron replicated slower, leading to 48% infected cells at 24 hpi. A similar pattern was seen in Vero E6 cells, where 60% and 41% of cells were positive for WT and Omi-S, respectively, at 48 hpi, in contrast to 10% positive cells for Omicron (Fig. 2c). The plaque assay showed that although both Omi-S and Omicron produced lower levels of infectious virus particles compared with WT, the viral titer of Omi-S was significantly higher than that of Omicron. In ACE2/TMPRSS2/Caco-2 cells, Omi-S produced 5.1-fold (p = 0.0006) and 5.5-fold (p = 0.0312) more infectious particles than Omicron at 12 hpi and 24 hpi, respectively (Fig. 2d). Similarly, in Vero E6 cells, the infectious virus titers of Omi-S were 17-fold (p = 0.0080) and 11-fold (p = 0.0078) higher than that of Omicron at 24 hpi and 48 hpi, respectively (Fig. 2e). The difference between viruses became less obvious at later time points due to higher cytotoxicity caused by Omi-S compared with Omicron (Fig. 2f). The higher infection efficiency of Omi-S relative to Omicron was also reflected in the plaque size; while WT produced the largest plaques (~ 4.1 mm), the size of Omi-S plaques (~2.2 mm) was 2-fold (p < 0.0001) larger than that of Omicron plaques (~1.1 mm) (Fig. 2g). These results indicate that while mutations in the S protein influence the infection efficiency of Omicron, they do not fully explain the infection behavior of Omicron in cell culture.

Note the percentages: In ACE2/TMPRSS2/Caco-233 cells original Wuhan strain (WT) infected 89% of cells in the culture media and Omi-S infected 80% of cells in culture media. Omicron—which is currently the dominant and very nearly the exclusive strain circulating in North America today—only infected 10% of cells in the culture media.

To reiterate, Omicron is the dominant strain of SARS-CoV-2 in North America today.

So the chimeric virus BU created displayed one hundred sixty percent of the infectiousness of Omicron in ACE2/TMPRSS2/Caco-2 cells, and four hundred ten percent of the infectiousness of Omicron in Vero E6 cells.

That’s what the BU team’s own write up of their own data says in black and white. Their chimeric strain is categorically shown to be more infectious than Omicron.

More importantly, the BU researchers explicitly tested for gain of function. They said so in their own write up of their own data:

To examine if Omi-S exhibits higher in vivo fitness compared with Omicron, we investigated the infection outcome of Omi-S relative to WT SARS-CoV-2 and Omicron in K18-hACE2 mice. In agreement with the published literature3,37–39, intranasal inoculation of mice (aged 12-20 weeks) with Omicron (104 PFU per animal) caused no significant weight loss, whereas inoculation with WT virus triggered a rapid decrease in body weight with all animals losing over 20% of their initial body weight by 8 days post-infection (dpi) (Fig. 3a). Importantly, 80% of animals infected with Omi-S also lost over 20% of their body weight by 9 dpi (Fig. 3a and Extended Data Fig. 2a). The evaluation of clinical scores (a cumulative measure of weight loss, abnormal respiration, aberrant appearance, reduced responsiveness, and altered behavior) also revealed a similar pattern; while Omicron-infected mice displayed little to no signs of clinical illness, the health of those infected with WT and Omi-S rapidly deteriorated, with the former inflicting a more severe disease (p = 0.0102) (Fig. 3b and Extended Data Fig. 2b). Since SARS-CoV-2 causes fatal infection in K18-hACE2 mice3,40,41, we leveraged this situation to compare the animal survival after viral infection. In agreement with the results of body-weight loss and clinical score, WT and Omi-S caused mortality rates of 100% (6/6) and 80% (8/10), respectively. In contrast, all animals infected with Omicron survived (Fig. 3c). These findings indicate that the S protein is not the primary determinant of Omicron’s pathogenicity in K18-hACE2 mice.

Omicron was not lethal to the mice, WT and Omi-S were highly lethal. Again, the BU research team has said this.

But Wait...”Scientist” Derek Lowe Says Omi-S Is Less Lethal

Against the explicit statements of the BU research team we now have the op-ed apologia by one Derek Lowe, an organic chemist (i.e., not a “real virologist”) and long-time paid researcher for Big Pharma, according to his bio:

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He’s worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer’s, diabetes, osteoporosis and other diseases.

No possibility of bias here, obviously!

Potentials of bias aside, there is an absolute certainty of spin and dissembling by Derek Lowe, as he tries to argue that the Omi-S is really “less dangerous”.

So what did the team find? Did they make a more dangerous version of the coronavirus? No. In fact, contrary to many of the people who are spouting off on this on social media, the new chimeric strain was less dangerous by comparison in animal tests. Some readers may have seen the figure of 80% of the mice exposed to the chimeric virus dying (because that one is sometimes passed around in ALL CAPS, it can be hard to miss). But before jumping out of your chair, consider that when these mice were exposed to the original Wuhan coronavirus that 100% of them died. This would also be a good time to mention that "exposed", in this experiment, means "large dose sprayed directly up their noses", not wafting around in the cage like some simulation of a mouse dinner party. And as another real virologist (Marion Koopmans of the Netherlands) notes from the data in the preprint, the chimeric virus actually had lower ability to replicate deep in the lung tissue, which may be some of the reason that it was less virulent than the ancestral strain.

As an aside, we should not allow the dripping condescension of characterizing other pro-gain-of-function researchers as "real virologists”, particularly as Derek Lowe is not himself one of those “real virologists”. Such snide arrogance alone is enough to dismiss his arguments as pure crap—ad hominems are eternally logical fallacy rather than logical argument, particularly when used in conjunction with an equally fallacious appeal to authority.

However, we do not need to rely on that one logical shortcoming in his gain-of-function apologia to realize its fecal content is sufficient to solve the world’s fertilizer shortage. The primary thrust of his argument that Omi-S is less lethal is that not every mouse infected with Omi-S died, but every mouse infected with original Wuhan strain died.

Within the study itself that is true. However, it is not universally true. In a separate study

Next, we investigated the infection outcome of infection with Omicron compared with SARS-CoV-2 WT, Alpha, Beta and Delta in K18-hACE2 mice. Our results showed that, compared with the WT and the previously emerged variants, the body-weight loss of mice infected with Omicron was significantly milder, with the onset time at a later stage during the course of infection (Fig. 3e). Importantly, we took advantage of the K18-hACE2 infection model and compared animal survival after infection with SARS-CoV-2 WT and variants. Under the same inoculum conditions, mouse survival was lowest for Alpha (0%), followed by WT (20%), Beta (33%), Delta (44%) and was highest for Omicron (57%) (Fig. 3f). Statistically, mouse survival for Omicron was significantly higher than Alpha (P = 0.0001) and WT (P = 0.0377), but did not reach significance for Beta and Delta. Nevertheless, the trend of mouse survival was consistent with the results of body-weight loss, which demonstrated a propensity for better survival in the order of Alpha, WT, Beta, Delta and Omicron (Fig. 3f).

In other words, Omi-S is arguably every bit as lethal as original Wuhan. It is demonstrably more lethal than naturally-occurring Omicron.

Moreover, there is no escaping the reality that original Wuhan strain is not dominant anywhere in the world. Omi-S might be slightly less lethal than original Wuhan, or as lethal, but that is a meaningless comparison when original Wuhan is simply not circulating in the wild—and has not been since September 2021 at the latest, when the Delta strain pushed all prior strains aside in North America.

Meanwhile, Omi-S remains many times more dangerous than Omicron, and the BU researchers provide the explicit statistics that say exactly that.

Derek Lowe conveniently omits that point.

Derek Lowe also attempts another bit of spin by pointing out that the XD recombinant variant earlier this year was a combination of Delta and Omicron, and it turned out not to be a problem.

But what if? What if this chimeric strain turned out to be more lethal than expected in the human population? What happens if you take an older strain of the virus and swap in the Omicron-level spike; doesn't that have the potential for trouble? Well, we've already seen a "natural experiment" like that, as Florian Krammer points out. There was a strain back in March called XD, which was a Delta that had the Omicron spike protein in it (via recombination). XD did not take off in the human population and did not seem to be more of a problem than the other strains, which is why you've probably never heard of it. That recombination domain-switching process very likely takes place in cases of infection with two viral strains at once.  The various sequences can get swapped around under these circumstances while things are replicating and reassembling in the same cells, and you'd overall rather not see much of that, because it just gives the virus more lottery tickets to play  with.

While XD was largely a recombination of Omicron and Delta, with the Omicron spike protein finding its way into the Delta genome, that was not the only mutation in the virus

The XD variant contains the genomic elements from the Delta variant and Omicron BA.1 variant (Fig. 1 a). The XD variant contains the genomic elements ORF1a and ORF1b integrated from the Delta variant, while the spike protein is integrated from the Omicron BA.1 variant. The other genomic parts (E, M, ORF6, ORF7a, ORF7b, ORF8, N, 3UTR) of the XD is incorporated from the Delta variant (Fig. 1b). Researchers have noted that approximately 1 bp to 21463 bp of the genomic element is integrated from the Delta variant. Similarly, the genomic element from 21643 bp to 25581 bp is integrated from the Omicron BA.1 variant (spike protein region). Again, from 25581 bp to the endpoint, the genomic element is from the Delta variant. Nevertheless, it has been observed that XD contains the novel mutation (E172D). The E172D mutation is located in the genomic region of NSP2 [6].

I am not suggesting that the single identified novel mutation outside of the spike protein in XD is responsible for it not being more pathogenic, but it is empirically certain that the XD recombinant virus was not structurally the same as Omi-S, nor was it a pristine swap of spike proteins from Omicron to Delta virions.

Unnecessary Risks, Useless Research

What makes the BU research all the more appalling is that it was and is completely unnecessary, and added nothing to the store of knowledge about the SARS-CoV-2 virus.

It had already been established that key features of the virus that influenced its pathogenecity resided outside the spike protein. A study

The less virulent human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 cause mild, self-limiting respiratory tract infections, while the more virulent SARS-CoV-1, MERS-CoV, and SARS-CoV-2 have caused severe outbreaks. The CoV envelope (E) protein, an important contributor to the pathogenesis of severe hCoV infections, may provide insight into this disparate severity of the disease. We, therefore, generated full-length E protein models for SARS-CoV-1 and -2, MERS-CoV, HCoV-229E, and HCoV-NL63 and docked C-terminal peptides of each model to the PDZ domain of the human PALS1 protein. The PDZ-binding motif (PBM) of the SARS-CoV-1 and -2 and MERS-CoV models adopted a more flexible, extended coil, while the HCoV-229E and HCoV-NL63 models adopted a less flexible alpha helix. All the E peptides docked to PALS1 occupied the same binding site and the more virulent hCoV E peptides generally interacted more stably with PALS1 than the less virulent ones. We hypothesize that the increased flexibility of the PBM in the more virulent hCoVs facilitates more stable binding to various host proteins, thereby contributing to more severe disease. This is the first paper to model full-length 3D structures for both the more virulent and less virulent hCoV E proteins, providing novel insights for possible drug and/or vaccine development.

This study was done by examining the molecular structures of coronaviruses and exploring their attributes via 3-D modeling software. No new viruses were created to obtain the knowledge conveyed in this research.

The notion that researchers need to manufacture “chimeric” viruses in order to learn about naturally occurring viruses is simply absurd. To learn about naturally occurring viruses one has to study naturally occurring viruses, not make up new viruses and assume that how the made up viruses behave is indicative of how naturally occurring viruses behave.

The argument is particularly silly when the knowledge purportedly gained from making new viruses is already known from prior research. Which makes the BU effort not actual research at all, but simply a bunch of out-of-control Faucists playing with their molecular engineering toys because it amused them to do so.

False Arguments And Bad Logic Lead To False Conclusion

The upshot of the Faucist spin in the Science op-ed is that Derek Lowe’s conclusion is false, facetious, and foolish.

So this was not a gain-of-function experiment, and it did not appear to make a more dangerous virus.

The BU research was a gain-of-function experiment, and it did appear to make a virus more dangerous than currently circulating Omicron. More importantly, that was the stated intent of parts of their research. We know this because the BU research team said it. We know also that the BU research was a complete waste of time.

When the apologists have to lie and spin to defend “science”, that’s when you know you’re dealing with Faucist fanatics. Apparently they’re everywhere in science these days.

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