Evidence of Genetic Modification

Just looking for a straight up-or-down on the assertion made in the recent publication about the Covid-19 origin:

Dr. Ralph Baric, assisted in creating a method to leave no trace of genetic modification as early as 2005.

I believe that it’s referring to the Reverse Genetics technique, but I don’t see any relevant information through Google about this (or any other genetic modification technique) as regards the ability of mankind to make modifications to an organism through lab techniques and have that be undetectable.

In what recent publication was this assertion made?

By Googling:

The Republican report also raises concern that scientists at the Wuhan lab, including American researchers, had the ability to modify genetically altered viruses without leaving any trace that they had been tampered with.

“An American scientist, Dr. Ralph Baric, assisted in creating a method to leave no trace of genetic modification as early as 2005,” the report states. “And as early as 2017, scientists working at the WIV were able to do the same. This makes it clear that claims by the scientific community that SARS-CoV-2 could not be man-made because it has no genetic modification markers are disingenuous.”

Full pdf report here.

I can’t answer the OP’s question, but I’ll offer this.

In the article:

The Republican report, which is based on open source material and draws conclusions from circumstantial reporting, also raises concern that the lab was conducting “gain of function” research, controversial medical research where scientists genetically modify a bacteria or virus to make it more infectious in an effort to study better preventative measures, in an unsafe environment.

So basically, they seem to be drawing on assorted news reports to say essentially “we should investigate, but there’s no proof one way or the other”. Calling a news release by a politician a scientific study doesn’t give it more credence as a real scientific paper.

It’s a matter of probabilities. If the goal was to study “gain of function” then why would they modify it in such a way as to make the modification undetectable? In experiments, you only change one thing at a time to be sure the changes observed are due to the changes made. Either they were doing gain-of-function or they were experimenting with making modifications undetectable.

Plus I’m going to guess an actual study of modifying viruses to make them undetectable would be done with relatively harmless viruses, specifically since the whole point is to grow the resulting viruses to study the obvious detectability of modifications. Why do that with a dangerous virus?

If they were in fact creating a weaponized, undetectably modified virus, that would happen after the other tests. That they would do so, in the middle of a city instead of an isolated remote and secure lab, and then not notice it had escaped and not be looking for it, is not credible. If they were aware of a leak and avoiding publicity, then the central government would have clamped down on news from the start - as it was, at least one doctor was able to post an observation about too many respiratory patients before he was suppressed, and several others verified it.

Just too many things don’t fit deliberate stealthy weaponized viral research.

Not to mention - a specifically engineered dangerous virus would be kept under far more security that a mere sample collected from a wild animal where the danger was not as apparent. Of course, any person could have easily “collected” a sample from the nearby wet market to start the problem,too so it wasn’t necessarily the lab.

Plus, as Delta is showing us (and Alpha, Beta, and Lambda) this virus does not need human assistance (except as a host) to modify.

I don’t see how reverse genetics could be scaring the Republican opposition in this instance, given this description (Wikipedia):

“Vaccines created through reverse genetics methods are known as attenuated vaccines, named because they contain weakened (attenuated) live viruses. Attenuated vaccines are created by combining genes from a novel or current virus strain with previously attenuated viruses of the same species.[9] Attenuated viruses are created by propagating a live virus under novel conditions, such as a chicken’s egg. This produces a viral strain that is still live, but not pathogenic to humans,[10] as these viruses are rendered defective in that they cannot replicate their genome enough to propagate and sufficiently infect a host. However, the viral genes are still expressed in the host’s cell through a single replication cycle, allowing for the development of an immunity.”

I don’t see anything in that article or in what certain Republicans are claiming that demonstrate that Baric et al succeeded in making gene alterations invisible. Baric has been involved in a lot of coronavirus/SARS-CoV-2 research, with many of his papers co-authored by a dozen or two dozen or more collaborators, so that suggests a really far-ranging conspiracy. :face_with_raised_eyebrow:

As we will see, you can be scared of anything if you are ignorant and/or seeking to mislead and smear.

Reverse genetics is a research technique for identifying the function of genes by looking for traits that arise when a gene of interest is artificially modified, not a technique for genetic modification and of itself.It is called that in contrast to forward genetics, which is the traditional technique for identifying the genes responsible for a particular existing trait. Reverse genetics creates traits

In the context of the vaccine synthesis portion of the Wikipedia article you linked, reverse genetics is used by making modifications to viral genes and looking to see if it induces traits that reduce pathogenicity and increase immune response.

Now for the meat.

After looking through the Senate report, I found the reference to “undetectable” genetic modifications. As expected, it is an example of scientifically uninformed individuals making incorrect and disingenuous conclusions. The Senate report, on page 39, singles out a quote from the 2005 paper “Development of Mouse Hepatitis Virus and SARS-CoV Infectious cDNA Constructs” (Development of Mouse Hepatitis Virus and SARS-CoV Infectious cDNA Constructs | SpringerLink).

This is the paragraph the quote comes from:

Molecularly cloned viruses were indistinguishable from wild type and contained the marker mutations and unique BglI and BstXI junction sequences used in the assembly of the infectious construct (Yount et al. 2000)

However, this quote does not refer to work done by Baric in 2005 but work done in 2000 (Strategy for Systematic Assembly of Large RNA and DNA Genomes: Transmissible Gastroenteritis Virus Model | Journal of Virology) and refers to phenotypic qualities, not genetic qualities. The relevant quote is

These data indicate that viruses derived from the infectious cDNA construct had phenotypes indistinguishable from those of wild-type TGEV in swine cells.

In other words, the synthetic viruses these quotes refer to have the same biological function, not identical genetics. In fact, the latter portion of the misused quote, “marker mutations and unique BglI and BstXI junction sequences used in the assembly of the infectious construct”, refer to identifiable markers of genetic modification. The singled out quote in the Senate report is wholly misconstrued and arguably an outright lie.

Similarly, subsequent references to “no-see-um” techniques are actually the author’s method of cloning smaller genetic fragments without leaving what are known as “scars” from the assembly of restriction enzyme-based cloning. Such a goal, regardless of method, is required when trying to assemble functional coding sequences without disrupting the original function from the addition of restriction sites. It is not an overarching technique for so-called “undetectable” genetic modification. They were undoubtedly influenced by the connotations of the phrase itself and, lacking requisite knowledge of genetic engineering to interpret these papers, simply ran with it.

Additionally, all of these techniques are a product of the comparatively immature state of DNA and RNA synthesis in the early 2000s. Modern synthesis techniques are able to synthesize much, much longer DNA fragments on demand without the need for the types of manipulation, side artifacts, and cloning methods described above. It would be possible to synthetically generate an edited portion of DNA without the kind of “cut and paste” techniques required in the past. This is not the product of some kind of shadowy conspiracy or malicious technology but simply the general state of synthetic biology available today. Even with an entirely synthetic genome, any genetic changes would be evident when compared to the genome of a wild-type sample.

The Senate report is ultimately a disingenuous scare piece taking misunderstood and out-of-context work to claim that because supposedly “undetectable” genetic engineering was used in research 15 years ago it must be the case SARS-CoV-2 is also such a product along with implying Baric and his colleagues are part of the conspiracy.