Ralph S. Baric

To ce Subject: RE: B Group Next Week Attachments: Baric BSEG Jan 2020.pptx My presentation a eel Sent: Thursday, January 23, 2020 3:16 PM -- Ci Subject: Re: B Group Next Week Hi Ralph, The Sponsor will be excited to hear that you are willing to lead this timely and important discussion.

Chairman Paul Letter to DNI Gabbard, p.7 · original PDF · in context

Nothing comes to mind, but if you have questions on that testimony I'll be glad to give you my current thinking.

Baric Transcribed Interview (Redacted), p.12 · original PDF · in context

It's in the testimony, I think, in the House.

Baric Transcribed Interview (Redacted), p.12 · original PDF · in context

We had an mRNA vaccine for MERS coronavirus that had been tested in mice, both young and DC.Scheduling@LexitasLegal.com old mice, and it was extremely effective.

Baric Transcribed Interview (Redacted), p.14 · original PDF · in context

I think that data was immediately incorporated into the discussions, that I was not part of, but discussions at the Federal level, in terms of prioritizing which vaccines might go forward.

Baric Transcribed Interview (Redacted), p.14 · original PDF · in context

So the reason, I think, that we were particularly so excited about that data is that most of the vaccines that I have tested against coronaviruses, epidemic or pandemic, not pandemic, epidemic coronaviruses like the original SARS 2003 strain, or the MERS strain, worked effectively in young animals.

Baric Transcribed Interview (Redacted), p.14 · original PDF · in context

But when you took them into aged animals, where the vaccines are less affected by about tenfold, the vaccines would fail.

Baric Transcribed Interview (Redacted), p.14 · original PDF · in context

And the beauty about the VRC mRNA vaccine was that the neutralizing titers in the immune responses were as effective in the old animals as the young animals, so they were fully protected.

Baric Transcribed Interview (Redacted), p.14 · original PDF · in context

Whether they actually manufactured the vaccine that was put in the animals or not, or whether NIH made that vaccine and put it in, I don't know.

Baric Transcribed Interview (Redacted), p.15 · original PDF · in context

In 2003, the NIH had purchased two, or the Federal Government had purchased two $20 million killed vaccines to test against SARS coronavirus.

Baric Transcribed Interview (Redacted), p.16 · original PDF · in context

So killed vaccines are pretty commonly used in humans.

Baric Transcribed Interview (Redacted), p.16 · original PDF · in context

We did a head-to-head comparison of remdesivir versus this drug, and had submitted it to Nature Communications for publication.

Baric Transcribed Interview (Redacted), p.21 · original PDF · in context

We had common interests, but we didn't effectively start working together until later in 2014, on some of the work on the 2015 paper, that was published in Nature Medicine.

Baric Transcribed Interview (Redacted), p.22 · original PDF · in context

Ian Lipkin, you'd have to look at his CV, but I believe he received a medal from China for his efforts in the original 2003 SARS coronavirus outbreak, helping them bring it under control.

Baric Transcribed Interview (Redacted), p.23 · original PDF · in context

He told me he'd worked extensively with people in China during the 20- -- I didn't ask him details DC.Scheduling@LexitasLegal.com about whether it was with Wuhan Institute of Virology or not.

Baric Transcribed Interview (Redacted), p.23 · original PDF · in context

She was able to culture WIV1 in cell culture, and they published a paper in Nature on that.

Baric Transcribed Interview (Redacted), p.24 · original PDF · in context

And they showed that WIV1 could infect and use human H2 receptors.

Baric Transcribed Interview (Redacted), p.24 · original PDF · in context

I know those emails have been FOIA'd multiple times, and it says exactly when I was supposed to meet them and where.

Baric Transcribed Interview (Redacted), p.26 · original PDF · in context

I don't recall that part being in the House, so I think the House testimony is actually accurate.

Baric Transcribed Interview (Redacted), p.28 · original PDF · in context

Ultimately, they got to, I think, what they really wanted to talk about was gain-of-function related experiments, or I think it should be potential gain-of-function related experiments, that were associated with this 2015 and 2016 paper.

Baric Transcribed Interview (Redacted), p.28 · original PDF · in context

I was a little surprised that they didn't seem to have the paperwork that was involved in my presentation on why I thought this might be more of a loss-of-function than a gain-of-function phenotype.

Baric Transcribed Interview (Redacted), p.28 · original PDF · in context

It would be a specialized series of documents associated with P3CO review.

Baric Transcribed Interview (Redacted), p.29 · original PDF · in context

One way was that if a grant was submitted that had the potential for gain-of-function research it would be reviewed before they funded it.

Baric Transcribed Interview (Redacted), p.30 · original PDF · in context

So in China there was a massive social media barrage of speculation that the 2015 virus was the cause of the pandemic.

Baric Transcribed Interview (Redacted), p.32 · original PDF · in context

Initially it came from the Chinese, social media speculation about what was the cause of the pandemic.

Baric Transcribed Interview (Redacted), p.33 · original PDF · in context

So there's no way it could ever be associated with the emergence of this virus.

Baric Transcribed Interview (Redacted), p.33 · original PDF · in context

I sort of told them why we felt that the data didn't demonstrate a gain-of-function phenotype, and that was because there was no change or increased replication of the virus in human DC.Scheduling@LexitasLegal.com cells.

Baric Transcribed Interview (Redacted), p.33 · original PDF · in context

So the details of the discussion about what's gain-of-function or what's not is dependent on NIH.

Baric Transcribed Interview (Redacted), p.51 · original PDF · in context

All I know is that the Trump administration has formed a committee to come up with final policy recommendations for what is gain-of-function and what's not.

Baric Transcribed Interview (Redacted), p.53 · original PDF · in context

Well, that's natural origin process that either occurs through nature or natural evolutionary processes that might occur in cell cultures.

Baric Transcribed Interview (Redacted), p.58 · original PDF · in context

So accidental release would have fallen under the category of natural evolutionary processes in cell culture.

Baric Transcribed Interview (Redacted), p.58 · original PDF · in context

So certainly when BSEG started it was not classified.

Baric Transcribed Interview (Redacted), p.60 · original PDF · in context

But I recall being told it was classified sometime later.

Baric Transcribed Interview (Redacted), p.60 · original PDF · in context

Yeah, he was certainly a member early on, and early on in BSEG they actually encouraged people to put their membership on that committee.

Baric Transcribed Interview (Redacted), p.60 · original PDF · in context

I recall that people challenged the idea that it could be a lab leak.

Baric Transcribed Interview (Redacted), p.67 · original PDF · in context

And the reason that is, is that they've published papers saying that they did their work at BSL-2.

Baric Transcribed Interview (Redacted), p.67 · original PDF · in context

So there are many more laboratory-acquired infections at BSL-2 than at BSL-3.

Baric Transcribed Interview (Redacted), p.67 · original PDF · in context

And so if you're working with viruses than use human receptors and growing human cells, and you're doing it at BSL-2, you DC.Scheduling@LexitasLegal.com cannot ever conclusively say that there was not a laboratory leak.

Baric Transcribed Interview (Redacted), p.67 · original PDF · in context

I was surprised that the ODNI member was there.

Baric Transcribed Interview (Redacted), p.72 · original PDF · in context

So if an ODNI member was there, there may have been more members from other intelligence groups there, as well, but they wouldn't have risen to my level of attention.

Baric Transcribed Interview (Redacted), p.72 · original PDF · in context

I mean, National Academy does a lot of work with the Federal Government, so they could do much more sensitive research with different DC.Scheduling@LexitasLegal.com members of the intelligence community and different groups.

Baric Transcribed Interview (Redacted), p.72 · original PDF · in context

But no, I do not know any reviewer for Proximal Origins.

Baric Transcribed Interview (Redacted), p.76 · original PDF · in context

There was a rumor that a pangolin virus existed with 100 percent identity, or close to 100 percent identity to SARS-2.

Baric Transcribed Interview (Redacted), p.78 · original PDF · in context

That turned out not to be true, as the pangolin, called the pangolin GD strain, which was about 90 percent identical, I believe, is the virus they were talking about.

Baric Transcribed Interview (Redacted), p.78 · original PDF · in context

It has a receptor binding domain that is almost identical, nearly identical to SARS-2, but it does have a couple point mutations in it.

Baric Transcribed Interview (Redacted), p.78 · original PDF · in context

BANAL-52 and BANAL-1-something or another, also had receptor binding domains that were virtually identical to SARS-2.

Baric Transcribed Interview (Redacted), p.79 · original PDF · in context

So there's two bad viruses and pangolin virus within the clade, within that branch of SARS-2 that had identical receptor binding domains, which means that it's not engineered.

Baric Transcribed Interview (Redacted), p.79 · original PDF · in context

Certainly the pangolin strains were identified, and I think the first paper that was published was in September of 2019, by non-WIV researchers.

Baric Transcribed Interview (Redacted), p.80 · original PDF · in context

In fact, the whole genesis around the pangolin strains, these pangolin strains, is confusing because the group that published first had one sequence.

Baric Transcribed Interview (Redacted), p.80 · original PDF · in context

And then, if I understand it correctly, those sequences and samples were picked up, I believe, by WIV researchers, or another group, and they published a completely different set of sequences.

Baric Transcribed Interview (Redacted), p.80 · original PDF · in context

If you have that and it doesn't DC.Scheduling@LexitasLegal.com have a furin cleavage site, you could drop in a cleavage site, using that clone.

Baric Transcribed Interview (Redacted), p.82 · original PDF · in context

And WIV1, they would take spike genes of other sarbecos and drop it into that clone because they had a difficult time making more clones.

Baric Transcribed Interview (Redacted), p.83 · original PDF · in context

So for a pan-coronavirus vaccine you have pan-coronavirus beta coronavirus vaccines and alpha coronavirus vaccines.

Baric Transcribed Interview (Redacted), p.84 · original PDF · in context

So the only thing that people have really worked on extensively are pan-beta coronavirus vaccines, focused heavily on SARS coronavirus and MERS coronavirus.

Baric Transcribed Interview (Redacted), p.84 · original PDF · in context

So I don't imagine that that would be included in any pan-beta coronavirus vaccine.

Baric Transcribed Interview (Redacted), p.84 · original PDF · in context

Now, for pan-alpha coronavirus vaccines, the classic human coronaviruses are 229E and LN63.

Baric Transcribed Interview (Redacted), p.84 · original PDF · in context

Linda Saif has swine models, gnotobiotic swine models that she can study viral pathogenesis and vaccine DC.Scheduling@LexitasLegal.com performance.

Baric Transcribed Interview (Redacted), p.85 · original PDF · in context

Now, if you want to know, down to the nucleotide level, what drives a cross-species jumping event, you are talking gain-of-function experiments.

Baric Transcribed Interview (Redacted), p.91 · original PDF · in context

They mention in there that this could involve gain-of-function research in their announcement.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

One was why don't sarbecoviruses have furin cleavage sites.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

There should be sarbecos out there that have furin cleavage sites, so they were going to look for them.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

They were going to drop those spike genes into pseudotypes and ask what's -- we were also going to look at the receptor binding domain, obviously, and I think we hypothesized in there that there should be strains with 25 percent variation in spike that could still use the ACE2 receptor.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

If we found the sarbecovirus with a furin cleavage site it would be dropped into a pseudovirus, and its biological characteristics evaluated by the Chinese.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

They would remove the furin cleavage site.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

They would introduce changes into the receptor binding domain and look in the context of those pseudotypes, which is the safe system, to ask questions about what the role of those mutations were in tropism and entry of viruses in receptor usage.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

Following gleaning that data, we would then use a zoonotic sarbecovirus as a receptacle to drop the spike genes of some of these viruses, and if we found one with full-on furin site we would put it in there and evaluate its biology.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

We would also remove that furin cleavage site and ask what the effect was on pathogenesis in replication.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

At the end of that there was speculation that if the furin cleavage site looked like it was having effect on replication of pathogenesis we would consider putting it into a gain-of-function scenario where we would drop it into a null backbone.

Baric Transcribed Interview (Redacted), p.92 · original PDF · in context

And my interpretation of that was gain-of-function, and they discuss gain-of-function.

Baric Transcribed Interview (Redacted), p.95 · original PDF · in context

Now, I found it very interesting that the letter that they provided shortly thereafter said that the experiments were DURC.

Baric Transcribed Interview (Redacted), p.95 · original PDF · in context

DURC is Dual-Use Research of Concern. involving 15 pathogens, none of which is a coronavirus.

Baric Transcribed Interview (Redacted), p.95 · original PDF · in context

Yeah, that was part of it, but the Michigan group also had a vaccine vector where we would put in viral antigens to try to immunize the bats.

Baric Transcribed Interview (Redacted), p.97 · original PDF · in context

If they were doing it in Michigan, what they were doing were pilot experiments to see if the approach, especially the double-stranded RNA approach, reduced virus titers for North American strains.

Baric Transcribed Interview (Redacted), p.97 · original PDF · in context

The other approach was that having identified strains of viruses that had spike genes that could infect human cells and potentially cause human disease, those spike genes would be isolated and placed in virus vaccine vectors that would then be delivered to the bats in the cave, is the second approach.

Baric Transcribed Interview (Redacted), p.99 · original PDF · in context

So if you go back to the NSABB P3CO regulations, the regulations state that viruses, like flu, SARS, and MERS coronavirus, are highly pathogenic viruses, and highly transmissible viruses are covered by this program.

Baric Transcribed Interview (Redacted), p.100 · original PDF · in context

And if you do anything on these particular viruses that are highly pathogenic or highly transmissible, and you do any manipulation to increase that, then that's considered gain-of-function and regulated by those documents, based on my read of them.

Baric Transcribed Interview (Redacted), p.100 · original PDF · in context

There are exemptions to that gain-of-function regulation framework.

Baric Transcribed Interview (Redacted), p.100 · original PDF · in context

The first is that if you work with zoonotic viruses, like WIV1, which has never been show to infect a human being, that has never shown to be transmissible in humans, it is not subject to the gain-of18 function regulatory framework.

Baric Transcribed Interview (Redacted), p.100 · original PDF · in context

As soon as we made full molecular clones, or chimeras, they were done in a WIV backbone, which meant that they're putting a zoonotic spike into a zoonotic strain, to eventually identify vaccine formulations that would be used in the cave, that's not subject to gain-of-function.

Baric Transcribed Interview (Redacted), p.101 · original PDF · in context

And in the grant in the very beginning it says that's not subject to gain-of-function.

Baric Transcribed Interview (Redacted), p.101 · original PDF · in context

Now, if I remember correctly there is one sentence in there somewhere that says that we will consider potentially moving spike gene, or furin cleavage site into SARS coronavirus.

Baric Transcribed Interview (Redacted), p.101 · original PDF · in context

That is definitely gain-of-function and would have to be reviewed before anything else was done.

Baric Transcribed Interview (Redacted), p.101 · original PDF · in context

You know, we're talking about eight steps down the line, where you gain a significant amount of data about the role of each spike, its ability to use different DC.Scheduling@LexitasLegal.com receptors, and the role of the furin cleavage site in the ability of that virus to replicate and cause disease, before you do anything about moving it into another strain.

Baric Transcribed Interview (Redacted), p.101 · original PDF · in context

After that paper, it said that there are threat viruses, followed by the WIV1 paper, that said there are threat viruses in nature, in bats, that can have the potential to cause serious human disease.

Baric Transcribed Interview (Redacted), p.102 · original PDF · in context

A good example of this is there are strains that use the DPP4, no, let's say the ACE2 receptor of SARS coronavirus, and you put them in K18 mice that overexpress that ACE2 molecule, you can find genome equivalents but no live virus.

Baric Transcribed Interview (Redacted), p.102 · original PDF · in context

So remember, one of those DC.Scheduling@LexitasLegal.com experiments was to take the virus that had the furin cleavage site in it, resurrect that virus, put it in animals, see what the effect was.

Baric Transcribed Interview (Redacted), p.103 · original PDF · in context

Remove the furin cleavage site, see what the effect was.

Baric Transcribed Interview (Redacted), p.103 · original PDF · in context

If the furin cleavage site is driving a massive disease phenotype, then that results in a judgment question about whether you would do the next experiment.

Baric Transcribed Interview (Redacted), p.103 · original PDF · in context

All that I know is that we were not awarded.

Baric Transcribed Interview (Redacted), p.104 · original PDF · in context

But I don't believe that, at least from the U.S. side, I don't believe there was any grant written, that I'm on, where we proposed to do experiments of furin cleavage sites.

Baric Transcribed Interview (Redacted), p.105 · original PDF · in context

My focuses, at the time, were to rapidly develop mouse models so that we could test mRNA-LNP-based vaccines against SARS-2, to work with Gilead to get their drug forward into clinical trials, to get molnupiravir, a second drug that was FDA approved for use in humans, into clinical trials.

Baric Transcribed Interview (Redacted), p.107 · original PDF · in context

Oh, the paper, generally, I disagreed with the idea that you could completely rule out the lab leak, and actually wrote a commentator, commentory piece -- what's the word?

Baric Transcribed Interview (Redacted), p.110 · original PDF · in context

A commentary piece that was published in Immunity, May 2020, that stated, equivocally, DC.Scheduling@LexitasLegal.com that it is unlikely that the lab leak hypothesis will go away because the safety procedures at the WIV, and I cited their paper where they worked with viruses at BSL-2.

Baric Transcribed Interview (Redacted), p.110 · original PDF · in context

It's the longest-running natural infection cohort on dengue virus, which has identified a large number of important features associated with what drives pathogenesis, and has informed the vaccine development.

Baric Transcribed Interview (Redacted), p.114 · original PDF · in context

It's called pangolin coronavirus GD strain, and it was published in Nature Microbiology.

Baric Transcribed Interview (Redacted), p.118 · original PDF · in context

So that's one example of where we specifically did not provide a sequence until after the pandemic started, when several researchers wrote Nature Medicine and said, "We want to look at the sequence to determine whether it's the cause of the pandemic."

Baric Transcribed Interview (Redacted), p.123 · original PDF · in context

So we provided that, and we also put the WIV1 sequence up in PubMed and they analyzed that sequence and agreed that it was not the cause of the pandemic.

Baric Transcribed Interview (Redacted), p.124 · original PDF · in context

And so in this case, Fang Li had been doing studies using biochemical approaches to identify DC.Scheduling@LexitasLegal.com the most optimal receptor binding domain possible to grab either the human ACE2 receptor or the mouse ACE2 receptor.

Baric Transcribed Interview (Redacted), p.124 · original PDF · in context

Yeah, if you have an email that suggested I did, I'd appreciate it, because I don't want to be put in the scenario where you're asking me to recall an event from 13 years back, and then I state it incorrectly.

Baric Transcribed Interview (Redacted), p.127 · original PDF · in context

So I talked at a WHO meeting early on in the pandemic to say that alumbased vaccines, which have a tendency to -- I probably need to explain what a Th2 immune response is.

Baric Transcribed Interview (Redacted), p.128 · original PDF · in context

So basically there's a massive inflammatory response that has the potential to be lifethreatening, and the SARS coronavirus vaccines, from 2003, that the NIH had purchased, were both adjuvanted with alum.

Baric Transcribed Interview (Redacted), p.129 · original PDF · in context

So my concern, and I expressed this to the WHO and to other groups, was that we needed to look carefully for vaccine-induced immune pathology.

Baric Transcribed Interview (Redacted), p.129 · original PDF · in context

That was one of the experiments we set up to do, where we took mRNA vaccines and we took killed vaccine preparations with alum and compared them head-to-head for the ability to induced Th2 responses.

Baric Transcribed Interview (Redacted), p.129 · original PDF · in context

Now, the Chinese vaccines were killed vaccines with alum, which I think was inappropriate.

Baric Transcribed Interview (Redacted), p.129 · original PDF · in context

The mRNA vaccines, though, were tested for that using homologous virus challenge.

Baric Transcribed Interview (Redacted), p.129 · original PDF · in context

At that point, the downstream question is whether if you have significant amounts of virus variation and you're infecting the original Wuhan mRNA vaccine, will breakthrough infection induce an immune pathology phenotype, and those are the kinds of things we're interested in studying now.

Baric Transcribed Interview (Redacted), p.130 · original PDF · in context

Yeah, I think maybe we should take a second and review the furin cleavage site, because you seem to think it is the critical event that drove SARS-2 to be pathogenic.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

So in the coronavirus literature, furin cleavage sites have a mixed history.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

So in feline enteric coronavirus, if that virus has a furin cleavage site it's DC.Scheduling@LexitasLegal.com asymptomatic.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

It's when you lose the furin cleavage site that it becomes a fulminant, deadly disease that is 100 percent fatal in cats.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

In mouse hepatitis virus, a couple of researchers had removed the furin cleavage site and said what happens to the pathogenesis?

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

Another group, taking pseudoviruses, had introduced furin sites into the SARS-coronavirus 2003 strain, and the only thing they found was slightly increased infectivity.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

Nothing that said "eureka." So now let's compare SARS from 2003 and SARS-2, and let's ask the question, what experiments were done to prove that the furin cleavage site drove severe disease in SAR-2 pathogenesis.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

The only way to really prove it is to take a virus that doesn't have a furin cleavage site and stick it in.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context

I can make the argument in this room, and I can argue it in front of scientists, that the introduction of the furin cleavage site in SARS-2 attenuated its pathogenesis and increased its transmissibility, and that was to its benefit.

Baric Transcribed Interview (Redacted), p.131 · original PDF · in context