Facts Matter: A Twitter Thread

There's a saying that there are 3 sides to every story. What you think happened, what "they" think happened, and what actually happened. Right now there's a story circulating on conservative media about funding of the Wuhan Institute of Virology. Begin thread to get to the truth.*

The claim circulating is that WIV was awarded a $3.7mil grant from NIAID under President Obama's administration and that illegal viral research was the reason we have #covid19. I was first made aware of this story on April 21 by my father who texted me about it.

I didn't know the specifics of where he was getting that idea, but I did my best to explain BSL4 labs and that any funding to WIV was likely a response to the knowledge that Sars-coV1 emerged in a bat populations in 2003. And that research on viruses wasn't illegal.

I will admit that after that conversation I didn't think about the narrative much. But now I see that Rudy Guiliani and others are actively trying to amplify this narrative to discredit Dr. Fauci's expertise and cast another shadow on the Obama administration.

Make a claim, you have to evidence to back it up.

So let's breakdown these claims. Aside from the glaring mistake that the Obama administration couldn't have awarded a grant in 2017, did the NIAID award money to WIV at any point in time? The short answer is yes - sort of. But then again so did the Trump administration.

Background: some of the first sources to make the claim that Obama era NIAID funded WIV were FL rep Matt Gaetz and the UK Daily Mail. They cited a Nov 2017 paper from researchers at WIV on coronaviruses as proof. Just a reminder that Gaetz showed up to work like this on 3/4.

Very subtle.

The paper in question can be read here: https://tinyurl.com/vp8vwbk

The funding in question is highlighted here. NIAID is the NIH institute that focuses on infectious disease. It's pretty easy to look up grants using R01 numbers. So let's see who the money was awarded to.

All research papers disclose the source of funding.

The grant was for a project entitled "UNDERSTANDING THE RISK OF BAT CORONAVIRUS EMERGENCE" and it was actually made to a non-profit in NY called EcoHealth Alliance. Their stated purpose is to aid scientists around the world to prevent pandemics.

EcoHealth Alliance Mission Statement

You can learn more about them on their Twitter feed. https://twitter.com/EcoHealthNYC/

So in 2014, the NIAID awarded $666,442 to EcoHealth Alliance for a project to study bat coronaviruses. This project was renewed in 2015, 2016, 2017, 2018, and 2019. The total money awarded to date is where the $3.7mil figure comes from.

EcoHealth Alliance distributed funds to researchers in multiple labs globally studying bat coronaviruses, including to WIV. Quite a few papers have been published that cite this R01 grant. A lot of work does center in China because that's where the bat reservoirs are.

One recent paper partially supported by R01AI110964

So the first part of the claim - that all $3.7mil went to WIV - is false. The funding was spread over 5 years, which spans both the Obama and Trump administrations. Let's consider the second part of the claim - that such grants were prohibited in 2014.

In October 2014, the Obama administration announced that they were pausing new funding related to gain-of-function research for influenza, SARS, and MERs. Gain-of-function is the key phrase here.

2014 White House Announcement

There was definitely a bit of debate about this type of research - engineering viruses known to cause human disease - because of mistakes made in certain labs. Here's an NPR piece from Nov 2014 about the moratorium.

So does that mean that research funded by R01AI110964 was prohibited? No. The research funded by this grant has centered on tracking and identifying naturally occurring coronaviruses - not engineering them. The research was carried out in facilities equipped to do that work.

Additionally, EcoHealth Alliance earned the initial grant award in May 2014 before the moratorium. The subsequent renewals indicate that the research funded by the grant money did not violate the moratorium. Otherwise the grant would not have been renewed.

For those of you who are curious, the US moratorium on funding for research into engineering viruses was lifted in December 2017. Who was president then?

HINT: Not President Obama

Rudy's claim #2 is false as well. So what's the truth? In 2014, EcoHealth Alliance applied for a grant to study coronaviruses because they posed a risk to human health. The funds they were awarded by NIAID were given to multiple research partners including those at WIV.

The grant was renewed for 5 years during both the Obama and Trump administrations. None of the published work funded by the research grant was gain-of-function experiments. However, it has been "legal" to do that work since Dec 2017 under Trump's administration.

The reality is that to prevent future global pandemics (and to deal with this one for that matter) we need all experts to be able to study emerging viruses, their reservoirs and collaborate. It cannot be an US versus them approach (pun intended).

And with that, I'm done.

* This post was previously a thread on Twitter.

get to the truth.

The Hunt for a COVID-19 Cure

A little refresher: SARS-coV2 is the RNA virus that infects our respiratory tract cells and causes the illness COVID-19. COVID-19 can lead to Acute Respiratory Distress Syndrome (ARDS), a chronic condition often requiring ventilator intervention and resulting in a mortality rate of up to 40%.

So naturally our healthcare teams are doing everything they can to try to prevent patients from getting to that stage. And that means both trying medication regimens typically used for other purposes and exploring novel therapies. 

Source: SMBC

It's really important to note that anecdotes aren't data though and the only way to be sure that a medical intervention actually works is to have a well-designed clinical trial. So what is a clinical trial? How do we get from a chemical compound in the lab to a drug that can be safely and effectively administered to human beings?

Source: NIH.gov

It all begins with preclinical (aka prehuman) research. A drug is discovered and tested in labs on cells in tissue culture and animal models of human disease. If it appears the drug has a positive effect on the disease outcome in these models, then the drug can begin study in a phase 1 clinical trial. (Note that it can take years to get out of the preclinical phase.) Phase 1 trials are small and designed to answer questions of safety and optimal dosage. They typically take a few months to complete. According to the FDA, about 70% of compounds that complete a Phase 1 trial will move onto Phase 2. Phase 2 is designed to test the efficacy of treatment (how many people get better and by how much?) as well as identifying side effects. This stage can last anywhere from a few months to a few years. Assuming the balance of efficacy versus side effects is favorable, the drug proceeds to Phase 3 (about 33% of drugs). Phase 3 trials are the largest and longest (1-4 years) and  focus on collecting more data about efficacy and safety in preparation for approval by the FDA. This is why it is not unusual for it to take a decade or longer for new treatments to come on the market.

I know what you're thinking. HOW CAN WE WAIT 10 YEARS FOR A TREATMENT?!? Quarantine's been less than a month and it already feels like the world's gone mad...

Try not to freak out, take a deep breath and consider this... It probably won't take 10 years to find something effective at combating COVID-19 for a couple of reasons. First and foremost of which is that traditional protocols tend to be broken during an epidemic. We saw this with the frantic and heroic efforts to find an effective Ebola vaccine after the 2014 outbreak. In just about a year, 12 clinical trials from phase 1 to phase 3 were completed. The vaccine was distributed for compassionate use during the 2018 outbreak and the FDA gave their final approval in December 2019. At present, research is already underway to develop a SARS-coV2 vaccine without the typical animal testing phase - at least half a dozen candidates in fact. (For more information about vaccine efforts, click here, here, here, here, here and here.)

Source: The Economist

Second, there are already drugs in the pipeline so to speak. With the emergence of SARS-coV, MERS-coV, and Ebola as real global threats, efforts to find drugs that affect RNA virus replication have been underway for sometime. One such drug that was discovered post 2014 Ebola outbreak is remdesivir. This intravenous drug works by inhibiting the enzyme necessary to replicate virus RNA. Remdesivir showed lackluster results in Ebola trials compared to other candidates so it was dropped. However, subsequent research suggested that it could be effective against coronaviruses. Clinical trials are already underway and results are forthcoming. (For more information about remdesivir, check here, here, here, here and here.) 

And finally - if not the most talked about strategy - is the fact that drugs currently approved for other illnesses are being evaluated for effectiveness in treating COVID-19. The practice of "off label" prescribing is not that unusual in medicine it turns out, though often (about 73% of the time) with little to no scientific evidence to support that use.

Source: Stanford University, 2006

Remember all the hoopla about chloroquine and hydroxychloroquine? These are long-approved anti-malarial drugs known to have anti-inflammatory properties. They are the primary candidates being investigated through off label use for COVID-19. It's unclear that these drugs are really capable of breaking coronavirus replication cycles and the preliminary trial data is tepid at best (or suspect at worst). The French study touted by many only included a small number of patients and treatment categories weren't blinded - meaning the researchers could choose which patients got the treatment, thereby potentially skewing the results. Another alley being investigated is the use of ritonavir/lopinavir, a combination drug used to treat HIV infections - but to date, that seems like a dead end. 

Source: Chemical & Engineering News

Perhaps the most promising drug news is about a compound called EIDD-2801 (discovered at Emory University's Institute for Drug Discovery). Prior to COVID-19, it was being investigated as a therapy for influenza infections - still in the preclinical phase of research. Like remdesivir, EIDD-2801 inhibits viral RNA polymerase - but apparently through a different mechanism so the drugs may turn out to have complementary action. A paper released on April 6th in Science Translational Medicine seems to demonstrate effectiveness at impeding multiple coronaviruses' replication in cell culture, including SARS-coV2. And more excitingly - it appears to reduce lung damage and other symptoms in mice infected with SARS-coV and MERS-coV. It appears that EIDD-2801 (which can be administered in pill form) will begin clinical trials soon.

So what's the take-away from all this? Please don't get suckered by anyone claiming a wonder drug is right around the corner or overselling anecdotes (President Trump and Dr. Oz - I'm looking at you). But also know that a lot of smart, dedicated folks are working their asses off right now to find as many safe preventative and therapeutic treatments as they can. Maybe check out some of their Twitter feeds to stay up to date: Kizzmekia Corbett, Timothy Sheahan, Angela Rasmussen, Amesh Adjala, Tom Inglesby to name just a few. Until next time...

Let's be careful out there.