Sunday, April 26, 2020

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.

Rudy Guiliani tweet
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.
Matt Gaetz gas mask
Very subtle.
The paper in question can be read here: tinyurl.com/vp8vwbk
PLOS Pathogens article abstract 2017

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.

funding disclosure PLOS Pathogens 2017 paper
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/

EcoHealth Alliance twitter page
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.

2019 paper abstract
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 virus funding announcement
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.
2014 NPR story virus research funding 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).

high school musical gif

And with that, I'm done.

done gif

* This post was previously a thread on Twitter.
Thread get to the truth.

Wednesday, April 8, 2020

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

cartoon how to make a scientists head explode smbc
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...

keep calm was your hands cdc poster

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-coVMERS-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 herehereherehere 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.

Tuesday, March 31, 2020

To Mask or Not To Mask

There's a stark difference between Asian and American cultures regarding the wearing face masks in public - embraced in Asia and shunned in America. And that difference seems to be having an effect on the control of the novel coronavirus outbreak. But before we jump into why that might be the case, I'd like to share something I witnessed on a flight to Florida in early February. 
Source: Jeremy P. Howard, Twitter
Our family was headed to Orlando to celebrate my father in law's birthday. On the flight down from Newark, we were seated behind a young Asian couple and a middle aged white man with Mickey Mouse ears on his head (we'll call him Mickey for the story). I say Asian because I don't know what ethnicity they were because their faces were largely obscured by face masks. The white man (seated directly in front of me) was traveling with a cheer squad but was seated away from the team and the rest of the chaperones. And he was very clearly unnerved by the couple seated next to him because this is what transpired.

coughing while asian is not a crime girl with sign gif
NOTE: The couple in our story never actually coughed the whole flight.
I'm distracted by my baby when a woman across the aisle from Mickey says loudly, "Did you just take a picture of them without asking their permission?" Everyone around becomes silent. Mickey sputters something unintelligible and tenses up.

The young man turns to Mickey and pulls down his mask. "Did you just take a picture of us? Why did you just take a picture?" His English is clear and his voice is measured. Lady across the aisle says, "That is really rude. You should delete that picture." Mickey continues to try to ignore both of the people talking to him.

The young man turns to his partner and says something in another language. Then he turns to Mickey and says "I would like you to delete that picture. Why did you take a picture of us without asking?"

Mickey finally responds. "Because I'm uncomfortable. Why are you wearing those masks?"

The young man says "We are wearing these masks to protect ourselves. I'm going to ask again. Please delete that picture off your phone."

But Mickey doesn't do it. He starts playing a game on his phone and acts like the interaction never happened. The couple speak to each other in their native language for a bit and the tension dissipates some. But let's just say it was a very long and uncomfortable flight to Florida for more than just Mickey and the young couple.

1918 flu pandemic mask ad
1918 Newspaper Ad: Helpful Hints for Making Your Own PPE
Interestingly, the history of many East Asian cultures (like China and Japan) embracing facial coverings dates back to the 1918 flu pandemic, a time when everyone was wearing face masks.

two women flu masks 1918
Why didn't this fashion trend stick?
The mask wearing habit has been reinforced in Asia over time as a way to grapple with both poor air quality and pollution as well as infectious diseases like SARS and bird flu. It can also be a bit of a fashion statement. But this tradition is looked at warily (or conversely fetishized) by many in the West - leading to outbursts of xenophobia like what we witnessed on our flight to Orlando.

Currently, both the WHO and CDC do not recommend wearing masks unless: 1) you know you are sick OR 2) you are caring for someone who is sick. But some folks are beginning to question whether or not those recommendations were put in place as a way to try to discourage the rush for N95 masks that has lead to shortages for healthcare workers. The personal protective equipment (PPE) shortages are so severe that many organizations have taken to encouraging people to make homemade cotton masks to provide to employees. It's like 1918 all over again.

trajectory covid19 spread financial times figure
Source: John Burn-Murdoch, Twitter
A few days ago a lot of people started to take note of the data compiled by John Burn-Murdoch about how efforts to control COVID19 are going. There is an obvious difference in the doubling speed of the virus in countries that use masks versus those that don't - of course there are a lot of other factors at play, like differences in quarantine policies and testing programs. The fact that more general mask usage didn't stop China from experiencing rapid exponential growth of the virus is a cautionary tale - correlation is not causation, folks. Just because two things occur simultaneously, it is not definitive proof that one thing made the other happen. We need more careful analysis to separate out the truth. Only time will tell exactly how strong of an impact the routine wearing of masks has on flattening the curve of COVID19 spread. 

In the meantime, when interviewed by Science magazine (March 27), George Gao, the head of the Chinese Center for Disease Control and Prevention, said the following:

"The big mistake in the U.S. and Europe, in my opinion, is that people aren’t wearing masks. This virus is transmitted by droplets and close contact. Droplets play a very important role—you’ve got to wear a mask, because when you speak, there are always droplets coming out of your mouth. Many people have asymptomatic or presymptomatic infections. If they are wearing face masks, it can prevent droplets that carry the virus from escaping and infecting others."

Sui Huang, MD, PhD of the Institute of Systems Biology in Seattle recently wrote a piece on Medium to explain this line of thinking further. Here's one of the figures from the article. It suggest that a 2007 study showed that homemade masks reduced the number of aerosol particles inhaled by two-thirds, although they weren't very effective at preventing particles from escaping into the environment. 

mask figure medium article

On Monday, Dr. Fauci (the infectious disease physician in charge of NIAID and the coronavirus task force) was interviewed on Good Morning America about the mask question. Here's a summary of what he said.
Source: Good Morning America
Sounds like a definite maybe to me. There are several well written pieces in the Washington Post, the NY Times, Wired Magazine and Politico about this topic if you would like to learn more about the push for more mask usage in the US. If you want to learn more about how to make masks to donate to our health care heroes or make for your own family, check out the Joann Fabrics website. Until next time...

Let's be careful out there.

Monday, March 30, 2020

Who Can You Trust?

I've taken a step back from writing about COVID-19 for the past couple of days. Not that I've stopped reading voraciously, but trying to sum up everything is overwhelming. But now I feel a little selfish about that decision. I may not be an epidemiologist or a virologist, but I have the benefit and privilege of having an education that makes it easy for me to interpret scientific and medical reports.

Quote: Maria V. Snyder, author
In undergrad, I earned a Bachelors of Science in Biology, while volunteering in a cytogenetics lab and being paid to deliver specimens (blood, sputum, feces etc) and setup cultures for microbiology in a general hospital lab. Then I spent 5 years earning a PhD in biomedical science with a concentration in genetics and developmental biology, followed by further post doctoral training in genetics. My research ranged from in vitro biochemistry (engineering and purifying proteins to test their affect on the cellular process of RNA splicing) to mouse husbandry. Then I spent a year creating continuing medical education programs for doctors and nurses on topics related to dermatology, allergy and diabetes. And I've spent the past nearly 13 years as an educator.

But most people don't have that luxury. Maybe they've taken one biology class once in high school. Maybe they've never taken biology. Should everyone be trying to make sense of the rapid fire barrage of COVID19 info?

I think Hobbes gets it.
Ideally, yes. The more educated folks are about what's going on, the better off we will be as a society. No one expects you to be an expert or to easily understand all the lingo. That's what professional science communicators are for.

But let me start with a few words of caution. Understand that not everyone who claims they have a doctorate of some kind is actually qualified to speak on what's going on.

Sometimes those people have made up their degree or purchased it from an online degree mill or earned it in something completely unrelated to public health. Other times people who legitimately went through rigorous training to become an MD or PhD will spout dangerous and misleading information. All of these folks tend to be motivated by a few things - desire for recognition / power and desire for monetary gain. I'll concede that some may even think they are helping people - after all the Dunning Kruger effect is a very real thing.

https://www.thedailystar.net/shout/health/news/judging-yourself-the-dunning-kruger-effect-1730974
DKE-19 is seriously making it hard to keep up with COVID-19
That being said - why should you trust me? I have nothing to gain by talking about science - other than relieving some of the busyness of my mind. My main motivation for writing is that I want as many people to be safe as possible. Since I can't wish this nightmare away, writing about what I do know is the next best thing.

So I think I need to make baby steps. Rather than covering every report that comes out, I'm going to start by compiling a list of reputable resources for folks to follow. There are a lot of great science writers out there - people with actual backgrounds in research and medicine - who can be trusted. If you don't already use Twitter, I would strongly recommend using it to get information directly from the folks on the front lines of research and hospitals. Here goes...

World Health Organization aka WHO - an organization of physicians and clinical researchers and epidemiologists based in Geneva Switzerland who track all kinds of diseases and compile best practices from data collected around the globe (also follow them on Twitter)

Centers for Disease Control aka CDC - the US government agency responsible for tracking diseases (Twitter)

Johns Hopkins School of Public Health - There's a ton of experts working at JHU and several of them (lead by Lauren Gardner) built a very cool COVID19 tracker. (Twitter)

Anthony Fauci, MD - Dr. Fauci is the head of the National Institutes of Health's National Institute of Allergy and Infectious Disease (NIAID) and President Trump's COVID19 task force. While he doesn't have his own social media accounts, he's all over social media these days.

Trevor Bradford, PhD - He's a molecular epidemiologist, meaning he tracks how viruses mutate and helps link specific patient samples to determine how infections spread. (Twitter)

David Gorski, MD, PhD - He's a surgeon and the creator of the blog Science Based Medicine. He has championed clinical practice based on actual evidence, rather than anecdote or historical precedence for years. He does a really good job of explaining why certain claims are crap. (Twitter)

Ed Yong, MPhil - He's a British science journalist with a masters degree in biochemistry. He started out writing for Nat Geo on a blog called Not Exactly Rocket Science, but is currently working for The Atlantic. He follows a lot of great physicians and scientists on his Twitter so you could get additional ideas of who to follow there.

This by no means is an exhaustive list, but it's a place to start. I'm going to sign off here with a quote from my high school choir teacher, Mr. Eckstein.

Let's be careful out there.

Wednesday, March 25, 2020

A Slippery Slope

In the past few days, some politicians have come out urging the public to consider returning to "normal" in a very short amount of time - counter to what health experts are telling us is necessary.
Tweet Tiffany Trump return to work
Get back to work by April 1st?
The idea is this: tanking our economy is worse than some people dying. Buoyed by President Trump's calls to get back to business as usual by Easter, the lieutenant governor of Texas basically said that older folks ought to take one for the team to save the economy for the children.
tweet Dan Patrick coronavirus
Bad economy worse than death?
There's quite a few problems with this interpretation, not the least of which is that it's encouraging a game of Russian roulette with your health. I mean you probably won't die if you contract the disease, right? Ignore the fact that folks who recover appear to have permanent lung damage, which would make them more susceptible to other illnesses in the future. Or the fact that we don't always know who has underlying conditions putting them at a higher risk of a fatal outcome. (Did you hear about the 21 year old Spanish soccer coach, the 36 year old Brooklyn school principal, the first person under 18 years old who died in LA and on and on?)

If we simply consider the healthcare system, you can see the fatal flaw (yes, pun intended) with the calls to live like we're not in the midst of a pandemic. There are only so many hospitals with so many health care professionals with so many supplies available at any given time. If we do not stop the exponential spread of the virus, these precious resources will be overwhelmed and consumed.

cartoon exponential growth flatten the curve
Source: Dr. Siouxsie Wiles
The healthcare system will fail and the death rate will climb. This is not just a thought experiment - we have evidence of this happening in Italy. We have evidence of it happening in the US too - if we look back at history to understand the 1918 flu pandemic.

So hopefully we can all agree - rushing to end social distancing prematurely will not get things back to "normal" like waving a magic wand. Believing it's a viable option is wishful thinking - highly dangerous wishful thinking. And with it the specter of eugenics begins to rear its ugly head once again. Let's not accept defeat already - we can minimize the loss of human life by listening to the folks on the frontline of this war. Stay home and be well everyone.

thank you workers

EDIT: A new interview with Dr. Bruce Ayland of the WHO just came to my attention - please read it.

Sunday, March 22, 2020

Social Distancing Outdoors

On Friday, my husband and I decided to take a walk through the Dismal Swamp - one of the last remaining wetlands in urban New Jersey - with our infant son. My husband had driven past the signs for the preserve many times on grocery store runs since we moved to the area in the fall, but had never stopped. With the weather cooperating and us feeling a little stir crazy, we set out on the Songbird Trail with high hopes.

man baby dog hiking
My loves on the trail
We made it easily through the clearing - the mud wasn't too bad and it was too early in the season for mosquitoes - but we didn't see any wildlife. We could definitely hear insects and birds, but they were apparently camera shy. It surprised us to find ourselves on another road (New York Blvd) so soon so we decided to cross to continue on. We saw a couple of houses ahead on a small road and decided to swing right along an abandoned railroad track. Here's when the swamp really started living up to its name.

All sorts of trash littered either side of the path - some in garbage bags, some strewn loose about the landscape. Discarded alcohol containers and other food waste, tires, even furniture! We remarked to each other that it was good that the baby was in a carrier and not able to roam around on his own. And how it was unlikely that we would come back...

A short distance along the trail - still near the shotgun style house on a cinder block foundation - our dog started rolling on the ground. The way that she does to signal she's found something particularly foul. Sure enough she was rolling in tuffs of black and white fur. I looked ahead just a bit and found the source.

Mystery Carcass
Much to my husband's amusement, I took the time to carefully document the critter - which I assumed was a skunk based on the fur coloration and the size of the body.

decomposing foot opossum
Decomposing Toes Can Still be Cute?

opossum skull beetles
Death Doesn't Stop Life or Beetle Sex on the Skull
We continued along our way, following the railroad tracks, trying to avoid the trash and remarking on the signs warning the area on our left was contaminated (with what?!?). When we got within sight of the end of the path, we stumbled across another skull.

groundhog skull
Mystery Skull #2
groundhog skull
Definitely a rodent

I'll be honest - even though I knew it was a rodent looking at the front teeth - I assumed it was a possum based on the size of the skull. I'm a geneticist after all and not a mammalogist or ecologist. I knew that #ScienceTwitter would set things right once I got home and uploaded my finds. I was not disappointed.

tweet
Skull 1 = Opossum & Skull 2 = Groundhog (aka marmot)
You'd think the story ends there, but upon the urging of some friends and a student, we decided to make the trip back to the trail yesterday to pick up the bones. I do teach forensic science after all. Husband and baby waited patiently while I ran back to grab the skulls in plastic ShopRite bags with nitrile gloves on (yes, we always have these around the house for cleaning, not just because of COVID-19). When I came upon the groundhog skull, I noticed that not too far off from it were several other bones we hadn't noticed the day before, though I am sure they were there considering the weathering they display. I'm pretty sure they are deer bones, though I could certainly be wrong again (#ScienceTwitter do your thing please).

Femur

Broken scapula?

Vertebrae
Of course as I was photographing these new finds with my bright blue gloves (plastic bags burgeoning with skulls), a jogger came down the path. He raised his eyebrows at me. To which I very gracefully blurted, "I'm a forensic science teacher. I'm grabbing these bones for my students." He gave a surprised "Oh", then went a little ways down the trail, turned around and ran back the other direction. So yeah. Hopefully I didn't get reported to the police for suspicious behavior. And I hope this post finds everyone well enough to enjoy the outdoors separately too.

Want to learn more about bones? This is an amazing blog by a teenage self taught naturalist Jake McGowan-Lowe.