Wednesday, January 27, 2021

Colchicine and COVID19

 The response from plant biologists was a unified "YIKES!"

Colchicine?  Really?  That's the stuff we use to wreck biology, or at least give its decedents too many chromosomes. 

A recent press release exclaimed the therapeutic effects of this regent in the treatment of COVID19.  A clinical trial of 6000 planned individuals was performed in a double-blind, randomized, placebo-controlled, multi institutional study. The study was piloted by the Montreal Heart Institute. Other international institutions are also examining its effect in separate clinical trials. 

Colchine is derived from the crocus flower, and is best known for its ability to arrest cell division by disrupting the molecular cables that attach to chromosomes. These tiny fibers pull normally pull half of the chromosomes into each new daughter cell. Colchicine disrupts their formation, meaning one cell gets a heavy load of genetic material. 

In plant biology that can be a good thing.  Plants with extra sets of chromosomes oftentimes have bigger fruits and flowers, and other production traits. Modern strawberry has four sets, banana three, sugar cane six. No big deal. 

But in animal biology there are other applications.  Some of the first where in cancer chemotherapy. Clearly colchicine stops cell division in vitro, so perhaps it would hinder growth of rapidly dividing tumor cells. There is some in vivo evidence of this, mostly from animal models. 

There is a lot of literature on colchicine, with mixed results from clinical application. One study showed a significant decrease in "all cancers" in male, Taiwanese patients using colchicine to treat gout (Kuo et al., 2015).

 Why gout?  Gout, arthritis, pericarditis and other inflammatory disorders rely on polymerization of the same microtubules, the tiny intracellular cables that help cells divide. Rearrangements of this cytoskeleton are hallmarks of inflammation. 

Inflammation is also an aspect of COVID19's effects, so testing a therapeutic application was a reasonable hypothesis.

The results were quite positive, suggesting fewer hospitalizations, decreased need for a ventilator, and less chance of dying from the infection.

That's great!  Or is it? 

The information did not come from a peer-reviewed paper or even a preprint.  It was a press release, and now many in the public are poking their health care providers for a dose of the miracle stuff (some hoping to pick some up on the way to the anti-vaccine rally). 

It puts physicians in a bad place.




The problem arises from the rather strong definitive wording from effects that are merely "approaching statistical significance" 


"This major scientific discovery makes colchicine the world’s first oral drug that could be used to treat non-hospitalized patients with COVID19." 

Are press releases writing checks peer-review can't cash? 


The problem comes from the fact that we do not know why the experiments were terminated early, mostly likely because they met a statistical endpoint.   They didn't discuss adverse effects (which are an issue with colchicine, as the digestive epithelium is affected leading to diarrhea, etc.), confidence intervals, and the results from PCR positives versus others.  

In other words, while results may be encouraging, there is not enough here to make an informed clinical recommendation.  

Most physicians understand the side effects and should be hesitant to prescribe based on a press release. 

On the other hand, this is all patients need to know it works. 

And we have now created the conspiracy vortex.  Physicians make a good decision, patients make a bad one, and the inability to get the drug/poison is viewed as the dirty work of Big Pharma and Bill Gates. 

Like hydroxyquinoline and ivermectin before it, there are legitimate applications for the drug, albeit with scant compelling application in treatment of COVID19. 

Unlike those other drugs, colchicine can be a deadly poison at relatively low doses. 

Just like before, a press release that jumps the gun causes more problems for physicians, more confusion for the public, and a fertile ground for conspiratorial claims-- especially if the results fail to reproduce in other trials or deleterious side effects are noted. 






Sunday, January 24, 2021

Anti-Vaxer Wins the Battle

In a recent online event, a graphic was posted to introduce the speakers of a COVID19 vaccine panel.

In the first 30 seconds a remotely-controlled cursor festooned the graphic with swastikas and grade-school-quality penis line art. The audio belched forth misogynist filth and racial epithets. The screen was commandeered with a pornographic video. A thought bubble over one the seminar’s presenters was stating, “I hate n — — rs.”


Red ink is mine. Leaving the words is just so much more visceral, but I can’t do it


Be disgusted. Understand the climate of thoughtful pandemic science communication in the Zoom Era.

The presentation was arranged by Dr. Miriam Fein from the Science Advocacy of Long Island (SALI). I was one of the speakers. All of us volunteered our time in the interest in promoting better public health, and pushing back against copious disinformation around SARS-CoV2 and its impending vaccinations.

The audience was good, over 50 at the start. Dr. Fein moved quickly and attempted to somehow mute the invading channel, but we had a strange glitch where nobody was the host, suggesting that the disruptive idiot somehow had control of the meeting.

Eventually she announced to check the SALI website for more information of where we would reconvene there. Five minutes later we were back online with a secure channel.

But with only 20-some participants.

The audience for free webinar about the current health crisis shrunk by more than half because of an invasion so vile that those interested in the science did not want to risk returning. Some attendees were clearly younger, perhaps in high school. I could understand a parent’s trepidation with the threat of gutter opposition to science communication.

The event was originally advertised far and wide through social media and we fully anticipated that there would likely be disruption. Questions for the panel submitted ahead of time also suggested a conspiratorial, non-scientific sentiment would be present.

That’s fine. I’ll take them on any day. Science ju-jitsu uses the opponent’s momentum against them, and I’m wearing a science black belt. We change hearts and minds best when dissenting opinions are engaged with grace.

That is why the disruption was so offensive. It was not about providing thoughtful opposition. It was about ensuring the event did not happen, that conscientious viewers would not enjoy access to the best scientific information.

It was about separating ideas from those that wanted them. Silencing science.

It was not about thoughtful debate, it was about deliberate disruption to interrupt information flow. Welcome to another reminder of our lives in the current hot climate.

How to fix it? We can lose a battle and win the war. Take this opportunity to forge your disgust into a new commitment to translate the science of the pandemic. Engage. Share information. Help others talk to family, friends, and other dissenters.

I apologize to all of those that had to endure that painful minute.

Don’t think of those moments as a way that a disruptive anti-vax hate monger defeated a science communication event — think of them as a corrupt movement waving a white flag. They are so defeated with logic, reason and evidence that their only tactic is to stop logic, reason and evidence from being disseminated.

Go share science.



Tuesday, December 15, 2020

Understanding mRNA Vaccines - Webinar

 





As the COVID19 vaccine rolls out it is critical to understand how it works, its efficacy, as well as its risks and benefits.  Actively opposing disinformation will be key in achieving broad public compliance and ultimately ensuring public health.

  • What is the history of the mRNA vaccine?  
  • How does this approach differ from previous vaccination strategies? 
  • Is this really new technology? 

These questions and many more will be answered, along with your specific questions. 

Hosted by Dr. Kevin Folta, molecular biologist and host of the Talking Biotech Podcast.




Thursday, November 12, 2020

Dr. Don Huber's Mystery Organism - A Legacy of Disinformation

Back before calling out disinformation was fashionable, I was busting biotech charlatans for lying about science to satisfy their personal agendas. 
 
It was seven years ago today that Dr. Don Huber, Emeritus Professor of Purdue University, stood in front of a room of people and scared the hell out of them. I was in the room. His stream of disinformation was disgusting, deliberately and intentionally lying to an audience assembled to learn about food and new technology. 

You can read about the event in detail here

At the event he reiterated his claims of a new organism he had isolated from "GMO" crops-- a deadly "virus-like fungus" or "microfungus" that killed plants, caused disease in people and triggered spontaneous abortion in livestock.  The audience was aghast, with audible discomfort in the room. 


Not "scientists" but one unscrupulous scientist that intentionally fabricated a story to influence public perception and sway federal policy.



Long-story short, during the Q&A I asked him if I could obtain a sample, sequence its DNA, and reveal the nature of the organism and stop the crisis. 

After a long, rambling retreat, he said that he and his team in China (yes, China) were sequencing the genome and would release the results shortly.  He refused to accept my generous offer. 

Seven years later... crickets. 

This is the same deadly organism that Dr. Huber reported to US Ag Secretary Tom Vilsack.  He wrote it from his position of authority as a university professor, and noted his military service. He claimed that it was a "pathogen of high-risk status" and "should be treated as an emergency."


 From Cooking Up a Story - A synopsis of the Huber letter to Vilsack

This established expert attempts to mobilize the resources of the United States of America to address a problem that only he can see, a move motivated by his anti-biotech views and a vendetta against a company.  It also was claimed to be caused by glyphosate, making it an harbinger of the future false claims made against the compound.

Seven years after I offered to help him solve this national emergency, there is still no news of progress on the deadly pathogen. 

Because he made it up.  He lied to the US Ag Secretary and millions of people to scare them away from modern farm technology. 

He also went after me personally, sending a brutal letter to my university, condemning my audacity to ask him questions, and explaining that I was "aggressive" and off base how I treated him.  I was nothing other than polite, as was revealed to my boss on audio recordings. 

So this is personal.  I want to hold him accountable, I want the public to not forget his lies.  He intentionally provided false information to influence public perception and policy around agriculture. 

While he had a solid career as a scientist, his disinformation and hostility towards the scientists that held him accountable should be the centerpiece of his legacy.  


Sunday, November 1, 2020

Ending COVID19 - The Decision is Ours

One message that is not being shared about COVID19- It is 100% controllable with changes in our personal behavior. A virus is just a tiny collection of infectious chemistry that only spreads when we permit it to spread. This is why testing, tracing, staying home, washing hands, controlling your respiratory aerosols, and keeping distance are so important. We each, control its spread together.

Australia did an excellent job at this and yesterday logged zero new cases. Life there is normal; their businesses can thrive. Hospitals can go back to treating the involuntarily ill and health care workers can know they are not risking their lives by treating someone that perhaps elected to become infected via their own negligence. How can we do reach zero in the States when we are turning the corner into increasingly unprecedented infections?

If everyone were to assume they were infected and took their most extreme efforts to protect others, the numbers would plummet within weeks. Unfortunately the message that this is in our hands to control means our politicians and science deniers can't blame someone else.

This is literally on us, individually. A chain is only as strong as its weakest link, and any chain completely fails when it is actively being cut with bolt cutters by 30-some percent of the population.

The pandemic's grip ends with leadership, cohesive federal response, aggressive programs to test and trace, guidance from medical experts, and most of all, an attitude change across the population.

The problem is not a virus. The problem is an infection of national narcissism that puts individual belief, selfishness, and even disinformation ahead of the basic science of viral transmission. We control how long this pandemic will affect the nation. It can be beat without new vaccines and therapeutics, packed hospitals and lockdown orders. Other countries have done it. We have to all commit to being our brothers' keepers, and realize that if we want to be part of a healthy, happy, and prosperous nation, our most patriotic duty is to prevent the preventable.

Friday, August 7, 2020

The Chemistry of the Beirut Tragedy

 The use of ammonium nitrate in explosives is nothing new. It is a potent oxidizing agent that accelerates the combustion of fuels, instantaneously liberating the energy within their bonds. This is how explosives work. The Oklahoma City bombing in 1995 is an example of its devastating potential. A rental vehicle filled with about 4,000 pounds of ammonium nitrate fertilizer prills (1–2 mm soluble beads) treated with diesel fuel (47:1) was detonated in front of the Alfred P. Murrah Federal Building, destroying the adjacent building and damaging 325 others in a substantial radius of the blast.

Ammonium nitrate is a readily-available fertilizer, as plants thrive on the nitrogen present in both the ammonium and the nitrate moieties of the compound. Malicious use has decreased with stiffened regulations and availability.

The use of ammonium nitrate to accelerate the combustion of fuel is common in industrial applications such as mining. The mixture is referred to as ANFO for ammonium nitrate and fuel oil. The actual detonation is a result of instant release of the energy within the fuel’s bonds, driven by the presence of ammonium nitrate.

But ANFO is a relatively slow burn. The explosive power is generated from the rapid formation of gases in a confined space leading to release.

The violent reaction witnessed in the Beirut tragedy is at first difficult to reconcile. You can actually put out a fire with ammonium nitrate — it is a relatively stable compound that does not simply ignite on its own. So while here was 2750 tons (>2.5 million kg) of ammonium nitrate in the warehouse in Beirut, there was no “fuel” component. So how does negligent fertilizer storage translate to a massive tragedy?

Analysis of the video shows a burning fire nearby, and some reports indicate that this started because a welding crew was repairing a gap in the warehouse that set of fireworks adjacent to the ammonium nitrate. Insert question mark here.

In the video you can see the fire burning, with small aerial bursts consistent with fireworks on site.

While relatively stable at room temperature, ammonium nitrate decomposes with heat. It is the degree of heating that dictates the products of the reaction. Below ~300°C ammonium nitrate breaks down into nitrous oxide (N<sub>2</sub>O) and water (H<sub>2</sub>0), plus the reaction releases heat. Neither of these compounds has much consequence under slow decomposition.

Image for post
The low temperature decomposition of ammonium nitrate.

At high temperatures the reaction is much different. The reaction produces gaseous nitrogen (N2) and oxygen (O2) along with water in a massively exothermic (heat producing), rapid release. This is what likely happened in Beirut. The high heat from this preliminary fire led to the rapid chain reaction decomposition of ammonium nitrate that instantaneously ignited the entire load, an explosion 1/5 of Hiroshima. That rapid decomposition led to the tremendous shock wave that broke windows miles away and was heard as far away as Cyprus.

Image for post
The reaction above 291°C

The evidence of ammonium nitrate decomposition in Beirut is also noted by the signature red gas cloud, an indicator of NO2 (nitrogen dioxide) formation.

It is also possible that the stored ammonium nitrate was already decomposing from years of improper storage, and could very well have gone through other transformations from moisture or if it was contaminated with fuels or other combustible materials. The circumstances may have hastened the reaction from the initial fire.

Many of us grew up milling gunpowder or creating model rocket engines, and nitrate-based oxidation compounds were something we always understood and respected. However, their use as principle components of a violent explosion is not immediately clear. Hopefully this short article provided that clarity.

Beirut is no stranger to violent explosions, as decades of civil wars and bombing from Israel have left a lasting impact on the population and its infrastructure. As of this writing the death toll stands as 78. However, there is no chance that this number will remain constant, as the ultimate tragedy of this event will probably take weeks to realize.


Monday, July 20, 2020

Condoning Car Attacks on Protesters

The interesting thing about COVID19 times is that whenever I sense we have hit the lowest low, society always seems to find a level lower.  At a time when we admire the work of physicians, nurses and other folks on the front line of the pandemic, there are equal magnitudes of disappointment from some that represent a significant mindset within our nation.

Today someone I knew from high school posted this on Facebook:




A new low in counter-protest swag endorses the recent trend of using vehicular violence to quash social movements. 


Clearly the All Lives Splatter is a play off of Black Lives Matter, and the car plowing into protesters depicts the increasingly frequent use of vehicles weaponized by those aggressively opposed to the requested social change.  Since the death of George Floyd in late May, there have been 66 vehicle attacks on protesters.

The tactic typically employed by Islamic militant groups has now been adopted by those wishing to limit the American tradition of protest.  The most notable case in recent memory comes from Charlottesville, VA where a white supremacy rally conjured nonviolent resistance. James Alex Fields rammed the crowd of counter protesters killing 32-year-old Heather Heyer. Fields is now serving life in prison.  Analysis of his computer unveiled images of cars ramming protesters, indicating his actions were inspired and premeditated.

The latest attacks were in Bloomington, Indiana and Seattle. Twenty-four year old veterinary assistant Summer Taylor died when she was run over by Dawit Ketele, who now is being held awaiting trial.   

There are three levels of wrong here. 

1.  Using a vehicle to attack protesters. 

2.  Making memes and t-shirts to celebrate using a vehicle to attack protesters.

3.  Extolling the virtue of memes and t-shirts celebrating using a vehicle to attack protesters on social media. 

With each level the hate and pathology grow even deeper, from committing a violent act to promoting it as cute, funny, and in some cases necessary. 

And if you want to buy your protester-ramming shirt you can get it here for $23, right next to the "If You Don't Like America, There's the Door" shirt. 


The irony is that America's framers welcomed civil protest against injustice, and terrorist-level attacks on Americans by fellow citizens are about as un-American as it gets. Maybe their rejection of acceptable civility can help them find the door.

And therein lies the problem. People opposing protest for needed change feel they are somehow doing a patriotic duty. They will commit a crime as a presumably patriotic act, they will wear a shirt celebrating it, or emote about it on social media, even if it means killing other Americans.  

It shows the fragile state of our union, and the polarization of a significant portion of our population that feels neutralizing bothersome speech that provokes needed change is worthy of a deadly and violent response.