Wednesday, March 18, 2020

Jacob Schor, ND, FABNO

hy·poth·e·sis

“a supposition or proposed explanation made on the basis of limited evidence as a starting point for further investigation.”

“It does take great maturity to understand that the opinion we are arguing for is merely the hypothesis we favor, necessarily imperfect, probably transitory, which only very limited minds can declare to be a certainty or a truth.” 
― Milan Kundera

The idea that drugs that target ACE binding sites will provoke Covid-19 infections, making them more transmissible and more deadly is a hypothesis.  

This hypothesis is based on the data that suggests people suffering from certain pre-existing illnesses, in particular diabetes, heart disease and high blood pressure have higher than expected infection and mortality rates from this virus.  

This idea stems from a letter to the editor of the Lancet published March 11, 2020.  In their letter Lei Fang and colleagues presented a hypothesis to explain certain observations. They wrote, “If this hypothesis were to be confirmed….” that then there would be a concern about using certain ACE inhibiting drugs in certain people at risk for Covid-19 infection. [i]

This hypothesis apparently was then extended to a concern about using NSAIDs and related drugs and supplements that impact ACE2.

A hypothesis is just that, a proposed explanation based on limited evidence.  It is a long way from accepted theory.  

An equally plausible hypothesis written by David Gurwitz based on similar data comes to nearly the opposite conclusion. Dr. Gurwitz is at the Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University in Israel.  Rather than avoiding ACE targeting drugs Gurwitz suggests, “… to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS-CoV-2 virus infections. This idea is based on observations that the angiotensin-converting enzyme 2 (ACE2) very likely serves as the binding site for SARS-CoV-2….”

Let me say that a second time: Using what seems to be the same data he reached the opposite conclusion.  His reasoning is not simple, and he clearly acknowledges this.  

“… the suggestion to treat SARS patients with AT1R antagonists for increasing their ACE2 expression seems counterintuitive.”

He lists a number of observations including references from the 2002 SARS epidemic and from HIV treatment in support of his hypothesis.  For those of you who wish to follow the details of this argument, a link to the full text of his paper is below.[ii]

https://onlinelibrary.wiley.com/doi/pdf/10.1002/ddr.21656

How do we pick one hypothesis over another? We don’t; we wait until there is more information, what we call data, to inform the discussion.

This is an interesting situation. We do not like hanging out with uncertainty especially now, We want the world to be black and white, true or false.

This uncertainty is the very nature of a hypothesis.  It is unproven.  It may be true, it may be false.  In this case of ACE inhibitor drugs, they may be harmful, or they may be beneficial.  We do not know at this point.  We need to carry some caution along with us into this new world of fake news.  Who do we believe?  What do we believe? 

Speaking of this dilemma, the PBS show that aired last night, Niall Ferguson’s NetWorld, was fascinating to watch and might help take your mind off this ACE2 debate. Except that in one visually fascinating segment Mr. Ferguson graphically represented the spread of fake news on the internet in three-dimensional graphs. Consistently fake news spreads faster and permeates deeper to more places than the truth does. Using that criteria alone we might be able to judge which of these competing ideas will eventually prove to be the more accurate.

https://www.pbs.org/wnet/networld/

“In this series hosted by Niall Ferguson and based on his bestselling book The Square and the Tower, Ferguson visits network theorists, social scientists and data analysts to explore the history of social networks. From the Reformation and 17th century witch-hunting, through the American Revolution and to the nightmare visions of Orwell’s 1984, Ferguson explores the intersection of social media, technology and the spread of cultural movements. Reviewing classic experiments and cutting-edge research, Ferguson demonstrates how human behavior, disruptive technology and profit can energize ideas and communication, ultimately changing the world.”

Or if you must obsess about what’s going to happen with this pandemic business, you can move the sliders on the NY Times graphic posted and see how various scenarios play out. “To put the estimates in context, we’re comparing the possible toll with other leading causes of death in the United States in 2018, the most recent year with data available. We’ve started with an estimate from a University of Nebraska public health researcher, Dr. James Lawler, that was recently presented to hospital executives: 480,000 American deaths over the course of the illness known as Covid-19.”

Or you can follow my example and train your newly adopted dog to get into a canoe in the hope that someday you’ll both get to try it on real water.  Note the pretend blue water.

Ruby, the new dog; canoe practice on dry land

[i] https://www.thelancet.com/pdfs/journals/lanres/PIIS2213-2600(20)30116-8.pdf

[ii] Gurwitz D. Angiotensin receptor blockers as tentative SARS-CoV-2 therapeutics.  Drug Dev Res. 2020 Mar 4. doi: 10.1002/ddr.21656.