(CNN) US explores possibility that coronavirus started in Chinese lab, not a market. With some confidence that WaPo articles are not written by right-wing conspiracy theorists, (WaPo) State Department cables warned of safety issues at Wuhan lab studying bat coronaviruses  is useful, though the lure of a good story cannot be ignored. I find myself conflicted.

Positive thoughts. I tend to sympathize with China hawks, for reasons that I think of as rational. About 17 years ago, a study concluded that Americans would not pay an extra dime for a light bulb made in the U.S.A.  In the indolent 90’s, up till 2010, the dollar store was China’s friendly ambassador. How can sentiment be mobilized for “buy American?”

With the guts ripped out of the manufacturing economy, many of us, myself included, wish for a Back to the Future solution. I would prefer that it be powered not by national prejudice, but by national preference. It’s wrong to hate a country for doing well. It’s right to love our country more.

Now switch to the negative. The research of the Wuhan Institute of Virology is not as unique or essential as the Post supposes. As far back as 2012, articles like (PubMed) Mechanisms of host receptor adaptation by severe acute respiratory syndrome coronavirus  elucidated the mechanisms. For academicians, a popular gambit is to restudy  a problem in hair-splitting detail until funding can no longer be obtained. The research referenced as valuable in the Post article is incremental to prior published efforts.

The unstated importance of the Wuhan Institute of Virology is the development of human resources, competence which could be directed towards bio-weapons development. Almost all “black” programs have unclassified precursors. Who thought it was smart to help China set up a BSL-4 facility? We’ve already seen what unweaponized COVID can do to an aircraft carrier.

Now, the ambiguous. If you’ve absorbed the above, it must be frustrating that the “escaped from a lab” idea is utterly unproveable. Even the likelihood is impossible to determine. It’s no help that COVID-19 is transmissible by asymptomatic carriers. At best, after some very complex analysis, someone may come up with a dubious number, like “30% chance it escaped from a lab”.  I  distrust such numbers, particularly when an issue becomes political, because the mutation of RNA is a frequent, random process that obscures its tracks with every jump to the next host.These are not betting odds.

Again, the positive. Consider that we don’t know how many cases we have, or what mutations exist. The  problem has completely run away from us in our own country. It is entirely possible that COVID-19 came from a Wuhan lab, and China can’t determine this, or any other theory of origin.

The politicization of a question that cannot have a definite answer is the use of animus to influence trade policy. Bad vibes can be reciprocated. Trade, human rights, and geopolitics have their own legitimacies. They don’t need help from plague-inspired hate.

We got caught with our pants down. The blame should start here, and it should stop here.

Now gas up the DeLorean, and make it happen.

(CNN) Beijing tightens grip over coronavirus research, amid US-China row on virus origin. The article quotes a researcher:

“I think it is a coordinated effort from (the) Chinese government to control (the) narrative, and paint it as if the outbreak did not originate in China,” the researcher told CNN. “And I don’t think they will really tolerate any objective study to investigate the origination of this disease.”

Could we have hit a nerve with Intelligence Community and COVID-19 Wuhan Patient Zero — for Junkies Only ?

To everybody outside of China, it’s too late to rewrite history.  This does not vitiate the importance of the question of why Beijing has decided to try. Widely disparate motives are possible:

• The Huanan Seafood Wholesale Market could be an example of severe regulatory incompetence, with graft lubricating commerce even when infection was evident.
• There really are mass graves of village dead, or documented traffic of crematoriums working overtime, resulting from minimal medical care and cover-up. The  misdeeds of local officials, these could still provoke national rage. Historic Chinese culture venerates the farmer, reflected in the Tang Criminal Code.
• The least dramatic, the futile attempt to rewrite history.

Who knows what evil lurks in the hearts of men? The Shadow knows. So does the National Reconnaissance Office.

FOR INTELLIGENCE JUNKIES ONLY. This is not the continuation of (CNN) Trump is wrong… About Hydroxychloroquine Studies…Facts. Part 1.

(ABC) Intelligence report warned of coronavirus crisis as early as November: Sources.  This was preceded by (Reuters) U.S. spies find coronavirus spread in China, North Korea, Russia hard to chart.

The data-intensive, technical collections that base IC efforts, possibly augmented by HUMINT, can’t be matched in open source. The logic is the same for both.

One purpose of this blog is to promote open-source analysis as skill that can be developed. Analysis is not a leap to an answer; it’s development of an inventory of questions. Some will be disposed of, others will lead to more questions, while some may lead to significant conclusions. So, questions:

The earliest open-source documentation of COVID  in Wuhan was authored by (Wikipedia) physician Ai Fen, with the date of 12/18:

On 18 December 2019, Ai came into contact with the first case of pulmonary infection showing “multiple patchy blurry shadows scattered in lungs” from a delivery person of Huanan Seafood Wholesale Market. On 27 December, she received a second patient, but this person had no history of contact of Huanan Seafood Wholesale Market. In the afternoon of 30 December, the test result of the second patient showed infection with a coronavirus. When she saw the words “SARS coronavirus,…

12/18 as the first official date is somewhat contradicted by the IC. Quoting Reuters,

As far back as late November, U.S. intelligence officials were warning that a contagion was sweeping through China’s Wuhan region, changing the patterns of life and business and posing a threat to the population, according to four sources briefed on the secret reporting.

A date difference of around around three weeks. How can this be resolved? Possibilities:

• A hidden parallel care system in Wuhan, with a separate medical database. But how could it muster the diagnostic resources? How would it control the grapevine? It’s not impossible, but leaks would be expected.
• A separate outbreak among rural communities that fed the Wuhan live animal market. Without the urban grapevine, local authorities could have concealed these outbreaks with minimal medical care and rapid burial.
• Misdiagnosis on a massive scale, as happened in Moscow.

Mortality is a separate question. It could have been concealed by surreptitious editing of the medical records database.  Does it fit with either of the above? Stepping back from this detail, in the period of late November to mid December, were there:

• One outbreak, heavily managed, so that even physicians such as Ai Fen would be out of the loop?
• Multiple outbreaks. Concealed by local authorities, or Beijing?
• Overlapping outbreaks, which grew into each other? This allows under counting or over counting by sheer confusion.

Deceit, usually for domestic reasons, is typical of governments which descend from former communist states. The only surprise is honesty. Nevertheless, the date discrepancy is not resolved to satisfaction. In place of the above, a simple question will suffice: What the hell was going on?

We’re done with annoying questions. Open source has a few basic hand tools to offer, Occam’s Razor, and combinatorics. This may help to redefine the quest for Patient Zero. In most cases, it is a quixotic quest. In Wuhan, combinatorics shows this.

There is an analysis tool, the sum of probabilities, that has been taught to CIA analysts. It is analogous to Feynman diagrams.  It assumes that the chance of an event is proportional to the sum of all the ways it could happen. The theory is very precise; the application is necessarily approximate.

Get the checkerboard out, to imagine a world of only 8 people. We want to know the origin of one case, the chain of transmission back to the first of these 8.

• Number the red and black edges 1 to 8, the 8 inhabitants of this tiny world.
• On the black edge, Number 4 is infected. We want to know the origin.
• The infection proceeds from red to black.
• Each step from red to black is a minimum of one unit of time.
• You are permitted to draw a chain that duplicates a number, provided they are adjacent. For example, 1-2-2-2-2-2-2-4 is a valid chain of infection that implicates #1. But 1-2-3-2-2-2-2-4 is not, because it implies #2 was infected twice.
• All the chains are assumed equally probable.
• The order of the chain members matters.
• What is the probability that Red #2 is the origin of #4’s infection?
• It is the sum of all possible chains connecting Red #2 to Black #4, divided by the total number of possible chains that connect the Red side of the board to Black #4.

Skipping to the obvious answer evades the point of the exercise. The counting reveals a form of transmission  where individual identity is meaningless, replaced from the outset by large-number statistics. The significance of Patient Zero is zero.

This model has little real-world utility. It appears that the Huanan Seafood Wholesale Market is an exception. Described as a slosh-pit of infectious blood and guts,  it  has intuitive use. Anybody can infect anybody, with back-and-forth animal-human-animal-human transfer likely. The model cannot be accurate, but it is compatible with multi-focal outbreaks, and the discrepancies noted by the IC.

There is always a Patient Zero. For the Wuhan outbreak, the significance of  Patient Zero is supervened by the statistical characteristics of the Huanan market. These characteristics, not those of a Patient Zero, are determinant of what the IC may have identified as a multi-focal outbreak.

(CNN) President Trump is wrong in so many ways about hydroxychloroquine studies. Here are the facts.

I don’t know whether hydroxychloroquine works. I managed to write about the drug without naming it in New Drugs for COVID and Double-Blind Testing, Part 1 and Part 2. 

Not a lot in the CNN article is objectively wrong. The French study is shoddy. But long on opinion and short on facts, the  article raises the question: Can the public be made to understand anything, or, as Walter Lippmann claimed, must public opinion remain under the wise care of the elite? I don’t know the answer to that either. But every article is an individual choice of these proportions: influence, as in “trust the experts”, and information. Could the popularity of anti-vaxer sentiment  be an allergic reaction to  an excess of influence, and a shortage of information?

The article pits “professional opinion of respected experts” [quotes mine, for effect] against a pol.  With this focus, the article omits the  self-knowledge  of the experts about their expertise, their differences of opinion, and opportunities for innovation. This laser sharp experts-versus-Trump focus squeezes out every possible procedural innovation in drug studies. That’s  why I quoted “professional opinion…”  And so,

• Author Cohen  homogenized a subject which has both a core and a frontier, agreement and diversity. There is no mention of any difference of opinion, on how to conduct studies, within the medical community. Is this a possible state of affairs?
• Possibly due to Cohen’s choice of “Boiled down to the essentials” she omits the meaning of  “double blind”. Too complicated for the hoi-polloi? Let’s say it here: It means nobody knows who’s getting the real drug.
• The efficacy of the drug is cast as a  political question. As right or wrong as Trump may be, it is not, unless you (literally) want to argue politics with your last dying breath.

The article implies that in a duel between Trump and the experts, on whether the drug ultimately works, Trump is a bad bet. It depends upon how you like 50/50, or maybe 60/40. The complicated truth is:

• Trump could be right, for the wrong reasons.
• The experts could be wrong, for the right reasons.
• It’s difficult for the press to make sense of in the editorial tradition of taking sides.

Hydroxychloroquine has activity against COVID-19 in the dish. It is a dangerous drug:

• The  therapeutic index, the range of  the effective dosage, at least for the malaria parasite, is narrow.
• Multi-system toxicity.
• It is a cardiac antiarrhythmic agent, which, like most such drugs, can cause cardiac arrest when used with the wrong patient in the wrong dose, which may conflict with the dose for COVID-19.

The CNN article addresses this well, a small departure from influence with an  insert of actual information.

Warning, before you scroll down. Three words are used that may offend some readers. One word has 3 letters, while two have 5. These words will be not be used in the context of any person, company, or politics.  They are essential to discussion of the Scientific Method.

The CNN article lives outside the Scientific Method. We’re going to tunnel inside it, with these words:

Lie, Cheat, Steal

Already, I’m wondering if the above words are too abstruse or offensive for the person in the street. If you’re hesitant about this vile exposure, it might be better to change the channel:

Chim Chim Cher-ee

To be continued shortly.

The command cultures of the U.S. Armed Forces are among the world’s best.  Any doubter should read Tom Clancy’s nonfiction biographies, Studies in Command. Another point of reference is the NOVA series, Carrier, filmed aboard the U.S.S. Nimitz, lead ship of the class of which the Theodore Roosevelt is a member.

Each of the services share the challenge of human resource management, but with differences in detail. The Army and the Marines share a problem unique to land warfare, the strain of combat where the soldier is directly and often personally responsible for killing the adversary and bearing witness to the death of one’s buddies. The challenge is to enable this frame of mind, with the soldier remaining psychologically whole in the non-combat world.

Sometimes the hardest task is the most perfectly done. Because land warfare is so upfront personal, the Army and the Marines had no choice but to excel in human resource management.  The last steps of perfection have come only in the past few years. The Navy is a little behind.  While PBS Carrier displays the best of Navy human resources, there have been serious lapses, concentrated in the commissioned ranks.

Within the past 20 years, four lapses have involved smaller ships. Two separate problems are demonstrated:

• Conflict resolution that over prioritizes command authority.
• Excessive “can-do” attitude, where the tempo of operations exceeds watchful human endurance.

USS Shiloh (CG-67) under the command of Captain Adam M. Aycock, when it was also known as the  (Navy Times) “U.S.S. Bread and Water.” Quoting Wikipedia (boldface mine):

…reported extensive morale problems universally blamed on the CO, Captain Adam M. Aycock. Among the complaints were widespread depression and suicidal tendencies, a dysfunctional ship that sailors felt was ill-prepared for combat, an overworked and deeply stressed crew, and a constant worry of extreme punishment for minor infractions. Sailors were dismayed that despite a significant number of the ship’s crew filing severely critical complaints of Aycock’s leadership in the command climate surveys, the only action taken by the Navy was to counsel him…

USS Cowpens (CG-63), under the command of Holly Graf. Between 2002 and 2010, Graf held positions with command authority. It took 8 years for the Navy to recognize Graf was not fit for command:

…Subsequent reports by Time revealed that Graf had a history of abusive treatment of subordinates as far back as her tenure on the Curtis Wilbur. Previous complaints had not been acted upon by Navy leaders. Many who served with her thought she was the closest thing they’d seen to an actual Captain Bligh.[8] For instance, while she was commander of the Churchill, a propeller snapped just as it was leaving port, leaving it dead in the water. Graf grabbed the navigator and dragged him to the outdoor bridge wing while cursing at him.…many Churchill sailors, knowing that Graf’s career would have ended if the Churchill had run aground, started jumping for joy and singing Ding-Dong! The Witch Is Dead on the fantail. Kaprow later said that the crew’s morale was the lowest he’d ever seen in his 20-year naval career.[5] … said that Graf frequently spat at other officers and threw things at them--including ceramic coffee cups and binders…

The resolutions of these situations over weighted the importance of command authority, motivated by  fear that the final authority of the captain would be undermined by removal for maltreatment of the crew.

In 2017, two Arleigh Burke class destroyers collided with commercial vessels, killing 17 sailors. Quoting from Wikipedia,

• USS Fitzgerald and MV ACX Crystal collision

On 17 August 2017, the two senior officers and the senior enlisted sailor in charge of the naval vessel were relieved of their duties.[24] The Navy planned to discipline up to a dozen sailors, including the commanding officer, for watchstanding failures that allowed the fatal collision.[25]

• USS John S. McCain and Alnic MC collision

On June 19, 2019 the National Transportation Safety Board (NTSB) released their report on the accident.[32] Their finding that the probable cause of the incident was a “lack of effective operational oversight of the destroyer by the US Navy, which resulted in insufficient training and inadequate bridge operating procedures.” Along with their complete report they provided a series of recommendations including changes to Navy bridge equipment and training procedures. This is the first independent investigation document released on any of the recent US Navy navigation incidents.

These factors have been cited, to combine and potentiate:

• Excessive tempo of operations.
• Lack of time for training.
• Lack of training.

Specific measures have been taken to remediate. This does not address culture, the ingrained habits of thought that linger even as the forms are changed. A super-carrier operates at high tempo with the discipline of doing things right, which is maintained only if you keep doing them.

To bring all of this to a halt, to have 10% of U.S. surface warfare capability stand down, is an extremely difficult decision, in denial of “can-do.” It requires a comprehension of COVID-19 dangers that has been slow coming to everybody.  Captain Crozier may have been more viscerally aware than most flag rank officers of a particular danger.

The virulence of a virus can change. For each general type, there probably is an upper limit, but this is not known. In the 1918-1919 flu pandemic, virulence increased rapidly in military encampments.

This is discussed in COVID-19: A Warning. From The U.S. Military and the Influenza Pandemic of 1918–1919,

…during Chesney’s third phase, August 23 to November 8, more than one-third of the 6th Artillery Brigade, 1,636 soldiers, contracted influenza and 151 died. Chesney concluded that “…these successive outbreaks tended to be progressively more severe both in character and extent, which would speak for an increasing virulence of the causative agent.”¹³

The commanding officer of Camp Grant couldn’t take it:

…fellow officers later told reporters that Hagadorn had been showing the strain of the epidemic.^26,27 Troubled as more than 500 soldiers died of pneumonia under his command, on October 7, he committed suicide with a pistol shot to his head.

Hypothetically, in the high density living quarters of the Theodore Roosevelt, COVID-19 could mutate to greater virulence. History is full of apocryphal stories. The modern record is held by a  Hantavirus strain in the Four Corners region. In 1993,  an apparently healthy person  died in 3 hours.  (CDC) Tracking a Mystery Disease: The Detailed Story of Hantavirus Pulmonary Syndrome (HPS)

(NY Times) Navy Captain Removed From Carrier Tests Positive for Covid-19. This could be his get-out-of-jail card. It might also deprive the Navy  of a learning experience.

Captain Crozier identified and responded to a novel hazard that, without action, in all probability would have substantially disabled his ship and cost lives in the process. His response was unorthodox because the novelty might have concealed a time bomb with a short fuse.

(CNN) Commander of aircraft carrier hit by coronavirus removed for ‘poor judgment’ after sounding alarm.

Kudos, Captain Crozier.  You sacrificed your career to put pressure on the Navy brass. You saved lives.

History will judge you kindly.

***Run for office.***

P.S. (CNN) Sailors cheer for aircraft carrier commander who was removed after issuing coronavirus warning.

(CNN) Asia may have been right about coronavirus and face masks, and the rest of the world is coming around.

Up until this point, the media has repeated, without question, a “fact” that does not exist: “Surgical masks don’t work to protect the wearer from inoculation with airborne viruses.”  There never has been such a fact. Two studies, one lab, one clinical, contradict each other. The clinical study provides evidence that they offer some protection.

On February 29, in Can Surgical Masks Protect Against COVID-19 ? Wear a Scarf!, I wrote,

Follow the logic: If N95 masks protect, and surgical masks work about as well in clinical settings, then surgical masks protect. Remember the caveat. Now translate that into unmanaged news-speak:

Surgical masks might offer some level of protection, but nobody knows for sure.

I’m feeling righteously indignant, which is a rare and uncherished feeling. It’s not because:

• The world response has been a bungle from the start.
• The experts have been mostly wrong.
• Epidemiology failed to impact public policy in a timely manner.

No, that isn’t it. It’s this:

The healthcare establishment invented a “fact”, that surgical masks don’t work. The media swallowed it hook, line, and sinker, with these possible motivations:

• Health care professionals have good reason for priority supply of masks.
• Media may themselves have believed the “fact”, or, with overweening respect for medical authority, neglected to read readily available studies.
• It was easier to go with the flow than dig for the truth.
• A sense of paternal responsibility supervenes the above.
• It’s a white lie for a good purpose, akin to political spin.

Maybe surgical masks protect, and maybe they don’t, but there is no “fact.” It’s the job of the press to question, and they did not question this easy to undermine pseudo-fact. A study that suggests they are effective is referenced in Can Surgical Masks Protect Against COVID-19 ? Wear a Scarf!.

The media could have presented the whole argument, and appealed to patriotism, or the common good. I wrote,

Treat people like adults, and they are more likely to act as such. Even if you’re [media] into managing, there is another reason to avoid it: If and when the shit hits the fan, they are more likely to follow your lead.

Put another way, telling the truth grows the public trust and sense of responsibility. Treat them like children, and you get children.

Consciously or no, this media error is a manipulation of truth. Whatever the purpose, it is not harmless.  As pure as  intentions may be, the nonexistent “fact” that surgical masks don’t work against COVID is the essence of a white lie. It feeds the conspiracy appetite of the unbalanced.

We’re shocked when the conspiracy nuts crawl out of the woodwork. The nuts grow on trees, which we plant.

(NY Times) 72 Hours Inside a Hospital Battling Coronavirus  interviews Dr. Colleen Smith at Elmhurst Hospital in Queens, NYC. The Times is providing COVID coverage free to non-subscribers; this video should be universally viewable. At 4:00 in the video, she says, “What’s getting a little scary now is that the patients we’re getting are much sicker”,… “young people without comorbidity” , that is, underlying health conditions.”

Dr. Smith’s observation is unavoidably subject to confounding factors, a.k.a. “noise.” The swell of sicker patients could be individuals who thought they could tough it out, or are not very aware of how they feel. Still, it’s appropriate to consider that COVID-19 may be gaining virulence in NYC. COVID-19: A Warning.

Plagues of the past were characterized by  virulence that increased in waves. Many mechanisms, including but not limited to, mutation-evolution, are involved. Some of these are understood. Virulence factors are identified features of a pathogen which affect the severity of a disease.

There are huge holes of understanding. Knowledge of how these factors  work at the viral level varies from complete to partial to slight. How they turn on or off is partly, or in a few cases, completely understood. There  is no quantitative understanding that connects biochemical understanding of virulence with epidemiology. Yet the macroscopic viewpoint of epidemiology, with centuries of observation,  has much to say about it.

There is no way to predict the virulence of a  novel virus from viral genes. Understanding has come from the reverse direction: the mechanism of virulence is observed, and then identified in the viral genetics. This is because, despite unraveling of the genetic code, and detailed knowledge of a minority of cellular enzyme systems, most enzyme systems remain a mystery. There are just too many of them.

If you’ve been following the news, you know there is no way to predict R_o, or lethality of COVID, at all. It’s purely observational, depending not just on the pathogen, but the behavior of people, and how they live. It may depend so much on local circumstances to be an invalid concept. Later on, we’ll understand more.

The demand to know the future fuels predictions that have no basis. (CNN) Coronavirus deaths in the US could reach peak in three weeks, epidemiologist says. Of the four authorities, three are doubtful, or subject to misinterpretation in the context of the article. Dr. Stefan Flasche is credible. Quoting,

Dr. Stefan Flasche, a disease modeler at The London School of Hygiene & Tropical Medicine, told CNN by email the peak was influenced by the efficiency of lockdown measures, and “may be anywhere between some time very soon and not for another few months.”

“One scenario is we can indeed reverse the spread as done in China and South Korea, then reach a point to lift the distancing measures,” Flasche said. “But (we may) have to repeat this cycle for a few times because of an inevitable resurgence of cases in the absence of population immunity. In that scenario, we would see multiple peaks in the upcoming 12 months.”

In this vagueness, we have found an honest man. An honest team may be found at (pdf 16 March 2020, Imperial College COVID-19 Response Team) Impact of non-pharmaceutical interventions to reduce COVID-19 mortality and healthcare demand. They are honest because they lay out all of their assumptions, which are unavoidably incorrect. They are predictably wrong, just as the CEP (circular error probable for a gravity bomb) is predictable.

But what is an epidemiologist to do? WHO couldn’t even predict COVID-19 would get out of China, and we now demand detail? Ignored in normal times, this honorable and troubled profession is now belabored with impossible demands. In the press, this includes a hopeful confusion of “peak deaths”, which is a rate, versus cumulative mortality, which most article writers ignore, and looms bleakly in our future.

In China, two variants of COVID-19 have already been identified, Type L and Type S. COVID-19: A Warning. This factor is absent from all the predictions. The epidemiologists have too much on their plates to deal with it.

How do you find an epidemiologist you can trust? Throw him in the snake pit:

The Fortune Cookie (Snake Pit)

My apologies to all epidemiologists. I couldn’t resist it.

To be continued shortly.

You might think that all there is to a mask are billions of very tiny holes, small enough to admit air, but block particles. This is wrong.

Before the electron microscope was invented in the 1930’s, biologists already knew of infectious agents that could pass through a block of unglazed porcelain. Hence the term, seldom heard these days, filterable virus.

So catching a virus that can pass through porcelain with something that looks like fabric is quite a trick. The secret: electrostatic charge. If on a dry day, you’ve ever had to unpack a box containing packing peanuts, and found that the peanuts tend to stick to you — that’s electrostatic charge.

It turns out that common, nonconducting materials can be so charged. Synthetic fibers can be placed between high voltage plates. When heated, the fibers become electrets, behaving  analogous to magnets, acquiring permanent electric polarization. An electret has a + side and a – side. There are excess electrons on the – side, and a shortage of electrons on the + side. (Don’t be confused by the + and -. It’s an old convention.)

Electret materials are found in most microphones, many furnace filters, and high efficiency masks. Electrets attract and grip most small particles, even if they are small enough to pass through the pores of the mask.

But electrets have a shelf life. The charge in the fibers equalizes in time, at which point the mask behaves like it is made of plain fabric.

This is also why a high efficiency mask cannot be washed. On contact with water, the electret charge leaks around and equalizes. The excess electrons on the – side fill the vacancies on the + side. After washing, the mask is about as good as your scarf.

Your scarf is not totally useless, but it’s not enough for the exposure of a clinical setting.

(CNN) Fauci says ‘there isn’t, fundamentally, a difference’ between his view and Trump’s on coronavirus. Quoting,

“I, on the other side, have said I’m not disagreeing with the fact anecdotally they might work, but my job is to prove definitively from a scientific standpoint that they do work,”

There is a disagreement. Fauci may not have ice-water in his veins, and Trump knows the meaning of “Show me the money”, but the two are close to opposite poles. Some philosopher, so obscure I can’t Google him up, said, “Truth is found at the meeting of opposites.” If we were flies on the wall, their differences might sound like that.

Medicine restricts “proof” to double blind testing, which means that neither the physician or the patient know whether the actual treatment, or a placebo, is being received. This avoids prejudice in the observations of the clinician. Even subjective observations of the clinician, like “patient seems stronger”,  have value in a double-blind study.

What of the patients who are harmed? The ethical rationale is that it saves lives in the long run.  Let’s consider a double-blind drug trial which enrolls 1000 patients. Half receive the drug-candidate. Half receive the placebo. Unknown to the experimenters, the drug has one of three actions:

• Promotes recovery.
• Has no effect.
• Harms the patient .

After some period of time, the results are “unblinded.” For the first time, it is possible to see who was getting what, and the likely effects of the drug. Results:

• If the drug is bad, no more than 500 patients will get hurt.
• If the drug has no effect, nobody gets hurt.
• If the drug is good, how many people get hurt?

A double blind trial, with patient consent, is a unique loophole in our legal system, and the exception to the Hippocratic “Do no harm.”  Suppose the drug is one which may have a very long use. For the next 50 years, the drug will be the standard of care.  The double blind method attempts to ensure the maximum benefit for all future patients. It does this by risking the lives of current patients for the benefit of the indefinite future.

Now I’m done extolling the virtues of double-blind testing. It has these disadvantages:

• It is too slow for a plague situation.
• It may be sacrificial of people’s lives.
• Alternatives exist that, sacrificing scientific purity of thought, would likely save more lives.

See (NCBI) Probability, proof, and clinical significance. We live in a world of probabilities. In a study of 1000 patients, there is a possibility that the study results, good, bad, or indifferent, are due to chance. This chance is called P.  Fauci’s acceptable P is probably the conventional choice, 0.05, a 5% chance the study is wrong.

Increasing P means the study can finish sooner, with earlier availability of a drug. This comes with a greater chance the study is wrong and the drug useless or harmful. This is hard to justify if we’re not in a plague situation. But note, compassionate availability of unapproved cancer drugs has been the standard for some years now.

Increasing P can be justified in a plague situation, because of the otherwise certain death of large numbers of patients. It means that regardless of the intent of the drug trial organizers, their choice of P directly affects the survival large numbers of non-study-participants.

This would be evident if a cost/benefit equation, for a drug trial in plague conditions, with the goal of optimizing P, were part of the canon of applied medical statistics. But it’s missing.

The technical resources available to Dr. Fauci could quickly provide the missing equation, minimizing cost by varying P in line  with the current crisis.

My guess: P= 0.25. It shortens the required length of the study, with the likelihood (chance always intrudes) of saving the lives of the large numbers of critically ill who are not study participants.