Last week, I called for scientists to come forward and make a public statement that the world’s response to COVID is not consistent with best public health practices. As if in answer to my prayer, a meeting was held at Great Barrington, MA, from which emerged this statement, signed by doctors and professors from the world’s most prestigious institutions, as well as hundreds of professionals and thousands of others. You can sign, too. In this video, the three main authors present their message.

Their proposed strategy is to protect the old and most vulnerable and quarantine people with COVID symptoms, while allowing the young and strong to go back to school, go back to work, acquire herd immunity for the benefit of everyone. This is fully aligned with past practice, and is just what Dr David Katz (Yale School of Public Health) proposed in the New York Times and in a video presentation back in March. 

What they didn’t say: The authors of the statement were cognizant of politics and avoided judgment and recrimination. I agree, this was wise. They avoided talking about the evidence that the virus was laboratory-made. I agree, this was wise. They avoided mentioning the ineffectiveness of face masks. I agree, this was wise. They avoided mentioning effective treatment strategies of which chloroquine is the best we have. I think this was a political judgment with which I disagree. Their statement would have been so much stronger if they were able to say that the limited risk that they proposed for the young and healthy will be that much lower because effective early and preventive treatment is available.

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Here are ten messages that are essential pieces of the standard COVID narrative, but which are unfounded in actual science, and the promised rebuttals to each.

1. “The origin of the SARS-CoV-2 virus was one of many random events in nature in which a virus jumps from one species to another.”
2. “Chloroquine kills patients and is too dangerous to use against COVID”
3. “The Ferguson model warned us of impending danger in time to take action and dodge a bullet.”
4. “American deaths from COVID: 200,000 and counting”
5. “Masks and social distancing are keeping the virus in check in our communities”
6. “New cases of COVID are expanding now in a dangerous Second Wave”
7. “Dr Fauci and the CDC are guiding our response to COVID according to the same principles of epidemic management that have protected public health in the past.”
8. “Asymptomatic carriers are an important vector of disease transmission, which must be isolated if we are to stop the spread of COVID”
9. “The lower death rates now compared to April are due to protective measures such as social distancing, mask-wearing, and limited travel.”
10. “With enough resources, pharmaceutical scientists can develop a vaccine in a matter of months, and provide reasonable assurance that it is safe.”

Detailed rebuttals and references

1. “The origin of the SARS-CoV-2 virus was one of many random events in nature in which a virus jumps from one species to another.”

Strong but not dispositive evidence points to genetic engineering as the most probable origin of the virus. I wrote about this in detail last April in two installments, [Part 1, Part 2].

There is no credible path by which a virus with the characteristics of SARS-CoV-2 could have appeared naturally in Wuhan last December. The “wet market” hypothesis died, while no one was looking. The bats that harbor SARS’s closest cousin virus live 1,000 miles west of Wuhan, and the pangolin viruses that harbor another part of the genome live 1,000 miles east of Wuhan. The SARS-CoV-2 genome includes a furin cleavage site and a spike protein matched to the human ACE-2 receptor. These very modifications to bat coronaviruses were the subject of published research, sponsored by our own NIAID and conducted at Univ of NC and the Wuhan Institute of Virology.

2. “Chloroquine kills patients and is too dangerous to use against COVID”

Evidence for the effectiveness of chloroquine + zinc is overwhelming. It was the drug of choice to treat the first SARS epidemic in 2003. Countries in which chloroquine is used have COVID death rates typically four times lower than countries in which use is restricted.

Dozens of credible studies have found major benefits of chloroquine, especially if it is used early and especially if it is accompanied by zinc supplementation. (Apparently, the mechanism of action is to open cell membranes to allow infected cells to be flooded with zinc, which effectively stops the virus from replicating. Quercetin is an over-the-counter supplement which has the same effect of opening cell membranes to zinc ions, and there are a few studies of quercetin for COVID [for example, one, two, three].)

Suppression of chloroquine treatment has defied historic precedents, and represents the most extreme denial of real science on this list of 10. Chloroquine is a cheap, widely-used drug with a 65-year history of use by millions of patients. It has a well-studied safety profile, since it is routinely prescribed not only for malaria treatment but as prophylactic protection for people traveling to areas where they are at risk of malaria exposure. It is also standard treatment of lupus.

For the first time, doctors have been restricted in the off-label prescription of a drug. (Why aren’t they screaming about this?) WIth the combined effects of intimidation of doctors, actual restrictions, and policies of pharmacies, chloroquine treatment is effectively unavailable in most US states.

A major study in May was published prominently in The Lancet, claiming that among 100,000 COVID patients on three continents, the death rate of those taking chloroquine was three times higher than those who did not receive chloroquine. Many smaller studies around the world were immediately canceled and never re-started. But when the authors could not produce data to support their calculations, the study was retracted by its authors without comment. I am not alone in calling the Lancet study a major scientific fraud, but none of the authors of the study or the editors of the Lancet have been held accountable to date.

Smaller frauds are perpetrated with studies that are designed to fail. (Anyone who has epidemiological experience knows how much easier it is to design a study to fail than to design a study that can succeed.) There are three ways this is usually done:

• Failure to incorporate zinc supplementation.
• Starting late. Once patients are in the hospital, treatment with HCQ is less effective, and by the time they are dying from a cytokine storm, HCQ is useless.
• Using toxic dosages, up to 4x the standard chloroquine dose, which triggers heart arrhythmias in some patients.

Some of these “designed to fail” studies actually showed significant benefit, and were reported in such a way as to understate their significance. (Anyone with experience in reading pharmacology studies has seen that almost always, the authors put their best results out front at the risk of overstating their significance.) Here’s an example of doublespeak in a recent review:

“Trials show low strength of evidence for no positive effect on intubation or death and discharge from the hospital, whereas evidence from cohort studies about these outcomes remains insufficient.”

Is this sentence intended deliberately to confuse with double negatives? “Low strength of evidence for no positive effect?” What they really found was “overwhelming evidence for YES positive effect”. In the only large study among the eight reviewed, the death rate of patients receiving chloroquine was half the death rate among controls, despite the fact that all patients were started on chloroquine much later than optimal, and without supplemental zinc.

3. “The Ferguson model warned us of impending danger in time to take action and dodge a bullet.”

Neil Ferguson is head of the UK-SAGE, The Scientific Advisory Group for Emergencies. Ferguson and his team at Imperial College have made draconian predictions that failed to materialize on many occasions in the past.

In 2002, he calculated that the mad cow disease would kill about 50,000 British people and another 150,000 once it was transmitted to sheep. There were only 177 deaths. In 2005, he predicted that the bird flu would kill 65,000 Britons. The total was 457 deaths…[Fergusson], true to his alarmist mindset, predicted with his “mathematical model” that 550,000 British people would die from Covid, as well as more than 2 million Americans, if a fierce lockdown did not come into effect. —Benjamin Bourgeois

Subsequently, the population death rate of COVID-19 was discovered to be an order of magnitude smaller than what Ferguson was assuming, the lockdown was shown to be ineffective (see below), and still the death tolls in Britain and the US were not close to Ferguson’s predictions.

Ferguson predicted that without a lockdown, Sweden would suffer 100,000 deaths through June, 2020. In reality, the COVID death count for Sweden is 5,895 (as of 1 October), and the death rate is below one per day.

Was Ferguson the most credible biostatistician that the European governments could find in planning a response to COVID last winter, or was he only the most terrifying? Why were no other experts consulted?

4. “American deaths from COVID: 200,000 and counting”

At every turn, the COVID death count has been overestimated.

• Hospitals were incentivized to add COVID to diagnosis and death certificates.
• In an unprecedented departure from past practice, CDC instructed doctors to report COVID as the cause of death whenever patients seemed to have symptoms consistent with COVID, or of they tested positive for COVID and died of something else. Cases about motorcycle accidents reported as COVID deaths are no joke.
• The tests themselves have a high false positive rate. PCR tests were previously used only for laboratory research, not for diagnosis. They involve making 35 trillion copies (based on 45 amplification stages) of every stretch of RNA in a sample from a patient’s nose or mouth and looking for some that match a stretch from the COVID genome.

It is impossible to know what the real death count has been, but three weeks ago CDC released the bombshell that people who died of COVID alone with no pre-existing chronic diseases was only 6% of the reported total.

5. “Masks and social distancing are keeping the virus in check in our communities”

Wearing a mask is perceived as an act of caring by a large proportion of Americans. But the actual benefit in slowing spread of the virus is small enough that not benefit has been detected in the overwhelming majority of studies to date. Here is a bibliography of 35 historic studies showing that face masks have no meaningful effect on the spread of viruses, and 7 more studies that document health hazards from masks. Yes, wearing masks for long periods of time imposes its own health risks, especially when the masks are not removed and washed frequently. This is certainly significant for people required to wear them many hours at a stretch.

Here is the conclusion of one meta-analysis from the CDC web page. The authors find that the benefit is too small to rise to statistical significance even in a compilation of ten studies:

In our systematic review, we identified 10 RCTs that reported estimates of the effectiveness of face masks in reducing laboratory-confirmed influenza virus infections in the community from literature published during 1946–July 27, 2018. In pooled analysis, we found no significant reduction in influenza transmission with the use of face masks (RR 0.78, 95% CI 0.51–1.20; I2 = 30%, p = 0.25)

In recent months, several studies have been published that contradict the historic findings, and seem to justify the use of masks. Here is one that is prominently published (PNAS) and highly cited:

Our analysis reveals that the difference with and without mandated face covering represents the determinant in shaping the trends of the pandemic. This protective measure significantly reduces the number of infections.

Here’s how this conclusion is reached: In three locations where face masks were introduced (Wuhan, Italy, NYC), the authors note a linear rise in incidence of COVID, followed by the curve bending over later on. Their estimate of effectiveness is derived by subtracting the number of actual cases from the number of cases which would have occurred if the linear increase had continued through the period of observation.

An obvious objection to this analysis is that the curve always bends over. The initial rise is exponential as the virus expands into an unexposed population, and then it bends over and eventually falls, as the virus runs out of susceptible people to infect. For a short stretch after the exponential phase, the curve may look like a straight line, but inevitably the curve is destined to decline as the population is gradually developing herd immunity. Authors of this study make no attempt to separate the effect of herd immunity from the effect of masking. To do the comparison correctly, it should compare these three cases to control cases, regions in which no masking requirement was decreed. Did the curve turn over more quickly in locations with masks compared to locations without?

This objection and others were voiced by Paul Hunter, Louise Dyson, and Ed Hill in (separate) responses to the study on the UK Science Media Center website. They point out that the kind of shoddy science published in PNAS would never have received such prominent attention in an unpoliticized environment.

Viruses are spread either by aerosols or by droplets. Droplets are exhaled water that contains virus particles, and masks can trap droplets. They are the dominant mode of spread when people are in very close contact, as in a doctor-patient relationship. But droplets fall quickly from the air, especially in humid summer weather, and droplets don’t penetrate deep in the lungs, where viruses are most dangerous. Aerosols are molecular-scale virus particles, far too small to be stopped by a mask. They are the predominant form of virus spread, and outdoors they are the only way the virus spreads.

In urban environments, there are always tiny quantities of prevailing viruses in the air, and for the great majority of people this is a benefit. It means that just going about their business, they are exposed to tiny quantities of virus that educate their immune systems without accumulating to a load sufficient to cause disease. The best outcome for populations—indeed, the normal outcome for every flu season in the past—is that most people acquire T-cell immunity in this way, and then the virus can no longer spread through the population. By imposing lockdown and social distancing, governments the world over have curtailed this well-known, natural process for acquisition of herd immunity.

What is the rationale for slowing spread of the virus? Originally, the stated goal was to “flatten the curve”, so that hospitals would not be overwhelmed by a sudden burden of severe cases all at once. If there was any danger of this, it passed back in April. So, at this point, slowing the spread of the virus is only important if we hope to stop the spread at some future date. This relies on the promise of a vaccine, which, I will argue in part 3, cannot be adequately tested in a relevant time frame. Hence, even the most optimistic assessment of masks and social distancing will not save lives, but only delay deaths by a few months.

NYU Prof. Mark Crispin Miller’s extended essay on masking cites copious evidence for their ineffectiveness as well more stories than you want to read about recent violence that has erupted between masked and unmasked factions, or between law enforcement officials and unmasked civilians.

Tentative conclusions

It was four years after 9/11 that I finally considered the possibility: this was never about brown-skinned men with boxcutters who hijacked airplanes; it was about restrictions on travel and free expression and a new Federal bureaucracy gathering information about our whereabouts and our contacts, all imposed in the name of keeping us safe. This time, I am a little less slow on the uptake, and I am beginning to suspect that COVID 19 is not about a viral pandemic; it is about restrictions on travel and free expression and a new Federal bureaucracy gathering information about our whereabouts and our contacts, all imposed in the name of keeping us safe.

END OF PART 2

Link to Part 3
Link to Part 1

The scientific community has something that American corporations and politicians want. It’s not technology or research. It’s not understanding or policy guidance. It’s the people’s confidence.

In recent decades, every institution in America has suffered decline in public confidence. The press, the Federal government, religious institutions, banking, corporations, even academia— confidence levels are all in the 30-40% range. But public confidence in science is still over 90%.

Sources: Gallup, Gallup, Gallup, Pew

It follows that if you want to market a product or win an election, claiming that “science is on my side” is a powerful selling point. If you want to halt human colonization of the global ecosphere or move people out of their cars into public transportation, the backing of science is natural and maybe even honest. If you have more sinister goals—shutting down democracy, dividing a nation so it is politically dysfunctional, destroying small businesses and handing their markets to multinational giants—then claiming the imprimatur of science is probably the only way to con hundreds of millions of people into a program so profoundly contrary to their interests.

Look around. You see responsible citizens and good neighbors cooperating to curtail the spread of a deadly virus. But if you blink and look again, you may see the widest, fastest, most successful mass deception in the history of the world.

They’ve come so far because they have money and government and the press on their side. But they could not have captured so many minds without the support of a few people who claim to speak for science. Of course, Bill Gates and Anthony Fauci and Neil Ferguson are not representatives of a scientific consensus. But, curiously, they have not been laughed off the stage. The scientific community has not come together, 8-million strong, with a public statement that “These men do not speak for science.” And years of anemic public education has taught the populace to accept a scientific world view, rather than to trust their own evidence-based thinking.

We the People will not pull out of this nightmare on our own. The public will continue sleepwalking into medical martial law without a strong and credible counter-narrative. There is a powerful need for We the Scientists to come together and override the mountebanks who have hijacked the mantle of science.

It’s not news that science is subject to political and financial influence. Examples from the past must start with the pharma industry as the most egregious offender; and also FDA diet recommendations, health effects of cell phones, suppression of energy technologies, past suppression of data about asbestos and tobacco and lead.

But never before 2020 have so few people with so little scientific credential claimed to speak for the scientific community as a whole; and never has the public been asked to modify our daily lives and sacrifice our livelihoods on such a scale.

Anecdotal Evidence

Biological weapons are an abomination. No government or research institute has even tried to convince the public that biowarfare research is a good idea, because it would so obviously stir more opposition than support.

After WW II, Nazi bioweapons programs were transplanted to the US, thanks to Operation Paperclip. The story is told in horrifying detail by Stephen Kinzer.

In the wake of international treaties and acts of Congress to outlaw bioweapons research, the US project was re-branded as pandemic preparation and transferred to civilian laboratories. The ruse was that in order to prepare for the next killer pathogen that may soon emerge from the wild, we must create laboratory-modified viruses so we can develop vaccines and treatments for them. The obvious flaw in this logic has been no obstacle to the bureaucratic momentum behind the project.

In 2005, 700 prominent scientists protested to the NIH, calling attention to the masquerade of biological warfare as public health [NYTimes]. Our largest and most prestigious association of scientists, AAAS issued a strong editorial denouncing biowarfare research. Though they did not succeed in halting the program, they created a public relations nightmare for NIH, and after Obama’s election, the NIH program was indeed curtailed, and had to be moved (temporarily) offshore.

The situation is very different in 2020. In April, Newsweek helped alert the public that Dr Fauci’s own NIAID was sponsoring gain-of-function research in Wuhan, China, that modified bat Coronaviruses so they could infect humans. President Trump got wind of this, and ordered that  gain-of-function research at NIAID be immediately defunded. I’m confident that scientists as well as the public were overwhelmingly supportive of this sensible, belated gesture.

But that was not the response of record. In short order, a prominent group of (geriatric? bamboozled?) scientists was reported to protest the move. 77 Nobel Laureates Denounce Trump Officials For Pulling Coronavirus Research Grant. And last month, AAAS produced editorials in support of continuing this insanely dangerous program. Even in a year as bizarre as 2020, I never expected to be siding with Donald Trump against the institutions of science. I read and reread the article in Science before I was forced to conclude that Trump was wearing the white hat.

COVID-19 and the Perversion of Science

The political response to COVID, in the US and elsewhere, has been not only contrary to well-supported medical science, but contrary to common sense and contrary to past practice. In every respect, the response has been either ineffective or likely to make the situation worse. We started too late for a quarantine program to be effective; then we failed to protect the most vulnerable and failed to quarantine the sickest patients. In fact, we forced nursing homes to take in COVID patients, triggering a predictable tragedy. Ventilators remained the standard of care long after it was reported by front-line doctors that they were killing COVID patients. Healthy, young people are at very low risk for serious complications, and should have been out there earning our herd immunity; instead, they were kept terrified and locked up. The economy and all cultural and religious institutions were closed down, leading to tens of thousands of deaths of despair [video by Glen Greenwald]. Masks and social distancing, the least effective protections, were endlessly promoted while simple, effective protections including vitamin D and zinc were actively disparaged by health authorities. And all the while, the most effective treatment of all, zinc + chloroquine, was criminally suppressed. Now, as deaths from COVID are down to a fraction of their April peak, government and media continue their campaign to terrorize us with a false narrative, while extending lockdowns, school closures, and masking into the indefinite future.

Call for a response by the scientific community

Mosts scientists are curious and open-minded, opinionated but cognizant of others’ opinions, the opposite of polemical. It is not a natural community from which to recruit activists. But the misrepresentation of science in this pandemic has been extreme, and it threatens the future of science and its role in guiding public policy. There have been many scientists who have stood up to counter the COVID narrative. Many more have been censored, their videos taken down from social media. This is a time when we, the scientific community, have been called to come together and call the misleadership of AAAS into account. There is an urgent need for scientists who have been shy about public stands in the past to come forward and speak out.

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Over the next week, I will post details of ways in which I have seen science distorted in support of a government and corporate COVID agenda. 

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Here are ten messages that are essential pieces of the standard COVID narrative, but which are unfounded in actual science. Stay tuned for a detailed rebuttal of each.

1. “The origin of the SARS-CoV-2 virus was one of many random events in nature in which a virus jumps from one species to another.”
2. “Chloroquine kills patients and is too dangerous to use against COVID”
3. “The Ferguson model warned us of impending danger in time to take action and dodge a bullet.”
4. “American deaths from COVID: 200,000 and counting”
5. “New cases of COVID are expanding now in a dangerous Second Wave”
6. “Masks and social distancing are keeping the virus in check in our communities”
7. “Dr Fauci and the CDC are guiding our response to COVID according to the same principles of epidemic management that have protected public health in the past.”
8. “Asymptomatic carriers are an important vector of disease transmission, which must be isolated if we are to stop the spread of COVID”
9. “The lower death rates now compared to April are due to protective measures such as social distancing, mask-wearing, and limited travel.”
10. “With enough resources, pharmaceutical scientists can develop a vaccine in a matter of months, and provide reasonable assurance that it is safe.”

END of Part 1
Link to Part 2
Link to Part 3

My fasting blood glucose has been creeping up over several years. (My fasting blood sugar is around 110, and HbA1c=5.7; fasting insulin=3.1, triglycerides=91.) Recently, I tried a continuous glucose monitor for the first time, to see what I could learn about eating and exercise habits that affect my blood glucose. The experiment led me to some reading and thinking that was worthwhile, but the results themselves were disappointing, limited (first) by flaws in the technology and (second) by wide variability that I could not trace to any of the usual behavioral correlates.

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Why concern ourselves with blood sugar?

Insulin is generated in the pancreas after we eat, with a cascade of effects on the body. The primary short-term effect is to prevent glucose levels in the blood from getting too high, by notifying the liver of the need to pull glucose out of the blood and store energy as fat.

Loss of insulin sensitivity is a primary hallmark of human aging. Most of the known life extension strategies in lab animals have to do with insulin in one way or another. For example, the worm gene daf-2 is the worm’s only insulin receptor, and mutating (weakening) the daf-2 gene doubles the worm’s lifespan. Life extension benefits of exercise and caloric restriction are thought to work, at least in part, through the insulin metabolism.

But glucose is also dangerous, and as we get older we are poisoned by excess sugar in the blood. High blood sugar leads to [list from Mayo Clinic]

• Cardiovascular disease
• Nerve damage (neuropathy)
• Kidney damage (diabetic nephropathy) or kidney failure
• Damage to the blood vessels of the retina (diabetic retinopathy), potentially leading to blindness
• Clouding of the lens of your eye (cataract)
• Feet problems caused by damaged nerves or poor blood flow that can lead to serious skin infections, ulcerations, and in some severe cases, amputation
• Bone and joint problems
• Teeth and gum infections

So for long-term health, the name of the game is to keep blood sugar down with as little insulin as possible, hence preservation of insulin sensitivity is the target. Metformin is a well-studied drug for keeping blood sugar down without insulin. I have been taking it (irregularly) for the last several years, intermixed with berberine and Gynostemma (Chinese name: jiaogulan = 绞股蓝).

This reasoning plus direct evidence for life extension in rodents and indirect evidence of life extension in humans has led me to take metformin, though it is not without side-effects.

Long-term effects of metformin 

Metformin is a credible longevity drug, statistically associated with lower risk of cancer, heart disease and especially dementia in humans. Six years ago, this study laid the foundation for metformin as a longevity drug with the claim that people taking metformin had lower all-cause mortality, despite the fact that a population of type-2 diabetics was being compared to a healthier population. This finding inspired Nir Barzilai to raise support for the TAME study.

But metformin has its risks. A long-time contributor to this site, Dr Paul Rivas pointed me to evidence that metformin can interfere with exercise metabolism. Paul notes his personal experience with loss of peak performance while taking metformin. My own experience is consistent with this, though I have never done a rigorous A/B comparison. This study, demonstrating a small but consistent decrease in peak performance, appears to me to be well-designed and analyzed. A plausible mechanism is the interference of metformin with mitochondrial function [ref, ref].  This article claims that metformin suppresses synthesis of ATP, which is the reservoir of energy for immediate use in all cell types. Ben Miller has done the most direct and most recently relevant human experiments in this area and his findings suggest the intriguing possibility that metformin blocks exercise adaptations almost completely in about half of individuals, but not at all in the other half. (If you want to know which half you’re in, you’ll have to wait for next year’s study.)

For the majority of Westerners who exercise little or not at all, metformin may show reduction in long-term risk of age-related disease; but there is no data I know of on the subset of people who do vigorous exercise, comparing metformin to no metformin. Does metformin block the health effects of exercise? Rhonda Patrick cites credible references on this subject as fast as she can get the words out, and her conclusion is that exercise is a better anti-aging program than metformin, and you really can’t have both.

Do glucose-control herbs also blunt the benefits of exercise?

I wrote a few years ago listing botanical alternatives to metformin. Much less research has gone into these herbs, so we must think theoretically about interference with benefits of exercise.

Berberine works by a mechanism of action that overlaps metformin. Both metformin and berberine promote AMPK (which in turn promotes sugar burning). Both metformin and berberine inhibit mitochondrial Complex I (slowing the conversion of sugar to usable energy). There is tentative experimental evidence that (unlike metformin) berberine does not inhibit adaptations to exercise [ref, ref, ref].

Gynostemma is a Chinese herb popularized by Life Extension Foundation in their proprietary compound called AMPK Activator. In animal models and in humans, Gynostemma suppresses blood sugar and blood cholesterol. Like metformin and berberine, it works through AMPK, which appears to be a good thing.  It is anti-inflammatory, and has a history in China as cancer therapy, supported by mouse and in vitro studies. In rodent studies, Gynostemma has a beneficial effect on strength and endurance [ref, ref, ref]. The one study I’ve found on human diabetes shows modest benefits after 12 weeks. The only counter-indication that I have seen is that it increases insulin release (in vitro), which I believe to be pro-aging.

Is it more important to suppress postprandial spikes or to depress fasting glucose levels? 

HbA1c is a standard blood test for diabetes. It is related to average blood glucose levels over the previous 90 days (= the half-life of hemoglobin in the blood). But the glycation of hemoglobin (as measured by A1c) happens predominantly during the brief glucose spikes, rather than the much longer periods of average glucose levels. So it might be fairer to say that A1c summarizes peak glucose events over a 90-day period. And we might guess that the long-term health risks of high blood sugar are similarly more sensitive to the peaks than to the average.

I believe that apoptosis is on a hair trigger as we age, and part of the reason for this is too much p53. This study links P53 activation to postprandial glucose spikes, rather than to high average glucose levels.  This study links deterioration in endothelial function (related to arterial disease) with glucose spikes. The same paper lists ROS and oxidative stress as additional risks.

For a long while, it has been established that high fasting blood sugar is associated with cardiovascular risk. Of course, there is also association with obesity and T2 diabetes, but for these, it is natural to think of fasting blood sugar as the result, rather than the cause.

Chris Kresser says the best indicator of metabolic health is blood glucose levels 2 hours after a meal. If you can bring your blood glucose down to normal within 2 hours after eating your insulin sensitivity is good. For me, unmedicated, it was 3 hours after dinner, but less than 2 hours after breakfast. Either berberine or metformin tamed the after dinner spikes within 2 hours.

Kresser claims that these guidelines from the American Diabetes Association are not strict enough, and that statistics show increased future risk of diabetes even for people in the ADA “normal” range. But he cites Petro Dobromylskyj, who makes an exception for anyone on a low-carb diet (how low isn’t specified). Paradoxically, low-carb diets are claimed to be healthy, even though they decrease insulin sensitivity. I have been unable to make sense of this.

Kresser emphasizes that all numbers should be interpreted in the context of a person’s other lifestyle and health indicators. In people who are active and not overweight, he is not inclined to worry about statistics in the “prediabetic” range. (I take comfort in this personally, and who can say if I’m fooling myself?) But I can learn something from the way my glucose stats respond to medications, eating and exercising, whether or not I believe the absolute levels are concerning.

Writing in Science Magazine last year, Charles Piller reviewed the ADA guidelines and found a consensus in the opposite direction — that they were probably too strict, and unnecessarily worrisome to a great many people. By ADA’s definition, 80 million Americans are “pre-diabetic”, which is 40% of the adult population. The conflict really is not over the statistics but the interpretation. You can say either “People with A1c levels above 6 are at increased risk of progressing to diabetes” or equally well, “Most people with A1c levels less than 6.4 will never develop diabetes.” Both statements are true.

As promised: my experience

The Freestyle Libre was very easy to use and set up. I followed the instructions and used a spring-loaded device to insert the monitor behind my biceps. It was painless. There’s a tiny wire that goes a few millimeters into the skin and an adhesive covering with a button containing the electronics.

The wearable button stores data for up to 8 hours. The other part of the kit is a reader that downloads data every time you bring the reader within an inch or two of the button. As long as you take a reading every 8 hours or less, you won’t lose any data. And you can do it as often as you like, to get real time feedback on your glucose state.

The wearable button ($45) is meant to last two weeks, and then it must be discarded. My insurance (Blue Cross Medicare Advantage) wouldn’t pay for it because I didn’t have a diagnosis of diabetes. I found this out only after several trips to the drug store, interspersed with phone calls to Blue Cross, where I got repeated assurances that it would be covered. The reader ($85) can be reused. Apparently, it doesn’t do anything that a cell phone app couldn’t do, but Abbott (parent company of Freestyle) has arranged it so that you can only use the cell phone app if you purchase the reader.

To analyze historic data, you can use capabilities built into the phone app, or plug the reader or cell phone into a computer, using a USB cable. The data is uploaded to a web site containing analysis tools and an option for creating a CSV file for more detailed manipulation in a spreadsheet. (The download button is not so easy to find, but I called Abbott’s tech support number, and connected without excessive wait time to a friendly and knowledgeable technician.)

My intention was to vary the glycemic content of my meals, my exercise schedule, eating and fasting schedule, and the medications I was taking (metformin and berberine) to learn what I could about glucose management. The first day I fasted, and I was concerned to see that all day my fasting glucose ranged between 110 and 120. (For reference: the standard healthy range for fasting glucose is 70-100. Below 70 is “hypoglycemia”. Above 100 is “pre-diabetes” and above 125 is “type 2 diabetes”.)

I ate a meal, and glucose shot up to 179 before bedtime, only gradually coming back down during the night. As it turned out, 179 was my high for the week.

The data is cut off after 10 days, though the monitor is supposed to have a lifetime of 14, because it fell off my arm. I looked for patterns in my data, and was able to learn only four things:

• Glucose rose after a meal. (I didn’t get as far as being able to distinguish a meal with more carbs from a meal with more fiber or protein.)
• Glucose also rose, to a lesser extent, when I exercised.
• Taking metformin with a meal substantially reduced the glucose spike after the meal, and raising the glucose trough a few hours later. The range (stdev) but not the average glucose was affected.
• Taking berberine did not have this immediate effect.
• There was a strong downward trend over the 10 days. I interpreted this to mean that the monitor was gradually loosening in my skin, probably because I am a long-distance swimmer.

(In a long phone support session with an Abbott representative, they acknowledged the reality of my experience: that the monitor can loosen over time, resulting in readings that are anomalously low. They were happy to replace the monitor, and advised me against long periods of swimming. )

Unresolved

I was left wondering all the things I wanted to discover at the beginning of my experiment.

• What kinds of meals minimize the glucose spike? High fat? High fiber? High protein?
• Could exercise before or after the meal help tame the spike?
• Could I detect short- and long-term effects of metformin, berberine, and jiaogulan?

The thing that impressed me most was the natural variability of blood sugar, changing from hour to hour, uncorrelated with either food or exercise. I trust the body knows what it’s doing. “Le corps a ses raisons que la raison ne connait pas.”*

I hope to try the monitor for 2 weeks again when swimming season is over.

In the meantime, I am taking a modest, common-sense approach. I am going to leave out metformin but continue daily exercise and low doses of berberine and Gynostemma, lightening my evening meal and ending the day’s food 3 hours before bedtime.

Walking burns calories (pulls sugar from the blood) 3 to 5 times as fast as sitting, and walking after a meal feels like a natural and pleasant thing to do. My doctor recommends it. I’m going to try walking half an hour after breakfast and dinner, pending my next experiment with the CGM.

Many of us are still shell-shocked by the changes in our lives that have been imposed this spring. We’re reacting to each unexpected event as it comes. But to anyone who has stepped back to make sense of this web of contradictory messages that pour out of our newsfeeds, it is clear that the government agencies and corporate news media are slanting their message toward fear. I am particularly concerned when they do this at the expense of honesty. This is a moment for the scientific community to be engaging in spirited dialog among diverse voices. Only with open debate can we hope to shed light to guide the momentous public policy decisions that are being made, directing our culture and global economy into unexplored territory. But instead of robust debate, what I see is a monolithic message, and censorship of the few brave scientists who dissent from that message. I’m ashamed to say that the scientific community has been part of the problem.

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I’m writing here about two issues: 

(1) Numbers reported by CDC have been gamed to make it appear that America is in the second wave of a pandemic. Instead of reporting COVID deaths, they began reported COVID cases. Then they conflated recovered individuals (who test positive for antibodies) with current cases (who test positive for the active virus). No wonder numbers are rising!

(2) A new report featured prominently in Nature purports to show that lockdowns have stemmed the spread of the virus and have saved lives. The article is by the same team whose flawed models produced apocalyptic predictions last March that justified lockdowns in Europe and the US. The new computer model assumes from the start that the number of COVID deaths would have expanded exponentially from their March levels, and that social distancing is the only factor responsible for lower death rates. That is, it assumes exactly what it purports to prove. Where is accountability? Why is this perspective promoted in the world’s most prestigious journal, while reasonable doubts are swept aside?

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Part One—CDC reporting

The global death rate from COVID-19 is down to about 4,000 per day. It is not even among the top ten causes. COVID is lower than traffic deaths, lower than diarrhea. Even compared to other respiratory infections, COVID is now a minority.

In the US, daily COVID deaths peaked in April, and are now down to 1/10 the peak rate, at about 400/day. COVID is now the sixth leading cause of death in America, but it no longer registers as a bump in total mortality.

But the headlines claim we are in the midst of a “second wave”, based on reported numbers of cases.

Deaths from COVID are being over-reported. Hospitals are incentivized to diagnose COVID with Medicare reimbursement rates that are higher than other diseases, and guaranteed coverage from every major insurer. Doctors are being instructed to report COVID as a cause of death when no testing is done, and when chronic illnesses contributed to the outcome. And with all this, the number of deaths continues to fall, even as the reported number of cases is rising. Why is this?

In part, the lower fatality rate is real. Doctors are learning from experience how to treat the disease. More chloroquine and zinc, less intubation. Like all viruses, this one is evolving toward greater contagion and lower lethality. But the most important explanation is an artifact in the way COVID cases are being reported. Before May 18, the “case count” was based on tests for the live virus, and counted only sick people. Then the definition was changed to count both people who tested positive for the virus and for antibodies to the virus. The latter group is mostly people who have recovered from COVID, or who developed antibodies with exposure. As the number of recovered patients increases, of course the rate of positive tests will increase.

Part Two—Models that “prove” lockdown has saved lives

In the past, Neil Ferguson’s group at Imperial College of London has produced scary computer models that overestimated the epidemics of Mad Cow Disease, Avian Flu, Swine Flu, and the 2003 SARS outbreak. In March, his group’s computer model was justification for England, Europe and America to shut down economies, prevent people talking and meeting, prohibit concerts and theater and church and every kind of public gathering, throw tens of millions of people out of work, deny the rights to freedom of assembly that are fundamental to democratic governance. His manuscript was not even peer reviewed, but only posted on a university server. Even before its details and assumptions were made known, the integrity of the model was assailed by other experts, including Stephen Eubank (UVA Biocomplexity Institute) and Yaneer Bar-Yam (New England Complex Systems Inst). After details of the assumptions were revealed at the end of April, the model was widely scorned by real experts (e.g. Andrew Gelman) and self-appointed pundits (Elon Musk).

I have enough experience with computer models to know that results are often highly leveraged with respect to details of the input. Sensitivity analysis is essential for interpreting results, but is almost never done. Too often, the output is reported without the qualification that small changes to the input produce very different results.

Against this background, the high-profile publication in Nature of Ferguson’s recent work is suspicious. I would have thought he had no credibility left among serious modelers of epidemiology, but I have ceased to be surprised when politics trumps competence for access to the most prestigious publication venues.

The Ferguson Article Vindicating Lockdown

They analyze spread of COVID in 11 Eurpoean countries this Spring, averaging over different countries but not contrasting the different local strategies. They take death counts as surrogate for case counts because reports of case counts are even more unreliable than death counts. But (one of several crucial failures) they don’t apply a time lag between death counts and case counts.

They take as input for each country the dates on which each of three different isolation strategies was implemented. They assume that the virus would have spread exponentially but for these measures, and credit the isolation measures with the entire difference between reported death rates and the theoretical exponential curve.

They conclude that Europe has dodged a bullet, that less than 4% of people had been infected, and by implication the lockdown has saved the other 96%. They imply but don’t state explicitly that there would have been about 4 million deaths in Europe instead of ~150,000 reported when the paper was written.

It is obvious that lockdown and social isolation slow the spread of the disease, but not obvious that they affect the eventual reach of the disease. Thus it is an open question whether the public policy prevented or only delayed deaths from COVID. This question can be addressed most directly by comparing regions that were locked down with regions that remained open. Instead of doing this, the Ferguson group lumped all regions together and compared their results with an unrealistic scenario in which the exponential curve would have expanded to infect every susceptible person in Europe.

Two schools of thought

There are fundamentally two hypotheses about the epidemiological events of this spring: Either the number of people exposed has been high and the fatality rate low, or else the number of people exposed has been low and the fatality rate higher. People in the first camp argue that the exposed population is over 50% in Europe and America, approaching or exceeding herd immunity, and the population death rate is in the range 0.0005. In the second camp, people estimate the population exposure about ten times lower (5%) and the fatality rate correspondingly higher (0.005).

The story told by people in the first camp is that social distancing slowed but did not prevent transmission of the disease through the population. By now, the presence of the virus is waning because people in many places have already been exposed.

The story of Ferguson and others in the second camp is that social distancing actually stopped spread of the virus, so that most people in Europe and American have never been exposed. It follows that if we ease restrictions, there is another wave of infections ahead, potentially 20 times larger than the first wave.

The deep flaw of the recent Ferguson paper is that his team does not consider the first scenario at all. Built into their model, they assume that population level immunity is negligible, and the only thing that has slowed spread of the virus has been social distancing. This is where they put the rabbit in the hat.

If they had considered the alternative hypothesis, how would it have compared?

To choose between the two hypotheses, we might compare a region before and after lockdown, or we might compare regions that locked down with regions that didn’t.

In a preprint response to Ferguson, Homburg and Kuhbandner do a good job with the first approach. They take Ferguson to task for not considering the immunity that spreads through the population along with the disease. They show that exponential expansion had already slowed in England before the effect of the lockdown on mortality data could have been felt.

Lockdown went into effect in Britain on March 23. If lockdown had a benefit, it would be in preventing new cases, and its effect on the death rate would show up about 23 days later (April 14), because 23 days is the median time to fatality for those patients who die of COVID. In the graph, we see that the death rate had already leveled off by April 14.

On this log graph, an exponential increase would appear as a straight line sloping upward. It’s clear that the exponential expansion phase ended long before the lockdown could have had any effect. Not only weren’t the numbers expanding exponentially, but the death rate had already started to decline before April 14, when the effect of lockdown was expected to kick in. The authors state they performed the same analysis for 10 other countries in the Ferguson study with similar results, though they show the graph for Great Britain alone.

“We demonstrate that the United Kingdom’s lockdown was both superfluous and ineffective.”
— [Homburg and Kuhbandner]

Here in the US, there was a natural experiment when people emerged into the streets to protest racism and police brutality at the end of May. Social distancing in this environment has been impossible. Allowing for a 23-day lag, we should have seen a surge in US mortality starting mid-June. In the plot below, there appears to be a leveling off of the death rate since mid-June, but no new disaster. This alone is strong evidence that US has substantial herd immunity, and that most of the population has already been exposed to the virus.

A second way to distinguish between the two hypotheses is to compare regions that locked down with regions that didn’t. One of their 11 European countries was Sweden, where the economy was kept open and quarantine was limited to people who were symptomatic with COVID. It is a glaring defect in the Nature paper that Sweden is lumped in with the other ten countries when it should have been contrasted. In fact, the mortality curve for Sweden was typical for the other ten countries, even as commercial and cultural institutions in Sweden continued normal operations. Sweden has had a higher death rate than Austria, Germany, France, and Denmark, but lower than Belgium, Italy, Spain, or UK. There is no evidence that Sweden’s COVID mortality was higher for having bucked the trend to remain open, but some indication that Germany and Austria had particularly effective containment policies.

We can ask the same question of the different states in the USA. Comparing death rates from COVID in the 42 states that locked down with 8 states that did not lock down, this article finds that the death rates in locked down states were 4 times higher. (Caveat: there was no correction for urban vs rural or for demographic differences.) The author concludes, “With the evidence coming in that the lockdowns were neither economically nor medically effective, it is going to be increasingly difficult for lockdown partisans to marshal the evidence to convince the public that isolating people, destroying businesses, and destroying social institutions was worth it.”

I’ve prepared a comparison of all states ranked by COVID mortality which you can view here.

The Politics of COVID

In 1933, Roosevelt told America we had nothing to fear but fear itself. It is common for government leaders to dispel panic because they know that a nation can better thrive when people feel confident and secure. Even G.W. Bush responded to the terror attacks of 9/11 by telling the American people, “keep shopping.” On the other side, despots sow fear in their subjects when they want to consolidate autocratic power, and when they want to stir up fervor for war.

It is clear from messaging in the corporate media that the COVID pandemic is being hyped to create more fear than is warranted.

• The fatality rate was vastly overestimated initially, and even now is probably overestimated at 0.002 to 0.005
• Doctors were told to report deaths from COVID without proof that COVID was the cause
• Reimbursement incentives for hospitals to diagnose COVID
• Repeated warnings of a second wave, etc, which has not materialized.
• Suppression of tests for well-studied, cheap treatments (chloroquine) while jumping into large-scale tests of vaccines that have not yet been tested on animals.
• No mention of vitamin D, which is a simple, cheap, and effective way people can lower their risk. [ref, ref, ref]. Our own CDC is silent, while the British equivalent agency actively discourages vitamin D for COVID prevention.
• The biggest scandal of all is that lockdown has been authorized in the US and elsewhere based on hypothetical safety benefits with no consideration of costs. Our health is affected by our communities, our cultural lives, our social lives, and our livelihoods. [Yale epidemiologist David Katz politely makes this point.]

Shamefully, the scientific community has been complicit in the campaign of fear. A handful of courageous doctors and epidemiologists have been outspoken. In addition to Katz, John Ioannidis and Knut Wittkowski are best known to me. But the most trusted journals continue to publish articles that are based on politics rather than sound science.

Who is benefiting from the international panic? Who is behind the media campaign and the distortion of science, and what is their intention?

I invite people who are more politically astute than I to speculate on these questions.

Animal experiments demonstrating the anti-aging effects of exchanging young blood plasma for old have been prominent in the last two months. Several groups are saying it’s time to translate their findings into human trials. But I’ve recently learned that others have been doing this for several years. What can we learn from their results to guide the next steps in experimentation?

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I had never heard of Grifols, the Spanish pharmaceutical company that is the world’s largest supplier of albumin. Since 2005, Grifols has been quietly funding world leaders in plasma exchange research in humans. Albutein® is their brand-name solution of human albumin.

Last month, the first results of the Grifol’s AMBAR trial were released. (AMBAR stands for Alzheimer’s Modulation By Albumin Replacement). It was a much larger-scale phase 2.5 trial, with 496 subjects recruited from sites in Spain and USA, and treated for 14 months. A single treatment consisted of removing 2.5 to 3 litres of blood (more than half the body’s inventory) and replacing it with Albutein. Patients began with 6 weekly treatments, and thereafter there were 12 monthly smaller plasma replacements (0.7 litres), again with Albutein.

Subjects were evaluated with two standard measures, one of cognitive ability and the other of ability to function independently. Most subjects got worse over the year, as AD is a progressive disease. But treated subjects progressed less than half as fast as sham-treated controls. There was enough variation among individuals that even this strong difference in averages was only marginally statistically significant.

Subjects were categorized as “mild” to “moderate” in their cognitive loss. “Moderate” subjects responded a little better than “mild”, within statistical limits.

In the Conboy paper which I recently reviewed, albumin was considered to be just a passive replacement of proteins that every mammal needs. Albumin was replaced in the blood because when harmful signaling proteins were diluted out of the blood, albumin was removed along with it. The body needs the albumin, while the protein signals were doing damage. Henced they replaced the albumin.

But in AMBAR, albumin is considered an active part of the therapy.

[P]lasma albumin from AD patients is more glycated and nitrotyrosinated than plasma from healthy subjects, reducing its ability to inhibit Aβ aggregation Grifols theorized that replacing AD patients’ albumin with therapeutic-grade albumin should overcome this problem. Further, therapeutic-grade albumin should more effectively bind plasma Aβ and sequester it than plasma albumin from AD patients. Albumin may protect neurons by additional mechanisms, including anti-oxidant and anti-inflammatory activities.  [review, referencing  this primary source].

In one branch of the AMBAR program, ¼ of subjects also received intravenous immunoglobulin (IVIG). This consists of antibodies which identify challenges to which the immune system can respond. Grifols has a proprietary IG product called Flebogamma®. The AMBAR trial was unable to detect a benefit from IVIG.

Plasma exchange has a long history for treatment of auto-immune disorders. Some of the diseases of old age are related to autoimmunity (e.g., diabetes, arthritis, chronic inflammation). Older persons have a higher generalized autoimmunity, but a lower incidence of explicitly autoimmune diseases. Presumably, there are antibodies to self that accumulate in the bloodstream with age, and in recent years this has been related to leaky gut disorders. It makes sense to me that blood dilution would be a downstream or stop-gap treatment for autoimmunity, but that better approaches would be directed at the source of the offending antibodies.

Dobri Kiprov was a co-author of the Conboys’ plasma dilution paper. Kiprov’s clinic has been a site in the AMBAR trials, with experience in plasma exchange going back 20 years. Kripov has studied plasma exchange for a variety of diseases. In these treatments, a patient’s blood is removed and separated. The patient’s own red and white blood are returned to him, but his plasma is replace with saline, albumin, and possibly other ingredients. When I spoke to him, he described work which is soon to be published in Alzheimer’s and Dementia involving a proprietary added ingredient in these plasma transfusions. Benefits last at least 6 months, he said, which suggests that there is some epigenetic re-programming of the cellular sources of blood constituents.

Kiprov claims that patients who receive frozen blood plasma for a variety of reasons have fewer adverse reactions when they receive plasma from young donors (18-24) compared to middle-aged donors (35-45). He has seen patients’ immune systems improve, and arthritis symptoms decrease. He’s eager to see formal trials proceed for these conditions (but someone has to fund them).

The bottom line

As a treatment for AD, these results are not impressive. Patients were already quite disabled, and the results were essentially to prolong their end-of-life institutional existence. There are no effective drugs for AD, so compared to any pharmaceutical, AMBAR looks good. But compare these results to Bredesen’s RECODE program, which aims to improve cognition, and in some cases has returned people to productivity from a non-functional state. RECODE works better the earlier you start it, whereas preliminary results suggests that AMBAR is more effective in late stages.

Inflammation is a driver of all the diseases of old age. Pro-inflammatory signals (cytokines) in the blood were among the elements diluted by AMBAR, and it may be that reduction in inflammation fully accounts for the program’s successes.

As a proof of principle, the results are quite informative. A benefit was demonstrated from plasma exchange in humans for the first time. Subjects did not become dramatically younger, despite much more dilution than in the Conboy mouse experiments (reviewed in this space earlier this month). They suggest that simple dilution as pioneered by the Conboys in mice might be effective in slowing senescence but not reducing biological age.

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Two plasma exchange doctors were kind enough to help me with this column. I’m grateful to David Haase (TX) and Dobri Kiprov (CA) for offering background and providing direction to my readings.

It’s hardly newsworthy that medical science is distorted by money. But last week, a case arose that is so blatant, so extreme, and so suspiciously criminal that it should become a rallying point for all of us interested in reform. It involves the two best-respected medical journals in the world, and a finding that immediately affected the lives of thousands of patients around the globe. Two papers purported to be derived from a large, worldwide database, but they were quietly withdrawn when the data was requested by outside reviewers, and none could be produced. Where is the outrage? Where is the passion for reform?

Hydroxychloroquine is a cheap, out-of-patent drug that literally millions of travelers have been using for 65 years for prevention of malaria. It is also taken on a daily basis by hundreds of thousands of lupus patients. Its safety profile and side-effects are well established. Front-line doctors in Wuhan told us early that, in combination with zinc, it was the most effective COVID treatment they knew. It had previously been used with success during the SARS epidemic of 2003. European doctors reported anecdotal success with chloroquine/zinc, and it became standard treatment in France, the Netherlands, and elsewhere [review]. There were about 70 ongoing clinical trials before the two articles appeared.

HCQ has been discouraged by Anthony Fauci and segments of the American medical establishment, and I have wondered if they were compromised by their investments. Fauci is associated, ideologically and financially, with vaccines. The primary competitor for HCQ is Remdesivir, belonging to Gilead Sciences, and selling for $1,000 per dose. Billions of dollars have already been invested in developing a COVID vaccine. That COVID seems to be treatable and that the pandemic is fading with the spring weather is welcome news for world health, but it is devastating for investors in Gilead, Moderna, AstraZeneca, and 20 other companies that are racing to produce a COVID vaccine.

Last month, the two most prestigious medical journals in the world reported large studies by prominent researchers, based on a large COVID data set from Asia, Europe, and America. The lead author is from Harvard’s Brigham and Women’s teaching hospital. Here is the Lancet article, claiming that hydroxychloroquine is worse than useless. The data appear to show that people treated with HCQ are dying at 3 times the rate of other, similar patients. Here is the New England Journal article, which analyzes comorbidities but does not mention HCQ.

The Lancet paper had been duly peer-reviewed and rushed into print by editors. But seasoned researchers in the field immediately smelled that something must be wrong. How could this huge database of patients exist, crossing four continents and going back to the earliest days of the virus, when no one thought the records would be valuable? How could comparable conditions be established in hospitals from Capetown to Beijing to New York? And how could a drug in use for 65 years have such powerful lethal side-effects that no one had previously identified?

Questioned and challenged to produce the data behind the study, the authors quickly retracted the paper and refused further comment.

“Dr. Desai declined a request from The Times to be put in contact with a hospital or health care facility that provided its data to Surgisphere. He did not respond to inquiries after the retractions.” NYTimes

Nirav Desai is a physician and researcher from Surgisphere, a small Chicago company that claimed to have compiled the impressive database. Both retracted studies were led by Mandeep R. Mehra, a widely published and highly regarded professor of medicine at Harvard, who may end up being the fall guy for this scandal.

But no one is investigating Surgisphere as the source of a criminal fraud. No one is holding the Lancet journal or its editors or reviewers to account. Certainly no one is questioning the broad system funding and publishing the medical research on which the practice of Western medicine is based. To their credit, Science Magazine published this article, hinting at a scandal and beginning to ask the right questions.

This is happening at a time when the medical establishment is making the largest demands ever on our beliefs and our behaviors. We are locked down based on the computer simulation of a compromised researcher, who also did not document the basis of his computation, and whose predictions have proved spectacularly inflated. Why did we trust him, when he had cried wolf twice previously (Ebola, Avian flu)? The liberal-intellectual press and the science journals speak with a unified voice. denouncing anyone who questions vaccines as ‘anti-science’. Every article in Wikipedia and every Google search is plastered with a message that tells us to trust the CDC. The head of Youtube goes on the air to explain why anyone who disagrees with the WHO must have their videos removed.

The largest of the studies evaluating HCQ were discontinued after the Lancet article raised the probability that the studies might be putting lives of experimental subjects at risk. Now they are being re-started, but a fresh scandal has arisen. Dr Meryl Nass has investigated details of the “Soldarity” and “Recovery” trials. She reports that these trials plan to use dosages that are at least 4 times larger than necessary, dosages that have been found to be unsafe in the past, in fact fatal to a few percent of sensitive patients. She does not mention that the trials are leaving out zinc supplementation, which doctors everywhere report to be an essential part of the treatment protocol. The studies have indirect ties to vaccine manufacturers, through the WHO and through the Gates Foundation.

It appears on its face that these trials are designed to fail, and will kill experimental subjects on the way to “proving” that HCQ is an ineffective treatment. These suspicions can only be amplified by an announcement today from FDA that chloroquine cannot be used for COVID cases. This intrusion into physician autonomy is unprecedented. For as long as FDA has existed, its policy has been to permit physicians to freely prescribe drugs off-label for any condition where the individual physician feels it might be useful.

The institutions in which Americans and Europeans have entrusted their health have betrayed our trust. There are narrow implications for the future of HCQ and treatment of COVID, and then there are broader implications about the need for overhauling the profit incentives in medical research.

Narrow perspective

For those of who dare to look beyond our own noses, a concerted campaign to discredit a good, cheap treatment for COVID is a hint that might help us make sense of the bizarre global events of the last five months. This is a real virus, a real pandemic, but it is being exploited for a political agenda far larger than the effects of the disease itself.

• Why have death rates been consistently overestimated in public reports?
• Why have hospitals been incentivized to over-report COVID deaths, and to treat patients with ventilators that don’t seem to be helping?
• Why has CDC failed to recommend simple, inexpensive prevention measures (vitamin D, zinc, immune-enhancing herbs, special measures for nursing homes)?
• Why have our government agencies encouraged shortcutting of safety tests in “warp-speed” vaccine development, while discrediting simple, cheap treatments (intravenous vitamin C, chloroquine/zinc, Artemisia) that work in other countries?
• Why has COVID become cause for bailouts of the financial sector that have little to do with the disease, while working families and small businesses have been forced into bankruptcy?

Many geneticists, including two Nobel laureates, cite evidence that COVID seems to be man-made, the product of genetic engineering (excellent technical summary). But this idea is off the table for discussion, censored by both the scientific community and by the mainstream press (original article, sanitized rewrite). Could it be that the same powerful forces benefiting from the lockdown and social control have power to censor both the scientific establishment and the popular press? These may seem wild speculations, but perhaps they are justified by wild events.

The rules we are asked to follow have been maximally destructive to our economy, our institutions, and our culture, while providing far less life-saving benefit than simpler strategies. Maybe the cultural and social isolation were intended to serve a different purpose than the protection of public health.

Broad perspective

“Two major study retractions in one month have left researchers wondering if the peer review process is broken.” NYTimes

The Times calls them “big blunders” but this is far too charitable. A big blunder is when you publish an article without noticing that a plus sign is really a minus. But when you fail to notice that the database of patient cases you are analyzing doesn’t exist, that is a fraud and not a blunder.

We like to think that medical practice is following medical research as the tail follows the dog. But look at the two economies—$3.5 trillion per year in health care revenues in America vs an NSF budget of only $8 billion spread over every kind of science. It may be too much to expect the dog to wag the tail when the tail is 500 times larger than the dog.

Meanwhile, medical consumers are voting with their feet. People flock to dietary supplements ($35 billion/year), acupuncturists, chiropractors, and alternative healers. 40% of Americans think that non-standard approaches to cancer are more likely to cure them than chemotherapy and radiation, while most of the purveyors of those alternatives have been driven overseas by aggressive FDA “oversight”.

If the medical science establishment wishes to regain the trust of the American public, they will have to demonstrate that the health of individual patients weighs more heavily in their calculations than the profit motive.

There is great promise in 2020 that we might be able to make our bodies young without having to explicitly repair molecular damage, but just by changing the signaling environment.

Do we need to add signals that say “young” or remove signals that say “old”?

Does infusion of biochemical signals from young blood plasma rejuvenate tissues of an old animal? Or are there dissolved signal proteins in old animals that must be removed?

For a decade, Irena and Mike Conboy have been telling us removal of bad actors is more important. But just last month, Harold Katcher reported spectacular success by infusing a plasma fraction while taking away nothing. Then, last week, the Conboys came back with a demonstration of the rejuvenating power of simple dilution. [Link to their new paper]

Dilution procedure

They simply replaced half of the blood plasma in 2-year-old mice with a saline solution containing 5% albumin. What is albumin? Blood plasma is chock full of dissolved proteins, about 10% by weight. About half of these are termed albumin. Albumin is the generic portion. It doesn’t change through the lifetime. It doesn’t carry information by itself. But albumin transports nutrients and minerals through the body.

The Conboys took care to show that albumin has no rejuvenation power on its own, and had nothing to do with their experimental results. Rather, they had to replenish albumin in diluting blood, because the animals would be sickened if half their albumin were removed. Replacing the albumin in a transfusion is akin to replacing the volume of water or maintaining the salinity.

In preparation for this experiment, the Conboys have invested years in miniaturizing the technology for blood transfusions, so that mice can be subjected to the same procedures that are commonplace in human hospitals.

Dose-Response

The Conboy lab replaced 50% of mouse blood plasma. They got spectacular results with a single treatment, based on a lucky guess. They have not yet experimented with 30% or 70%. They don’t know yet how long the treatment will last and how often it needs to be repeated.

Evidence of rejuvenation

As with previous papers from the Conboy lab, the group focused on repair and stem cell activity as evidence of a more youthful state. Three separate tissue samples were taken from liver, muscle, and brain.

“Muscle repair was improved, fibrosis was attenuated, and inhibition of myogenic proliferation was switched to enhancement; liver adiposity and fibrosis were reduced; and hippocampal neurogenesis was increased.”

• They measured nerve growth factors in the brain, and detected a more robust response, typical of young mice
• They lacerated muscles and showed repair rates typical of much younger animals
• They examined microscope slides of liver tissue, and showed that it is less fatty and striated than is typical of older mice

What’s missing? They did not test any measures of physical or cognitive performance at the level of the organism.

• Evidence of behavioral changes (learning and memory, endurance, strength)
• Inflammatory markers
• Blood lipids
• Methylation clock (Horvath, UCLA) or proteomic clock (Lehallier, Stanford)

Some of this is planned for future research. Mike and Irina plan to submit tissue samples for analysis by the Horvath mouse methylation clock.

Clock?

I am a committed enthusiast for the methylation and proteomic clocks that are the best surrogates we have for aging. These technologies can tell us whether anti-aging interventions have been effective without having to wait for animals (or humans) to die before reporting results. But the Conboys still regard these technologies as unproven, and they bristle at the word “clock”.  The closest they come is to catalog the entire proteome of treated mice, comparing it to untreated young and old mice.

Multi-dimensional t-SNE analyses and Heatmapping of these data revealed that the ONBE proteome became significantly different from OO and regained some similarities to the YY proteome. Supplementary Figure 4 confirms the statistical significance of this comparative proteomics through Power Analysis, and shows the YY vs. OO Heatmap, where the age-specific differences are less pronounced than those between OO vs. ONBE, again emphasizing the robust effect of NBE on the molecular composition of the systemic milieu.

Translation: As controls, they had mice that underwent plasma exchange with mice of similar age. YY were young, positive controls, and OO were old, negative controls. Treated mice were ONBE=”Old—Neutral Blood Exchange”. Rather than relying on “clock” algorithms that compute an age from the proteome, they compared the entire proteomes of test animals with those of old and young animals, and foud that they resembled the young animals more closely.

Aging and epigenetics

I was an early advocate of the theory that aging is driven primarily by changes in epigenetics. Other proponents include Johnson, Rando, and Horvath. This theory is now mainstream, though its acceptance is far from universal. (The main reason people have difficulty with the idea is the question, “why would the body evolve to destroy itself?” I present a comprehensive answer in my popular book and my academic book.)

On the face of it, the new Conboy result is powerful evidence for the epigenetic theory. They have shown that there are proteins in the blood that actively retard growth and healing. Remove half theses proteins and the animals are able to grow youthful tissues and to heal better. The obvious conclusion is that, with age, there are signaling changes in the blood that weaken the animal and inhibit repair.

There are, however, other ways to interpret the changes. Aubrey de Grey has said (personal communication)

“When everything in the blood except the cells and the albumin is replaced by water, the body will definitely respond by synthesising and secreting everything that it detects a shortage of, whereas the bad stuff will not be so rapidly replaced, since by and large it was only there in the first place as a result of impaired excretion/degradation.”

The Conboys don’t embrace the programmed aging perspective, but neither is their understanding of what they see the same as Aubrey’s. The way Irina explained it to me is that the age of the biological of the body is simply a measure of how much damage has accumulated, but that cycles of epigenetics and catalysis are self-reinforcing.

“Epigenetic, mRNA, and protein are steps of one process, regulation of gene expression. And none of these steps are permanent they all actively and constantly respond to cell environment — tissue and systemic milieu…With aging there is a drift which is re-calibrated by a number of rejuvenation approaches…When an auto-inductive age-elevated ligand is diluted, it cannot activate its own receptor and induce its own mRNA, so ligand levels diminish to their younger states for prolonged time.”

The Conboys theorize that these harmful proteins are part of a positive feedback loop, in other words, a cycle that is self-sustaining

epigenetic state ⇒ gene expression ⇒ translation to circulating proteins ⇒ feedback that alters the epigenetic state

With age, the body has slipped into a dysfunctional, self-sustaining cycle, and with the shock of disruption, they are able to nudge it back into a more robust and youthful cycle, also self-sustaining.

For me, the surprising thing in Irina’s account is that there is no hysteresis in this system. The reprogramming responds to changes in the blood levels of signals within minutes. It is difficult for such a system to be homeostatic. I wonder how that can be. Life is all about homeostasis, and intuitively, we all imagine that negative feedback loops are more common than positive feedback loops. (Negative feedback loops lead to homeostasis; positive feedback loops lead to runaway, exponential change.)

Is there a clock somewhere? Is the brain special?

In the Conboy view, signals in the blood are emitted from all over the body, and not especially from the hypothalamus. If brain tissue responds in a seemingly exceptional way to proteins in the blood, it is because of selective passage of those proteins by the blood-brain barrier.

The authors remind us that in past parabiosis experiments (where blood is exchanged between old and young mice), the brain tissue of the young mice grew older but brains of the old mice didn’t get younger. This was an indication that brain aging is caused by affirmative action of “bad actors” in the plasma, and that these are able to penetrate the blood-brain barrier. This observation was part of the inspiration for the current experiments.

The corresponding procedure in humans is already FDA approved

Therapeutic Plasma Exchange (TPE) is a well-established medical procedure, and has already been performed on an experimental basis by co-author Dobri Kiprov. There is anecotal history of suggestive results, which I will write about in my next post.

Comparison with Katcher’s Elixir

This week’s announcement from the Conboys and last month’s preprint from Katcher/Horvath come from the same school of thought: that aging is coordinated through the body by signal molecules in the blood. Both demonstrated dramatic rejuvenation in rodents based on a short-term intervention, and both have plans for commercialization and human trials to begin ASAP.

So it is curious that in other ways, the programs of Katcher and Conboy are so different.

• While both approaches are rooted in differing compositions of blood plasma between young and old, the Conboys focus exclusively on removing species that are inhibiting youthful regeneration, while Katcher’s approach is to add back the proteins that formerly kept the animal young.
• The Conboys have fully disclosed all aspects of their experimental protocol, whereas the content of Katcher’s elixir remains a trade secret.
• Katcher is on the fringe of academic research, and the Conboys’ lab is at one of the premier academic institutions in the world.
• Katcher is a year further along, having experimented with different dosages and timings. Neither Katcher nor the Conboy lab has yet demonstrated life extension.
• The Conboys demonstrate rejuvenation with wound healing, tissue structure, and renewal of nerve growth. Katcher’s claim is based on physiology (especially inflammation), cognitive performance, and methylation clock algorithms.
• In fact, Katcher regards restoration of youthful methylation patterns as the best evidence he could offer for rejuvenation (I agree), while the Conboys are reserving judgment about the importance of methylation, and bristle at the language of a methylation “clock”.
• Katcher understands the effects of plasma transfusions in terms of a broad theory (which I support). Aging is an epigenetic program, governed and enforced by a “clock” that operates via a feedback loop between circulating proteins that govern gene expression and gene expression that generate those proteins. The Conboys recognize they are working this feedback loop (their Fig 6) but they resist the theory that it is the essential cause of aging.

My guess is that a combination of their two approaches will be necessary for full remediation of aging, and that a combination of their resources, credibility, theoretical foundations, and contacts would be a transformative event for medical science, for biotech industry, and for biological theory. It is my fervent hope that Katcher and the Conboys might work together.

If you eschew hyperbole and hang in for the long haul, maintaining a discipline of understatement in the midst of a flashy neon world, you may be offered a modicum of credence when you make an extraordinary announcement. No one is entitled to this courtesy twice. If the news that you trumpet to the moon does not pan out, your readers will be justified in discounting everything you say thereafter.  

Here goes.

I believe major rejuvenation has been achieved in a mammal, using a relatively benign intervention that shows promise of scaling up to humans. I’m going to stake my reputation on it.

In the race to effect substantial, system-wide rejuvenation, Harold Katcher is a dark horse. He has the right academic credentials and a solid history of research. In fact, in earlier life he was part of a team that discovered the breast cancer gene, brca1. I asked Harold for a biographical sketch, and have printed it in a box at the end of this posting.

But Katcher has no research grants or university lab or venture capital funding, no team of grad students mining databases and screening chemicals in the back room.

One thing Katcher has going for him is the correct theory. Most of the explosion in aging research (and virtually all the venture capital startups) are looking to treat aging at the cellular level. Their paradigm is that aging is an accumulation of molecular damage, and they see their job as engineering of appropriate repair mechanisms.

The truth, as Katcher understands it, is that, to a large extent, aging is coordinated system-wide via signal molecules in the blood. It was our common realization of this vision that brought Katcher and me together more than a decade ago. Katcher briefly describes his 2009 epiphany below. It was the source of his 2013 essay (it took a few years to get it into print) on the significance of parabiosis experiments for the future of aging science.

Of course, Katcher was not the only one to get the message about the power of signal molecules in the blood to reprogram tissues to a younger state throughout the body. The problem is that there are thousands of constituents represented in tiny concentrations in blood plasma, but conveying messages that cells read. Which of these are responsible for aging? A small number of labs, including the Conboys at Berkeley, Amy Wager at Harvard, and Tony Wyss-Coray at Stanford have been searching for the answer over the last decade and more.

Katcher has been able to guess or intuit or experimentally determine the answer to this question. With seed funding from Akshay Sanghavi, he set up a lab in Mumbai two years ago, and tried to rejuvenate old lab rats, using a fraction extracted from the blood of younger rats. The first round of experiments were encouraging, published in this space a year ago. He obtained the next round of funding from a reader of this blog, and had enough rats to titrate dosages experimentally, and to see if treated rats who aged again over time could be re-treated successfully.

There is a hole in this story that awaits the resolution of intellectual property rights. Katcher and Sanghvi have not applied for patents and have not yet found a suitable partner to provide financing for human trials. They have not revealed any details of the treatment, besides the fact that it is in four intravenous doses, and that it is derived from a fraction of blood plasma. Katcher thinks that the molecules involved will not be difficult to manufacture, so that when a product is eventually commercialized, it will not require extraction from the blood of live subjects, rodent or human.

We’re still waiting for longevity curves of these treated rats. In the meantime, the best available surrogate measure of age comes from methylation clocks, as developed by Steve Horvath at UCLA, and other scientists as well. Crucially, Katcher found an ally in Horvath, who didn’t just test his rejuvenated rats, but did the needed statistical analysis to develop a set of six methylation clocks specialized to rats. FIve of the clocks are optimized for different tissues, and one is calibrated across species, so that it can measure age in humans as well as corresponding age in “rat years” (about 1/40 human year). The two-species clock was a significant innovation, a first bridge for translating results from an animal model into their probable equivalent in humans.

In a paper posted to BioRxiv on Friday, Katcher and Horvath report results of the methylation measurements in rejuvenated rats. “Crucially, plasma treatment of the old rats [109 weeks] reduced the epigenetic ages of blood, liver and heart by a very large and significant margin, to levels that are comparable with the young rats [30 weeks]….According to the final version of the epigenetic clocks, the average rejuvenation across four tissues was 54.2%. In other words, the treatment more than halved the epigenetic age.”

Besides the methylation clock, the paper presents evidence of rejuvenation by many other measures. For example:

• IL-6, a marker of inflammation, was restored to low youthful levels
• Glutathione (GSH), superoxide dismutase (SOD), and other anti-oxidants were restored to higher youthful levels
• In tests of cognitive function (Barnes maze), treated rats scored better than old rats, but not as well as young rats.
• Blood triglycerides were brought down to youthful levels
• HDL cholesterol rose to youthful levels
• Blood glucose fell toward youthful levels

A major question in blood plasma rejuvenation experiments has been how often the cure must be administered. Many of the components of blood plasma are short-lived, secreted into the blood and absorbed continuously throughout the day. The good news from Katcher’s results is that it seems only four injections are needed in order to achieve rejuvenation.

A second question which these experiments resolve is whether rejuvenation requires both adding and removing molecular species from the blood plasma. For example, pro-inflammatory cytokines are found in old blood at much higher levels. Irina and Mike Conboy, people who I regard as most credible in the field, have said that removing bad actors from the blood is probably more important than restoring youthful levels of beneficial signals. They were grad students at Stanford 15 years ago, when the modern wave of parabiosis science was initiated, and have pursued the subject continuously ever since. Katcher’s experiments have achieved their results only by adding blood components, not by removing or even neutralizing others. This suggests that he has found the necessary formula for re-programming epigenetics, so that lower levels of the bad actors occur as a result. But it remains to be seen whether even better results can be obtained if some plasma constituents are removed.

A question that remains unresolved concerns the location and mechanism of the aging clock. I have been undecided over the years between two models:

1. There is a central aging clock, perhaps in the hypothalamus, which keeps its own time and transmits signals throughout the body that coordinate methylation state of dispersed tissues
2. Information about epigenetic age is dispersed through the body, and the body’s clock is a feedback loop that is continually updating methylation age locally in response to signals received about the methylation age globally.

There is a suggestion in the data that the hypothalamus may be more difficult to rejuvenate than other tissues. Does it play a more important role than other tissues in coordinating the age of the entire body? Horvath (personal communication) counsels caution in drawing this inference until measurements are corroborated and more experiments are done.

The Bottom Line

These results bring together three threads that have been gaining credibility over the last decade. Mutually reinforcing, the three have a strength that none of them could offer separately.

• The root cause of aging is epigenetic progression = changes in gene expression over a lifetime.
• Methylation patterns in nuclear DNA are not merely a marker of aging, but its primary source. Thus aging can be reversed by reprogramming DNA methylation.
• Information about the body’s age state is transmitted system-wide via signal molecules in the blood. Locally, tissues respond to these signals and adopt a young or an old cellular phenotype as they are directed.

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Harold Katcher, Biographical Sketch So, you might consider me a late bloomer.  While I have thousands of citations in the literature, with publications ranging from the discovery of the human ‘breast cancer gene’, to protein structure, bacteriology, biotechnology, bioinformatics, and biochemistry, there was no center or direction to my work as I had given up my personal goal of solving/curing aging when I learned that ‘wear and tear’ was the cause of it.  Yet something happened in year 1985 when I was in California working with Michael Waterman and Temple Smith (fathers of bioinformatics) that is inexplicable: I found myself in Intensive Care with a tube inserted into my trachea and the knowledge that I might not live.   And then I had a dream: I dreamed that somehow in the far future (and on another world), I was being feted for ‘bringing immortality to mankind’. Clearly, I survived that incident (started with an infected tooth).    I lived a wonderful life – becoming a computer programmer (which I loved), leaving that for the University of Maryland’s Asian division, becoming a full professor and then the Academic Director for the Sciences, in Tokyo, Japan.  By the time I left Japan in 2004, (my daughter Sasha was a fourth-grader, (yonensei), in the Japanese school system), I was teaching for U of M online – somewhat retired, and looking forwards to writing computer programs for fun and profit. Yet I never ever forgot that dream. It was clearly impossible; I had no lab – and really, there was no way to repair all damaged cells – it’d be like sweeping back the ocean. And then, in 2009, I read an old paper from 2005, a paper written by the Conboys, (Michael and Irina), Tom Rando and others, coming from Irv Weisman’s lab, that completely changed my life; that showed me that everything I believed about aging was wrong – that aging occurred at the organismic level, not at the cellular level and could be reversed. Well, the rest of the story is about persistence and the blessed intervention of Akshay Sanghvi who too saw there was another way and provided the structural, monetary, and emotional support (and some good ideas) that had me start a new career at age 72 in Mumbai, India.  I feel twenty years younger than I did three years ago, I guess that’s another hint about aging. Now the ‘mystical’ dream?  It wouldn’t be the first time in history that that happened – take that as a datum.

Last week, I outlined genetic evidence that the present pandemic had its origin in a laboratory. In the segment below, I tell two stories of how this might have occurred, one as leak from an American lab and one from a Chinese lab. I was surprised to find that there is a history of collaborative work between American and Chinese bioweapons labs on exactly the kind of Coronavirus responsible for the current epidemic, in which a protein that binds with ACE2 was artificially spliced onto the genome of the bat virus ancestor.

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After I posted this, Yuri Deigin, who is a frequent commenter on this page, posted this article on Medium. It is great background reading for anyone who wants to understand more deeply how viruses get inside cells, how they manipulate the cell chemistry, and how SARS-CoV2 is related to its ancestors. Spoiler: The virus seems to combine the backbone from a known bat virus genome with a spike protein (the part that binds to a target cell) from a pangolin virus. These two animals share no common habitat, so it is possible but unlikely that they could have combined in nature. Newly added to the SARS-CoV2 binding protein is a precisely placed insert that acts as an instruction to the cell, “cut here” making the virus a great deal more infective.

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Here’s a puzzle worthy of Sherlock Holmes’s story of the dog who didn’t bark. The Chinese are eagerly promoting narratives about the SARS-CoV2 virus originating in America, while the Americans assume that, of course, the virus evolved where the first cases were identified, in Wuhan, China. But both sides agree, SARS-CoV2 had a natural origin, and had nothing to do with genetic engineering or breeding in a laboratory.  As we shall see below there are credible links to both the Wuhan Institute of Virology and to the US bioweapons HQ at Fort Detrick, MD and a university lab at Chapel Hill.

Why wouldn’t these two propaganda machines be eager to demonize one another by promoting stories about leaks from the other’s weapons lab? If one but not the other of these spin-control states were too eagerly dismissing the bioweapons meme, I know what I would suspect. But what does it mean that both these rivals are suppressing all discussion of the issue?

Two stories—they can’t both be true

There is a plausible story about a Chinese origin for COVID. There is another story, in my view equally plausible, about an American origin. The two stories are not easily reconciled, and that suggests to me that I have been suckered by disinformation, one way or the other. Some part of what I am about to report is not true. More confusion: there are hints that fall short of being a “story” about coordinated bioweapons development between China and the US. I like to think of it as a real-life mystery novel. I ask you, dear readers, to help figure out who is telling the truth, who is lying, and whodunnit. America? China? A cooperation between the two?

Or maybe it was Professor Pangolin*.

Outline of the Chinese story:

• China’s main bioweapons research facility is right there in Wuhan, where the first patients were identified.
• The laboratory has published papers in which they were doing closely-related research. [2009, 2013, 2015]
• In fact, we know that they were harvesting bats from SW China, extracting SARS virus from them, genetically modifying the virus to enable “gain-of-fuinction” to infect human cells in vitro. (see 2015 link above)
• Even the human ACE2 receptor used by SARS-CoV2 is mentioned in published articles from the Wuhan research facility.  (see 2015 link above)
• Security at Chinese facilities is reported to be more lax than at comparable American facilities.
• The Chinese government has reportedly silenced discussion of bioweapons research at the Wuhan facility, and of a possible leak. (Here’s an early complaint about lack of transparency. I offer this video as a source because it documents well the Chinese suppression of discussion of the bioweapon question. In other respects, the video is misleading, blaming the Chinese government as if the American government were not equally culpable.)

Outline of the American story:

• The world’s most extensive bioweapons facility is at Fort Detrick, MD.
• The Fort Detrick lab was closed by CDC for undisclosed security leaks last August.
• I personally had a persistent cough for more than 2 months beginning in November. Other (American) friends have told me of similar unusual respiratory infections last fall and early in the winter. CDC reported in early December that “The U.S. winter flu season is off to its earliest start in more than 15 years.” [NBC news] Could this have been early cases of COVID-19, undetected as such?
• The SF Chronicle reports today that an American who had not traveled recently died of COVID Feb 6, so he must have contracted the disease early January, a month earlier than the previous “first” American case which arrived in Seattle from Wuhan in February. It may be that we have not found even earlier examples because we have not been looking.
• Late last October, there were military games, a kind of Olympic competition for the world’s armies, held in Wuhan. This was 6 weeks before the first COVID-19 cases were recognized by the Chinese, but only 3 weeks before the first Chinese case identified with hindsight.
• Some of the American military personnel attending the Games in Wuhan were stationed in Maryland and had recently frequented Fort Detrick.
• The entire American team, 300 strong, stayed at the Oriental Hotel, just a half mile from the infamous open-air market which has been blamed for the outbreak.
• According to one report, the entire first cluster of 42 COVID patients were employees and their families of the Oriental Hotel.
• Genetic diversity analysis can be used to estimate how long a virus has been mutating away from Patient Zero. One such analysis is consistent with an origin last fall.
  
• Maximum Likelihood Analysis for the evolutionary tree of the SARS-CoV2 virus worldwide indicates that the “A” strain from which all other strains were derived is present only in America and Australia. The predominant strain in China is “B”. [ScienceDaily]
• According to ABC News, “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.” The Defense Intelligence Agency had already identified it as a coronavirus in November. But the “first 41 patients” in the Lancet article were admitted to Wuhan hospitals in December. Please stop and consider the implications of the fact that the US Dept of Defense knew that there was a dangerous coronavirus and knew it was in Wuhan before the first reported COVID patients. Pepe Escobar conjectures.
• The only countries in the world where all known strains of COVID have been identified are China and USA.

Reports of bioweapon collaboration between USA and China

Exhibit A for this hypothesis is this Nature Medicine article from 2015. It describes a collaboration between University of North Carolina scientists and the Wuhan Virology Laboratory, funded jointly by American agencies, including Fauci’s NIAID, and the Chinese National Science Foundation. They describe modifying the bat coronavirus, the very one that is most closely related to the SARS-CoV2 pandemic. They use genetic engineering to add an ability to bind to the human (and mouse) ACE2 receptor, the very same modification that makes SARS-CoV2 so contagious.

The nominal justification for such research is to understand how such recombinations might occur in nature, so that we might be better prepared to defend against them if such a recombination should happen to take place. The number of such recombinations that could conceivably take place is enormous. But this group was lucky to anticipate the exact virus and the exact modifications that would make it a problem five years later. They had a jump on the competition. “Our work suggests a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.” Prophetic. And the research took place in the Chinese city where the current pandemic was first recognized. Coincidental.

It is morally outrageous that such research should be proceeding. It has been against International Law since 1975 (based on a 1969 treaty), and explicitly outlawed in the US since 1989. “Whoever knowingly develops, produces, stockpiles, transfers, acquires, retains, or possesses any biological agent, toxin, or delivery  system for use as a weapon, or knowingly assists a foreign state or any organization to do so, shall be fined under this title or imprisoned for  life or any term of years, or both.” The law singles out research in gain-of-function engineering, as described in the Nature Medicine article.

Layered on my moral outrage is a head scratch: Why would a government agency steeped in secrecy publish such research? Even if we grant that their intent was not to produce a bioweapon but to learn about what might, at some future date, happen in nature, the fact remains that the paper contains explicit instructions that anyone with hostile intent might use to create a bioweapon.

Earlier in my career, I had security clearance as part of my research at Physical Sciences, Inc in the 1970s. I saw just enough of the Defense Department’s security system to extrapolate that the CLASSIFIED stamp was used liberally on any finding that might conceivably be used as part of a weapon system, even if the work described basic physics that had been well known for a century or more. Contrast this institutional paranoia with treatment of the Nature Medicine article, which is published freely, though it includes explicit instructions with which a competent but malevolent biochemist might produce an artificial pandemic.

What were the authors thinking when put such research out for the world to read? I have written to two of the authors to ask them.

• Luc Montagner, French national hero and Nobel laureate in medicine, worked in China for several years. He claims there is a cooperative bioweapons program between China and the West.
• Francis Boyle, professor of international law and world expert on bioweapons law, claims to have first-hand knowledge of cooperation in developing weapons between China and USA. He also says that the original SARS virus from 2003 was an American bioweapon, and that the high-security facility within Wuhan Virology Lab was set up to study it [interview transcript]
• Three Published papers on SARS-derived viruses that were authored by scientists at the Wuhan Institute of Virology list sponsorship by American funding agencies, including NIAID, which has been directed by Anthony Fauci for 35 years. [2009, 2013, 2015]
• Last summer, the National Microbiology Laboratory in Winnipeg abruptly cut off a Chinese-Canadian researcher’s access to her own laboratory. Details of the reasons were not disclosed. “A number of observers have speculated that case involves concerns about the improper transfer of intellectual property to China,” according to Science Magazine. What the Science article omits to say is that NML Winnipeg is Canada’s primary bioweapons laboratory.
• The chair of Harvard’s Chemistry Department is a specialist in the technology of microparticles. He has had long-standing contracts with the Wuhan University of Technology (not to be confused with the Virology Institute), and was recently dismissed by Harvard, where the Administration claimed to be ignorant until recently of his work with the Chinese university. [February news article from Nature] [EuroWeekly article] [Wall St Journal]

American work on bioweapons can be traced to Nazi scientists who had been experimenting with non-consenting human subjects, exempted from being charged as war criminals and imported to the US to continue their work under Operation Paperclip. The current wave of research sponsored not by the Defense Department but by civilian NIAID was begun in 2003, and protested widely in 2005.

More than 700 scientists sent a petition on Monday to the director of the National Institutes of Health protesting what they said was the shift of tens of millions of dollars in federal research money since 2001 away from pathogens that cause major public health problems to obscure germs the government fears might be used in a bioterrorist attack. [NYTimes]

Regardless of whether COVID-19 derived from a laboratory, let’s put an end to state-sponsored bioweapons research. It’s already illegal.

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The case for the Wet Market origin has gained popular acceptance despite evidence that is thin to nonexistent. Pictures like this one are used to appeal to our lizard brains. Of course something so disgusting must be a breeding ground for germs.

Here’s how we do it in America. Is it any less distasteful?

Yes, the way in which animals are killed for food is disgusting, and we don’t like to look at it. But does it have anything to do with the way viruses mutate and acquire new functions?

Standard evolutionary theory tells us that mutations are random. (I’ve been a critic of standard evolutionary theory, but for reasons that I think are not relevant to the present discussion.) Occasionally, a random mutation makes it possible for a virus to jump from one species to another. But these mutations are rare enough that we don’t expect them to occur simultaneously with three other gain-of-function mutations that make a virus both more lethal and more contagious. Computer models based on the full SARS-CoV2 genome have trouble accounting for all the differences from the bat genome in a sufficiently short time frame. The wet market hypothesis is a politically convenient fallback, without a proposed mechanism. The bats that harbor SARS viruses live 1,000 miles from Wuhan and are not sold in the local meat market at Wuhan.

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* The pangolin that has been proposed as an intermediate host is an endangered species. It cannot be sold legally in China, and the idea that there were underground pangolin vendors in the Wuhan wet market has not even been alleged, let alone researched. This Guardian article is appropriately skeptical. The Nature article which is the original source of the pangolin theory does not claim there were pangolins at the Wuhan market. A follow-up Nature article points to further weaknesses in the pangolin hypothesis, and clarifies that the pangolin virus genome is not closer than the bat virus to SARS-CoV2.