Tuesday, September 22, 2020

The Astonishing Connectome


Gray matter isn't the big story. Connection—the connectome—is the astonishing feature of the brain.



 We hear a good deal about the gray matter (the neurons) in the brain. They are often considered synonymous with thinking. For a long time, it was believed that the white matter did not do very much and its signals were generally excluded from brain mapping studies as noise. But that has all changed in recent years:

You might think that the brain is mostly gray matter, as it certainly looks that way, but in actuality there is more white matter in the brain. White matter is the infrastructure of the brain and includes the long nerve axons and their protective layer of fat, called myelin. Gray matter, on the other hand, is composed of the neurons themselves. Scientists have long thought that white matter didn’t play an active role in the brain, but new research has shown that this is untrue and that white matter actively affects both how the brain learns and how it dysfunctions.

From the little we understand about our hundred-billion neuron brains, connection is everything. Thus the Human Connectome Project (HCP), launched 2009, seeks to understand some of those connections better by surveying the brain imaging data from hundreds of people.

The challenge? The unthinkably large number of connections:

As of yet, scientists have only identified one connectome: that of a nematode (Caenorhabditis elegans). Its modest nervous system consists of 300 neurons. In the 1970s and 1980s, a team of researchers traced a map of its 7,000 interneural connections. The name for that map, as we mentioned before, is the connectome. Obviously, human beings are much more complex, with more than 100 billion neurons and 10 thousand times more connections.

The surprise? The brain is quite orderly, not the haphazard accumulations of aeons of evolution that the researchers expected:

LONDON’S STREETS ARE a mess. Roads bend sharply, end abruptly, and meet each other at unlikely angles. Intuitively, you might think that the cells of our brain are arranged in a similarly haphazard pattern, forming connections in random places and angles. But a new study suggests that our mental circuitry is more like Manhattan’s organised grid than London’s chaotic tangle. It consists of sheets of fibres that intersect at right angles, with no diagonals anywhere to be seen.

Van Wedeen from Massachusetts General Hospital, who led the study, says that his results came as a complete shock. “I was expecting it to be a pure mess,” he says. Instead, he found a regular criss-cross pattern like the interlocking fibres of a piece of cloth. …

Wedeen’s maps may not reveal all the details about the brain’s network, but it does show how that network is structured. “If you look at brain connections in an adult human, it’s really a massive puzzle how something so complex can emerge,” says Behrens. “If we can establish any sort of organisation, we get a clue about how these things grow. If it obeys some rules, you could start to work out how it follows those rules. You have something to hang onto.”

At Medical Daily,we learn more about the project itself:

The project comprises 36 investigators, including biologists, physicians, physicists, and computer scientists, at 11 institutions across the nation. The primary centers of research are USC’s Laboratory of Neuroimaging, Massachusetts General Hospital’s Martinos Center, Washington University’s Van Essen Lab, and the University of Minnesota’s Center for Magnetic Resonance Research.

The project was carried out in two phases. During Phase I, which spanned the years 2010 through 2012, research teams designed the project’s 16 major components. During Phase II, which ranged from 2012 through this past summer, the various scientists performed the actual work of gathering data. More importantly, however, during the most recent phase investigators made their datasets publicly available at regular intervals so that scientists around the world could begin to use them in their own projects.

But the surprise factor has not abated:

What’s been discovered so far?

Many surprises. Scientists have been amazed to see that, instead of chaos, the connecting fibers are organized into an orderly 3D grid, where axons run up and down and left and right, minus any diagonals or tangles. Science magazine compares the brain’s 3D layout to New York City, with its streets running in two directions and buildings’ elevators running up and down. Strangely, in flat areas of the grid, the fibers overlap at precise 90 degree angles and weave together much like a fabric, the scientists say.


While there is much more to learn—the project was described to MedicalDaily as “a 30,000-foot fly-by view”—new findings amount to teasing out the innumerable details of a fundamentally orderly structure. But trying to completely understand the brain would be like trying to completely understand New York City.

Help with understanding schizophrenia?

Because the brain is an unexpectedly orderly structure, close examination of the connectome can help medical researchers see what is going wrong when our brains don’t co-operate with us. For example, there is some evidence that schizophrenia has a basis in faulty brain connections:

Researchers have consistently found patterns of abnormally high or low connectivity in the brains of schizophrenic patients. So delusions, hallucinations, and depression-like symptoms might not be a result of one region acting strangely—they could instead arise from flawed communication among regions.

Brains of persons who suffer from schizophrenia also lack “small-worldness.” That’s the quality by which most brain nodes cluster into thickly connected modules in which one node is a hub that connects long range across the network. It’s somewhat like a local club where one member volunteers for the duty of communicating with the central organization and the local media. But what if communications are less frequent and more haphazard?

But while the healthy brain is a small-world network, the schizophrenic brain is measurably less so—it can still be organized into modules, but those modules aren’t as densely connected. If small-worldness helps the brain undertake a variety of processes effectively and efficiently, its lack in the schizophrenic brain could someday help to explain the disease’s symptoms.

By itself, that finding doesn’t point to a cure. But as knowledge of unexpected patterns accumulates, a clearer picture of the problem is forming. Down the road, that ever more precise picture will suggest possible treatments.

Materialism may keep us from important insights. Computational neuroscientist Sebastian Seung, a rising star in the study of the connectome (connectomics), announced at TED, “I am my connectome.” No, he isn’t his connectome or his brain either. Or his brain and body. The unexpected orderly structure of the brain suggests a bigger picture. And it is within that structure that answers will be found.

Monday, September 21, 2020

Millennial and Gen Z Holocaust survey spells doom for our democracy


Millennial and Gen Z Holocaust survey spells doom for our democracy


You’ll notice that the pollsters almost always ask the American people opinion questions — are you feeling like more of a donkey or an elephant these days? — to which there are no wrong answers. Because when they ask questions to which there are wrong answers, boy, do they get a lot of them.

This week we learned that 19 percent of young New Yorkers — millennials and Gen Z — believe Jews caused the Holocaust. Do these people also believe President Kennedy assassinated Dallas and that the Civil War was fought between the Crips and the Bloods? A shocking 58 percent of New York state adults between 18 and 39 could not cite the name of any concentration camp, death camp or ghetto.

I’m not sure why this survey of 1,000 Americans only went after people under 40, though. A thing young people have in common is that they have at least spent some time in school fairly recently. Old folks haven’t. Are the youngs really any dumber than the olds? Polls that don’t break out groups by age routinely find that Americans are so breathtakingly ill-informed it’s a wonder they can open a can of soda without leaving the tip of their index finger floating in their Diet Pepsi.

A survey in 2013 by the Public Religion Research Institute found that 27 percent of Americans think God helps determine the outcome of football games. (Obviously wrong: It’s Satan, hence the success of his nephew Bill Belichick). A 2012 survey by the National Science Foundation found that 26 percent of Americans believe the sun goes around the Earth instead of the other way around, which indicates people haven’t been keeping up with the newspapers since about 1532. Last year a YouGov survey found that 45 percent of Americans believe ghosts and demons exist, with 22 percent saying they “definitely” do. Republicans (54 percent) are especially likely to believe in demons, and 41 percent of women (as against 31 percent of men) have personally felt the presence of a demon or a ghost. Eighty-four percent of women believe in angels, as do 72 percent of men (Gallup, 2004). As for Democrats, 67 percent of them said (in a 2018 YouGov poll) that Russia “tampered with vote tallies in order to get Donald Trump elected.” There is no more evidence for this than there is for the existence of vampires.

survey last year found that the majority of residents in every state except Vermont would have failed a citizenship test, but then again Vermont keeps sending Bernie Sanders to the Senate, and people who vote for a guy who thinks Fidel Castro is a cool leader definitely flunk out as Americans.

Enlarge Image
Last year a YouGov survey found that 45 percent of Americans believe ghosts and demons exist, with 22 percent saying they “definitely” do.Alamy

It’s not just civics that people fail, though, it’s the conceptual basics of how government works. A 2009 Gallup poll found that 71 percent want to reduce the size of government spending, but don’t want to touch the stuff that makes up that spending (Social Security, Medicare and Medicaid). So what do people think is driving the budget deficit? “Waste.” It’s 50 percent of federal spending, according to that Gallup survey. Another poll the following year, by the World Public Opinion, found that Americans think we can fix the budget deficit by curbing “foreign aid,” which respondents believe constitutes 27 percent of federal spending. That figure is off by more than 26. Foreign aid is a tiny fraction of federal spending, well under 1 percent.

It’s obvious that young people are too dumb to vote. So are old people, women, Democrats, men, Republicans, Vermonters and non-Vermonters. When you ask yourself why democracy isn’t working, consider who is responsible for it. John Adams warned us about this when he said democracy couldn’t work if people weren’t paying attention: “A frequent recurrence to the fundamental principles of the Constitution, and a constant adherence to those of piety, justice, moderation, temperance, industry, and frugality, are absolutely necessary to preserve the advantages of liberty, and to maintain a free government,” Adams said, adding, “this crap carnival is gonna get outta hand if voters don’t know anything.” At least I feel he said that, and feelings must be at least as important as facts. That’s in the Ninth Amendment, I’m pretty sure.

Kyle Smith is critic-at-large at National Review.

Plastic eating microbes - evolution too rapid for Darwin


Plastic-Eating Microbes — “Rapid Evolution” May Not Be Darwinian at All

Evolution News @DiscoveryCSC

September 17, 2020, 2:01 PM


plastic in the ocean

Photo credit: tkremmel via Pixabay.

Environmental scientists warn frequently that the world is drowning in plastic. In addition to the plastic bottles that circle in gyres out at sea, synthetic microfibers from the laundry loads of millions of people each week are being found at coral reefs and in almost every bucket of sea water dredged up by marine biologists. According to Wired, “A single pair of jeans may release 56,000 microfibers per wash.” Run the numbers and multiply that by billions of people wearing blue jeans, and you glimpse the scope of the problem. Blue jean fibers have been found in the Arctic. Marine biologists are rightly concerned about the rapidly rising accumulation of plastics and synthetic fibers at sea, and the impacts these could have on sea turtles, fish, coral reefs, and the entire marine ecosystem.

Unexpected Good News

In this worrying context, the following should not at all appear to minimize the environmental crisis of plastic in the oceans. It is, however, interesting and unexpected. A team of scientists from Saudi Arabia wrote a paper for the biology preprint server bioRxiv recently with the intriguing title, “Rapid Evolution of Plastic-degrading Enzymes Prevalent in the Global Ocean.” They were surprised that plastic input (production by humans, some 150 teragrams of plastic waste) is not matching plastic output (measurements at sea). What could account for the mismatch? The team discovered that microbes are learning to eat plastic!

Estimates of marine plastic stocks, a major threat to marine life, are far lower than expected from exponentially-increasing litter inputs, suggesting important loss factors. These may involve microbial degradation, as the plastic-degrading polyethylene terephthalate enzyme (PETase) has been reported in marine microbial communities. An assessment of 416 metagenomes of planktonic communities across the global ocean identifies 68 oceanic PETase variants (oPETase) that evolved from ancestral enzymes degrading polycyclic aromatic hydrocarbons. Twenty oPETases show predicted efficiencies comparable to those of laboratory-optimized PETases, suggesting strong selective pressures directing the evolution of these enzymes. We found oPETases in 90.1% of samples across all oceans and depths, particularly abundant at 1,000 m depth, with a strong dominance of Pseudomonadales containing putative highly-efficient oPETase variants in the dark ocean. Enzymatic degradation may be removing plastic from the marine environment while providing a carbon source for bathypelagic microbial communities. [Emphasis added.]

They say that “99 percent of the plastic that entered the oceans cannot be accounted for.” Now while this “rapid evolution” sounds like good news, it raises a number of questions. How did multiple species of microbes independently “evolve” the ability to digest plastic? How did they do it so fast? Is it a case of Darwinian evolution? The authors have no reason to doubt it, since they refer to “selection pressures” pushing the microbes to evolve the oPETase enzymes, presumably for their selfish fitness. It just adventitiously provides ecological benefits (a carbon source) for deep microbial communities. 

The first case of a natural oPETase enzyme able to digest polyethylene, they note, was observed very recently.

Exponential growth in plastic production along with poor waste management practices have led to over 150 Tg plastic waste delivered to the ocean since 1950, where it harms marine life, from zooplankton to whales. Synthetic plastic polymers are derived from oil hydrocarbons and designed to be durable in the environment, being largely resistant to microbial degradation. However, a newly-evolved plastic-degrading enzyme, polyethylene terephthalate hydrolase (PETase), was recently discovered in a Japanese waste processing plant. This PETase was inferred to have evolved since 1970, when the polyethylene terephthalate polymer was introduced at industrial scale.

Evolution’s Edge

Whatever happened “evolved” very rapidly, not in the slow-and-gradual Darwinian way. Readers might recall the case of the “nylonase” enzyme that evolutionists used to tout Darwinian evolution, leading to a flurry of debates about it in these pages (e.g., see Ann Gauger, “Adaptation in Action Yields a Repurposed Enzyme”). Gauger agrees with Michael Behe that adaptation by mutation and selection can occur in limited cases where the number of required mutational steps is small (one or two), the number of trials is large, and each step yields a benefit. These kinds of changes fall within the “Edge of Evolution,” and are within the reach of chance, provide an existing enzyme exists and the modifications are minor. Examples of this can be found in Behe’s book, The Edge of Evolution. Clearly ocean microbes are abundant enough for many trials to take place.

In that same article, Gauger called attention to a discovery by Austin et al., published in 2018 in PNAS, of a PET enzyme that not only dissolved a type of polyesterase, but appeared to get more efficient at it over time. The functional change was minor; it involved a change to the size of a cleft in an existing enzyme to accommodate the new substrate. Further slight modifications to the cleft improved the efficiency since there was an immediate benefit to the microbe to digest the molecule at each step. The evolution of an enzyme de novo by a major chance event such as a frameshift mutation, she argued, is beyond the reach of chance, because enzymes must fold to work, and the space of possible folds is vanishingly small compared to the sequence space of random amino acid chains. The discovery, therefore, was within the edge of evolution and not a threat to intelligent design.

A Boon to the Biosphere

What’s new in the current study? The authors refer to the same paper by Austin et al. from 2018, adding that rapid adaptation of enzymes to digest plastics appears to be much more widespread than thought. Like Gauger, the authors see this is as a boon to the biosphere, providing hope that at least some of human plastic pollution can be ameliorated by microbes. Plastics are derived from hydrocarbons, after all, which microbes have been digesting from the beginning. Indeed, environmental scientists rushing to clean up catastrophic oil spills have been surprised to see how quickly microbes aided the effort.

In summary, the results obtained confirm that PETases are prevalent and abundant in the global ocean microbiome, where they must have evolved recently, following the mass production of polyethylene terephthalate [reference to Austin et al.]. PETases are widespread from the surface to the deep ocean, reaching a maximum abundance and prevalence at about 1,000 m, where Pseudomonas has evolved an efficient PETase. PETases were found in high abundance in some areas known to receive high loads of plastic waste, such as waters off the Indian subcontinent, Brazil, and Southern Africa. The phylogeny constructed also shows a putative pathway for the evolution of oPETases from ancestral genes involved in hydrocarbon degradation. The increased efficiency of the PETase along the phylogenetic sequences, along with the high abundance of bacteria containing efficient PETases, points at an ongoing evolutionary process driven by selection pressures providing advantages to bacteria able to use an increasingly available resource, plastic polymers, in the deep ocean, mainly where all other naturally-occurring organic substrates are extremely diluted. The widespread prevalence, 90.1%, of PETases across the ocean together with the acute carbon limitation in bathypelagic waters suggests that the ocean microbiome is rapidly evolving to degrade plastic waste, providing a hopeful, nature-based solutions for plastic already in the marine environment.

It’s great news. None of this should rationalize pollution, of course; humans need to be responsible stewards of the environment. It is encouraging, though, to see microbial helpers with complex molecular machines that can be repurposed or retooled to clean up some of our waste products without our help.

Another Possible Design Hypothesis

Evolutionists tend to look at life as a collection of selfish individuals competing for their own fitness. Individuals with the good fortune to hit on the right mutations outcompete others and become predominant. Lately, Darwinians have been noticing more cases of cooperation in nature. Advocates of intelligent design might look wider and see a global case of design here. Is it not remarkable how quickly these microbes adapted to help other organisms unrelated to them? Is more than chance involved?

Physiologists know of another case where apparent “random” mutations serve a greater good: the human adaptive immune system. In the B-cell genes, a programmed pathway randomly assembles gene segments, providing millions of combinations of antibodies, one or more of which matches an antigen. When successful, the resulting antibody fits the intruder and is rapidly cloned, stopping the infection. Is the winning antibody selfish? In a way, yes; it does benefit if the host lives, so that it doesn’t “go down with the ship” so to speak. But the complexity of the immune system looks more like a case of foresight, using a stochastic process to provide robustness for unpredictable threats. Perhaps in a wider context, the ocean ecosystem is like that. If it was designed for the good of biosphere, it would make sense that robustness is built in to resist catastrophic perturbations, providing ecological homeostasis. Given that de novo enzymes are beyond the reach of chance anyway, a designer would make them “evolvable” to a point — as in the antibody system — able to “find” a match for an unexpected intruder (like plastic) and reduce its harm. Biochemists already know that mutational hotspots exist in genomes, indicating that not all mutations are purely random. 

One clear difference is that the random antibody search occurs within a body, while microbes are solitary organisms. Still, microbes are good at signaling one another and sharing genetic information by horizontal gene transfer. How could the hypothesis of a guided search for plastic-digesting enzymes be tested? We’ll leave that up to a creative scientist intrigued with the thought. The rapid adaptation of existing complex molecular machines to handle unpredicted environmental threats, though, resulting in benefit to other organisms and homeostasis for the biosphere, looks too good for a blind, unguided, natural process.


Thursday, September 10, 2020

Widespread literacy at the end of the first temple

Police forensic handwriting expert teams up with archaeologists to make major discoveries about life during biblical times.

By Yakir Benzion, United With Israel

A handwriting expert from the Israel Police teamed up with archaeologists from Tel Aviv University in a groundbreaking new study announced Wednesday that showed far more people in the ancient Kingdom of Judah were literate than previously thought.

It appears to be the first time modern day police and researchers examining the biblical period around 600 BCE have worked together. Their results show that literacy was not the exclusive domain of a handful of royal scribes.

The police experts were brought in to examine ink-inscribed pottery shards from an excavation of the Tel Arad military post on the southern border of the kingdom of Judah that housed 20 to 30 soldiers. The archaeological dig is a well-known historic site with the remains of a fortified city that dates from the early Bronze Age.

The pottery shards were found in the 1960s and are from when the site was used by forces of the kingdom.

Researchers compared the algorithmic methods with forensic results and brought in forensic specialist Yana Gerber, who served for 27 years in the police’s forged documents unit. She to read the pottery fragments that were discovered at the Tel Arad site in the 1960s. Gerber found that the writings were by 12 different people, with varying degrees of certainty.

“This study was very exciting, perhaps the most exciting in my professional career,” said Gerber, who happens to have degree in classic archaeology and ancient Greek. “These are ancient Hebrew inscriptions … utilizing an alphabet that was previously unfamiliar to me.”

“I delved into the microscopic details of these inscriptions written by people from the First Temple period, from routine issues such as orders concerning the movement of soldiers and the supply of wine, oil and flour, through correspondence with neighboring fortresses, to orders that reached the Tel Arad fortress from the high ranks of the Judaite military system. I had the feeling that the time stood still and there was no gap of 2,600 years between the writers … and ourselves,” she said.

Gerber explained that “writing patterns are unique to each person and no two people write exactly alike.” She examined the microscopic details of each inscription down to the spacing between each letter.

“We were in for a big surprise: Yana identified more authors than our algorithms did,” Dr. Arie Shaus said.

The findings shed new light on Judaite society on the eve of the destruction of the First Temple – and on the setting of the compilation of biblical texts.

“We can conclude that there was a high level of literacy throughout the entire kingdom,” Shaus said, adding the fact that so many soldiers were literate points to “the existence of an appropriate educational system in Judah at the end of the First Temple period.”

“If in a remote place like Tel Arad there was, over a short period of time, a minimum of 12 authors of 18 inscriptions, out of the population of Judah which is estimated to have been no more than 120,000 people, it means that literacy was not the exclusive domain of a handful of royal scribes in Jerusalem,” said archeologist Prof. Israel Finkelstein.


Tuesday, September 8, 2020

When Politics Corrupts Science


When Politics Corrupts Science

by Jonathan Rosenblum
Mishpacha Magazine
September 2, 2020


When Politics Corrupts Science

By Yonoson Rosenblum | SEPTEMBER 2, 2020

How politics polluted our search for a COVID cure

Lawrence Krauss writes in the Wall Street Journal ("The Ideological Corruption of Science," July 12) how as a young physics professor at Yale, he and his colleagues in the hard sciences looked with bemusement at the dominant deconstructionism of the comparative literature department, which denied the existence of objective truth itself. That could never happen in the sciences, they assured themselves, except under a totalitarian regime such as Stalin's.

That idealized view of science as a separate realm devoted to the pursuit of truth and devoid of all political bias, Krauss notes, is no longer sustainable. In June, the American Physical Society, representing 55,000 physicists, declared a one-day "strike for black lives" to eradicate "systemic racism" in science. No evidence was adduced for the latter, other than the underrepresentation of blacks in the sciences.

One of the day's activities was to organize a protest campaign that resulted in the removal of physicist Stephen Hsu as vice president for research at Michigan State University. His crimes: his own studies in computational genomics to study how human genetics might be related to cognitive ability, and research by MSU psychology professors that did not support the narrative of racial bias in police shootings.

A distinguished Canadian chemist was censured by his university provost for calling for merit-based hiring, and the editors of a journal that accepted an article by him were suspended. Meanwhile, Francis Collins, the director of NIH, declared that he will no longer attend scientific conferences where white males, like him, predominate, regardless of their professional merit.

The pure objectivity of science is further clouded by fact that scientists are also human beings, prey to normal human temptations, such as the billions of dollars at stake in the race to produce medical cures or the quest for academic advancement. In 2005, Stanford professor Dr. John Iaonnidis published a paper titled "Why Most Published Research Findings are False," analyzing how bias creeps into study designs; it quickly became the most downloaded article in the history of the Public Library of Science. And in 2014, his group argued in the Journal of the American Medical Association that 35 percent of the results of controlled clinical trials could not be replicated upon reanalysis of their raw data.

THE POLITICALLY CHARGED field of climate science has been beset by data manipulation by leading research centers. And now there is evidence that politics has crept into the search for cures to COVID-19, argues Dr. Norman Doidge in a lengthy article in Tablet, "Hydroxychloroquine: A Morality Tale."

On March 21, President Trump tweeted that a combination of hydroxychloroquine (HCQ) and azithromycin might be a real "game changer" in treating COVID-19. Since that moment, the mainstream media, led by the Washington Post and CNN, has trumpeted every piece of evidence that HCQ is ineffective against COVID-19 and/or potentially dangerous, and downplayed or ignored all evidence to the contrary, in order to establish that Trump is a dangerous idiot. The MSM has, uniquely in the history of pandemics, engaged in what Doidge terms "unwishful thinking" — fervently hoping that a drug with the potential to save tens of thousands of lives, at a low cost, and without dangerous side effects, would turn out to be a bust.

Now, I would not recommend getting one's medical information from the president's Twitter feed. And his tweet was, in any event, premature. At most, there was, at the time of his tweet, tantalizing evidence of a "proof of concept." A study from China published in Nature, a respected science journal, showed that HCQ inhibits COVID-19 in cells in test tubes. As often happens in medicine, the idea of testing HCQ arose when front-line physicians in Wuhan noticed serendipitously that none of those admitted to hospital for COVID-19 were being treated with HCQ for diseases of the connective tissues.

In May, however, Dr. Didier Raoult, the most cited microbiologist in Europe, and a researcher with long experience repurposing existing generic drugs for new diseases, published a study of 1,061 COVID-19 patients given a combination of HCQ and azithromycin, which showed that over 90 percent showed a significant decrease in viral load over the course of treatment. Around that time, a survey of 6,000 front-line physicians in 30 countries showed that a large plurality — 37 percent — chose HCQ, out of 15 possible medicines, as the best response to a diagnosis of COVID-19.

But a non-peer-reviewed Veterans Administration study, a month after President Trump's tweet, showed a much higher percentage of patients treated with HCQ died than those who were not treated with it. The CNN headline trumpeted: "No Benefits; Higher Death Risks."

That VA study, however, proved highly flawed. It had ignored a crucial confounding factor: Those patients receiving HCQ in the study were much sicker than those who did not. At that time, HCQ was only approved for use as a desperation measure for seriously ill patients. Dr. Anthony Fauci was still recommending doing nothing for patients quarantined at home.

Yet no proponent of the HCQ-azithromycin combination had ever suggested it is anything more than an early intervention remedy to reduce the viral load and thus the severity of the disease. No one ever proposed it was a wonder drug that could repair failing organ systems at a late stage of the illness.

If the VA study was flawed, sister studies published in Lancet and the New England Journal of Medicine, two of the world's leading medical journals, and whose lead author was an eminent Harvard professor, constituted, according to Lancet editor Richard Horton, "monumental fraud." The studies, which purported to be based on data obtained from 96,000 patients on six continents, showed a 30 percent higher mortality rate for patients treated with HCQ and a greater danger of adverse cardiac events. But when 100 scientists around the world wrote to Lancet seeking the underlying data, the studies' authors immediately withdrew the two articles.

By labeling the articles a "monumental fraud," Lancet's editor sought to divert attention from the no less monumental failure of the peer-review process. Anyone with even a rudimentary knowledge of medical record-keeping, argues Doidge, would have been extremely skeptical that there existed comparable data sets from around the world. (Incidentally, the week before publishing the study, Lancet called editorially for Trump's defeat in November.)

DEEPLY FLAWED, EVEN FRAUDULENT, negative studies of HCQ do not establish either its efficacy or safety. But if I tested positive for COVID-19, I would not hesitate to take the HCQ-azithromycin combination.

HCQ has been in use for 65 years and has been given to at least one billion people to treat malaria and lupus. Physicians know what dosages are safe. Yale Medical School epidemiologist Dr. Harvey Risch terms the risk from proper doses, administered over a ten-day period, negligible — 9/100,000. In addition, it is cheap — sixty cents per tablet — and can be taken at home with water.

No doubt other early intervention drugs will be developed: No single drug is appropriate for every patient, and the possibility of better drugs is always there.

On July 1, the Henry Ford Medical Center in Detroit published in the International Journal of Infectious Diseases a study of patients in which the severity of illness was fully taken into account, which showed that HCQ reduced the mortality hazard (mortality over a fixed period of time) by 66 percent. Another study from Italy at the end of July found the same 66 percent reduced mortality rate.

And yet Margaret Sullivan, the Washington Post's media critic, opened her July 31 column (nearly a month after the Henry Ford study was published), ridiculing "fringe doctors spouting dangerous falsehoods about HCQ as a COVID-19 wonder cure." She was engaged in "unwishful thinking" that Donald Trump would prove right about something.

Doidge's enumeration of the multiple errors of experts and institutions we trusted to help us solve our most pressing scientific and medical problems includes "academics who increasingly see all human activities as 'political' power games, and so in good conscience can justify inserting their own politics into academic pursuits and reporting."

What, for instance, besides "implicit bias," at a minimum, can explain a presumably intelligent Harvard medical school professor making the following self-contradictory statements in one breath: HCQ is possibly dangerous, and we must save it for patients suffering from lupus or rheumatoid arthritis. Be wary of the experts.

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