How “Blind” Is a Double-Blind Trial When Volunteers Know the Side-Effects of the Vaccine?

(p. A8) George Washington University had vaccinated 129 people since its share of the trials started. I would be No. 130. Altogether, Moderna planned to enroll 30,000 people in its trial. Half would be given the actual vaccine and half would get the placebo. The protocol called for two shots spaced a month apart.

Finally, it was time for my injection, which is when things got a little weird.

“We have to leave you now, because this is a double-blind study and we are blinded,” Dr. Malkin said. “You’ve been randomized.”

Before I could ask her to translate what she had just said, she was gone, and two nurses arrived with my vaccine. The first nurse left, and the second nurse, Linda Witkin, asked whether I was right-handed or left-handed, then proceeded to inject my right arm.

“Which one are you giving me, the vaccine or the placebo?” I asked. She gave me a look, clearly not pleased with my questioning.

. . .

With the Moderna trial, the side effects reported so far have been typical: fever, chills, muscle and joint soreness.

. . .

The night after my shot, I took my temperature: 97.5. I felt under my arms for glandular swelling and felt only mild joint pain.

. . .

“You all gave me the placebo, didn’t you?” I demanded of Dr. Diemert on Wednesday, during my one-week checkup. “I cannot believe I went through all of this and got the placebo.”

He told me that the actual vaccine shot was more “viscous” than the placebo, which was why neither he nor Dr. Malkin could be in the room when I got it, because they would have been able to easily determine. And so he really couldn’t answer because the double-blind program is meant to protect doctors like him from patients like me. He said I wasn’t to badger Ms. Witkin, if I ever even saw her again. He also said that most people reacted more to the second shot than the first one.

I texted the peanut gallery, “I feel no different.”

For the full story, see:

Helene Cooper. “From Reporting on Ebola to Being a Volunteer in a Covid-19 Vaccine Trial.” The New York Times (Saturday, September 12, 2020): A8.

(Note: ellipses added.)

(Note: the online version of the story has the date Sep. 11, 2020, and has the title “Covering Ebola Didn’t Prepare Me for This: I Volunteered for the Covid-19 Vaccine Trial.”)

Leo Szilard Was “Ever-Resourceful”

I remember Milton Friedman, in an aside during his price theory class at Chicago, telling us that Leo Szilard used to walk up to him as he walked across campus, and articulately raise some issue in economics. Friedman was clearly impressed with the range of Szilard’s mind. My thought was ‘what’s the big deal about this guy Leo Szilard?’ Since then I have learned that he indeed was a big deal, at least for fans of the survival of Western civilization.

(p. 12) Fatefully, the Fermis sailed from Italy the same week that two Berlin radiochemists discovered nuclear fission.

That discovery was totally unexpected. In spring 1939, working at Columbia with the Hungarian physicist Leo Szilard, Fermi set out to answer a crucial question about it. Uranium atoms release a burst of energy when they fission, enough per atom to make a grain of sand visibly jump. But what then? Was there a way to combine those individual fissions, to turn a small burst into a mighty roar?

Szilard, ever-resourceful, acquired hundreds of pounds of black, greasy uranium-oxide powder from a Canadian mining corporation. Fermi and his students packed the powder into pipe-like tin cans and arranged them equally spaced in a circle within a large tank of water mixed with powdered manganese. At the center of the arrangement they placed a neutron source.

Neutrons from the source, slowed down by the water, would penetrate the uranium atoms in the cans and induce fissions. If the fissioning atoms released more neutrons, those “secondary” neutrons would irradiate the manganese. Measuring the radioactivity induced in the manganese would tell Fermi if the fissions were multiplying. If so, then a chain reaction might be possible, one bombarding neutron splitting a uranium atom and releasing two neutrons, those two splitting two other uranium atoms and releasing four, the four releasing eight, and so on in a geometric progression that could potentially produce vast amounts of energy for power — or for an atomic bomb. The experiment worked.

For the full review, see:

Richard Rhodes. “Quantifying the World.” The New York Times Book Review (Sunday, January 28, 2018): 12.

(Note: italics in original.)

(Note: the online version of the review has the date Jan. 24, 2018, and has the title “A Remarkable Man Among Remarkable Men and Women.”)

The book under review is:

Schwartz, David N. The Last Man Who Knew Everything: The Life and Times of Enrico Fermi, Father of the Nuclear Age. New York: Basic Books, 2017.

Infectious Disease Specialist Asks If Chinese Labs Did “Gain of Function” Research on Covid-19

(p. D7) For decades, Dr. Daniel R. Lucey, an infectious disease specialist at Georgetown University, has crisscrossed the globe to study epidemics and their origins. His attention now is on the Covid-19 pandemic, which first came to public notice late last year in Wuhan, China. Its exact beginnings are sufficiently clouded that the World Health Organization has begun a wide inquiry into its roots. The advance team is to leave for China this weekend, and Dr. Lucey has publicly encouraged the health agency to address what he considers eight top questions.

“It’s not a legitimate investigation if the team doesn’t ask them,” Dr. Lucey said in a recent interview. He cited public reports and scientific articles as starting points for his queries, adding that Beijing “has never come out and answered these questions.”

Clear answers, Dr. Lucey said, would cast light on how the deadly pathogen spread so rapidly and, perhaps, how exactly the outbreak began. China has not been forthcoming with information, . . .

. . .

The sixth and seventh questions go to whether the deadly pathogen leapt to humans from a laboratory. Although some intelligence analysts and scientists have entertained that scenario, no direct evidence has come to light suggesting that the coronavirus escaped from one of Wuhan’s labs.

Even so, given the wet market’s downgrading in the investigation, “It is important to address questions about any potential laboratory source of the virus, whether in Wuhan or elsewhere,” Dr. Lucey wrote in his blog post.

To that end, he urges the W.H.O. investigators to look for any signs of “gain of function” research — the deliberate enhancement of pathogens to make them more dangerous. The technique is highly contentious. Critics question its merits and warn that it could lead to catastrophic lab leaks. Proponents see it as a legitimate way to learn how viruses and other infectious organisms might evolve to infect and kill people, and thus help in devising new protections and precautions.

Debate over its wisdom erupted in 2011 after researchers announced success in making the highly lethal H5N1 strain of avian flu easily transmissible through the air between ferrets, at least in the laboratory.

In his blog, Dr. Lucey asks “what, if any,” gain-of-function studies were done on coronaviruses in Wuhan, elsewhere in China, or in collaboration with foreign laboratories.

“If done well scientifically, then this investigation should allay persistent concerns about the origin of this virus,” he wrote. “It could also help set an improved standard for investigating and stopping the awful viruses, and other pathogens, in the decades ahead.”

Finally, Dr. Lucey asks the W.H.O. team to learn more about China’s main influenza research lab, a high-security facility in Harbin, the capital of China’s northernmost province. In May [2020], he notes, a Chinese paper in the journal Science reported that two virus samples from Wuhan were studied there in great detail early this year, including in a variety of animals. It reported that cats and ferrets were highly susceptible to the pathogen; dogs were only mildly susceptible; and pigs, chickens and ducks were not susceptible at all.

For the full story, see:

William J. Broad. “Disease Detective Puts Forth Pointed Questions.” The New York Times (Tuesday, July 14, 2020): D7.

(Note: ellipses, and bracketed year, added.)

(Note: the online version of the story has the date July 8, 2020, and has the title “8 Questions From a Disease Detective on the Pandemic’s Origins.”)

The blog posting in which Dr. Lucey asked his eight key questions, is:

Lucey, Daniel R. “Covid-19: Covid: Eight Questions for the Who Team Going to China Next Week to Investigate Pandemic Origins.” Science Speaks: Global ID News blog, posted June 30, 2020.

Covid-19 More Severe If You Inherited a Neanderthal Gene on Chromosome 3

(p. A6) A stretch of DNA linked to Covid-19 was passed down from Neanderthals 60,000 years ago, according to a new study.

Scientists don’t yet know why this particular segment increases the risk of severe illness from the coronavirus. But the new findings, which were posted online on Friday [July 3, 2020] and have not yet been published in a scientific journal, show how some clues to modern health stem from ancient history.

. . .

Last month, researchers compared people in Italy and Spain who became very sick with Covid-19 to those who had only mild infections. They found two places in the genome associated with a greater risk. One is on Chromosome 9 and includes ABO, a gene that determines blood type. The other is the Neanderthal segment on Chromosome 3.

But these genetic findings are being rapidly updated as more people infected with the coronavirus are studied. Just last week, an international group of scientists called the Covid-19 Host Genetics Initiative released a new set of data downplaying the risk of blood type. “The jury is still out on ABO,” said Mark Daly, a geneticist at Harvard Medical School who is a member of the initiative.

The new data showed an even stronger link between the disease and the Chromosome 3 segment. People who carry two copies of the variant are three times more likely to suffer from severe illness than people who do not.

. . .

(p. A7) Tony Capra, a geneticist at Vanderbilt University who was not involved in the study, thought it was plausible that the Neanderthal chunk of DNA originally provided a benefit — perhaps even against other viruses. “But that was 40,000 years ago, and here we are now,” he said.

It’s possible that an immune response that worked against ancient viruses has ended up overreacting against the new coronavirus. People who develop severe cases of Covid-19 typically do so because their immune systems launch uncontrolled attacks that end up scarring their lungs and causing inflammation.

Dr. Paabo said the DNA segment may account in part for why people of Bangladeshi descent are dying at a high rate of Covid-19 in the United Kingdom.

For the full story, see:

Carl Zimmer. “String of Neanderthal Genes May Increase Risk of Severe Illness.” The New York Times (Monday, July 6, 2020, 2020): A6-A7.

(Note: ellipses, and bracketed date, added.)

(Note: the online version of the story was updated July 8, 2020, and has the title “DNA Inherited From Neanderthals May Increase Risk of Covid-19.”)

The unpublished paper, mentioned above, is:

Zeberg, Hugo, and Svante Pääbo. “The Major Genetic Risk Factor for Severe Covid-19 Is Inherited from Neandertals.” bioRxiv (posted July 3, 2020).

Wearing Even Homemade Masks Could Bring Covid-19 “Under Control”

(p. A6) Face masks are emerging as one of the most powerful weapons to fight the novel coronavirus, with growing evidence that facial coverings help prevent transmission—even if an infected wearer is in close contact with others.

Robert Redfield, director of the Centers for Disease Control and Prevention, said he believes the pandemic could be brought under control over the next four to eight weeks if “we could get everybody to wear a mask right now.” His comments, made Tuesday [July 14, 2020] with the Journal of the American Medical Association, followed an editorial he and others wrote there emphasizing “ample evidence” of asymptomatic spread and highlighting new studies showing how masks help reduce transmission.

. . .

Researchers from around the world have found wearing even a basic cloth face covering is more effective in reducing the spread of Covid-19 than wearing nothing at all. And many are now examining the possibility that masks might offer some personal protection from the virus, despite initial thinking that they mostly protect others.

. . .

“It was surprising in a good way to see that a homemade mask could do so well . . . that we don’t have to get a very fancy mask,” Dr. Verma said.

. . .

Wearing a mask is “one of the most urgent things we can do to get our country under control,” said Melanie Ott, director of the Gladstone Institute of Virology. “We’re all waiting for the vaccine, we’re waiting for therapeutics, and we’re not there.”

For the full story, see:

Caitlin McCabe. “Evidence Mounts That Masks Help Curb Infections.” The Wall Street Journal (Monday, July 19, 2020): A6.

(Note: ellipses between passages, and bracketed date, added. Ellipsis internal to passage, in original.)

(Note: the online version of the story has the date July 18, 2020, and has the title “Face Masks Really Do Matter. The Scientific Evidence Is Growing.”)

The editorial in the Journal of the American Medical Association (JAMA), mentioned above, is:

Brooks, John T., Jay C. Butler, and Robert R. Redfield. “Universal Masking to Prevent Sars-CoV-2 Transmission—the Time Is Now.” JAMA (published online, in advance of print, on July 14, 2020).

Some of the new evidence supporting the use of masks can be found in the following two academic articles:

Verma, Siddhartha, Manhar Dhanak, and John Frankenfield. “Visualizing the Effectiveness of Face Masks in Obstructing Respiratory Jets.” Physics of Fluids 32, no. 6 (published online on June 30, 2020).

Wang, Xiaowen, Enrico G. Ferro, Guohai Zhou, Dean Hashimoto, and Deepak L. Bhatt. “Association between Universal Masking in a Health Care System and Sars-Cov-2 Positivity among Health Care Workers.” JAMA (published online, in advance of print, on July 14, 2020).

If Aerosols Transmit Covid-19, It Is Even More Prudent to Wear Masks

(p. A1) The coronavirus is finding new victims worldwide, in bars and restaurants, offices, markets and casinos, giving rise to frightening clusters of infection that increasingly confirm what many scientists have been saying for months: The virus lingers in the air indoors, infecting those nearby.

If airborne transmission is a significant factor in the pandemic, especially in crowded spaces with poor ventilation, the consequences for containment will be significant. Masks may be needed indoors, even in socially-distant settings. Health care workers may need N95 masks that filter out even the smallest respiratory droplets as they care for coronavirus patients.

Ventilation systems in schools, nursing homes, residences and businesses may need to minimize recirculating air and add powerful new filters. Ultraviolet lights may be needed to kill viral particles floating in tiny droplets indoors.

The World Health Organization has long held that the coronavirus is spread primarily by large respiratory droplets that, once expelled by infected people in coughs and sneezes, fall quickly to the floor.

But in an open letter to the W.H.O., 239 scientists in 32 countries have outlined the evidence showing that smaller particles can infect people, and are calling for the agency to revise its recommendations. The researchers plan to publish their letter in a (p. A5) scientific journal this week.

. . .

Dr. Benedetta Allegranzi, the W.H.O.’s technical lead on infection control, said the evidence for the virus spreading by air was unconvincing.

. . .

But interviews with nearly 20 scientists — including a dozen W.H.O. consultants and several members of the committee that crafted the guidance — and internal emails paint a picture of an organization that, despite good intentions, is out of step with science.

Whether carried aloft by large droplets that zoom through the air after a sneeze, or by much smaller exhaled droplets that may glide the length of a room, these experts said, the coronavirus is borne through air and can infect people when inhaled. Continue reading “If Aerosols Transmit Covid-19, It Is Even More Prudent to Wear Masks”

Many Men “in the West” View Mask-Wearing to Be “a Sign of Weakness”

(p. A4) As countries begin to reopen their economies, face masks, an essential tool for slowing the spread of coronavirus, are struggling to gain acceptance in the West. One culprit: Governments and their scientific advisers.

Researchers and politicians who advocate simple cloth or paper masks as cheap and effective protection against the spread of Covid-19, say the early cacophony in official advice over their use—as well as deeper cultural factors—has hampered masks’ general adoption.

There is widespread scientific and medical consensus that face masks are a key part of the public policy response for tackling the pandemic. While only medical-grade N95 masks can filter tiny viral particles and prevent catching the virus, medical experts say even handmade or cheap surgical masks can block the droplets emitted by speaking, coughing and sneezing, making it harder for an infected wearer to spread the virus.

. . .

Male vanity . . . appears to be a powerful factor in rejecting masks. A study by Middlesex University London, U.K., and the Mathematical Sciences Research Institute in Berkeley, Calif., found that more men than women agreed that wearing a mask is “shameful, not cool, a sign of weakness, and a stigma.”

For the full story, see:

Bojan Pancevski, Jason Douglas. “Mask-Wearing Still Meets Resistance.” The Wall Street Journal (Monday, June 29, 2020): A4.

(Note: ellipses added.)

(Note: the online version of the story was updated June 29, 2020, and has the title “Masks Could Help Stop Coronavirus. So Why Are They Still Controversial?”)

“All You Need Is a Pair of Eyes”

(p. 1) MUNICH — Dr. Camilla Rothe was about to leave for dinner when the government laboratory called with the surprising test result. Positive. It was Jan. 27 [2020]. She had just discovered Germany’s first case of the new coronavirus.

But the diagnosis made no sense. Her patient, a businessman from a nearby auto parts company, could have been infected by only one person: a colleague visiting from China. And that colleague should not have been contagious.

The visitor had seemed perfectly healthy during her stay in Germany. No coughing or sneezing, no signs of fatigue or fever during two days of long meetings. She told colleagues that she had started feeling ill after the flight back to China. Days later, she tested positive for the coronavirus.

. . .

Dr. Rothe and her colleagues were among the first to warn the world. But even as evidence accumulated from other scientists, leading health officials expressed unwavering confidence that symptomless spreading was not important.

In the days and weeks to come, politicians, public health officials and rival academics disparaged or ignored the Munich team. Some actively worked to undermine the warnings at a crucial moment, as the disease was spreading unnoticed in French churches, Italian soccer stadiums and Austrian ski bars. A cruise ship, the Diamond Princess, would become a deadly harbinger of symptomless spreading. Continue reading ““All You Need Is a Pair of Eyes””

Mainstream Science, and Governments, Rejected Early Evidence of Symptomless Transmission

(p. 1) MUNICH — Dr. Camilla Rothe was about to leave for dinner when the government laboratory called with the surprising test result. Positive. It was Jan. 27 [2020]. She had just discovered Germany’s first case of the new coronavirus.

But the diagnosis made no sense. Her patient, a businessman from a nearby auto parts company, could have been infected by only one person: a colleague visiting from China. And that colleague should not have been contagious.

The visitor had seemed perfectly healthy during her stay in Germany. No coughing or sneezing, no signs of fatigue or fever during two days of long meetings. She told colleagues that she had started feeling ill after the flight back to China. Days later, she tested positive for the coronavirus.

. . .

Dr. Rothe and her colleagues were among the first to warn the world. But even as evidence accumulated from other scientists, leading health officials expressed unwavering confidence that symptomless spreading was not important.

In the days and weeks to come, politicians, public health officials and rival academics disparaged or ignored the Munich team. Some actively worked to undermine the warnings at a crucial moment, as the disease was spreading unnoticed in French churches, Italian soccer stadiums and Austrian ski bars. A cruise ship, the Diamond Princess, would become a deadly harbinger of symptomless spreading.

. . .

(p. 10) Though estimates vary, models using data from Hong Kong, Singapore and China suggest that 30 to 60 percent of spreading occurs when people have no symptoms.

. . .

After two lengthy phone calls with the woman, doctors at the Robert Koch Institute were convinced that she had simply failed to recognize her symptoms. They wrote to the editor of The New England Journal of Medicine, casting doubt on Dr. Rothe’s findings.

Editors there decided that the dispute amounted to hairsplitting. If it took a lengthy interview to identify symptoms, how could anyone be expected to do it in the real world?

“The question was whether she had something consistent with Covid-19 or that anyone would have recognized at the time was Covid-19,” said Dr. Eric Rubin, the journal’s editor.

“The answer seemed to be no.”

The journal did not publish the letter. But that would not be the end of it.

. . .

On Monday, Feb. 3, the journal Science published an article calling Dr. Rothe’s report “flawed.” Science reported that the Robert Koch Institute had written to the New England Journal to dispute her findings and correct an error.

. . .

Dr. Rothe’s report quickly became a symbol of rushed research. Scientists said she should have talked to the Chinese patient herself before publishing, and that the omission had undermined her team’s work. On Twitter, she and her colleagues were disparaged by scientists and armchair experts alike.

“It broke over us like a complete tsunami,” Dr. Hoelscher said.

. . .

If Dr. Rothe’s paper had implied that governments might need to do more against Covid-19, the pushback from the Robert Koch Institute was an implicit defense of the conventional thinking.

Sweden’s public health agency declared that Dr. Rothe’s report had contained major errors. The agency’s website said, unequivocally, that “there is no evidence that people are infectious during the incubation period” — an assertion that would remain online in some form for months.

French health officials, too, left no room for debate: “A person is contagious only when symptoms appear,” a government flyer read. “No symptoms = no risk of being contagious.”

. . .

(p. 11) Dr. Rothe, . . ., was shaken. She could not understand why much of the scientific establishment seemed eager to play down the risk.

“All you need is a pair of eyes,” she said. “You don’t need rocket-science virology.”

. . .

While public health officials hesitated, some doctors acted. At a conference in Seattle in mid-February, Jeffrey Shaman, a Columbia University professor, said his research suggested that Covid-19’s rapid spread could only be explained if there were infectious patients with unremarkable symptoms or no symptoms at all.

In the audience that day was Steven Chu, the Nobel-winning physicist and former U.S. energy secretary. “If left to its own devices, this disease will spread through the whole population,” he remembers Professor Shaman warning.

Afterward, Dr. Chu began insisting that healthy colleagues at his Stanford University laboratory wear masks. Doctors in Cambridge, England, concluded that asymptomatic transmission was a big source of infection and advised local health workers and patients to wear masks, well before the British government acknowledged the risk of silent spreaders.

The American authorities, faced with a shortage, actively discouraged the public from buying masks. “Seriously people — STOP BUYING MASKS!” Surgeon General Jerome M. Adams tweeted on Feb. 29.

. . .

By the end of the month [March 2020], the U.S. Centers for Disease Control announced it was rethinking its policy on masks. It concluded that up to 25 percent of patients might have no symptoms.

Since then, the C.D.C., governments around the world and, finally, the World Health Organization have recommended that people wear masks in public.

Still, the W.H.O. is sending confusing signals. Earlier this month, Dr. Van Kerkhove, the technical lead, repeated that transmission from asymptomatic patients was “very rare.” After an outcry from doctors, the agency said there had been a misunderstanding.

“In all honesty, we don’t have a clear picture on this yet,” Dr. Van Kerkhove said. She said she had been referring to a few studies showing limited transmission from asymptomatic patients.

Recent internet ads confused the matter even more. A Google search in mid-June for studies on asymptomatic transmission returned a W.H.O. advertisement titled: “People With No Symptoms — Rarely Spread Coronavirus.”

For the full story, see:

Matt Apuzzo, Selam Gebrekidan and David D. Kirkpatrick. “How the World Missed Covid’s Symptom-Free Carriers.” The New York Times, First Section (Sunday, June 28, 2020): 1 & 10-11.

(Note: ellipses, and bracketed dates, added.)

(Note: the online version of the story was updated June 27, 2020 and has the title “How the World Missed Covid-19’s Silent Spread.”)

Modern Physics Puts Elegance and Beauty Over Practical Value

(p. C9) Fundamental physics, says David Lindley, has lost its way. “I am ready to declare that research in this area, no matter its intellectual pedigree and exacting demands, is better thought of not as science but as philosophy.” His book aims to show how physics emerged out of airy speculation in the 17th century and, in recent years, has sunk back into it. “The Dream Universe” is not a book that will please philosophers, nor indeed historians, though physicists will find the argument a familiar one.

The problem, says its author, has been an excessive reliance on “mathematical elegance and beauty and whatnot” in fields such as “particle physics, the unification of gravity with quantum mechanics, and cosmology.” . . .

“The Higgs mechanism is no one’s idea of beautiful mathematics,” Mr. Lindley writes. “There’s nothing natural or inevitable about it, certainly nothing elegant. But it does its job.” The same applies, it appears, to one of the biggest breakthroughs in astronomy of recent decades, the confirmed reality of a previously theorized quantity driving universal expansion at an accelerating rate. “The beauty or otherwise of the cosmological constant is a non-issue,” the author writes. “It has practical value, and that’s what matters.”

. . .

The modern rot set in, he maintains, with theoreticians such as Hermann Weyl and Paul Dirac, who spoke of beauty as well as truth in physics. “Galileo would have been aghast,” Mr. Lindley writes. “He had no patience with mystical blather.”

. . .

Mr. Lindley complains that “the more physics pushes into the subatomic world, the more arcane the mathematical tools it draws upon.”

For the full review, see:

Andrew Crumey. “Pulling on a String.” The Wall Street Journal (Saturday, June 13, 2020): C9.

(Note: ellipses added.)

(Note: the online version of the review has the date June 12, 2020, and has the title “‘The Dream Universe’ Review: Pulling on a String.”)

The book under review, is:

Lindley, David. The Dream Universe: How Fundamental Physics Lost Its Way. New York: Doubleday, 2020.