Former FDA Research Virologist Suggests “Accelerated Approvals” of Covid-19 Vaccines

(p. A15) Covid-19 is a genuine emergency. Drug and biotech companies and academic institutions are doing their part, and regulators need to, as well. Having been a research virologist who spent 15 years at the FDA as the agency’s “biotechnology czar,” I have some suggestions:

. . .

• The FDA should issue “accelerated approvals” after testing in only limited populations. Additional subgroups—children, pregnant women, etc.—can be tested after approval. The accelerated approvals should be granted before the duration of postvaccination immunity has been ascertained. More-comprehensive trials can then confirm safety, efficacy and the length of time that immunity lasts.

• Establish reciprocity of approvals between the FDA and trusted counterparts in certain foreign countries (Australia, Canada, New Zealand, Japan, the Scandinavian countries and the European Medicines Agency), so that if one of them approves a vaccine, it is automatically approved in the other countries.

For the full commentary, see:

Henry I. Miller. “A Covid Vaccine: Faster, Please.” The Wall Street Journal (Thursday, April 23, 2020): A15.

(Note: ellipsis added.)

(Note: the online version of the commentary has the date April 22, 2020, and has the title “A Coronavirus Vaccine: Faster, Please.”)

Patients Die Due to Doctors Who Are “Busy Entering Health Care Data” Required by “Mandated Protocols”

(p. 18) Doctors today often complain of working in an occupational black hole in which patient encounters are compressed into smaller and smaller space and time. You can do a passable job in a 10-minute visit, they say, but it is impossible to appreciate the subtleties of patient care when you are rushing.

Enter “Slow Medicine: The Way to Healing,” a wonderful new memoir by Dr. Victoria Sweet.

. . .

One of the most compelling stories in the book is about Joey, a 3-year-old who is diagnosed with terminal lung disease after a near-drowning but against the odds makes it off the ventilator and out of the hospital. Sweet interprets Joey’s recovery in part as a victory for prayer. “Prayer worked,” she writes, “at least that once and maybe sometimes and maybe always.” I would see it differently: Joey was saved because a lung specialist slowly decreased airway pressure and tidal volume over several weeks in a patient with acute respiratory distress syndrome. And, as Sweet points out, it was slow medicine that allowed that doctor to make the proper adjustments.

Perhaps Sweet’s most depressing conclusion is that Joey would have died today. His doctors “would have been too busy entering health care data” that was required “according to all the mandated protocols.”

For the full review, see:

Sandeep Jauhar. “Heals Over Time.” The New York Times Book Review (Sunday, January 28, 2018): 18.

(Note: ellipsis added.)

(Note: the online version of the review has the date Jan. 26, 2018, and has the title “A Doctor Argues That Her Profession Needs to Slow Down, Stat.”)

The book under review is:

Sweet, Victoria. Slow Medicine: The Way to Healing. New York: Riverhead Books, 2017.

“Fat Cats” Fund Cancer Detection “Holy Grail”

(p. A15) So often the future shows up when you’re looking for something else. In 2013, DNA sequencing company Illumina bought Verinata Health and began offering noninvasive prenatal testing. Using a pregnant woman’s blood, a now-$500 DNA test can spot Down syndrome and other chromosomal conditions. Since then, the use of very invasive needle-to-the-womb amniocentesis testing has dropped.

But that’s not the story here. Of the first 100,000 women tested, 10 (or 0.01%) had unusual chromosome patterns. The fetus was fine, but in each case, the mother had cancer of differing types.

. . .

So Illumina spun out a new company named Grail in Menlo Park, Calif., to do what’s known as Circulating Cell-free Genome Atlas studies. Running DNA sequencing on regular blood samples, Grail generates hundreds of gigabytes of data per person—the well-known A-T-G-C nucleotides, but also the “methylation status,” or whether a particular DNA site’s function is turned on or off (technically, whether or not it represses gene transcription).

. . .

. . . , Grail’s chief medical officer Josh Ofman tells me, “cancer may show up as thousands of methylation changes, a much richer signal to teach machine learning algorithms to find cancer” vs. a single site. “There are 30 million methylation sites in the entire human genome on 100,000 DNA fragments. Grail looks at a million of them.” It takes industrial-grade artificial intelligence to find patterns in all this data, something a human eye would never see.

. . .

Grail is detecting the signature of actual cancer cells in your blood. According to validation data published in the Annals of Oncology, the test can find 50 different types, more than half of all known cancers.

. . .

Grail has raised almost $2 billion, including from Bill Gates and Jeff Bezos. Isn’t that interesting? Though much maligned as fat cats sitting on piles of gold coins and monopolists out to control the world, Messrs. Gates and Bezos are investing in technology—this is not philanthropy—that may save you or a relative’s life someday.

Innovation comes through surprises. This is a big one. And while worrywarts brood over artificial intelligence and robot overlords, early detection of cancer is really what machine learning is meant for. This is the Holy Grail.

For the full commentary, see:

Andy Kessler. “INSIDE VIEW; Cancer Screening Leaps Forward.” The Wall Street Journal (Monday, July 6, 2020): A15.

(Note: ellipses added.)

(Note: the online version of the commentary has the date July 5, 2020, and has the same title as the print version.)

Fauci Criticizes Russia for Allowing Citizens to Take Covid-19 Vaccine After Passing Phase 2 Safety Trials

Milton Friedman thought that, at the very least, the FDA should allow Americans the freedom to choose to take drugs or vaccines after their safety has been established (basically meaning after passing the Phase 2 safety trials). Isn’t it strange that in the FDA’s United States, citizens may not do so, but in Putin’s authoritarian Russia, citizens are allowed that choice?

(p. A4) In a panel discussion, Dr. Anthony S. Fauci, the nation’s top infections disease expert, criticized Russia’s rushed clearance of a coronavirus vaccine. The vaccine, called Sputnik V, was approved without evidence that Phase 3 clinical trials had been completed, an essential part of the development pipeline to prove a product is safe and effective in people.

. . .

Dr. Fauci called attention to the many other coronavirus vaccines vying for eventual clearance, including several that are in Phase 3 trials in the United States. The process for testing vaccines can last months and usually involves thousands of people.

“So if we wanted to take the chance of hurting a lot of people or giving them something that doesn’t work, we could start doing this, you know, next week if we wanted to,” Dr. Fauci said. “But that’s not the way this works.”

For the full story, see:

Barron, James. “Coronavirus Update.” The New York Times (Thursday, August 11, 2020): A4.

(Note: ellipsis added.)

(Note: the online version of the story was updated August 14, 2020, and has the title “U.S. Coronavirus Death Toll Reflects Sun Belt Outbreaks.” Where there are slight differences in wording between the versions in the passages quoted, the online version appears above. The online version does not list an author. I cite James Barron, who is listed as the author in the print version.)

Viruses Mutate More Nimbly Than Therapies Hobbled by FDA Regulations

(p. A7) In a laboratory in New York City, researchers coaxed a key piece of the coronavirus — its infamous outer “spike” — to mutate so that it became invisible to disease-fighting antibodies, according to a new study that has not yet been published in a scientific journal.

The provocative finding should not set off alarm bells, experts said. The altered spikes were not attached to the real coronavirus, which mutates at a much slower pace than most laboratory viruses. But the study does underscore the need for treatments and vaccines that attack the virus in different ways, so that if the pathogen manages to evade one approach, another will be waiting in the wings.

“It’s an old story for virology,” said Dr. Sallie Permar, a virologist and pediatrician at Duke University who was not involved in the study. “If you only target one little region, that virus is going to find a way to get away from it. It’s why viruses are so successful in this world.”

. . .

Several types of monoclonal antibodies are now in clinical trials. If all goes well, such concoctions might not only treat coronavirus infections but also prevent them. That could help millions of people, especially as the world awaits a vaccine, said Akiko Iwasaki, an immunologist at Yale University who was not involved in the study.

But the new findings also hint that single-antibody formulations “may not be as successful,” Dr. Taylor said, at least in the long term. Developing a cocktail containing a diverse blend of antibodies could be a safer bet.

Such mixtures would also more accurately mimic the body’s natural response to the coronavirus. In the study, viruses flushed with samples of convalescent plasma — fractions of blood donated by people who have recovered from Covid-19 — struggled to infect cells.

Some scientists, including those at American biotechnology company Regeneron, are already attempting this combo approach, mixing two potent types of monoclonal antibodies into a single treatment.

But Dr. Iwasaki pointed out that antibody cocktails might be tougher to bring to market. “Every time you make a drug, you get approval for each component separately,” she said. . . .

The lesson of diversity might be even more powerful for vaccines, which can marshal a multifaceted immune response. Some immune cells and molecules will be tailored to home in on the spike, whereas others might prefer other parts of the virus. Vaccines that present the body with many pieces of the coronavirus, rather than the spike alone, could have a better shot at triggering a suite of these defenses, said Dr. Taia Wang, an immunologist at Stanford University who was not involved in the study.

For the full story, see:

Katherine J. Wu. “Experiment on Spike Protein Shows Obstacles of Mutation.” The New York Times (Wednesday, July 29, 2020): A7.

(Note: ellipsis added.)

(Note: the online version of the story has the date July 28, 2020, and has the title “The Coronavirus Could Dodge Some Treatments, Study Suggests.” The online version has an extra paragraph that does not appear in the print version. In my quotations above, I stick to the print version.)

Paper Towels Spread Fewer Germs Than Hot-Air Drying

(p. R1) In the age of coronavirus, handwashing can save lives. But proper hand-drying matters, too.

“It might sound pedantic, but it’s actually critical,” says John Gammon, professor of infection prevention and control at Swansea University in the U.K.

Prof. Gammon was the lead author of a review of hand-drying research and published his findings in the March 2019 issue of the Journal of Infection Prevention. His paper, “The Neglected Element of Hand Hygiene,” examined the effectiveness of paper towels, cloth towels and dryers that use hot air or high-velocity air.

In a clinical situation, such as a hospital, disposable paper towels are generally the quickest, most efficient and hygienic method of hand drying. “The mechanical action of rubbing with paper towels has an effect on reducing microorganisms on hands,” Prof. Gammon says. Paper towels are also less likely to spread germs into the surrounding environment than hot-air and high-velocity air dryers, he adds.

For the full story, see:

Beth DeCarbo. “The Best Way to Dry Your Hands.” The Wall Street Journal (Friday, April 3, 2020): R1.

(Note: the online version of the story was updated April 2, 2020, and has the title “You’ve Perfected Your Handwashing Technique. Here’s How to Dry Them.” Where there is a slight difference in wording between the versions, the passages quoted above follow the online version.)

Gammon’s academic paper, mentioned above, is:

Gammon, John, and Julian Hunt. “The Neglected Element of Hand Hygiene – Significance of Hand Drying, Efficiency of Different Methods and Clinical Implication: A Review.” Journal of Infection Prevention 20, no. 2 (March 2019): 66-74.

After Age 65, Men Lose More “Antibody-Producing B Cells” Than Women Lose

(p. B5) By examining gender-based distinctions in the immune system, cell structure, brain and other systems, researchers are discovering how and why men and women grow older in clearly different ways.

Their findings could help explain why Covid-19 has had a greater impact on older men than older women. A recent study found that men, after the age of 65, lost important antibody-producing B cells in the blood, while women didn’t.

“It was surprising,” said Duygu Ucar, an associate professor who led the study at the Jackson Laboratory for Genomic Medicine in Farmington, Conn. The research team also found that men, as they age, experience greater inflammation in their blood, which has been associated with severe cases of Covid-19.

. . .

Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine, looked at the blood of men and women between the ages of 65 and 95 and found protein levels changed at different rates. Less change means more stability, he said. Men’s levels changed far more than women’s, with 600 significant changes versus 277 for women, according to the study, published in December.

“The female biology seems to be more stable than men’s,” says Dr. Barzilai, the author of “Age Later” who specializes in geroscience.

For the full story, see:

Clare Ansberry. “Women and Men Age Differently—-And in More Ways Than Just Longevity.” The Wall Street Journal (Wednesday, July 15, 2020): A13.

(Note: ellipsis added.)

(Note: the online version of the story has the date July 14, 2020, and has the title “Women and Men Age Differently—in More Ways Than Just Longevity.” The last couple of paragraphs quoted above, appeared in the online, but not the print, version of the article.)

The “recent study” mentioned above is:

Márquez, Eladio J., Cheng-han Chung, Radu Marches, Robert J. Rossi, Djamel Nehar-Belaid, Alper Eroglu, David J. Mellert, George A. Kuchel, Jacques Banchereau, and Duygu Ucar. “Sexual-Dimorphism in Human Immune System Aging.” Nature Communications 11, Article #751 (Feb. 6, 2020): 1-17.

The book by Barzilai, mentioned above, is:

Barzilai, Nir. Age Later: Health Span, Life Span, and the New Science of Longevity. New York: St. Martin’s Press, 2020.

Reduce Spread of COVID-19 “With Plenty of Fresh Air” in Buildings

(p. B5) One way to reduce the spread of coronavirus is to maintain ventilation .

. . .

Modifications from equipment manufacturers such as Trane Technologies PLC, Carrier Global Corp. and Johnson Controls International PLC include filtering indoor air more thoroughly, drawing more outdoor air into buildings and deploying ultraviolet light against the virus inside ventilation systems.

“More fresh air and cleaner air are the direction that customers are going. This is top-of-mind for building owners and contractors,” said Jeff Williams, president of global products for Johnson Controls, maker of York-brand heating and air-conditioning equipment.

. . .

Research released this spring by the Department of Homeland Security found that coronavirus particles decay faster at a room temperature of 78 degrees Fahrenheit with a relative humidity of 50% than at lower temperatures and humidity. Add in a strong dose of ultraviolet light, and the virus decays by 90% in less than seven minutes, according to the department. Humans’ immune systems also are more effective against viruses in warmer, more humid conditions, according to a Yale University study published in May 2019.

“We can minimize the spread of the virus in the summer when there is plenty of sunlight and higher humidity. They’re actually effective in a defined space,” said Luke Leung, epidemic task force leader for the American Society of Heating, Refrigerating and Air-Conditioning Engineers, a trade association.

. . .

Recirculated air should include about 20% outdoor air to effectively dilute coronavirus particles, the Atlanta-based engineers’ society says. Many buildings’ air handlers were set up to draw less outdoor air, to maximize energy efficiency.

“The past few years there was a lot of emphasis on energy saving and there was less outside air in buildings,” said Seth Ferriell, chief executive of SSC Services for Education, a Tennessee-based company that manages ventilation systems for schools and universities. The firm has a contract to upgrade air handlers at Texas A&M University.

Mr. Ferriell estimated that increasing the amount of outdoor air in a building by 50% would drive up natural gas or electricity costs by as much as 15% a year because that additional air has to be cooled or heated to match the desired interior temperature.

For the full story, see:

Bob Tita. “Virus Spurs Ventilation Boost.” The Wall Street Journal (Thursday, July 9, 2020): B5.

(Note: ellipses added.)

(Note: the online version of the story has the date July 8, 2020, and has the title “Offices Try to Combat Coronavirus With More Fresh Air.” The last couple of paragraphs quoted above, appeared in the online, but not the print, version of the article.)

Masks “Absolutely Essential” to “Get Control of the Virus”

(p. 6A) Adm. Brett Giroir, a member of the White House coronavirus task force, called mask-wearing in public, which has been met with resistance in some U.S. states, “absolutely essential.”

Giroir, the assistant secretary at the Health and Human Services Department, told ABC’s “This Week” on Sunday [July 12, 2020] that “if we don’t have that, we will not get control of the virus.”

For the full story, see:

AP. “As U.S Wrestles With Virus Florida Sets Daily Record.” Omaha World Herald (Monday, July 13, 2020): A6.

(Note: bracketed date added.)

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.

Blacks in Detroit Have Public Transit to Die For

(p. A1) DETROIT — Paris Banks sprayed the seat with Lysol before sliding into the last row on the right. Rochell Brown put out her cigarette, tucked herself behind the steering wheel and slapped the doors shut.

It was 8:37 a.m., and the No. 17 bus began chugging westward across Detroit.

. . .

This hardscrabble city, where nearly 80 percent of residents are black, has become a national hot spot with more than 7,000 infections and more than 400 deaths. One reason for the rapid spread, experts say, is that the city has a large working-class population that does not have the luxury of living in isolation. Their jobs cannot be performed from a laptop in a living room. They do not have vehicles to safely get them to the grocery store.

(p. A12) And so they end up on a bus. Just like the No. 17 — a reluctant yet essential gathering place, and also a potential accelerant for a pandemic that has engulfed Detroit.

For the full story, see:

John Eligon. “No Choice but Shoulder to Shoulder on the Bus.” The New York Times (Thursday, April 16, 2020): A1 & A12-A13.

(Note: ellipsis added.)

(Note: the online version of the story was updated April 16, 2020, and has the title “Rolling Through the Pandemic.”)