“Greatness in Science Often Comes From the Well-Prepared Mind Turning a Chance Observation Into a Major Discovery”

(p. 27) Takuo Aoyagi, a Japanese engineer whose pioneering work in the 1970s led to the modern pulse oximeter, a lifesaving device that clips on a finger and shows the level of oxygen in the blood and that has become a critical tool in the fight against the novel coronavirus, died on April 18 [2020] in Tokyo.

. . .

Mr. Aoyagi’s contribution to medical science was built on decades of innovation and invention. In an essay about Mr. Aoyagi, John W. Severinghaus, a professor emeritus of anesthesia at the University of California, San Francisco, wrote in 2007 that Mr. Aoyagi’s “dream” had been to detect oxygen saturation levels without having to draw blood.

. . .

But he soon ran into a problem. Blood does not flow smoothly like an open tap, but pulses through the body irregularly, thus preventing an accurate recording of dye levels. The problem, however, turned out to be an opportunity. By devising a mathematical formula to correct for this “pulsatile noise,” he created a device that measured oxygen levels with greater accuracy than before.

“Greatness in science, often, as here, comes from the well-prepared mind turning a chance observation into a major discovery,” Dr. Severinghaus wrote.

For the full obituary, see:

John Schwartz and Hikari Hida. “Takuo Aoyagi, 84; Invented Medical Device.” The New York Times, First Section (Sunday, May 3, 2020): 27.

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

(Note: the online version of the obituary was updated June 20, 2020, and has the title “Takuo Aoyagi, an Inventor of the Pulse Oximeter, Dies at 84.”)

The essay about Aoyagi mentioned above is:

Severinghaus, John W. “Takuo Aoyagi: Discovery of Pulse Oximetry.” Anesthesia & Analgesia 105, no. 6 (Dec. 2007): S1-S6.

“The F.D.A. and the Drug Houses Were in Bed Together”

(p. A22) Dr. John S. Najarian, a groundbreaking transplant surgeon who made headlines for taking on difficult cases, and who weathered a different type of headline when he was accused, and then exonerated, of improprieties related to a drug he had developed, died on Aug. 31 in Stillwater, Minn., east of Minneapolis.

. . .

In November 1982, Dr. Najarian performed what may have been his highest-profile surgery. The patient was Jamie Fiske, who became the youngest successful liver transplant recipient when Dr. Najarian performed the operation a few weeks before her first birthday. Her parents had made a widely publicized appeal for a donor.

“They were told that she wouldn’t survive that kind of an operation,” Dr. Najarian said in an oral history recorded in 2011 for the University of Minnesota’s Academic Health Center. “I’m not the kind of guy that takes that lightly. So I told them, ‘If a liver becomes available, we’ll transplant it, and it will work’ — a pretty brash statement, but it did.”

Dr. Najarian’s success with transplants was aided by a drug he developed in 1970, a type of antilymphocyte globulin known as Minnesota ALG, which addressed the biggest problem with early transplants: the rejection of the new organ. He said the drug, which he began using around 1970, gave the Minnesota transplant teams notably better results than other surgical centers were getting with a product offered by a pharmaceutical company.

“Everybody thought we were lying,” Dr. Najarian said, “because we could take patients and we could transplant them, and 65 to 70 percent of them did extremely well, whereas they were lucky to have 50 percent with the commercially available product from Upjohn.”

Other transplant centers began asking for the product, and it turned into a multimillion-dollar business for the university. But in 1992, the Food and Drug Administration, which had approved ALG as an investigational drug but not for interstate sale, stopped the program, and the federal authorities began an investigation. The university turned on Dr. Najarian, pressuring him to resign, and in 1995 he was charged with violating drug safety laws and other crimes.

Dr. Najarian maintained that the case was an attempt by the pharmaceutical industry and its friends in the F.D.A. to squash a successful treatment that was costing drug companies money by besting their products.

“The F.D.A. and the drug houses were in bed together,” he said bluntly in the oral history.

His trial in federal court in St. Paul, Minn., in 1996 provided vindication. Judge Richard Kyle threw out six of the charges, and a jury acquitted him of the other 15. The judge then took the extraordinary step of blasting the F.D.A. and the prosecutors.

“I have some questions as to why we were here at all,” Judge Kyle said.

The F.D.A., he added, “was certainly aware of what was going on, and yet they came in here as a witness to testify that somehow they were hoodwinked by this defendant and his colleagues and other people at the university.”

“We had a program here in Minnesota,” the judge added, “which, for all its problems and shortcomings, was a good program, literally saved thousands of lives.”

For the full obituary, see:

Neil Genzlinger. “John Najarian, 92, Revered Transplant Surgeon Who Took Tough Cases, Dies.” The New York Times (Monday, September 29, 2020): A22.

(Note: ellipsis added.)

(Note: the online version of the obituary was updated Sept. 19, 2020, and has the title “John Najarian, Pioneering Transplant Surgeon, Dies at 92.”)

Natural Experiments Are Equal to Randomized Double-Blind Clinical Trials in Showing Causality

(p. B6) . . . randomized controlled trials are the gold standard in medicine. Using randomization (by, say, flipping a coin to assign patients to a new treatment or not) is the best way to determine whether treatments work.

Unfortunately, randomized trials take time — which is a problem when doctors need answers now. So doctors and public health officials have been turning to available real-world data on patient outcomes and trying to make sense of them.

. . .

“Large-scale randomized evaluations have been less common in economics, prioritizing the need for economists to identify often creative but sometimes narrow natural experiments to estimate the causal effects of treatments,” said Amitabh Chandra, an economist at the Harvard Business School and the Kennedy School of Government.

Ashish Jha, recently appointed the dean of the Brown University School of Public Health, said that while “natural experiments have causal interpretations, typical associational studies in medicine do not, which may make some medical researchers less comfortable interpreting the results.”

. . .   Most doctors can relate to recent comments by the Food and Drug Administration director Stephen Hahn in last week’s congressional pandemic hearing. “In a rapidly moving situation like we have now with Covid-19,” he said, decisions are made “based on the data that’s available to us at the time.”

For the full commentary, see:

Anupam B. Jena and Christopher M. Worsham. “THE UPSHOT; What Coronavirus Researchers Can Learn From Economists.” The New York Times (Thursday, July 2, 2020): B6.

(Note: ellipses added.)

(Note: the online version of the commentary has the date June 30, 2020, and has the same title as the print version.)

Advanced Colon Cancer Patients Lived Longer When They Drank Coffee

(p. D6) Researchers studied 1,171 patients diagnosed with advanced or metastatic colon or rectal cancer who could not be treated with surgery.

. . .

Compared with people who drank none, those who drank a cup a day had an 11 percent increased rate of overall survival, and a 5 percent increased rate of living progression-free. The more coffee they drank, the better. Those who drank four or more cups a day had a 36 percent increased rate of overall survival and a 22 percent increased rate of surviving without their disease getting worse. Whether the coffee was decaf or regular made little difference.

The study, in JAMA Oncology, controlled for race, smoking, alcohol intake, aspirin use, diabetes, and the addition of milk, nondairy creamers or sweeteners to the coffee.

For the full story, see:

Nicholas Bakalar. “Coffee for Better Outcomes.” The New York Times (Tuesday, September 29, 2020): D6.

(Note: ellipsis added.)

(Note: the online version of the story was updated September 23, 2020, and has the title “Drinking Coffee Tied to Better Outcomes in Colon Cancer Patients.”)

The article in JAMA Oncology mentioned above is:

Mackintosh, Christopher, Chen Yuan, Fang-Shu Ou, Sui Zhang, Donna Niedzwiecki, I-Wen Chang, Bert H. O’Neil, Brian C. Mullen, Heinz-Josef Lenz, Charles D. Blanke, Alan P. Venook, Robert J. Mayer, Charles S. Fuchs, Federico Innocenti, Andrew B. Nixon, Richard M. Goldberg, Eileen M. O’Reilly, Jeffrey A. Meyerhardt, and Kimmie Ng. “Association of Coffee Intake with Survival in Patients with Advanced or Metastatic Colorectal Cancer.” JAMA Oncology (published online in advance of print on Sept. 17, 2020).

Litan and Mankiw Endorse Paying People to Take Vaccine

(p. 5) What’s the best way to get the economy back on track after the Covid-19 recession? Simple: Achieve herd immunity. And what’s the best way to achieve herd immunity? Again, simple: Once a vaccine is approved, pay people to take it.

That bold proposal comes from Robert Litan, an economist at the Brookings Institution. Congress should enact it as quickly as possible.

. . .

Recent research by the University of Chicago economists Austan Goolsbee and Chad Syverson has found that the government-mandated shutdowns account for just a small part of the decline in economic activity. The main reason people aren’t spending is that they are afraid to leave their homes and contract the virus. That hypothesis explains my own behavior. I have not stepped foot on an airplane or inside a restaurant for six months.

. . .

Immunology, meet economics. One of the first principles of economics — perhaps the most important — is that people respond to incentives. Applying this principle to the case at hand, Mr. Litan recommends that the government pay $1,000 to whoever gets the vaccine. With a large enough incentive, most Americans are likely to get vaccinated.

This proposal is textbook economics. (I’ve written some of the textbooks.) As all economics students learn, when an activity has a side effect on bystanders, that effect is called an externality. In the presence of externalities, the famous theorems of economics that justify laissez-faire do not apply. Adam Smith’s vaunted invisible hand can no longer work its magic.

A classic example of a negative externality is pollution, and the simplest and least invasive policy solution is a tax on emissions. In economics-speak, such a tax internalizes the externality: It induces polluters to take the cost of pollution into account by giving them a financial incentive to cut emissions. That’s why I have written here many times that a tax on carbon emissions is the best way to deal with global climate change.

Vaccination confers a positive externality. When you get vaccinated, you benefit not only yourself but also your fellow citizens by helping society take a step toward herd immunity. In this case, internalizing the externality requires not a tax but a subsidy, as Mr. Litan suggests.

For the full commentary, see:

N. Gregory Mankiw. “A Vaccine Subsidy Licks 2 Crises With One Shot.” The New York Times, SundayReview Section (Sunday, September 13, 2020): 5.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Sept. 9, 2020, and has the title “Pay People to Get Vaccinated.”)

The Robert Litan op-ed mentioned above is:

Litan, Robert E. “Want Herd Immunity? Pay People to Take the Vaccine.” Brookings Institute Op-Ed. (Tues., Aug. 18, 2020) URL: https://www.brookings.edu/opinions/want-herd-immunity-pay-people-to-take-the-vaccine/.>

The Goolsbee and Syverson NBER working paper mentioned above is:

Goolsbee, Austan, and Chad Syverson. “Fear, Lockdown, and Diversion: Comparing Drivers of Pandemic Economic Decline 2020.” NBER Working Paper #27432, June 2020.

“Operation Warp Speed, . . . , Is More Imaginative Than the Bureaucratic Norm”

(p. 11) . . . the blundering of the Trump administration, while real and deadly, may not be responsible for the bulk of America’s coronavirus fatalities.

. . .

. . . : the absence of challenge trials for vaccines (in which young, healthy participants agree to be vaccinated and then infected with the virus), the predictable expert resistance to at-home testing. But the most important one was the straightforward bureaucratic calamity at the C.D.C. that delayed effective testing for a fateful month.

An effective president might have addressed some of these problems. (Although Operation Warp Speed, the White House’s vaccine initiative, is more imaginative than the bureaucratic norm.) But overall they are problems with structures and habits rather than personalities — an institutional decadence that predated Trump and will persist when he is gone.

. . .

. . . the third thing you see when you look beyond Trump [is] the fact that so many countries in Western Europe, to say nothing of our neighbors in the Americas, have had death rates similar to ours.

This reality speaks not of exceptionalism but of convergence — and the possibility that the trends of the early 21st century have left us sharing more in common not only with France and Spain but also with Mexico and Brazil than most Americans might expect.

This, too, may matter long after Trump is gone. Where there are crises, in this dispensation, they are likely to be general rather than just American. Where there is decadence, it is the shared experience of late modernity. And if renewal comes to an exhausted West, it will not necessarily come through America alone.

For the full commentary, see:

Ross Douthat. “What Isn’t Trump’s Fault.” The New York Times, SundayReview Section (Sunday, September 13, 2020): 11.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Sept. 12, 2020, and has the same title as the print version.)

Open Offices Reduce Productivity and Spread Diseases

(p. B4) When historians of the early 21st century look back on the pre-Covid era, one of the absurdities they might highlight is the vogue for gigantic, open-plan offices. The apotheosis of this trend of breaking down barriers between co-workers must surely be Facebook Inc.’s 433,555-square-foot Frank Gehry-designed open-plan office at its headquarters in Menlo Park, Calif. Opened in 2015, it’s now a ghost town, a monument to offices vacated by the pandemic.

Cramming cavernous spaces with as many desks as they could hold might have increased serendipitous interactions, but it almost certainly reduced productivity and helped spread communicable diseases, including coronavirus.

. . .

Cue the “dynamic workplace,” a pivot away from the open plan, built on the idea that with fewer employees coming to work on any given day, offices can offer them more flexibility of layout and management.

While open offices and dynamic workplaces share similar components—privacy booths and huddle rooms to escape the hubbub, cafe-like networking spaces, etc.—they’re philosophically distinct. One is intended to be a place where people come (at least) five days a week, and get most of their work done on site. The other is planned for people rotating in and out of the office, on flexible schedules they have more control over than ever.

. . .

Research on hot-desking in office spaces, for example—where employees give up a dedicated space in favor of first-come-first-serve seating—finds that it decreases socialization and trust. This happens because employees figure they might never again see the person they sit next to on a given day, says Dr. Sander. In other studies, employees complain they can’t find their colleagues, that it’s a hassle to find a new spot to work every day, and that such arrangements ignore humans’ innate territoriality and desire to make a space their own.

For the full commentary, see:

Christopher Mims. “Goodbye, Open Office. Hello, ‘Dynamic Workplace.” The Wall Street Journal (Saturday, September 12, 2020): B4.

(Note: ellipses added.)

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

Russia Approves Covid-19 Vaccine Before Completing Phase 3 Clinical Trial

(p. A6) MOSCOW — Russia has become the first country in the world to approve a vaccine for the coronavirus, President Vladimir V. Putin announced on Tuesday, though global health authorities say the vaccine has yet to complete critical, late-stage clinical trials to determine its safety and effectiveness.

Mr. Putin, who told a cabinet meeting on Tuesday [Aug. 11, 2020] morning that the vaccine “works effectively enough,” said that his own daughter had taken it. And in a congratulatory note to the nation, he thanked the scientists who developed the vaccine for “this first, very important step for our country, and generally for the whole world.”

. . .

If Russian scientists have taken an unorthodox route to the coronavirus vaccine, it would not be the first time. Back in the 1950s, a team of researchers tested a promising, and ultimately successful, polio vaccine on their own children.

For the full story, see:

Andrew E. Kramer. “Putin Says Russia Is First to Approve Vaccine, but Skepticism Abounds.” The New York Times (Wednesday, August 12, 2020): A6.

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

(Note: the online version of the story was updated Aug. 11, 2020, and has the title “Russia Approves Coronavirus Vaccine Before Completing Tests.”)

Shanghai Immunologist Says Phase 1 and Phase 2 Tests Show Chinese Vaccine Is Safe and “Highly Likely” to Protect Against Covid-19

(p. A8) The United Arab Emirates has become the first country outside China to approve emergency usage of a Chinese Covid-19 vaccine candidate, in a vote of confidence for a state-backed drugmaker racing global rivals to stop the spread of the coronavirus.

. . .

Tao Lina, a former immunologist with the Shanghai CDC, said in an interview that it makes sense for authorities to approve the usage of Chinese vaccines that have proved safe during the first two phases of clinical trials, given the scale of the Covid-19 crisis. Unlike medical drug treatments, vaccines work by triggering a person’s own immunity, he said. “I’m not at all worried about the safety of the vaccines,” Mr. Tao said.

While the level of efficacy of the Chinese vaccines being used including those of Sinopharm isn’t yet clear, Mr. Tao said the Chinese vaccines’ ability to induce the body to produce antibodies during previous clinical trials meant that they were highly likely to confer some degree of protection from the virus.

For the full story, see:

Chao Deng, and Rory Jones. “U.A.E. Approves Use of China-Made Covid-19 Vaccine.” The Wall Street Journal (Wednesday, September 16, 2020): A8.

(Note: ellipsis added.)

(Note: the online version of the story was updated Sep. 15, 2020, and has the title “In Global Covid-19 Vaccine Race, Chinese Shot Receives First Foreign Approval.”)

600-Year-Old Ginkgo Trees Are as Vigorous as 20-Year-Old Ginkgo Trees

(p. D2) . . . a January [2020] study on ginkgo trees, which can live for over a thousand years . . . found that 600-year-old ginkgos are as reproductively and photosynthetically vigorous as their 20-year-old peers. Genetic analysis of the trees’ vascular cambium — a thin layer of cells that lies just underneath the bark, and creates new living tissue — showed “no evidence of senescence,” or cell death, the authors wrote.

For the full story, see:

Cara Giaimo. “Holding On; Can Trees Live Forever? A New Study Adds Kindling to the Debate.” The New York Times (Tuesday, August 4, 2020): D2.

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

(Note: the online version of the story was updated July 27, 2020, and has the title “Can Trees Live Forever? New Kindling for an Immortal Debate.”)

The January 2020 study mentioned above is:

Wang, Li, Jiawen Cui, Biao Jin, Jianguo Zhao, Huimin Xu, Zhaogeng Lu, Weixing Li, Xiaoxia Li, Linling Li, Eryuan Liang, Xiaolan Rao, Shufang Wang, Chunxiang Fu, Fuliang Cao, Richard A. Dixon, and Jinxing Lin. “Multifeature Analyses of Vascular Cambial Cells Reveal Longevity Mechanisms in Old Ginkgo biloba Trees.” Proceedings of the National Academy of Sciences 117, no. 4 (Jan. 28, 2020): 2201-10.

Blocking Some of the Virus Reduces Odds of Catching Covid-19 and Reduces Odds of a Severe Case, If Covid-19 Is Caught

(p. D8) As the world awaits the arrival of a safe and effective coronavirus vaccine, a team of researchers has come forward with a provocative new theory: that masks might help to crudely immunize some people against the virus.

The unproven idea, described in a commentary published Tuesday in the New England Journal of Medicine, is inspired by the age-old concept of variolation, the deliberate exposure to a pathogen to generate a protective immune response. First tried against smallpox, the risky practice eventually fell out of favor, but paved the way for the rise of modern vaccines.

Masked exposures are no substitute for a bona fide vaccine. But data from animals infected with the coronavirus, as well as insights gleaned from other diseases, suggest that masks, by cutting down on the number of viruses that encounter a person’s airway, might reduce the wearer’s chances of getting sick. And if a small number of pathogens still slip through, the researchers argue, these might prompt the body to produce immune cells that can remember the virus and stick around to fight it off again.

. . .

Experiments in hamsters have hinted at a connection between dose and disease. Earlier this year, a team of researchers in China found that hamsters housed behind a barrier made of surgical masks were less likely to get infected by the coronavirus. And those who did contract the virus became less sick than other animals without masks to protect them.

. . .

But despite decades of research, the mechanics of airborne transmission largely remain “a black box,” said Jyothi Rengarajan, an expert in vaccines and infectious disease at Emory University who was not involved in the commentary.

That is partly because it is difficult to pin down the infectious dose required to sicken a person, Dr. Rengarajan said. Even if researchers eventually settle on an average dose, the outcome will vary from person to person, since factors like genetics, a person’s immune status and the architecture of their nasal passages can all influence how much virus can colonize the respiratory tract.

For the full story, see:

Katherine J. Wu. “Masks May Act as a Crude Vaccine.” The New York Times (Tuesday, September 15, 2020): D8.

(Note: ellipses added.)

(Note: the online version of the story has the date Sept. 8, 2020, and has the title “A New Theory Asks: Could a Mask Be a Crude ‘Vaccine’?”)