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.

Our Government Sends 19-Year-Olds to War but Does Not Allow Them to Try High-Risk, High-Reward Covid-19 Drugs and Vaccines

(p. A11) “Many drug programs are suspended or not pursued at all—not because of flaws in the science but because of commercial and strategic reasons,” Mr. Milken says. Researchers screen those programs, and he calls in his partners either to fund the ideas or promote their development at other companies if the inventors make them available.

It’s a niche in the pharmaceutical world that public funding can’t fill. Mr. Milken sustains a model “where a person could just give me a five-page summary and get a meeting. Government isn’t going to fund that, but philanthropy does.” “These little companies,” he adds—“they’re not Johnson & Johnson, they’re not Novartis, they’re not Amgen. They need financial capital.”

. . .

Mr. Milken’s deals not tinged by controversy, such as his 1983 issuance of bonds to finance telecom company MCI’s long-distance network, show the same preference that shapes his philanthropy: high risk for a high reward.

. . .

A perennial struggle for Mr. Milken has been to convince regulators to share that urgency. He says drug trials generally are too rigid: “We send 19-year-olds into war zones knowing that no matter what we do, some number—greater than zero—will lose their lives or their limbs. But we tell a patient who is going to die not to try something because it could be dangerous.”

Nonetheless, the partners he’s made in his search for cures prove that imagination and activity are still scattered through the country. Discussing the coronavirus with biotech founders and Nobel Prize winners, Mr. Milken says he’s been “thrust back into the 1970s and early ’80s, where any time someone had a new idea—a new company, a passion for something—I had set aside time every day to listen.” On the day a vaccine or effective cure for Covid-19 is finally announced, Americans will owe thanks to such risk takers, who Mr. Milken says “invest in where the world is going, not where it is.”

For the full interview, see:

Mene Ukueberuwa, interviewer. “THE WEEKEND INTERVIEW; What Would You Risk for a Faster Cure?” The Wall Street Journal (Saturday, May 2, 2020): A11.

(Note: ellipses added.)

(Note: the online version of the interview has the date May 1, 2020, and has the same title as the print version.)

The Duopoly of Intel and AMD Vigorously Compete

(p. B4) While Intel has struggled to move into mass production of its most advanced chips, rival chip maker Advanced Micro Devices Inc. has been challenging the company’s dominance. AMD’s market share in personal computer CPUs climbed above 17% in the first quarter, more than doubling from five years ago, according to Mercury Research. Intel holds almost all of the remaining market share.

. . .

Intel’s struggles with seven-nanometer chips mirror delays in designing and producing its earlier generation of chips based on a 10-nanometer process, an industry term tied loosely to the size of transistors that chips use to make calculations. Intel executives have told investors in the past that once the company conquered its challenges in 10-nanometer technology, sizing down to seven nanometers and beyond could happen more quickly.

. . .

There aren’t any “fundamental roadblocks” with the design of seven-nanometer chips, Chief Executive Bob Swan told analysts on a conference call, adding that Intel had found the root cause of the issue and was taking steps to avert further delays. He said Intel could turn more to external manufacturers, perhaps in combination with its own factories, to meet customers’ needs—a significant shift for a company that has mostly relied on its own manufacturing muscle.

The seven-nanometer delay could harm Intel’s competitive position because Taiwan Semiconductor Manufacturing Co., the largest contract manufacturer of chips in the world, is expected to be making processors with even smaller, more efficient transistors by the time Intel comes out with its chips.

For the full story, see:

Asa Fitch. “Intel Gets Lift From Work at Home.” The Wall Street Journal (Friday, July 24, 2020): B4.

(Note: ellipses added.)

(Note: the online version of the story was updated July 23, 2020, and has the title “Intel Reports Profit Surge but Warns of Further Delays on Advanced Chips.”)

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.)

Agnes Chow Is “the Real Mulan”

The first “Mulan” below is the Disney actress Liu Yifei, who has expressed support for the suppression of freedom in Hong Kong. The third “Mulan” below is Agnes Chow, the 23 year-old Hong Kong freedom activist who the Beijing communists arrested under their new Hong Kong “security” law.

Meme viral on Twitter.

(p. A10) HONG KONG — Soon after one of Hong Kong’s best-known democracy activists was arrested this week under the national security law imposed on the city by the Chinese government, supporters turned her into a “Mulan” meme.

The social media storm around the activist, Agnes Chow, coincided with Disney’s online campaign for its upcoming movie “Mulan,” about the Chinese folk heroine who disguises herself as a man to stand in for her ailing father in the army. Disney’s slogan: “The legend arrives.”

Supporters on Twitter quickly anointed Ms. Chow, 23, “the real Mulan.” One meme featured three images, each accompanied by text: the “Mulan” star Liu Yifei (“I want the real Mulan”); the cartoon version of Mulan from Disney’s animated 1998 film (“I said the real Mulan”); and Ms. Chow (“Perfection”).

. . .

Ms. Chow, a former leader of the now-disbanded pro-democracy group Demosisto, was among 10 people arrested on Monday [August 10, 2020] on suspicion of violating the security law. She was detained hours after 200 police officers converged on the newsroom of Apple Daily, a publication owned by the media mogul Jimmy Lai, who is a vocal critic of the Chinese government. He, his two sons and other executives from his company were arrested.

. . .

Ms. Liu, the Chinese actress who plays Mulan in the movie, drew a backlash last August when she sided with the Hong Kong police against the protesters on the microblogging platform Weibo, where she had nearly 66 million followers at the time. The police have been accused of excessive force in dealing with the protests.

When Ms. Liu shared the quote “I support the Hong Kong police, you all can beat me up now,” adding a heart and a bicep emoji, the blowback was swift, with supporters of the protests calling for a boycott of “Mulan.”

For the full story, see:

Elaine Yu. “Supporters of Activist in Hong Kong Draft Mulan.” The New York Times (Friday, August 14, 2020): A10.

(Note: ellipses added.)

(Note: the online version of the story has the date August 13, 2020, and has the title “After Agnes Chow Is Arrested in Hong Kong, a ‘Mulan’ Meme Is Born.” 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.)

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.)

Environmentalism Is a “Substitute Religion” Offering “Purpose and Transcendence”

(p. A13) There is a recurring puzzle in the history of the environmental movement: Why do green activists keep promoting policies that are harmful not only to humans but also to the environment? Michael Shellenberger is determined to solve this problem, and he is singularly well qualified.

He understands activists because he has been one himself since high school, when he raised money for the Rainforest Action Network. Early in his adult career, he campaigned to protect redwood trees, promote renewable energy, stop global warming, and improve the lives of farmers and factory workers in the Third World. But the more he traveled, the more he questioned what Westerners’ activism was accomplishing for people or for nature.

He became a different kind of activist by helping start a movement called ecomodernism, the subject of “Apocalypse Never: Why Environmental Alarmism Hurts Us All.” He still wants to help the poor and preserve ecosystems, but through industrialization instead of “sustainable development.” He’s still worried about climate change, but he doesn’t consider it the most important problem today, much less a threat to humanity’s survival—and he sees that greens’ favorite solutions are making the problem worse.

. . .

Mr. Shellenberger makes a persuasive case, lucidly blending research data and policy analysis with a history of the green movement and vignettes of people in poor countries suffering the consequences of “environmental colonialism.” He realizes, though, that rational arguments alone won’t convince devout environmentalists. “I was drawn toward the apocalyptic view of climate change twenty years ago,” he writes. “I can see now that my heightened anxiety about climate reflected underlying anxiety and unhappiness in my own life that had little to do with climate change or the state of the natural environment.”

For him and so many others, environmentalism offered emotional relief and spiritual satisfaction, giving them a sense of purpose and transcendence. It has become a substitute religion for those who have abandoned traditional faiths, as he explains in his concluding chapter, “False Gods for Lost Souls.” Its priests have been warning for half a century that humanity is about to be punished for its sins against nature, and no matter how often the doomsday forecasts fail, the faithful still thrill to each new one.

For the full review, see:

John Tierney. “BOOKSHELF; False Gods for Lost Souls.” The Wall Street Journal (Monday, June 22, 2020): A13.

(Note: ellipsis added.)

(Note: the online version of the review has the date June 21, 2020, and has the title “BOOKSHELF; ‘Apocalypse Never’ Review: False Gods for Lost Souls.”)

The book under review is:

Shellenberger, Michael. Apocalypse Never: Why Environmental Alarmism Hurts Us All. New York: HarperCollins Books, 2020.

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.)

Tough Advice from Experienced Advisers Helps Us Acquire Skills

(p. R6) Recent studies suggest that people tend to favor advisers who are positive, cheerleader-types over tough talkers and voices of experience. But such preferences, the researchers also say, often lead to detrimental results, a finding with wide-ranging implications for companies and managers.

A paper published in March [2020] in the Journal of Experimental Psychology: General summarized the findings of six connected studies. Subjects of inquiry included: what characteristics people predict they will use when selecting an adviser; those people’s actual adviser selections; and the potential consequences of these decisions.

. . .

And when researchers looked at the outcomes of these decisions, they noted a disturbing pattern. Those who relied primarily on cheerleader-types generally underperformed those who were guided more by expertise.

Catherine Shea, an assistant professor at Carnegie Mellon’s Tepper School of Business who focuses on organizational behavior and theory, says that choosing an experienced mentor who may be rough around the edges can be like taking cough medicine.

“It tastes awful, but it works,” she says. “Sometimes you really do need the skill set, and sometimes the nice person is not going to give it to you.”

For the full story, see:

Cheryl Winokur Munk. “People Want Mentors Who Are Their Cheerleaders. That May Not Be Wise.” The Wall Street Journal (Monday, June 15, 2020): R6.

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

(Note: the online version of the story has the date June 14, 2020, and has the title “People Like Their Mentors to Be Cheerleaders. That May Be a Mistake.”)

The March 2020 paper mentioned above is:

Hur, Julia D., Rachel L. Ruttan, and Catherine T. Shea. “The Unexpected Power of Positivity: Predictions Versus Decisions About Advisor Selection.” Journal of Experimental Psychology: General (published online in advance of print on March 16, 2020).