Isaacson Reprises His Themes of “Science, Genius, Experiment, Code, Thinking Different” in Book on CRISPR

(p. 12) The landmark research that brought Doudna and Charpentier to the pinnacle of global acclaim has the potential to control future pandemics — either by outwitting the next viral plague through better screening and treatment or by engineering human beings with better disease resistance programmed into their cells. The technique of gene editing that they patented, which goes by the unwieldy acronym of CRISPR-Cas9, makes it possible to selectively snip and alter bits of DNA as though they were so many hems to take up or waistbands to let out. The method is based on defenses pioneered by bacteria in their ages-old battle against viruses.

. . .

The CRISPR history holds obvious appeal for Walter Isaacson, a biographer of Albert Einstein, Benjamin Franklin, Steve Jobs and Leonardo da Vinci. In “The Code Breaker” he reprises several of his previous themes — science, genius, experiment, code, thinking different — and devotes a full length book to a female subject for the first time.

. . .

Isaacson keeps a firm, experienced hand on the scientific explanations, which he mastered through extensive readings and interviews, all of which are footnoted.

For the full review, see:

Dava Sobel. “Deus Ex Machina.” The New York Times Book Review (Sunday, March 21, 2021 [sic]): 12.

(Note: ellipses added.)

(Note: the online version of the review has the date March 8, 2021 [sic], and has the title “A Biography of the Woman Who Will Re-Engineer Humans.”)

The book under review is:

Isaacson, Walter. The Code Breaker: Jennifer Doudna, Gene Editing, and the Future of the Human Race. New York: Simon & Schuster, 2021.

Risk of Bat Disease Spillover to Humans Is Small and Decreasing

(p. A15) The World Health Assembly in May is poised to divert $10.5 billion of aid away from tackling diseases such as malaria and tuberculosis. Instead, that money will go toward combating the threat of viruses newly caught from wildlife. The assumption behind this initiative, endorsed by the Group of 20 summit in Bali in 2022, is that the threat of pandemics from spillovers of animal viruses is dramatically increasing.

That assumption is almost certainly false. A new report from the University of Leeds, prepared in part by former World Health Organization executives, finds that the claims made by the G-20 in support of this agenda either are unsupported by evidence, contradict their own cited sources, or fail to correct for improved detection of pathogens. Over the past decade the burden and risk of spillover has been relatively small and probably decreasing. The Leeds authors conclude: “The implication is that the largest investment in international public health in history is based on misinterpretations of key evidence as well as a failure to thoroughly analyze existing data.”

. . .

It is a misconception that population growth or prosperity leads humanity to encroach on wildlife habitats. The poorest people in Africa encroach on forest wildlife by hunting for bush meat; when they grow richer, they shop for chicken or pork instead. Humans visited bat caves more frequently in the distant past.

. . .

The prospect of spending $31 billion a year on pandemic prevention, a third of which would be new money and a third diverted from other programs, provides an incentive for international bureaucrats to ignore or misrepresent evidence that the problem is small.

But a dollar spent on spillover can’t be spent on something else, and the evidence is clear that sanitation, nutrition and vitamins are more cost-effective ways to save lives in poor countries—from infectious diseases as well as other causes.

For the full commentary, see:

Matt Ridley. “Why Scientists Love Chasing Bats.” The Wall Street Journal (Thursday, March 7, 2024): A15.

(Note: ellipses added.)

(Note: the online version of the commentary has the date March 6, 2024, and has the same title as the print version.)

The University of Leeds report mentioned above is:

Bell, David, Garrett Brown, Blagovesta Tacheva, and Jean von Agris. “Rational Policy over Panic: Re-Evaluating Pandemic Risk within the Global Pandemic Prevention, Preparedness and Response Agenda.” REPPARE Report. University of Leeds, UK, Feb. 2024, URL: https://essl.leeds.ac.uk/downloads/download/228/rational-policy-over-panic.

By Serendipity and Persistence, Epstein Found the Epstein-Barr Virus That Can Cause a Cancer

(p. A23) In March 1961, Dr. Anthony Epstein, a pathologist at Middlesex Hospital in London, almost skipped a visiting physician’s afternoon lecture about children with exceptionally large facial tumors in Uganda.

. . .

Despite Dr. Epstein’s initial reluctance to attend the talk — he sat in the rear so he could make a quick escape — his excitement grew the longer Dr. Burkitt spoke. By the time the lecture was over, he knew that he would drop all of his ongoing projects to find the cause of that unusual malignancy.

. . .

“To have the insight and to be able to follow his hypothesis, with a little acknowledged serendipity, and identify the novel virus was pioneering,” Dr. Darryl Hill, who heads the University of Bristol’s School of Cellular and Molecular Medicine in England, said in an email.

. . .

When the 50th anniversary of E.B.V.’s discovery was celebrated in 2014, Dr. Epstein told an interviewer with the BBC what he had been thinking as he listened to Dr. Burkitt speak in 1961.

“I thought there must be some biological agent involved,” Dr. Epstein said. “I was working on chicken viruses which cause cancer. I had virus-inducing tumors at the front of my head.”

. . .

The discovery of the virus was not quick. Dr. Burkitt sent tumor biopsies to London from Kampala, Uganda, but Dr. Epstein couldn’t find viruses in the early specimens, according to Dr. Hill, who wrote a remembrance of Dr. Epstein for the University of Bristol.

When another biopsy shipment was diverted from Heathrow Airport to another airport, in Manchester, England, because of fog, the sample seemed doomed, Dr. Hill said.

“By the time the sample reached Tony, it had gone cloudy — usually a sign of bacterial contamination that would consign it to the bin,” Dr. Hill wrote in his tribute. “Tony did not throw it away but examined it carefully.”

“He discovered, to his surprise, that the cloudiness was due to lymphoid tumor cells that had been shaken off the biopsy in transit and were now floating merrily in suspension.” He continued, “Tony exploited this chance finding to grow cell lines, derived from the tumor, in culture. He showed that these stayed alive indefinitely.”

Studying his new sample with a powerful electron microscope, Dr. Epstein was able to spot the distinct viral signature of a herpes virus. Dr. Hill called the discovery a eureka moment.

For the full obituary, see:

Delthia Ricks. “Dr. Anthony Epstein, 102, Who Discovered Epstein-Barr Virus, Dies.” The New York Times (Friday, March 8, 2024): A23.

(Note: ellipses added.)

(Note: the online version of the obituary was updated March 11 [sic], 2024, and has the title “Dr. Anthony Epstein, Pathologist Who Discovered Epstein-Barr Virus, Dies at 102.” Where there are minor differences in wording between versions, the passages quoted above follow the online version.)

If Your Disease Has No “F.D.A.-Stamped” Cure, Try Rational Experiments Rather Than Give Up

(p. 9) My whole family was sick in March with Covid-like symptoms, and though the one test we obtained was negative, I’m pretty sure we had the thing itself — and my own symptoms took months rather than weeks to disappear.

But unlike many of the afflicted, I didn’t find the experience particularly shocking, because I have a prior long-haul experience of my own. In the spring of 2015, I was bitten by a deer tick, and the effects of the subsequent illness — a combination of Lyme disease and a more obscure tick-borne infection, Bartonella — have been with me ever since.

Lyme disease in its chronic form — or, per official medical parlance, “post-treatment Lyme disease syndrome” — is a fiendishly complicated and controversial subject, and what I learned from the experience would (and will, at some point) fill a book.

. . .

If you feel like you need something else to get better, some outside intervention, something more than just your own beleaguered body’s resources, be impatient — and find a way to go in search of it.

. . .

EXPERIMENT, EXPERIMENT, EXPERIMENT.

There is no treatment yet for “long haul” Covid that meets the standard of a randomized, double-blind, placebo-controlled trial, which means that the F.D.A.-stamped medical consensus can’t be your only guide if you’re trying to break a systemic, debilitating curse. The realm beyond that consensus has, yes, plenty of quacks, perils and overpriced placebos. But it also includes treatments that may help you — starting with the most basic herbs and vitamins, and expanding into things that, well, let’s just say I wouldn’t have ever imagined myself trying before I become ill myself.

So please don’t drink bleach, or believe everything you read on Goop.com. But if you find yourself decanting Chinese tinctures, or lying on a chiropractor’s table with magnets placed strategically around your body, or listening to an “Anti-Coronavirus Frequency” on Spotify, and you think, how did I end up here?, know that you aren’t alone, and you aren’t being irrational. The irrational thing is to be sick, to have no official treatment available, and to fear the outré or strange more than you fear the permanence of your disease.

. . .

. . . I believe that with enough time and experimentation, I will actually be well.

That belief is essential. Hold on to it. In the long haul, it may see you through.

For the full commentary, see:

Ross Douthat. “What to Do When Covid Doesn’t Go Away.” The New York Times, SundayReview Section (Sunday, August 9, 2020 [sic]): 9.

(Note: ellipses and bracketed year added. A few words in the original are italicized, but you cannot see that since my blog formatting has all quoted words italicized.)

(Note: the online version of the commentary has the date Aug. 8, 2020 [sic], and has the title “China Wants to Move Ahead, but Xi Jinping Is Looking to the Past.” The heading EXPERIMENT, EXPERIMENT, EXPERIMENT was in bold in both the online and print versions. In the print version it was all in caps. In the online version only the first letter of each word was capitalized.)

Douthat’s The Deep Places book can be viewed as a substantial elaboration of the commentary quoted above:

Douthat, Ross. The Deep Places: A Memoir of Illness and Discovery. New York: Convergent Books, 2021.

“If You Burn Out, Relight the Fire”

(p. A11) Dr. Gladys McGarey, 103, continues to consult, give talks and podcast interviews after nearly eight decades in the medical field. She started an Instagram account that has nearly 47,000 followers.

“If you burn out, relight the fire,” says McGarey. She ran a clinic while raising six children and had to start a new one when her husband and clinic partner left her when she was 69 and married one of their colleagues.

. . .

Not everyone wants to work in their later years, says Dr. Robert Waldinger, a professor of psychiatry at Harvard Medical School.

“It’s not burnout. It’s just ‘I don’t want to do this anymore,’ ” says Waldinger, director of the Harvard Study of Adult Development, a longitudinal study on how people thrive.

As people get older, they are better at discerning what really matters, he says, and what they can let go of. The goal isn’t necessarily an 80-year career, but finding purpose in whatever we chose to do in our 80s and beyond, whether that is taking care of a grandchild, playing the piano, or joining a community theater.

For many, there is passion, purpose and love in the work.

. . .

Like others who have remained engaged in their careers in their later years, she says the secret is to find things that make life important and our “hearts sing.”

For the full commentary, see:

Clare Ansberry. “At 103, Work Still Makes Heart Sing.” The Wall Street Journal (Wednesday, Jan. 3, 2024): A11.

(Note: ellipses added.)

(Note: the online version of the commentary has the date December 29, 2023, and has the title “TURNING POINTS; How to Work—and Love It—Into Your 80s and Beyond.”)

The memoir by McGarey mentioned above is:

McGarey, Gladys. The Well-Lived Life: A 102-Year-Old Doctor’s Six Secrets to Health and Happiness at Every Age. New York: Atria Books, 2023.

Is Bill Gates Correct in Saying Money Is “The Most Important Thing in the Fight Against Disease”?

Money is important. But I believe that what is even more important is giving doctors and patients the freedom to choose and act, within a system of innovative dynamism.

(p. A2) Decades of data and experience suggest that money is the most important thing in the fight against disease.

For the full commentary, see:

Bill Gates. “The Best Investment I’ve Ever Made.” The Wall Street Journal (Saturday, Jan. 19, 2019 [sic]): A1-A2.

(Note: the online version of the commentary has the date Jan. 16, 2019 [sic], and has the same title as the print version.)

“Xi Is Dampening the Energy and Optimism of the Chinese People”

(p. A1) A song called “Tomorrow Will Be Better” became a sensation in mainland China in the 1980s, when the nation was emerging from the poverty and turmoil of Mao Zedong’s rule.

Its inspirational lyrics, which exhorted listeners to “look upward for the wings in the sky,” came to represent a generation that was starting to believe in a brighter future.

Now people in China are listening to the song again—but for a very different reason. Videos of the song are circulating on WeChat and other communications apps, often with taglines expressing sadness about the end of that era.

“The 1980s are gone forever,” wrote one listener. “So long, those years of burning passion,” wrote another.

For many Chinese, especially those who came of age during the past 40 years of reform and opening, China appeared to be on an irreversible path forward toward more growth, openness and opportunity.

But now China’s leader, Xi Jinping, is restoring aspects of Mao’s rule, forcing people to confront a more uncertain future rooted in China’s past.

Xi’s predecessors, beginning with Deng Xiaoping, embraced market forces, growth and limited freedoms. Xi, by contrast, is placing national security over the economy, tightening government control, and putting the Communist Party—and himself—at the center of Chinese society.

A Dec. 16 [2023] article published by the party’s influential journal, Qiushi, elevated Xi to the same historical status as Mao, calling Xi “the People’s leader”—a title previously reserved for China’s Great Helmsman.

Gone is the booming China that inspired many young people and entrepreneurs to take risks and bet on the future. Home prices are falling, youth unemployment is at a record high, private investment is shrinking, the financial system is drowning in debt and deflation is setting in.

. . .

(p. A9) “Xi is dampening the energy and optimism of the Chinese people,” said Susan Shirk, a former senior diplomat during the Clinton administration and author of a recent book, “Overreach: How China Derailed Its Peaceful Rise.”

“In a system so dominated by one leader,” Shirk said, “everyone feels powerless to effect positive change.”

. . .

In Shenzhen, Deng’s reform policies helped transform the former fishing village in the shadow of neighboring Hong Kong into a cosmopolitan city of 13 million, home to globally competitive tech companies such as Tencent.

“Time is money, efficiency is life” was the slogan that guided the city’s early development.

Today, Shenzhen has a new slogan: “Follow the party, start your business”—with the party coming first.

Communist Party direction doesn’t seem to be brightening the city’s future. More than a quarter of Shenzhen’s office space sits empty after Xi started a campaign in 2020 to rein in risk-taking at private firms. The regulatory crackdown wiped out more than $1 trillion in market value from publicly-listed tech firms and triggered layoffs and business retrenchment.

. . .

Faced with growing economic headwinds and challenges to order, Xi is doubling down on Mao-style control, embracing a Mao-era tool as a way to ensure national security.

The practice, called the “Fengqiao experience,” is named after a town in eastern China that gained national fame in the early 1960s when Mao praised the way its officials mobilized people to identify and punish so-called enemies of the proletariat—capitalists, traditionalists and the like.

People were encouraged to report on one another, with husbands informing on wives and children on their parents, leading to some of the most brutal aspects of the Cultural Revolution. After that tumultuous period, the “Fengqiao experience” faded into history.

Xi is trying to revive aspects of it to mobilize people to fix problems at the local level before they lead to widespread social unrest.

. . .

John Ling, an e-commerce entrepreneur in Shanghai in his late 40s, recalls a far more liberal environment in the early 2000s. Lured back home by China’s seemingly limitless opportunities after studying in the U.S., he started a business trading goods online.

Back then, “I did feel like you could realize your American dream in China, as long as you worked hard,” Ling recalled.

Year by year he felt greater government interference. As more capital poured into e-commerce, he said, Beijing grew concerned that the sector was diverting resources away from more strategic areas such as semiconductors, an industry in which China still heavily relies on Western firms.

Ling said it became so difficult to raise fresh funding for e-commerce that he decided to shut his venture earlier this year. “It’s all about hard-tech these days,” he said, referring to sectors now favored by the government. “But can you sustain the entire economy with just hard-tech?”

“It feels like nothing is possible” nowadays, he said.

For the full commentary, see:

Lingling Wei. “China Is Looking to Move Ahead, But Xi Revives Mao-Era Playbook.” The Wall Street Journal (Friday, Dec. 29, 2023): A1 & A9.

(Note: ellipses and bracketed year added.)

(Note: the online version of the commentary was updated December 28, 2023, and has the title “China Wants to Move Ahead, but Xi Jinping Is Looking to the Past.” The fourth and eighth paragraphs quoted above appear in the online, but not the print, version of the commentary. In other sections where the online version is more detailed than the print version, the passages quoted above follow the online version.)

The book by Shirk mentioned above is:

Shirk, Susan L. Overreach: How China Derailed Its Peaceful Rise. New York: Oxford University Press, 2023.

Super Agers “Have a Purpose”

I have personally benefitted from Vernon Smith’s longevity, since he graciously wrote two drafts of a positive blurb for my Openness to Creative Destruction book.

(p. A5) Vernon L. Smith, 97, is a very busy man.

The economist at Chapman University just finished writing a book about Adam Smith and works about eight hours a day, seven days a week in his home office in Colorado Springs, Colo. He enjoys chatting with friends on Facebook and attending concerts with his daughter.

“I still have a lot of stuff to do. I want to keep at it,” said Smith, who won the Nobel Prize in economics in 2002.

. . .

(p. A10) Researchers studying “super agers,” people over 80 who have mental faculties of people decades younger, said strong social relationships are important for keeping brains sharp.

The same is true for people who live beyond 100, said Stacy Andersen, a behavioral neuroscientist at Boston University and co-director of the New England Centenarian Study.

“They have a purpose. They have things they want to go out and do every day,” Andersen said.

Smith says his work and his family keep him motivated and driven.

“I want to go to at least 106,” he said.

For the full story, see:

Dominique Mosbergen. “Several Factors Help Ward Off Mental Decline.” The Wall Street Journal (Friday, Feb. 16, 2024): A5.

(Note: ellipsis and bracketed year added.)

(Note: the online version of the story was updated Feb. 15, 2024, and has the title “How to Stay Mentally Sharp Into Your 80s and Beyond.” The last sentence quoted above appears in the online, but not in the print, version of the article.)

My book mentioned above is:

Diamond, Arthur M., Jr. Openness to Creative Destruction: Sustaining Innovative Dynamism. New York: Oxford University Press, 2019.

FDA Delays Apple Offering Consumers Quick and Convenient Blood Pressure Readings

Doesn’t the FDA do harm by requiring that Apple watch blood pressure monitor be equal in accuracy to a standard clinical blood pressure monitor? Many people will not take the time and effort to get frequent readings from a standard blood pressure monitor in a clinic. But many of them would check their blood pressure conveniently on their watch. Isn’t a less accurate reading better than no reading at all?

(p. A1) Apple’s widening effort to turn its nine-year-old watch from a luxury timepiece into the ultimate all-in-one medical device is taking it into territory that is legally treacherous as well as potentially profitable.

. . .

(p. A2) “The studies that we’ve seen are not yet reassuring that they’re ready for prime time or for clinical use,” said Jordana Cohen, associate professor of medicine and epidemiology at the University of Pennsylvania.

To secure Food and Drug Administration clearance for selling a blood-pressure monitor, companies must demonstrate through the FDA’s 510(k) process that their device’s accuracy is comparable to an existing, already cleared device, she added.

Similarly, tracking glucose through noninvasive skin sensors is generally less precise than direct blood analysis, with factors such as skin tone and temperature affecting accuracy.

For the full story, see:

Dalvin Brown and Aaron Tilley. “Tech and Legal Hurdles Hinder Apple’s Quest for Medical Watch.” The Wall Street Journal (Friday, Dec. 29, 2023): A1-A2.

(Note: ellipsis added.)

(Note: the online version of the story has the date December 28, 2023, and has the title “Apple Keeps Chasing the Ultimate Health-Tracking Watch—but It Could Take Years.”)

“Adoption of Singular ‘Gold Standard’ Models” Closes “Off Other Important Avenues of Inquiry”

(p. A15) Ubiquitous and persuasive, models . . . drive decisions—one reason why, in Ms. Thompson’s view, they require our urgent attention. She tells us that, as a graduate student studying North Atlantic storms, she noticed how different models predicted different overall effects and produced contradictory results.

. . .

The problem is that Model Land is easy to enter but difficult to escape. Having built “a beautiful internally consistent model,” Ms. Thompson writes, it can be “emotionally difficult to acknowledge that the initial assumptions on which the whole thing is built are literally not true.”

There are all sorts of ways that models can lead us astray. A small measurement error on an input can lead to wildly inaccurate forecasts—a phenomenon known as the Butterfly Effect. Fortunately, this type of uncertainty is often manageable. Far more problematic are what Ms. Thompson calls “unquantifiable unknowns”—things that are left out of a model’s calculation because they can’t be anticipated, such as the unexpected arrival of a transformative technology or the abrupt collapse of a robust market. It is not always true, she observes, that the data we have now will be relevant to the future—as traders discovered in the stock-market crash of 1987, when their models catastrophically failed.

. . .  We may be inclined to regard models as objective expressions of truth, yet they are deliberately constructed interpretations, imbued with the values and viewpoints of the modelers—primarily, as Ms. Thompson notes, well-educated, middle-class individuals. During the pandemic, models “took more account of harms to some groups of people than others,” resulting in a “moral case” for lockdowns that was “partial and biased.” Modelers who worked from home—while others maintained the supply chain—often overlooked “all of the possible harms” of the actions their models were suggesting.  . . .

The promise and peril of models, Ms. Thompson recognizes, has deep resonance in biomedicine, where so-called model organisms, like yeast and zebrafish, have led to foundational insights and accelerated the development of therapeutics. At the same time, treatments that work brilliantly in Model Land often fail in people, devastating patients and disappointing drug developers. The search for improved disease models can be complicated when proponents of one model suppress research into alternative approaches, as the late journalist Sharon Begley documented in a powerful 2019 report. Ms. Thompson perceptively critiques the adoption of singular “gold standard” models, noting that the “solidification” of one set of assumptions can lock us into one way of thinking and close off other important avenues of inquiry.

For the full review see:

David A. Shaywitz. “BOOKSHELF; Seduced By Numbers.” The Wall Street Journal (Wednesday, Dec. 28, 2022): A15.

(Note: ellipses added.)

(Note: the online version of the review has the date December 27, 2022, and has the title “BOOKSHELF; ‘Escape From Model Land’ Review: Seduced by Numbers.”)

The book under review is:

Thompson, Erica. Escape from Model Land: How Mathematical Models Can Lead Us Astray and What We Can Do About It. New York: Basic Books, 2022.

Sharon Begley’s “powerful” 2019 report, mentioned above, is:

Begley, Sharon. “The Maddening Saga of How an Alzheimer’s ‘Cabal’ Thwarted Progress toward a Cure for Decades.” STAT; Reporting from the Frontiers of Health and Medicine, Posted June 25, 2019. Available from https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/.

Thiel Says British Public Supports National Health System Because They Suffer from the Stockholm Syndrome

Peter Thiel claims that the British public supports their National Health System because they suffer from the Stockholm Syndrome. The claim is amusing, thought-provoking, and may be partly true. But I suspect that there are other reasons for the British public’s support. I suspect they assume that future advances in health care inevitably will be more expensive than they will be able to afford. They do not understand that in a laissez-faire health system substantial incentives would exist to develop effective low-cost cures and therapies.

(p. 8) It began with a £1 contract.

In the hours after a pandemic was declared in March 2020, Palantir, the secretive American data analytics company, was invited to 10 Downing Street along with other tech groups, including Amazon, Google and Meta, to discuss how it could help the British government respond.

Within days, Palantir’s software was processing streams of data from across England’s National Health Service, with Palantir engineers embedded to help. The company’s services, used by the C.I.A. and Western militaries for more than a decade, were deployed to track emergency room capacity and direct supplies of scarce equipment.

Palantir charged the government just one pound.

The deal provided the company with a valuable toehold. Since then, Palantir, which is chaired by Peter Thiel, the billionaire investor and one of President Donald J. Trump’s major 2016 donors, has parlayed the work into more than £60 million in government health contracts. Its biggest reward may be yet to come: a seven-year contract worth up to £480 million — about $590 million — to overhaul N.H.S. England’s outdated patient data system.

. . .

Palantir declined to comment on its bid but said it was proud to support “the world’s most important private and public institutions.” The company defended the quality of its work and said, “We are now helping to reduce the N.H.S. backlog, cut the amount of time nurses and doctors need to spend on administrative tasks and speed up cancer diagnosis — all while rigorously protecting data privacy.”

. . .

Speaking at Oxford University in January [2023], Mr. Thiel went off script. The N.H.S. makes people sick and should embrace privatization, he said in response to a question. The British public’s support for the service, he said, was “Stockholm syndrome.”

For the full story, see:

Euan Ward and Adam Satariano. “Uproar in U.K. Over Data Giant’s Push for Heavier Role in Health Care.” The New York Times, First Section (Sunday, October 1, 2023): 8.

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

(Note: the online version of the story has the date Sept. 29, 2023, and has the title “How Peter Thiel’s Palantir Pushed Toward the Heart of U.K. Health Care.”)