Passion, Dedication, and Caffeine Led to Muscular Dystrophy Progress, After Mutating Millions of Viruses to Find One That Works

Trial and error still matters in science and medicine.

(p. D1) CAMBRIDGE, Mass. — When Sharif Tabebordbar was born in 1986, his father, Jafar, was 32 and already had symptoms of a muscle wasting disease. The mysterious illness would come to define Sharif’s life.

Jafar Tabebordbar could walk when he was in his 30s but stumbled and often lost his balance. Then he lost his ability to drive. When he was 50, he could use his hands. Now he has to support one hand with another.

No one could answer the question plaguing Sharif and his younger brother, Shayan: What was this disease? And would they develop it the way their father had?

As he grew up and watched his father gradually decline, Sharif vowed to solve the mystery and find a cure. His quest led him to a doctorate in developmental and regenerative biology, the most competitive ranks of academic medical research, and a discovery, published in September in the journal Cell, that could transform gene therapy — medicine that corrects genetic defects — for nearly all muscle wasting diseases. That includes muscular dystrophies that affect about 100,000 people in the United States, according to the Muscular Dystrophy Association.

Scientists often use a disabled virus called an adeno-associated virus, or AAV, to deliver gene therapy to cells. But damaged muscle cells like the ones that afflict Dr. Tabebordbar’s father are difficult to treat. Forty percent of the body is made of muscle. To get the virus to those muscle cells, researchers must deliver enormous doses of medication. Most of the viruses end up in the liver, damaging it and sometimes killing patients. Trials have been halted, researchers stymied.

Dr. Tabebordbar managed to develop viruses that go directly to muscles — very few end up in the liver. His discovery could allow treatment with a fraction of the dosage, and without the disabling side effects.

. . .

(p. D4) There, fueled by caffeine, he works typically 14 hours a day, except on the days when he plays soccer with a group at M.I.T.

“He is incredibly productive and incredibly effective,” said Amy Wagers, who was Dr. Tabebordbar’s Ph.D. adviser and is a professor and co-chair of the department of stem cell and regenerative biology at Harvard. “He works all the time and has this incredible passion and incredible dedication. And it’s infectious. It spreads to everyone around him. That is a real skill — his ability to take a bigger vision and communicate it.”

. . .

He got a position in the lab of Pardis Sabeti at the Broad Institute and set to work. His plan was to mutate millions of viruses and isolate those that went almost exclusively to muscles.

The result was what he’d hoped — viruses that homed in on muscle, in mice and also in monkeys, which makes it much more likely they will work in people.

As scientists know, most experiments fail before anything succeeds and this work has barely begun.

“I will do 100 experiments and 95 will not work,” Dr. Tabebordbar said.

But he said this is the personality that is required of a scientist.

“The mind-set I have is, ‘this is not going to work.’ It makes you very patient.”

. . .

Now Dr. Tabebordbar has moved on to his next step. His life, other than his brief stint in biotech, has been in academia, but he decided that he wants to develop drugs. About a year ago, he co-founded a drug company, called Kate Therapeutics, that will focus on gene therapy for muscle diseases and will move there for the next phase of his career.

For the full story, see:

Gina Kolata. “Determined Yet Patient, He Looks for a Cure.” The New York Times (Tuesday, November 9, 2021): D1 & D4.

(Note: ellipses bracketed date added.)

(Note: the online version of the story has the date Nov. 4, 2021, and has the title “He Can’t Cure His Dad. But a Scientist’s Research May Help Everyone Else.”)

Infrastructure Can Be Privately Provided

(p. B5) In less than a decade, four tech giants— Microsoft, Google parent Alphabet, Meta (formerly Facebook ) and Amazon —have become by far the dominant users of undersea-cable capacity. Before 2012, the share of the world’s undersea fiber-optic capacity being used by those companies was less than 10%. Today, that figure is about 66%.

And these four are just getting started, say analysts, submarine cable engineers and the companies themselves. In the next three years, they are on track to become primary financiers and owners of the web of undersea internet cables connecting the richest and most bandwidth-hungry countries on the shores of both the Atlantic and the Pacific, according to subsea cable analysis firm TeleGeography.

By 2024, the four are projected to collectively have an ownership stake in more than 30 long-distance undersea cables, each up to thousands of miles long, connecting every continent on the globe save Antarctica.

. . .

Undersea cables can cost hundreds of millions of dollars each. Installing and maintaining them requires a small fleet of ships, from surveying vessels to specialized cable-laying ships that deploy all manner of rugged undersea technology to bury cables beneath the seabed. At times they must lay the relatively fragile cable—at some points as thin as a garden hose—at depths of up to 4 miles.

All of this must be done while maintaining the right amount of tension in the cables, and avoiding hazards as varied as undersea mountains, oil-and-gas pipelines, high-voltage transmission lines for offshore wind farms, and even shipwrecks and unexploded bombs, says Howard Kidorf, a managing partner at Pioneer Consulting, which helps companies engineer and build undersea fiber optic cable systems.

In the past, trans-oceanic cable-laying often required the resources of governments and their national telecom companies. That’s all but pocket change to today’s tech titans. Combined, Microsoft, Alphabet, Meta and Amazon poured more than $90 billion into capital expenditures in 2020 alone.

The four say they’re laying all this cable in order to increase bandwidth across the most developed parts of the world and to bring better connectivity to under-served regions like Africa and Southeast Asia.

For the full commentary, see:

Christopher Mims. “KEYWORDS: Tech Giants Weave a Web Of Power Under the Sea.” The Wall Street Journal (Saturday, January 15, 2022): B5.

(Note: ellipsis added.)

(Note: the online version of the commentary has the same date as the print version, and has the title “KEYWORDS: Google, Amazon, Meta and Microsoft Weave a Fiber-Optic Web of Power.”)

“In a World Filled With Distraction,” Apolo Ohno Praises “Deep Work”

(p. C12) Cal Newport’s “Deep Work” eloquently describes how to find an advantage in a world filled with distraction.

For the full review, see:

Apolo Ohno. “12 Months of Reading; Apolo Ohno.” The Wall Street Journal (Saturday, Dec. 11, 2021): C12.

(Note: the online version of the review has the date December 10, 2021, and has the title “Who Read What: Business Leaders Share Their Favorite Books of 2021.”)

The book praised by Ohno is:

Newport, Cal. Deep Work: Rules for Focused Success in a Distracted World. New York: Grand Central Publishing, 2016.

Silicon Valley Pioneer at Age 16 Survived on 5 Cents of Carrots a Day

(p. A23) Jay Last, a physicist who helped create the silicon chips that power the world’s computers, and who was among the eight entrepreneurs whose company laid the technical, financial and cultural foundation for Silicon Valley, died on Nov. 11 [2021] in Los Angeles.

. . .

Ultimately, he agreed to join the Shockley Semiconductor Laboratory because it sat in the Northern California valley where he had spent a summer harvesting fruit after hitchhiking there from his home in Pennsylvania steel country.

But he and seven of his collaborators at the lab clashed with Dr. Shockley, who later became infamous for his theory that Black people were genetically inferior in intelligence to white people. They quickly left the lab to create their own transistor company. They later came to be called “the traitorous eight,” and their company, Fairchild Semiconductor, is now seen as ground zero for what became known as Silicon Valley.

. . .

With the blessing of his parents — and carrying a letter from the local police chief saying he was not running away from home — he hitchhiked to San Jose, Calif., which was then a small farming town. He had planned on making a little money picking fruit, but he arrived before the harvest began.

Until it did, he lived, as he often recalled in later years, on a nickel’s worth of carrots a day. Whenever he faced a difficult situation, he said in an interview for the Chemical Heritage Foundation (now the Science History Institute) in 2004, he told himself, “I got through that when I was 16, and this is not that bad a problem.”

. . .

Using materials like silicon and germanium, Dr. Shockley and two other scientists had shown how to build the tiny transistors that would one day be used to store and move information in the form of an electrical signal. The question was how to connect them together to form a larger machine.

After using chemical compounds to etch the transistors into a sheet of silicon, Dr. Last and his colleagues could have cut each one from the sheet and connected them with individual wires, much like any other electrical device. But this was enormously difficult, inefficient and expensive.

One of the founders of Fairchild, Robert Noyce, suggested an alternative method, and this was realized by a team Dr. Last oversaw. They developed a way of building both the transistors and the wires into the same sheet of silicon.

This method is still used to build silicon chips, whose transistors are now exponentially smaller than those manufactured in the 1960s, in accordance with Moore’s Law, the famous maxim laid down by another Fairchild founder, Gordon Moore.

For the full obituary, see:

Cade Metz. “Jay Last, 92, Physicist and a Pioneer of Silicon Valley.” The New York Times (Monday, November 22, 2021): A23.

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

(Note: the online version of the obituary has the date Nov. 20, 2021, and has the title “Jay Last, One of the Rebels Who Founded Silicon Valley, Dies at 92.”)

Regulators Allow U.S. Carmakers to Offer Consumers the Same Safer Adaptive Driving Beam Headlights Already Allowed in Europe

(p. B5) I am driving in the California hills high above Malibu, in a deep-blue electric Audi E-tron, and I turn onto a pitch-black winding road. Instinctively, I reach to turn on the high beams. But before I have a chance to do so, the low beams automatically rise and spread out like a hand fan, filling the entire roadway with light and projecting it far into the distance.

A few seconds later, the headlights of an approaching vehicle set my headlights in motion; the high beams angle down as the light continually shape-shifts, changing patterns to avoid illuminating the oncoming car.

I had just experienced adaptive driving beam, or A.D.B., headlights, one of the most important advances in vehicle lighting technology in decades. With A.D.B. lighting, a vehicle’s headlights are essentially always on high beam, while cameras and software instruct them to constantly reshape the beam to avoid blinding oncoming drivers or shining in the rearview mirrors of those close ahead.

The bad news is that while widely used in Europe and Asia for over a decade, these smart headlights are illegal in the United States. On my demonstration drive, I was piloting a not-for-sale-here European model of the E-tron equipped with Audi’s futuristic digital matrix headlighting system.

The good news is that after years of unsuccessful attempts to allow the technology, A.D.B. lights will soon be on American cars and trucks, thanks to a section in the recently passed Infrastructure Investment and Jobs Act that mandates their use.

According to the infrastructure act, adaptive beam headlights must be approved for U.S. use within two years.

. . .

The changeover to A.D.B.-capable headlamps could be swift for some drivers who own Audi, BMW or Mercedes models with deactivated units. Once the A.D.B. standard is approved, it’s possible that a simple software upgrade will activate them.

Some owners who could not wait for legalization say they have figured out how to activate their matrix headlights, and at least one aftermarket service dealer in Southern California will turn them on for $900.

For the full commentary, see:

Eric A. Taub. “WHEELS: Coming Soon: The Perfect Glow on the Road.” The New York Times (Friday, January 14, 2022): B5.

(Note: ellipsis added.)

(Note: the online version of the commentary was updated Jan. 18, 2022, and has the title “WHEELS: Smart Headlights Are Finally on Their Way.”)

Arctic Sea Ice Was 25 Percent Higher in 2021 Than in 2020

(p. A9) Sea ice in the Arctic Ocean has reached its minimum extent following the summer melt season, and coverage is not as low as it has been in recent years, scientists said Wednesday [September 22, 2021].

The National Snow and Ice Data Center, at the University of Colorado, said that the minimum had most likely been reached on Thursday and estimated this year’s total ice extent at 1.82 million square miles, or 4.72 million square kilometers.

That is the 12th-lowest total since satellite sensing of the Arctic began in 1979 and about 25 percent higher than last year.

In a statement, Mark Serreze, the director of the center, described this year as a “reprieve” for Arctic sea ice, as colder and stormier conditions led to less melting. In particular, a persistent zone of colder, low pressure air over the Beaufort Sea north of Alaska slowed the rate of melting there.

For the full story, see:

Henry Fountain. “Colder Conditions Eased Melting of Arctic Sea Ice.” The New York Times (Thursday, September 23, 2021): A9.

(Note: bracketed date added.)

(Note: the online version of the story has the date Sept. 22, 2021, and has the title “Arctic Sea Ice Hits Annual Low, but It’s Not as Low as Recent Years.”)

Charles Morris Uncovered “Tantalizing Nuggets” on Innovation and Entrepreneurship

In researching my Openness to Creative Destruction, I found two of Charles Morris’s books very useful, providing thought-provoking analysis and compelling examples. The two were The Dawn of Innovation and The Tycoons.

(p. A24) Charles R. Morris, a former government official, banker and self-taught historian of economics who as a prolific, iconoclastic author challenged conventional political and economic pieties, died on Monday [December 13, 2021] in Hampton, N.H.

. . .

Mr. Morris wrote his signature first book, “The Cost of Good Intentions: New York City and the Liberal Experiment” (1980), after serving as director of welfare programs under Mayor John V. Lindsay and as secretary of social and health services in Washington State.

The book was a trenchant Emperor’s New Clothes analysis of how the Lindsay administration’s unfettered investment in social welfare programs to ward off civil unrest had delivered the city to the brink of bankruptcy, and it pigeonholed Mr. Morris as a neoconservative.

But as a law school graduate with no formal training in economics, he defied facile labeling.

While his 15 nonfiction books often revisited well-trodden topics — including the Great Depression, the nation’s tycoons, the cost of health care, the Cold War arms race and the political evolution of the Roman Catholic church — he injected them with revealing details, provocative insights and fluid narratives.

“The Cost of Good Intentions” (1981) was less a screed about liberal profligacy as it was an expression of disappointment that benevolent officials had become wedded to programs that didn’t work. He concluded that the best and the brightest in the government, as well as complicit players on the outside, had figured that if a day of reckoning ever came, it would not be on their watch.

. . .

He would . . . belie Thomas Carlyle’s characterization of economics as “the dismal science” by injecting tantalizing nuggets.

Reviewing Mr. Morris’s “A Time of Passion: America 1960-1980” (1984) for The Times Book Review, Michael Kinsley wrote that “some of the most vivid moments in this book come when he stops the rush of history to describe incidents from his own time as a poverty-program and prison administrator.”

“He truly has been ‘mugged by reality,’ in Irving Kristol’s famous definition of a neoconservative,” Mr. Kinsley added, but concluded, “Overall, his book radiates a generosity and good will that set it apart from the typically sour neoconservative creed.”

. . .

“I think we’re heading for the mother of all crashes,” Mr. Morris wrote his publisher, Peter Osnos, the founder of PublicAffairs books, early in 2007, adding, “It will happen in summer of 2008, I think.”

Mr. Osnos recalled that after the book was published, “George Soros and Paul Volcker called me and asked, ‘Who is this Morris, and how did he get this so right, so early?’”

For the full obituary, see:

Sam Roberts. “Charles R. Morris, Author Who Disputed Economic Dogma, Dies at 82.” The New York Times (Wednesday, December 15, 2021): A24.

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

(Note: the online version of the obituary was updated Dec. 15, 2021, and has the title “Charles R. Morris, Iconoclastic Author on Economics, Dies at 82.”)

The books by Morris that I found especially useful were:

Morris, Charles R. The Dawn of Innovation: The First American Industrial Revolution. Philadelphia, PA: PublicAffairs, 2012.

Morris, Charles R. The Tycoons: How Andrew Carnegie, John D. Rockefeller, Jay Gould, and J. P. Morgan Invented the American Supereconomy. New York: Times Books, 2005.

EU Plans to Color Nuclear and Natural Gas as “Green,” Allowing a “Nuclear Renaissance”

(p. B6) The European Union has drawn up plans to classify some nuclear power and natural gas plants as green investments that can help Europe cut planet-warming emissions, a landmark proposal that, if approved, could set off a resurgence of nuclear energy on the continent in the coming decades.

The European Commission said it had begun consultations with European Union countries on the proposal, which is intended to provide a common set of definitions of what constitutes a “sustainable investment” in Europe. Any final plan can be blocked by a majority of member states or by the European Parliament.

“The Commission considers there is a role for natural gas and nuclear as a means to facilitate the transition towards a predominantly renewable-based future,” the statement, released on Saturday [January 1, 2022] said.

. . .

. . ., the political tide has increasingly turned in favor of nuclear power as a low-carbon solution to mitigate climate change — especially a new generation of smaller, cheaper plants across the globe, said George Borovas, head of nuclear practice at the global law firm Hunton Andrews Kurth.

“There will be a nuclear renaissance,” he said. “It’s not going to be for everyone, but it will be for a number of countries.”

Investment money wouldn’t start flowing right away, noted Ms. Drew of Credit Suisse. Banks will need to update their sustainable investment governance for funds offered to clients, to include nuclear and gas alongside renewable energy sources like wind and solar power.

And small modular nuclear reactor projects, in particular, still need to get off the ground. “It’s early days. You have a few people with business plans looking for funding,” she noted.

But as the industry scales up, so will the investments. A number of companies, from Rolls-Royce to Westinghouse, are working on models that can be put together in factories and assembled on site at the fraction of the cost of traditional behemoth nuclear plants.

For the full story, see:

Liz Alderman and Monika Pronczuk. “Europe Prepares to Classify Nuclear and Natural Gas as Green.” The New York Times (Tuesday, January 4, 2022): B6.

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

(Note: the online version of the story was updated Jan. 4, 2022, and has the title “Europe Plans to Say Nuclear Power and Natural Gas Are Green Investments.”)

Entrepreneurial Bystander Identifies Stranger’s Cancerous Mole and Saves His Life

(p. B9) Nadia Popovici kept shifting her eyes from the hockey game to the back of Brian Hamilton’s neck.

Mr. Hamilton, an assistant equipment manager for the Vancouver Canucks, had a small mole there. It measured about two centimeters and was irregularly shaped and red-brown in color — possible characteristics of a cancerous mole, signs that Ms. Popovici had learned to spot while volunteering at hospitals as a nursing assistant.

Maybe he already knew? But if so, why was the mole still there? She concluded that Mr. Hamilton did not know.

“I need to tell him,” Ms. Popovici, 22, told her parents at the Oct. 23 [2021] N.H.L. game between the Canucks and the Seattle Kraken at the Climate Pledge Arena in Seattle.

Ms. Popovici typed a message on her phone and waited for the game to end. After waving several times, she finally drew Mr. Hamilton’s attention, and placed her phone against the plexiglass.

“The mole on the back of your neck is possibly cancerous. Please go see a doctor!” the message read, with the words “mole,” “cancer” and “doctor” colored bright red.

Mr. Hamilton said he looked at the message, rubbed the back of his neck and kept walking, thinking, “Well, that’s weird.”

. . .

Indeed, Ms. Popovici was correct, and she had just saved his life.

. . .

Specifically, doctors later told him, it was type-2 malignant melanoma, a type of skin cancer that, because it was detected early, could be easily removed and treated.

For the full story, see:

Eduardo Medina. “Discovering Cancerous Mole From Stands, She Saves a Life.” The New York Times (Tuesday, January 4, 2022): B9.

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

(Note: the online version of the story was updated Jan. 4, 2022, and has the title “Hockey Fan Spots Cancerous Mole at Game and Delivers a Lifesaving Note.”)

Rational Environmentalism Takes Account of Costs of Climate Regulations

Source of graph: online version of WSJ article cited below, based on Nordhaus model.

(p. A19) The U.N. estimates that even if no country does anything to slow global warming, the annual damage by 2100 will be equivalent to a 2.6% cut in global gross domestic product. Given that the U.N. also expects the average person to be 450% as rich in 2100 as today, that figure falls only to 434% if the temperature rises unimpeded. This is a problem, but not the end of the world.

That means we don’t have to panic but instead can decide policy rationally. Economist William Nordhaus won the Nobel Prize in 2018 for his work on effective climate solutions, and the chart nearby shows the outcome of his model to find the optimal climate policy. His crucial point is that the damage global warming inflicts aren’t the only costly part of climate change; climate policies also create significant economic harm. Since we have to pay both costs, his model aims to minimize their sum.

. . .

That model shows that the optimal policy mix would be one that slows the average temperature’s rise so that by 2100 it only reaches 6.3 degrees. That’s the option that minimizes the total damages from climate change and climate policies.

. . .

. . . carbon taxes aren’t the only smart way to ameliorate climate change. There are two other effective solutions.

The first is innovation. If research could drive the cost of one source of clean energy below that of fossil fuels, consumers would switch with no prompting.

. . .

The second is economic growth. Just about every problem, including the dangers of global warming, are easier to deal with when people are more prosperous.

For the full commentary, see:

Bjorn Lomborg. “A Reasonable Alternative to Preaching Climate Doom.” The Wall Street Journal (Thursday, Nov. 11, 2021): A19.

(Note: ellipses added.)

(Note: the online version of the commentary was updated November 10, 2021, and has the title “A Reasonable Alternative to COP26 and Preaching Climate Doom.”)

The survey mentioned above is reported in detail in:

Association, American Psychological. “Stress in America™ 2021: Stress and Decision-Making During the Pandemic.” Washington, D.C., 2021.

“Intolerance Leads Not to Progress, but Stagnation”

(p. C10) . . . this past year I revisited the works of Friedrich Hayek, the great 20th-century expositor of classical liberalism. His most sweeping work is “The Constitution of Liberty”—a legal history as much as a defense of freedom—which includes a timely case for tolerance. We cannot foresee the particulars of human progress, which means “we shall never get the benefits of freedom, never obtain those unforeseeable developments for which it provides the opportunity,” if freedom “is not also granted where the uses made of it by some do not seem desirable.” Thus intolerance leads not to progress, but stagnation.

For the full review, see:

Raymond Kethledge. “12 Months of Reading; Raymond Kethledge.” The Wall Street Journal (Saturday, Dec. 11, 2021): C10.

(Note: ellipsis added.)

(Note: the online version of the review has the date December 10, 2021, and has the title “Who Read What: Business Leaders Share Their Favorite Books of 2021.”)

The book praised by Kethledge is:

Hayek, Friedrich A. The Constitution of Liberty. Reprint ed. Chicago: University of Chicago Press, 2011.