Category: Entrepreneurship

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.”)

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.

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.”)

“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.

At the University of Austin, the Intellectually Diverse Will Discuss, Rather Than Censor, “Provocative Questions”

(p. A16) A group of scholars and activists are planning to establish a new university dedicated to free speech, alarmed, they said, “by the illiberalism and censoriousness prevalent in America’s most prestigious universities.”

The university, to be known as the University of Austin, or UATX for short, will have a soft start next summer with “Forbidden Courses,” a noncredit program that its founders say will offer a “spirited discussion about the most provocative questions that often lead to censorship or self-censorship in many universities.”

The university then plans to expand to master’s programs and, in several years, to undergraduate courses.

. . .

The prospective university’s board of advisers features some of the most prominent iconoclasts in the country, including Lawrence H. Summers, the former Harvard president; Steven Pinker, a Harvard linguist and psychologist; David Mamet, the playwright; and Glenn Loury, an economist at Brown.

. . .

“I think new models for a university are important,” Dr. Pinker said, “because current universities are locked into a strange business model: exorbitant tuition, a mushrooming bureaucracy, and obscure admissions policies that are neither meritocratic nor egalitarian, combined with plummeting intellectual diversity and tolerance for open inquiry (which is, after all, a university’s raison d’être).”

For the full story, see:

Anemona Hartocollis. “Organizers Plan New University They Say Will Defend Free Speech.” The New York Times (Tuesday, November 9, 2021): A16.

(Note: ellipses added.)

(Note: the online version of the story has the date Nov. 8, 2021, and has the title “They Say Colleges Are Censorious. So They Are Starting a New One.”)

Louise Slade Was “Well Compensated” for Her Role in 47 Kraft Patents

(p. B7) Louise Slade, a groundbreaking food scientist whose work you can thank for soft-from-the-freezer ice cream, extra-chewy cookies and potato chips that retain their satisfying crunch despite being baked and not fried, died on Oct. 7 [2021] in Morristown, N.J.

. . .

It has been said that cooking is an art but baking is a science, and perhaps no one understood that adage better than Dr. Slade, whose research focused on how to keep dough, bread, cookies and crackers tasting delicious even after weeks on a grocery store shelf.

. . .

Dr. Slade’s great insight, which she developed over some 25 years as a scientist at General Foods and Kraft, was to consider food not as a combination of discrete ingredients but as a system of interacting molecules. By understanding those interactions, one could build predictive models for how, for example, to tweak a bread recipe to make it stay fresh longer without chemical preservatives.

“She was the only person I knew who could swim among the molecules and understand them at their most fundamental level,” Hamed Faridi, the executive director of the McCormick Science Institute, said in an interview. “Her strength was her impressive knowledge of how those molecules interact to create flavor and texture.”

. . .

“A lot of what Louise established was how to make products consistent and stable without putting in a lot of additives consumers don’t want,” Todd Abraham, who worked with Dr. Slade at Kraft, said in an interview.

Dr. Slade provided not just a framework for answering those challenges but also a voluminous amount of research: She and Dr. Levine, who worked together for much of their professional careers, published some 260 papers and received 47 patents. She once estimated that the patents she received for her corporate employers were worth more than $1 billion.

. . .

She also began to work with the Monell Chemical Senses Center, an independent research institution in Philadelphia that studies taste and smell; she eventually joined its board.

Personally frugal and well compensated for her corporate work, Dr. Slade became one of Monell’s chief donors, giving more than $2 million in her lifetime, Dr. Gary Beauchamp, the center’s emeritus director, said.

For the full obituary, see:

Clay Risen. “Louise Slade, Scientist Who Ensured Your Goodies Stay Good, Is Dead at 74.” The New York Times (Monday, November 1, 2021): B7.

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

(Note: the online version of the obituary was updated Nov. 1, 2021, and has the title “Louise Slade, Scientist Who Studied the Molecules in Food, Dies at 74.”)

Pharmaceutical Entrepreneur Solomon Got Rich by Finding a Drug to Help His Son

(p. A19) Howard Solomon was building the pharmaceutical company Forest Laboratories, not by manufacturing drugs but by licensing them. In his search for deals in the United States and Europe, he learned about citalopram, a Danish antidepressant. He did not license it, though, believing the U.S. market was saturated with drugs to treat depression.

Then, in 1994, a family crisis intervened: His older son, the writer Andrew Solomon, had fallen into a deep depression. Mr. Solomon moved Andrew into his apartment on the Upper East Side of Manhattan and took weeks off from work to take care of him; . . . .

. . .

After two types of antidepressants were unable to help Andrew, a third did. His experience persuaded his father to make the deal a few years later for citalopram, which, under the name Celexa, became a billion-dollar drug for Forest Labs in the class of selective serotonin reuptake inhibitors, along with Prozac, Zoloft and Paxil.

. . .

Forest Labs was transformed by licensing Celexa from H. Lundbeck, the Danish company that developed it. But Lundbeck’s chief executive, Erik Sprunk-Jansen, was initially reluctant to speak to Mr. Solomon because licensing deals with some other U.S. companies had unraveled.

“Howard flew to Denmark to meet with him,” Phil Satow, a former executive vice president of Forest Labs, said in a phone interview. “Both were lovers of ballet, which became the common chord between them, and they developed a strong relationship.”

Celexa’s sales grew quickly, peaking at nearly $1.5 billion in 2003. Forest Labs then licensed Lexapro, an upgraded version of Celexa, which first reached $2 billion in sales in 2007.

. . .

His desire to work into his 80s was, he said, inspired by the example of Giuseppe Verdi.

“Growing up, he’d talk about Verdi writing ‘Falstaff’ in his 80s,” Andrew Solomon said. “‘Imagine that,’ he’d say, ‘in his 80s, he wrote some of the greatest music ever written.’ That was the path he hoped to follow.”

For the full obituary, see:

Richard Sandomir. “Howard Solomon, 94, Whose Business Feats Were Personal, Is Dead.” The New York Times (Wednesday, January 19, 2022): A19.

(Note: ellipses added.)

(Note: the online version of the obituary was updated Jan. 18, 2022, and has the title “Howard Solomon, 94, Dies; His Business Success Had a Personal Connection.”)

Boeing Maximized Short-Term Profits Instead of Long-Term Quality (and Profits)

(p. A19) Boeing remains one of America’s leading manufacturers, but it is reduced in reputation as well as equity. The “fall” that Mr. Robison’s subtitle alludes to is the corrosion of a culture that had emphasized quality.

. . .

Mr. Robison is upset that Boeing followed the unremarkable philosophy of the Business Roundtable (recently revised under woke pressure) that the first duty of any company is to its shareholders. He says that Boeing focused on metrics that “tend to favor investors over employees and customers.” This is an easy but misworded critique. In the long term, the interests of shareholders and customers are aligned. A manufacturer that disregards either customers or employees will eventually not have profits to distribute.

In fact, Boeing forgot that its long-term success depended on its reputation for superior engineering. Executives like Alan Mulally, project leader in the 1990s for the costly but highly successful Boeing 777, were passed over for the top job. The corporate metamorphosis was accelerated by the 1997 merger with rival McDonnell Douglas. The executive suite was colonized by such figures as McDonnell’s Harry Stonecipher, a Jack Welch protégé who was explicit about changing the culture. His intent, he said, was to run Boeing “like a business rather than a great engineering firm.” Increasingly that meant doing whatever it took to hike the share price. Phil Condit, the CEO who orchestrated the merger, pushed his managers to quintuple the stock in five years, which suggested that his eye was on Wall Street and not on the planes.

. . .

Test flights showed a tendency for the MAX to pitch up. Designers corrected the problem on the cheap, with software that pushed the nose down. Somewhat perilously, a single sensor measuring the angle of the wings against oncoming air could force the plane into a downward trajectory. An optional cockpit indicator—alerting pilots that the sensor might be faulty—was not included on cheaper models. And the sensors, which sat outside the plane, were vulnerable to bird strikes or improper installation.

. . .

. . ., the FAA, as Mr. Robison shows, was compromised by years of having adapted its regulatory role to promote manufacturers. Even after the first plane went down, it kept the MAX flying—despite an agency analysis predicting more crashes.

For the full review, see:

Roger Lowenstein. “BOOKSHELF; Downward Trajectory.” The Wall Street Journal (Monday, Nov. 29, 2021): A19.

(Note: ellipses added.)

(Note: the online version of the review has the date November 28, 2021, and has the title “BOOKSHELF; ‘Flying Blind’ Review: Downward Trajectory.”)

The book under review is:

Robison, Peter. Flying Blind: The 737 MAX Tragedy and the Fall of Boeing. New York: Doubleday, 2021.