Category: Entrepreneurship

“Advances in Gene Sequencing” Have Not “Unlocked the Key to Cures for Cancer”

(p. 10) In his new book, “The Song of the Cell,” Siddhartha Mukherjee has taken on a subject that is enormous and minuscule at once. Even though cells are typically so tiny that you need a microscope to see them, they also happen to be implicated in almost anything to do with medicine — and therefore almost anything to do with life.

. . .

If Mukherjee were another kind of storyteller — tidier, if less honest — he could have showcased a more linear narrative, emphasizing how developments in cell research have yielded some truly amazing possibilities. He himself has been collaborating on a project to engineer certain cells in the immune system so that they eat tumors without stirring up an indiscriminate inflammatory response.

But as a practicing physician, he has seen too much suffering and death to succumb to an easy triumphalism. He recalls the “exuberance” of the mid-2000s, when spectacular advances in gene sequencing had made it appear as if “we had unlocked the key to cures for cancer.” Such exuberance turned out to be fleeting; the data from clinical trials were “sobering.”

Many medical mysteries remain unsolved. If the book’s protagonist — our understanding of cell biology — seemed to be riding high again on new advances in immunology, such “self-assuredness” was laid low by the Covid-19 pandemic. Mukherjee presents a string of questions that are still unsettled. “The monotony of answers is humbling, maddening,” he writes. “We don’t know. We don’t know. We don’t know.”

For the full review, see:

Jennifer Szalai. “Building Blocks.” The New York Times Book Review (Sunday, November 13, 2022): 10.

(Note: ellipsis added.)

(Note: the online version of the review was updated Nov. 2, 2022, and has the title “Siddhartha Mukherjee Finds Medical Mystery — and Metaphor — in the Tiny Cell.”)

The book under review is:

Mukherjee, Siddhartha. The Song of the Cell: An Exploration of Medicine and the New Human. New York: Scribner, 2022.

Toyota Pressured to “Dial Back” Its Defense of Hybrids as a Practical Bridge to EVs

(p. B2) Mr. Toyoda, Toyota’s chief, has been one of the industry’s most prominent voices of caution about EVs. He has questioned whether the vehicles are as environmentally friendly as advertised and expressed doubt that consumers want them.

Toyota has said it believes hybrids can reduce carbon emissions while the battery supply chains and charging networks necessary to support big fleets of EVs are built globally over the coming decades. Hybrid cars—which made up nearly 30% of Toyota and Lexus global shipments for the most recent quarter—are helping the auto maker meet tightening emissions rules in markets like Europe.

Demand for hybrids also helped Toyota reach a record operating profit of ¥3 trillion, equivalent to $21 billion, for the fiscal year ended in March. Its stock price on the Tokyo Stock Exchange has held up reasonably well, down 9% this year, while other auto makers have suffered steeper declines.

Mr. Toyoda has been trying to understand why some investors and environmental groups remain unconvinced about the company’s electrification strategy.

. . .

People at Toyota said company executives have been advised by public-relations specialists and others in the company to dial back negative comments about EVs and instead highlight their benefits as well as Toyota’s extensive investments in the technology.

Sage Advisory Services, an investment management firm in Austin, Texas, that holds Toyota bonds, said it has sensed a shift in rhetoric.

Sage Advisory had approached the car maker last year with concerns about its EV stance, to which Toyota responded with its usual arguments, including about hybrid cars, said Sage Vice President Emma Harper. She said the points made sense to her but were hard for the general public to grasp.

More recently, she said, Toyota has “flipped over and they’ve felt the change in the tide and how consumers and politicians and other stakeholders are feeling about the transition away from fossil-fuel cars.”

For the full story, see:

River Davis. “Toyota Aims to Face Critics of Its EV Policies.” The Wall Street Journal (Monday, Sept. 26, 2022): B1-B2.

(Note: ellipsis added.)

(Note: the online version of the story has the date September 25, 2022, and has the title “Toyota Softens Toward Critics of Its EV Push.” Where the versions differ, the quotes above follow the more detailed online version.)

The Sassoon Family’s Rags-to-Riches-to-Rags Story

(p. 8) The rise and fall of the Sassoon family, who, at their height, traded in opium, tea, silk and jewels, is charted in delectable detail in “The Sassoons: The Great Global Merchants and the Making of an Empire,” by the historian Joseph Sassoon, a distant relative who seems just as pleased as anyone unrelated might be to uncover the grit and gains of a tribe of fascinating figures.

. . .

Rags-to-riches stories may all be the same, but it’s the way in which a fortune is lost that’s truly compelling. Sassoon’s detailed account of the decentralization of family power and the proliferation of descendants interested in spending but not making money is well paced and supremely satisfying. An observer of the clan notes that “nothing suppresses an appetite for commerce more than a diet of gentlemanly pursuits,” and readers are treated through the second half of the book to a slow-motion sputtering out of David Sassoon’s great machine. You find yourself feeling for them: While masters of the universe inspire little sympathy, knowing from the first page that this empire has crumbled allows you to mourn the sunset of a particular kind of existence, even as a part of you revels in it.

For the full review, see:

Adam Rathe. “Dynasty.” The New York Times Book Review (Sunday, November 6, 2022): 8.

(Note: ellipsis added.)

(Note: the online version of the review was updated Oct. 25, 2022, and has the title “The Rise and Fall of a Great Dynasty.”)

The book under review is:

Sassoon, Joseph. The Sassoons: The Great Global Merchants and the Making of an Empire. New York: Pantheon, 2022.

“I Was There and I Was a Part of This Wonderful Thing That He Was Doing”

(p. A20) If Snow White looked suitably snowy in “Snow White and the Seven Dwarfs,” if Pinocchio’s nose grew at just the right rate, if Dumbo was the correct shade of elephantine gray, all that was due in part to the largely unheralded work of Ruthie Tompson.

. . .

In 1922, after her parents divorced and her mother married John Roberts, a plein-air painter, Ruthie and her sister moved with her mother and stepfather to Los Angeles, where her mother worked as an extra in Hollywood movies. The family lived down the street from Robert Disney, an uncle of Walt Disney and his brother Roy.

The Disney brothers founded their first film studio nearby in 1923, and it happened to be on Ruthie Tompson’s route to school. Walking past it each day, she peered through a window, transfixed, as the work of animation unfolded.

One day, Walt Disney spied her.

“He came out and said, ‘Why don’t you go inside and watch?’” Ms. Tompson recalled some nine decades later in a podcast for the Walt Disney Family Museum.

“I was really fascinated,” she said. She returned to the studio many times, becoming something of a fixture there.

During those years, the studio was shooting the Alice Comedies, a series of silent shorts combining animation and live action, and sometimes enlisted neighborhood children as extras.

Among them was Ruthie, who appeared in several pictures, receiving 25 cents for each. Her cinematic salary, Ms. Tompson recalled, went toward licorice.

Her association with the Disneys might well have ended there had it not been for the fact that a decade later Walt and Roy chose to take polo lessons.

. . .

“Ruthie Tompson!” Walt Disney declared on seeing her there. “Why don’t you come and work for me?”

“I can’t draw worth a nickel,” she replied.

No matter, Mr. Disney told her: The studio would send her to night school to learn the rudiments of inking and painting.

“Of course,” Ms. Tompson recalled, “everybody around me said: ‘Don’t say no! Don’t say no!’”

. . .

In 1948, she was promoted to the dual role of animation checker and scene planner. As an animation checker, she scrutinized the artists’ work to see, among other things, that characters literally kept their heads: In the animators’ haste, different parts of a character’s body, often done as separate drawings, might fail to align.

The scene planner was tasked with working out the intricate counterpoint between the finished setups and the cameras that photographed them: which camera angles should be used, how fast characters should move relative to their backgrounds, and the like.

“She really had to know all the mechanics of making the image work on the screen as the director, the layout person and the animator preferred: how to make Peter Pan walk, or fly, in the specified time,” Mr. Canemaker explained. “What she did ended up on the screen — whether you see her hand or not — because of the way she supported the directors’ vision.”

. . .

In the Walt Disney Family Museum podcast, Ms. Tompson fondly recalled her long-ago association with Walt Disney and the unexpected career to which it gave rise.

“I never got over being awe-struck at the fact that I was there and I was a part of this wonderful thing that he was doing,” she said.

For the full obituary, see:

Margalit Fox. “Ruthie Tompson, Invisible Hand Behind Pinocchio’s Nose, Dies at 111.” The New York Times (Wednesday, October 13, 2021): A20.

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

(Note: the online version of the obituary has the date Oct. 12, 2021, and has the title “Ruthie Tompson Dies at 111; Breathed Animated Life Into Disney Films.”)

Through Evolution, Body Parts Are Inelegantly Repurposed into Workaround Kluges

If the body itself is an amalgam of workaround kluges, then maybe our regulators should be more tolerant of medical MacGyvers who attempt to keep the body working through medical workaround kluges.

(p. A15) Mr. Pievani is a professor of biology at the University of Padua. His brief and thoughtful book (translated from the Italian by Michael Gerard Kenyon) isn’t just a description of imperfection, but a paean to it. There’s plenty of description and discussion, too, as “Imperfection” takes the reader on a convincing whirlwind tour of the dangers as well as the impossibility of perfection, how imperfection is built into the nature of the universe, and into all living things—including ourselves.

. . .

Readers wanting to get up to speed on imperfection would do well to attend to two little-known words with large consequences. The first is “palimpsest,” which in archaeology refers to any object that has been written upon, then erased, then written over again (sometimes many times), but with traces of the earlier writings still faintly visible. Every living thing is an evolutionary palimpsest, with adaptations necessarily limited because they’re built upon previous structures.

Consider, for example, childbirth. As smart critters, we’ve been selected (naturally) to have big heads. But in becoming bipedal, we had to rotate our pelvises, which set limits on the size of the birth canal. As a result, an unborn baby’s head is perilously close to being too big to get out. Usually, they manage it, but not without much painful laboring and sometimes, if this cephalopelvic disproportion is too great, or if the baby is malpositioned, by means of a cesarean delivery. In such cases, obstetricians take the newborn out the obvious way: through that large, unobstructed abdominal space between pelvis and lower ribs. Things would have been much easier and safer for mother and baby if the birth canal were positioned there, too, but our palimpsest nature precludes such a straightforward arrangement.

Which brings us to our second unusual word: “kluge,” something—assembled from diverse components—that shouldn’t work, but does. A kluge is a workaround: often clumsy, inelegant, inefficient, but that does its job nonetheless. Because we and all other living things are living palimpsests, we are kluges as well.

For the full review, see:

David P. Barash. “BOOKSHELF; Unintelligent Design.” The Wall Street Journal (Wednesday, October 26, 2022): A15.

(Note: ellipsis added.)

(Note: the online version of the review has the date October 25, 2022, and has the title “BOOKSHELF; ‘Imperfection’ Review: Unintelligent Design.”)

The book under review is:

Pievani, Telmo. Imperfection: A Natural History. Translated by Michael Gerard Kenyon. Cambridge, MA: The MIT Press, 2022.

California Law Mandating $22 Wage for Restaurant Workers Is “Discouraging” Entrepreneurs

(p. A3) A government-appointed council could increase wages for California’s estimated half-million fast food workers to as much as $22 an hour starting next year, under a new law signed by Gov. Gavin Newsom Monday [September 5, 2022].

. . .

“You can’t charge enough for food to offset what will happen from a labor perspective,” said Greg Flynn, president of Flynn Restaurant Group, which operates franchise brands in 44 states and owns 105 restaurants in California. “California is already the most difficult state in the nation to operate as a restaurateur. This just makes it more difficult and less attractive.”

. . .

Michaela Mendelsohn, an El Pollo Loco franchisee in Southern California, said she recently put on hold plans to add to her group of six stores because of the measure.

If wages shoot up, she added, she will consider eliminating cashier positions or installing kiosks in her California locations that allow customers to input orders.

“We’ve gone too far here,” Ms. Mendelsohn said. “It’s just really discouraging.”

For the full story, see:

Christine Mai-Duc and Heather Haddon. “California Fast-Food Bill Signed, Opening Path to Higher Pay.” The New York Times (Tuesday, September 6, 2022): A3.

[Note: ellipses, and bracketed date, added.]

(Note: the online version of the story was updated Sept. 5, 2022, and has the title “California Governor Signs Fast Food Bill, Opening Way to Higher Wages.” The last two sentences quoted above appeared in the online, but not the print, version.)

Entrepreneurs Harvest Useful Protein Collagens From “Precision Fermentation” Rather Than From Slaughter of Animals

(p. B4) The multibillion-dollar push to make animals obsolete in the food industry has already produced pea-protein “bratwurst,” fungus molded into “ham” and “leather,” and “meat” cultured from chicken cells. Geltor, a seven-year-old company based in the Bay Area, is taking a different tack: bioengineering bacteria cells to produce animal proteins you’ll likely never taste.

Geltor is producing forms of collagen they say are identical to the proteins extracted from skin and bones. For now, those vegan collagens can be found in high-end skin care creams. But as the company grows, it’s eyeing other ingredients few Americans associate with animal farming, such as the elastin in your shampoo, the collagen peptides in your smoothie, and even the gelatin (which is hydrolyzed, or slightly broken-down, collagen) in your marshmallows. Alex Lorestani, co-founder and chief executive of Geltor, likes to talk about how the company’s proteins impose a lighter burden on the environment than the meat industry. The challenge, however, is how the company gets to the scale necessary to exert that kind of impact.

In 2012, Dr. Lorestani and co-founder Nick Ouzounov, both 35, were both pursuing doctorates in molecular biology at Princeton University when the invention of Crispr turbocharged the field of bio-design. “We can bio-design medicine,” Dr. Lorestani recalled discussing with his labmates that summer. “Why can’t we bio-design everything?”

Dr. Ouzounov eventually came up with a method — which he and Dr. Lorestani, in typical Bay Area techspeak, call “a platform” — for genetically modifying bacteria cells to reproduce a wide variety of animal proteins, a process that biotech firms are calling “precision fermentation.” In 2015, the two scientists formed Geltor.

For the full story, see:

Jonathan Kauffman. “Going Beyond Vegan ‘Meat’ to Bio-Designed Collagen.” The New York Times (Wednesday, August 3, 2022): B4.

(Note: the online version of the story has the date August 2, 2022, and has the title “Is Bio-Designed Collagen the Next Step in Animal Protein Replacement?”)

Medical Entrepreneurs “Muster the Courage and Determination to Forge Brazenly Ahead”

(p. C7) The accidental birth and stuttering development of cell biology is the focus of Siddhartha Mukherjee’s “The Song of the Cell.” It is an audacious, often mesmerizing, frequently dizzying, occasionally exhausting and reliably engaging tour of cell biology and scientific inquiry. Dr. Mukherjee, an oncologist at Columbia University and the author of “Emperor of All Maladies: A Biography of Cancer” (2010), enthusiastically instructs and, much of the time, delights—all the while hustling us across a preposterously vast and intricate landscape.

. . .

In the course of describing the evolution of cell biology, Dr. Mukherjee reminds us of the critical role of technological innovation, like the microscopes used by Leeuwenhoek and Hooke, which first revealed the existence of the cellular world. Similarly, it was the invention of the electron microscope, and its deliberate application to biology by pioneering Rockefeller University scientist George Palade, that afforded researchers the resolution needed to examine the components of an individual cell.

. . .

Dr. Mukherjee’s dual roles as clinical oncologist and cell biologist find a common voice as he grapples with the complexity of cancer, “cell biology visualized in a pathological mirror.” He notes the heterogeneity of tumors, observing that while “two ‘breast cancers’ may look identical under the pathologist’s microscope,” the cancers may differ genetically and require different treatments. Even a single breast tumor, he writes, “is actually a collage of mutant cells—an assembly of non-identical diseases.” Because of the maddening similarity between cancer cells and normal cells, targeting cancer can be challenging: A promising therapy may fail, as it did for one of his friends, because it also attacks healthy cells.

Ultimately, Dr. Mukherjee seems to decide, we must accept, rather than rationalize away, the baffling idiosyncrasies that we observe in cell biology and see reflected in the behavior of cancers. Why did his friend’s cancer spread to some organs but spare others? Why did the treatment his friend received eliminate tumors in the skin but not the lungs? “There are mysteries beyond mysteries,” he writes, and he cautions us against succumbing to reductionist explanations. Cells, by themselves, are “incomplete explanations for organismal complexities.” We must understand the context in which a cell exists, he emphasizes, its local environment. Even then, he admits, we often “don’t even know what we don’t know.”

Dr. Mukherjee’s hard-won lessons contain a message for us all: We should resist simple, universal explanations in life science—cell biology, in particular, is rarely that cooperative. The journey he relates also reminds us to appreciate the researchers who, despite the unforgiving and rarely predictable terrain before them, muster the courage and determination to forge brazenly ahead.

For the full review, see:

David A. Shaywitz. “Fantastic Voyage Within.” The Wall Street Journal (Saturday, October 29, 2022): C7.

(Note: ellipses added.)

(Note: the online version of the review has the date October 28, 2022, and has the title “‘The Song of the Cell’ Review: Fantastic Voyage Within.”)

The book under review is:

Mukherjee, Siddhartha. The Song of the Cell: An Exploration of Medicine and the New Human. New York: Scribner, 2022.

Chargers for Electric Vehicles “Are Often Broken”

(p. B1) The electric vehicle revolution is nearly here, but its arrival is being slowed by a fundamental problem: The chargers where people refuel these cars are often broken. One recent study found that about a quarter of the public charging outlets in the San Francisco Bay Area, where electric cars are commonplace, were not working.

. . .

Many sit in parking lots or in (p. B3) front of retail stores where there is often no one to turn to for help when something goes wrong. Problems include broken screens and buggy software. Some stop working midcharge, while others never start in the first place.

Some frustrated drivers say the problems have them second-guessing whether they can fully abandon gas vehicles, especially for longer trips.

“Often, those fast chargers have real maintenance issues,” said Ethan Zuckerman, a professor at the University of Massachusetts Amherst who has owned a Chevrolet Bolt for several years. “When they do, you very quickly find yourself in pretty dire straits.”

In the winter of 2020, Mr. Zuckerman was commuting about 150 miles each way to a job at the Massachusetts Institute of Technology. The cold winter weather can reduce the driving range of electric cars, and Mr. Zuckerman found himself needing a charge on the way home.

He checked online and found a station, but when he pulled up to it, the machine was broken. Another across the street was out, too, he said. In desperation, Mr. Zuckerman went to a nearby gas station and persuaded a worker there to run an extension cord to his car.

“I sat there for two and a half hours in the freezing cold, getting enough charge so that I could limp to the town of Lee, Mass., and then use another charger,” he said. “It was not a great night.”

The availability and reliability of public chargers remains a problem even now, he said.

. . .

There are few rigorous studies of charging stations, but one conducted this year by Cool the Earth, an environmental nonprofit in California, and David Rempel, a retired professor of bioengineering at the University of California, Berkeley, found that 23 percent of 657 public charging stations in the Bay Area were broken. The most common problems were that testers could not get chargers to accept payment or initiate a charge. In other cases, screens went blank, were not responsive or displayed error messages.

“Here we have actual field data, and the results, frankly, were very concerning,” said Carleen Cullen, executive director of Cool the Earth.

. . .

At most gas stations, a clerk is usually on duty and can see when some problems arise. With chargers, vandalism or other damage can be more difficult to track.

“Where there’s a screen, there’s a baseball bat,” said Jonathan Levy, EVgo’s chief commercial officer.

For the full story, see:

Niraj Chokshi. “E.V. Hassle: Locating A Charger That Works.” The New York Times (Tuesday, August 16, 2022): B1 & B3.

(Note: ellipses added.)

(Note: the online version of the story has the same date as the print version, and has the title “A Frustrating Hassle Holding Electric Cars Back: Broken Chargers.”)

Steve Jobs “Was Not Driven by the Financial Results”

(p. B2) Apple Inc. Chief Executive Tim Cook on Wednesday [Sept. 7, 2022] shot down any hope of ending the great blue-bubble, green-bubble divide between users of his iPhones and Google’s Android devices.

. . .

Mr. Cook shared the stage Wednesday with Jony Ive, the tech company’s former chief design officer, and Laurene Powell Jobs, Mr. Jobs’s widow, as they reminisced 15 years after the introduction of the iPhone.

. . .

“He was not driven by the financial results,” Mr. Cook said. Instead, he said, Mr. Jobs was focused on making products. “He was never confused about focusing on the indirect consequence—on the market and the financial results,” Mr. Cook said. “He focused on the inputs: getting the products right, making sure they were the best; making sure they were making a difference in people’s lives.”

. . .

“There was something beautiful about the way Steve thought,” Mr. Ive said.

For the full story, see:

Tim Higgins. “Apple CEO Reflects on Jobs Legacy.” The Wall Street Journal (Friday, September 9, 2022): B2.

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

(Note: the online version of the story has the date September 8, 2022, and has the title “Tim Cook Advises Man Concerned About Green Text Bubbles: ‘Buy Your Mom an iPhone’.”)

“Self-Taught Rocket Engineer” and Entrepreneur Nimbly Launches “Light Rockets”

(p. B12) On Thursday [August 4, 2022] a spy satellite run by the U.S. National Reconnaissance Office shot into space from New Zealand. The rocket carrying it, the Electron, was built by Rocket Lab increase; green up pointing triangle, a U.S.-Kiwi startup founded in 2006 by self-taught rocket engineer Peter Beck.

Shortly after Russia’s invasion of Ukraine, satellite-intelligence firm BlackSky asked Rocket Lab for an orbit change just days before it was due to launch, in order to place its satellites more directly over the conflict zone. While changing such missions has traditionally taken months, Rocket Lab pulled it off in 45 days.

These are examples of the new opportunities opened up by governments’ desire for “responsive launch.” While Elon Musk’s SpaceX has spent years revolutionizing the space economy with its large reusable Falcon rockets, a raft of startups have recently stepped in to provide light rockets that are more expensive in terms of price per kilogram, but can send small satellites to specific orbits with extremely fast turnaround times.

. . .

After a year of unrestrained euphoria, when all sorts of “pre-revenue” startups merged with special-purpose acquisition companies, or SPACs, rising interest rates have prompted traders to shun speculative ventures, including fintech innovations, air taxis and, yes, small-satellite launchers.

This has shrouded Rocket Lab, Virgin Orbit and Astra Space, which all went public through SPACs last year, in a cloud of negative sentiment.

. . .

Beyond launching 149 satellites into space so far, Rocket Lab also sent NASA’s CAPSTONE spacecraft on its way to the moon’s orbit in June. A month earlier, it caught an Electron booster in midair with a helicopter—a key step toward making the rocket reusable.

For the full commentary, see:

Jon Sindreu. “Rocket Lab Is Science, Not Fiction.” The Wall Street Journal (Wednesday, Aug. 10, 2022): B12.

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

(Note: the online version of the commentary has the date August 9, 2022, and has the title “Rocket Lab Is Already Science, Not Fiction.”)