Category: Entrepreneurship

Executive Chose “Exciting” Entrepreneurship, and Failed

We read the stories of those who choose entrepreneurship and succeed. The stories of those who choose entrepreneurship and fail, are less often told. Those who fail do not always regret their choice, nor should they.

(p. A21) Alex Mandl was a leading contender for the chief executive job at AT&T Corp. in 1996 when he defected to head a wireless-telecommunications startup that became Teligent Inc.

. . .

Heading a startup, he said, was “the most exciting thing to do.”

Teligent had ambitious plans to undercut prices of traditional phone companies by setting up a microwave network that would beam voice and data to business users via rooftop antennas. But Teligent had technical problems, losses piled up and investors fled. Mr. Mandl resigned as chief executive in April 2001, shortly before the company filed for Chapter 11 bankruptcy.

For the full obituary, see:

James R. Hagerty. “Executive Risked Career on a Startup.” The Wall Street Journal (Saturday, April 2, 2022): A21.

(Note: ellipsis added.)

(Note: the online version of the obituary has the date April 1, 2022, and has the title “Alex Mandl, Who Gave Up a Top AT&T Job to Lead a Startup, Has Died at Age 78.”)

Discoverer of Catalyst Role of mRNA Had Trouble “Getting His Work Published”

(p. B12) Sidney Altman, a molecular biologist who was awarded the Nobel Prize for Chemistry for sharing in the discovery that ribonucleic acid, or RNA, was not just a carrier of genetic information but could also be a catalyst for chemical reactions in cells — a breakthrough that paved the way for new gene therapies and treatments for viral infections — died on April 5 [2022] in Rockleigh, N.J.

. . .

HAs seems to happen so often in science, Dr. Altman stumbled upon his discovery. “I wasn’t looking for what I found,” he said in a 2010 interview with Harry Kreisler at the Institute for International Studies at the University of California, Berkeley.

He had studied how a small RNA molecule, called transfer RNA, carries genetic code to make new proteins. Some of the code is not necessary, so an enzyme cuts it out before it is used.

Then, in 1978, Dr. Altman began studying an RNA-cutting enzyme from E. coli bacteria that was composed of an RNA molecule and a protein. He managed to separate the two pieces and test them to see how they reacted in the enzyme process. Much to his surprise, he discovered that the protein did not perform as an enzyme without the RNA molecule. He later discovered that the RNA molecule could be the catalyst, even without the protein.

The finding ran completely contrary to what at the time was established theory, which held that it was the proteins that were the catalysts in enzymes.

The discovery of what are now known as ribozymes was so radical that Dr. Altman had trouble getting it accepted.

Joel Rosenbaum, a professor of cell biology at Yale and a colleague of Dr. Altman’s, told Chemistry World magazine that when Dr. Altman first tried to get other scientists to accept his research, “the community of molecular biologists, including several at Yale working on RNA, did not want to believe the work.”

“He had a hard time obtaining invitations to speak at scientific meetings and, indeed, getting his work published,” Dr. Rosenbaum said.

For the full obituary, see:

Dylan Loeb McClain. “Sidney Altman, Who Stumbled on a Breakthrough in Genetics, Dies at 82.” The New York Times (Saturday, April 16, 2022): B12.

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

(Note: the online version of the obituary was updated April 18, 2022, and has the same title as the print version.)

CAR T Therapy Is a Durable “Cure” for Some Leukemia Cancers

(p. A17) Doug Olson was feeling kind of tired in 1996. When a doctor examined him she frowned. “I don’t like the feel of those lymph nodes,” she said, poking his neck. She ordered a biopsy. The result was terrifying. He had chronic lymphocytic leukemia, a blood cancer that mostly strikes older people and accounts for about a quarter of new cases of leukemia.

“Oh Lordy,” Mr. Olson said. “I thought I was done for.” He was only 49 and, he said, had always been healthy.

Six years went by without the cancer progressing. Then it started to grow. He had four rounds of chemotherapy but the cancer kept coming back. He had reached pretty much the end of the line when his oncologist, Dr. David Porter at the University of Pennsylvania, offered him a chance to be among the very first patients to try something unprecedented, known as CAR T cell therapy.

In 2010, he became the second of three patients to get the new treatment.

At the time, the idea for this sort of therapy “was way out there,” said Dr. Carl June, the principal investigator for the trial at Penn, and he had tempered his own expectations that the cells he was providing to Mr. Olson as therapy would survive.

“We thought they would be gone in a month or two,” Dr. June said.

Now, a decade later, he reports that his expectations were completely confounded. In a paper published Wednesday in Nature, Dr. June and his colleagues, Dr. J. Joseph Melenhorst and Dr. Porter, report that the CAR T treatment made the cancer vanish in two out of the three patients in that early trial. All had chronic lymphocytic leukemia. The big surprise, though, was that even though the cancer seemed to be long gone, the CAR T cells remained in the patients’ bloodstreams, circulating as sentinels.

“Now we can finally say the word ‘cure’ with CAR T cells,” Dr. June said.

Although most patients will not do as well, the results hold out hope that, for some, their cancer will be vanquished.

For the full story, see:

Gina Kolata. “Potential Leukemia Cure Leads to New Mysteries.” The New York Times (Thursday, February 3, 2022): A17.

(Note: the online version of the story has the date Feb. 2, 2022, and has the title “A Cancer Treatment Makes Leukemia Vanish, but Creates More Mysteries.”)

BioNTech Is Running Clinical Trials for mRNA Cancer Vaccines

(p. C2) Scientists are . . . advancing mRNA vaccines and therapies to treat cancer, which poses a particular challenge because tumor cells arise from the body’s own cells and can easily deceive the immune system into thinking they are normal. Cancer patients today receive varying types of treatments, but they involve therapies manufactured outside the body. The mRNA researchers believe that the body’s own immune system can be used against cancer if it’s given the right tools.

BioNTech, now a household name for its Covid-19 vaccine with Pfizer, was founded in 2008 to pursue mRNA cancer treatments. The German company says that even at a low dose, a strong enough mRNA treatment can be developed to prompt immune cells to make certain proteins and to train the rest of the immune system to recognize and target tumor cells that express these same proteins. “It needs to be louder and more aggressive for cancer because the immune system needs stronger persuasion to attack something that appears to resemble a normal cell which it should respect and not attack,” said Özlem Türeci, BioNTech’s chief medical officer.

The company’s pipeline includes at least 10 cancer vaccines in human clinical trials using mRNA for skin, pancreatic, ovarian and other tumors. Two of its most advanced programs in mid-stage clinical studies, one for melanoma and the other for head and neck cancer, harness mRNA to make specific proteins seen with these cancers that will prompt a vigorous response from the patient’s immune system. Research from BioNTech published in 2020 in the journal Nature showed that the treatment caused the lesions of melanoma patients to shrink.

Some of BioNTech’s other cancer treatments are tailored to individual patients. A tumor is removed surgically and then shipped to the company’s laboratories, where researchers sequence the DNA and search for proteins, using machine learning to decide which ones are needed for that individual’s therapy. To address how quickly cancer can spread in the body, BioNTech designs and develops these clinical-trial treatments in just four to six weeks—a potentially lifesaving turnaround time for more pressing cases.

For the full essay, see:

Jared S. Hopkins and Felicia Schwartz. “Can the Technology Behind Covid Vaccines Cure Other Diseases?” The Wall Street Journal (Saturday, February 5, 2022): C1-C2.

(Note: ellipsis added.)

(Note: the online version of the essay has the date February 4, 2022, and has the same title as the print version.)

Some Venture Capitalists “Act as Mentors,” Some Install Seasoned Veterans as C.E.O.s, and Some Are “Founder-Friendly,” Allowing Genius “to Do Its Work”

(p. C4) . . . Mallaby never quite settles on the story he wants to tell. He introduces the book by laying out what he intends to do: “to explain the venture-capital mind-set” and “to evaluate venture capital’s social impact.” This mind-set, he says, revolves around the “power law” of his title — the idea that the distribution of phenomena is not “normal” but skewed. Instead of a bell curve, picture a long tail, where “winners advance at an accelerating, exponential rate.” Adapt or die, sink or swim — there’s no middle ground. This is why V.C.s like to talk about “grand slams” and “moon shots”; Peter Thiel says that a fund’s top investment should generate returns so spectacular that it will outperform everything else in the fund put together.

This, clearly, isn’t the kind of logic that has much use for steady, incremental growth, to say nothing of a flourishing middle class. You might therefore wonder about the “social impact” of venture capital, which Mallaby deems to be, on the whole, good. He concedes that “V.C.s as individuals can stumble sideways into lucky fortunes,” or can sometimes do unhelpful things. But he is ultimately bullish on what they have to offer: “Venture capital as a system is a formidable engine of progress — more so than is frequently acknowledged.” That engine, Mallaby reminds us, has funded such ventures as the development of synthetic insulin and, more recently, plant-based alternatives to ecologically damaging meat.

. . .

He gives examples of the different kinds of funds, with their various personalities and philosophies. There are V.C.s who see it as their role to act as mentors and coaches to inexperienced founders. There are V.C.s who insist on installing seasoned outsiders at start-ups to serve as C.E.O.s. There are also “founder-friendly” V.C.s, who promise to be hands-off, allowing genius, no matter how unorthodox or weird, to do its work.

For the full review, see:

Jennifer Szalai. “BOOKS OF THE TIMES; A Funder-Friendly Look at Venture Capital.” The New York Times (Tuesday, February 1, 2022): C4.

(Note: ellipses added.)

(Note: the online version of the review has the date Jan. 31, 2022, and has the title “BOOKS OF THE TIMES; ‘The Power Law’ Is a Funder-Friendly Look at the World of Venture Capital.”)

The book under review is:

Mallaby, Sebastian. The Power Law: Venture Capital and the Making of the New Future. New York: Penguin Press, 2022.

Venture Capital’s “Massive” Role in Funding Innovation

(p. A15) The average venture-capital fund launched in 2011 outperformed the S&P 500 by 7% per year. But that statistic understates the astronomical returns earned by a few top performers—and the mediocre returns earned by the rest. Between 1979 and 2018, the median fund underperformed the S&P 500, while the top 5% of funds nearly tripled the index’s performance.

The investor Bill Gurley, of Benchmark, describes venture capital as a “grand-slam business.” In “The Power Law,” business journalist Sebastian Mallaby argues that venture is defined by its most extravagant successes. A few deals explain the majority of returns, a few funds drive the majority of asset-class performance, a few wild ideas change the world.

Venture’s contribution to innovation and entrepreneurship is massive. Mr. Mallaby notes that between 1995 and 2019 venture-backed companies accounted for nearly half of U.S. nonfinancial IPOs. These firms are orders of magnitude more likely to launch an IPO than startups that don’t receive venture backing. The U.S. economy’s dynamism depends in large part on the Silicon Valley ecosystem.

. . .

Though the book focuses on the winners, Mr. Mallaby doesn’t shy away from criticism, especially in his description of the decline of Kleiner Perkins. The firm was successful in the 1990s, but lead partner John Doerr became more interested in virtue signaling than in profit making. He started a cleantech fund, based on a conversation with his teenage daughter about saving the planet, that put a significant dent in the firm’s long-term track record. And he embarked on a highly publicized gender-equity campaign to hire female partners, only to see some of the most talented women quit and then see the firm be sued by a disgruntled employee for gender discrimination.

. . .

In his closing words in “The Power Law,” Mr. Mallaby warns that it’s “unwise” to bet against venture. But public markets have recently turned against IPOs and other venture-backed companies, sending venture-style portfolios like Cathie Wood’s ETF into steep losses. With the IPO window closing and tech stocks selling off, some venture investors might well be thinking: “There but by the grace of God go I.”

For the full review, see:

Daniel Rasmussen. “BOOKSHELF; Chasing Unicorns.” The Wall Street Journal (Thursday, February 3, 2022): A15.

(Note: ellipses added.)

(Note: the online version of the review has the date February 2, 2022, and has the title “BOOKSHELF; ‘The Power Law’ Review: Chasing Unicorns.”)

The book under review is:

Mallaby, Sebastian. The Power Law: Venture Capital and the Making of the New Future. New York: Penguin Press, 2022.

Large Retailers Chartered Ships to Avoid the Most Crowded Ports

(p. A1) Global supply-chain delays are so severe that some of the biggest U.S. retailers have resorted to an extreme—and expensive—tactic to try to stock shelves this holiday season: They are chartering their own cargo ships to import goods.

Port delays, Covid-19 outbreaks and worker shortages have snarled the flow of products between Asia and North America, threatening the supplies of everything from holiday decorations and toys to appliances and furniture. It is taking roughly 80 days to transport goods across the Pacific, or twice as long as before the pandemic, retail and shipping executives said.

Walmart Inc., Home Depot Inc., Costco Wholesale Corp. and Target Corp. —some of the biggest U.S. retailers by revenue—are among the companies that are paying for their own chartered ships as part of wider plans to mitigate the disruptions, a costly and unattainable option for most companies.

For the full story, see:

Sarah Nassauer and Costas Paris. “Retailers Charter Ships to Ensure Supplies.” The Wall Street Journal (Monday, October 11, 2021): A1 & A6.

(Note: the online version of the story has the date October 10, 2021, and has the title “Big U.S. Retailers Charter Private Cargo Ships Amid Port Delays.”)

To Get “Free” Covid Pills from 60 Miles Away You Pay Private Uber to Deliver

(p. 1) Just after 1 p.m. on Tuesday last week, my phone buzzed with a text message from my mother: “Well, came down with cold, aches, cough etc over wknd.” She had taken an at-home coronavirus test. It was positive.

Having spent the past year writing about Covid-19 vaccines and treatments for The New York Times, I knew a lot about the options available to people like my mother. Yet I was about to go on a seven-hour odyssey that would show me there was a lot I didn’t grasp.

. . .

(p. 3) In the end, my scramble to find a prescriber turned out to be unnecessary. In the early evening, my mother got an unexpected call from a doctor with her primary care provider. She told the doctor about her symptoms and about the Rite Aid I had found with Paxlovid in stock.

The doctor told her that he was surprised that we had been able to track down Paxlovid. He phoned in a prescription to the Rite Aid.

Now we just needed to pick up the pills before the pharmacy closed in about an hour.

Uber came to the rescue. I requested a pickup at the Rite Aid and listed the destination as my mother’s home, some 60 miles away.

Once a driver accepted the ride, I called him and explained my unusual request: He’d need to get the prescription at the pharmacy window and then drive it to my mother’s. I told him I’d give him a 100 percent tip.

The driver, who asked me not to use his name in this article, was game. He delivered the precious cargo just after 8 p.m. My mother swallowed the first three pills — the beginning of a five-day, 30-pill regimen — within minutes of the driver’s arrival.

. . .

. . . the fact that the process was so hard for a journalist whose job it is to understand how Paxlovid gets delivered is not encouraging. I worry that many patients or their family would give up when told “no” as many times as I was.

I was also reminded that even a “free” treatment can come with significant costs.

The federal government has bought enough Paxlovid for 20 million Americans, at a cost of about $530 per person, to be distributed free of charge. But I spent $256.54 getting the pills for my mother. I paid $39 for the telemedicine visit with the provider who told my mother that she would need to visit in person. The rest was the Uber fare and tip. Many patients and their families can’t afford that.

President Biden recently called the Pfizer pills a “game changer.” My experience suggests it won’t be quite so simple.

For the full story, see:

Rebecca Robbins. “A 7-Hour Odyssey to Get My Mom Covid Pills.” The New York Times, SundayBusiness Section (Sunday, January 23, 2022): 1 & 3.

(Note: ellipses added.)

(Note: the online version of the story has the date Jan. 19, 2022, and has the title “When My Mom Got Covid, I Went Searching for Pfizer’s Pills.”)

Less-Ventilated Energy-Efficient Buildings Reduce Indoor Air Quality, Harming Cognitive Performance

(p. D6) A new study shows that poor indoor air quality is associated with subtle impairments in a number of cognitive functions, including our ability to concentrate and process information. The study tracked 302 office workers in commercial buildings in six countries — the United States, Britain, China, India, Mexico and Thailand — for 12 months.

The scientists used monitors to measure ventilation and indoor air quality in the buildings, including levels of fine particulate matter, which includes dust and minuscule particles from smoking, cleaning products and outdoor air pollution that seeps into the building. The workers were asked to use an app to take regular cognitive tests during the workday. The tests included simple math problems, as well as a tricky color and word brain teaser called the Stroop test, in which a word like “blue” or “purple” is printed in green or red ink.  . . .

The study found that the office workers in buildings with the poorest indoor air quality tended to perform worse on the brain teasers. While the effect wasn’t dramatic, the findings add to a growing body of evidence suggesting that the air we breathe affects brain health.

. . .

“This study looked at how several factors in the indoor environment have an immediate impact on our cognitive function and performance,” said Joseph G. Allen, the director of the Harvard Healthy Buildings program and the study’s senior author. “This study shows that the air you’re breathing at your desk at that moment has an impact on how well you think.”

In the past, air quality control in buildings has been mostly focused on energy efficiency and comfort, with little consideration given to infection control or overall worker health.

. . .

Dr. Allen is the co-author of a new book, “Healthy Buildings: How Indoor Spaces Drive Performance and Productivity.” He said he’s been encouraged to see more businesses and individuals taking indoor air quality more seriously as a result of the pandemic. Recently he saw a job posting at a major company advertising for a “head of healthy buildings” in the company’s global real estate division.

“It tells you that serious companies are changing how they approach their buildings, and they’re not thinking about this as a one-off during Covid,” said Dr. Allen.

. . .

“The pressure is coming from employees, parents of kids in school, teachers — there’s a heightened level of awareness and expertise,” said Dr. Allen. “How many people were talking about MERV 13 filters prior to the pandemic? This knowledge that our indoor spaces have been underperforming is not going away. I think people are rightly frustrated and fed up with it.”

For the full story, see:

Tara Parker-Pope. “What Bad Indoor Air Could Do to Your Brain.” The New York Times (Tuesday, September 28, 2021): D6.

(Note: ellipses added.)

(Note: the online version of the story was updated Sept. 28, 2021, and has the title “Is Bad Indoor Air Dulling Your Brain?”)

The book co-authored by Allen, and mentioned above, is:

Allen, Joseph G., and John D. Macomber. Healthy Buildings: How Indoor Spaces Drive Performance and Productivity. Cambridge, MA: Harvard University Press, 2020.

“People Are Now Coming to Their Own Conclusions About Covid”

(p. 3) Lauren Terry, 23, thought she would know what to do if she contracted Covid-19. After all, she manages a lab in Tucson that processes Covid tests.

But when she developed symptoms on Christmas Eve, she quickly realized she had no inside information.

“I first tried to take whatever rapid tests I could get my hands on,” Ms. Terry said. “I bought some over the counter. I got a free kit from my county library. A friend gave me a box. I think I tried five different brands.” When they all turned up negative, she took a P.C.R. test, but that too, was negative.

With clear symptoms, she didn’t believe the results. So she turned to Twitter. “I was searching for the Omicron rapid test efficacy and trying to figure out what brand works on this variant and what doesn’t and how long they take to produce results,” she said. (The Food and Drug Administration has said that rapid antigen tests may be less sensitive to the Omicron variant but has not identified any specific tests that outright fail to detect it.) “I started seeing people on Twitter say they were having symptoms and only testing positive days later. I decided not to see anybody for the holidays when I read that.”

She kept testing, and a few days after Christmas she received the result she had expected all along.

Though it’s been almost two years since the onset of the pandemic, this phase can feel more confusing than its start, in March 2020. Even P.C.R. tests, the gold standard, don’t always detect every case, especially early in the course of infection, and there is some doubt among scientists about whether rapid antigen tests perform as well with Omicron. And, the need for a 10-day isolation period was thrown into question after the Centers for Disease Control and Prevention announced that some people could leave their homes after only five days.

“The information is more confusing because the threat itself is more confusing,” said David Abramson, who directs the Center for Public Health Disaster Science at the N.Y.U. School of Global Public Health. “We used to know there was a hurricane coming at us from 50 miles away. Now we have this storm that is not well defined that could maybe create flood or some wind damage, but there are so many uncertainties, and we just aren’t sure.”

Many people are now coming to their own conclusions about Covid and how they should behave. After not contracting the virus after multiple exposures, they may conclude they can take more risks. Or if they have Covid they may choose to stay in isolation longer than the C.D.C. recommends.

And they aren’t necessarily embracing conspiracy theories. People are forming opinions after reading mainstream news articles and tweets from epidemiologists; they are looking at real-life experiences of people in their networks.

For the full story, see:

Alyson Krueger. “Covid Experts, the Self-Made Kind.” The New York Times, SundayStyles Section (Sunday, January 23, 2022): 3.

(Note: the online version of the story has the date January 21, 2022, and has the title “So You Think You’re a Covid Expert (but Are You?).”)