Category: Regulations

Genetic Diversity Limits Number of Patients for Large Randomized Trials

(p. A9) . . . in the era of personalized medicine, where care can be tailored to a person’s genetic make-up and doctors analyze a patient’s DNA to figure out treatments, big trials are falling out of favor.

. . .

To Ursula Matulonis, who treats ovarian cancer and other women’s cancers at Dana-Farber Cancer Institute in Boston, the debate over trial size has a special urgency: Many of her patients are desperately sick.

“You can’t wait years to get these medications approved. What we are dealing with are women with cancers and their lifespans are limited. They need medications and they need them now, and they are not looking to wait for five years,” says Dr. Matulonis, chief of gynecologic oncology.

That is why flexibility in a trial’s size is crucial, she contends. “As we become more genetically astute, and understand a type of cancer better, I think those large randomized trials will be hard to do. There won’t be that many patients,” that fit into one big group, she added.

One of her patients, Janet Sheehan, is grateful for the small clinical trial she has taken part in for the past five years. Ms. Sheehan, a 63-year-old nurse near Boston, was diagnosed with advanced ovarian cancer a dozen years ago. It has come back three times, and at one point she learned that she had a mutation in the BRCA1 gene which indicates a strong predisposition to breast and ovarian cancer. Dana-Farber suggested in 2013 that she go on a randomized 90-person trial for a drug named Olaparib that showed promise among women with a BRCA1 gene mutation.

She has been taking capsules twice a day and going for check-ups every 28 days since then. Despite side-effects, she has been able to work and carry on. “I have seen my children [grow] and I have seen grandchildren I didn’t have then,” she says. Ms. Sheehan was on a randomized trial where both groups of patients received treatment with Olaparib. One group got the drug only, the other received Olaparib in combination with another drug, her doctor said, adding, “there was no placebo.”

In remission, Ms. Sheehan has become a fan of small trials that offer women such as herself options. She also is a realist. If Olaparib fails, she hopes other trials now going on may yield treatments for her.

For the full commentary, see:

Lucette Lagnado. “Is the Big Clinical Trial Obsolete? The New York Times (Wednesday, May 30, 2018): A9-A10.

(Note: ellipses added; bracketed word in original.)

(Note: the online version of the commentary has the date May 29, 2018, and has the title “Are Big Clinical Trials Relevant? Researchers Disagree.” The sentence that starts with “In remission,” was in the online version, but not the print version. )

When Labor Market Regulations Increase, Firms Hire Fewer Workers

(p. B5) “It’s serial stagnation,” said Nicola Borri, a finance professor at Luiss, a university in Rome. “The economy doesn’t contract, it doesn’t grow. Italy is a country that is weak, that is old, where there is no investment in new ideas.”

. . .

Thirty-five miles east of Naples, in the town of Avellino, Sabino Basso has halted plans to hire 30 more people at the olive oil bottling plant started by his great-grandfather.

Mr. Basso’s company buys olive oil from growers in Italy, Spain and Greece, exporting 80 percent of its wares to countries around the globe — especially the United States, where Walmart is a major customer. He had planned to increase marketing and online sales.

But then Five Star tightened legal requirements for companies that hire workers on temporary contracts, effectively limiting stints to one year. The change was aimed at forcing businesses to hire permanent workers.

Mr. Basso was aghast. All but five of his 100 workers are permanent, he said. The others are apprentices, a status that has allowed him to hire using temporary contracts.

“In order to understand if I want to keep people their whole lives, I have to test them,” he said. The new rules did not allow him sufficient time. “I just stopped hiring.”

For the full story, see:

Peter S. Goodman. “History, Views and ‘Serial Stagnation’.” The New York Times (Saturday, Aug. 10, 2019): B1 & B5.

(Note: ellipsis added.)

(Note: the online version of the story has the date Aug. 9, 2019, and has the title “Italy’s Biggest Economic Problem? It’s Still Italy.”)

James Knott Exposed the EPA’s Doctoring of Water-Test Results They Used to Indict Him

(p. A9) James Knott helped build a better lobster trap.

Though the world didn’t beat a path to his door in Northbridge, Mass., Mr. Knott eventually persuaded most manufacturers of lobster traps to use his product—plastic-coated wire mesh—rather than wood to make their devices.

. . .

He built a business, Riverdale Mills Corp., that employs more than 150 people and has withstood price competition from China and a 1997 raid by pistol-packing agents of the Environmental Protection Agency. Then came an indictment alleging Mr. Knott violated the Clean Water Act by dumping acidic wastewater. He fought back, providing evidence that the EPA had doctored water-test results. The charges were dropped.

“What am I supposed to do—lay down and get stomped on?” he asked in a 2001 interview with the television news show “60 Minutes.”

. . .

When he was indicted by a federal grand jury in the water-pollution case in 1998, Mr. Knott faced a possible prison term of six years. He hired a retired FBI handwriting analyst, who found EPA test records had been altered to show an illegal degree of acidity in the wastewater. The government soon dropped its charges.

Mr. Knott fought a long and ultimately fruitless battle to require the government to reimburse him for his legal costs.

For the full obituary, see:

James R. Hagerty. “Entrepreneur Helped Create a Better Lobster Trap.” The Wall Street Journal (Saturday, Aug. 24, 2018): A9.

(Note: ellipses added.)

(Note: the online version of the obituary has the date July 27, 2018, and has the title “James Knott Pioneered Modern Lobster Traps and Fended Off the EPA.”)

Manic Energy from Bipolar Disorder May Enable “Heights of Success”

(p. A17) Dr. Ronald R. Fieve, who was a pioneer in the prescription of lithium to treat mania and other mood disorders — while avowing that some gifted individuals, like Abraham Lincoln, Theodore Roosevelt and Winston Churchill, might have benefited from being bipolar — died on Jan. 2 [2018] at his home in Palm Beach, Fla.

. . .

He cited estimates that as many as one in 15 people experienced a manic episode during their lifetimes, and that bipolar disorder — characterized by swings from elation, hyperactivity and a decreased need for sleep to incapacitating depression — was often misclassified as schizophrenia or other illnesses, or undiagnosed altogether.

He cautioned, however, that some highly creative, exuberant and energetic people have derived benefits from the condition because they have what he called “a hypomanic edge.”

“I have found that some of the most gifted individuals in our society suffer from this condition — including many outstanding writers, politicians, business executives and scientists — where tremendous amounts of manic energy have enabled them to achieve their heights of success,” Dr. Fieve told a symposium in 1973.

But without proper treatment, he said, those individuals afflicted with manic depression “more often than not either go too ‘high’ or suddenly crash into a devastating depression that we only hear about after a successful suicide.”

In contrast to antidepressant drugs or electroshock treatments, he said, regular doses of lithium carbonate appeared to stabilize mood swings without cramping creativity, memory or personality.

. . .

Before it was approved to treat depression, lithium was found in the late 1940s to be potentially unsafe as a salt substitute. But Dr. Fieve pointed out that lithium had been found in natural mineral waters prescribed by Greek and Roman physicians 1,500 years earlier to treat what were then called manic insanity and melancholia.

For the full obituary, see:

Sam Roberts. “Dr. Ronald Fieve, Pioneer In Lithium, Is Dead at 87.” The New York Times (Wednesday, Jan. 17, 2018): A17.

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

(Note: the online version of the obituary has the date Jan. 12, 2018, and has the title “Dr. Ronald Fieve, 87, Dies; Pioneered Lithium to Treat Mood Swings.”)

Plastic Bags Have Lower Carbon Footprint Than Paper or Cotton Bags

(p. B5) The backlash against single-use plastic has engulfed straws, bags and takeout containers, but the plastics industry is fighting back, arguing alternatives can be worse for the environment and disruptive for businesses.

. . .

Critics of bans say single-use plastic bags are often used several times, and that they can be recycled at many supermarkets.

The American Progressive Bag Alliance, a trade body for plastic-bag manufacturers, is battling proposed bag bans in states including Maine and New Jersey.

. . .

The APBA highlights a U.K. government analysis that found paper bags must be used three times for their carbon footprint to drop below that of single-use plastic bags made from high-density polyethylene—or HDPE—and cotton bags 131 times. The study measured the impact of making paper bags by counting the use of energy and palm oil, and the disposal of ash from production. It said growing cotton and producing yarn depletes natural resources, emits damaging chemicals and depletes oxygen in water bodies.

The trade group, which says bans aren’t successful at reducing overall waste, said a study found thicker, reusable plastic bags wound up in Austin’s waste stream after the Texas city banned single-use plastic bags in 2013.

. . .

Some companies feel caught in the middle. McDonald’s Corp. scrapped plastic straws in the U.K. last year but now faces a backlash. Over 44,000 people recently signed a petition calling for the chain to bring back plastic straws, complaining that paper replacements go soggy and make it hard to drink milk shakes.

Others point to their use of plastics as a sustainability selling point.

Garçon Wines—a London-based firm that makes flat plastic wine bottles that fit through a mail slot—said its recycled bottles are 87% lighter than glass and shaped to allow more wine to be shipped in the same space, reducing emissions.

For the full story, see:

Saabira Chaudhuri. “In Plastics War, the Industry Fights Back.” The Wall Street Journal (Tuesday, May 21, 2019): B5.

(Note: ellipses added.)

(Note: the online version of the story has the date May 20, 2019, and the title “In Plastic-Bag Wars, the Industry Fights Back.” Where there are minor differences in wording, the passages quoted above follow the online version.)

Regulators Allowed New York City to Exploit Taxi Medallion Buyers

(p. A1) . . . The New York Times published a two-part investigation revealing that a handful of taxi industry leaders artificially inflated the price of a medallion — the coveted permit that allows a driver to own and operate a cab — and made hundreds of millions of dollars by issuing reckless loans to low-income buyers.

The investigation also found that regulators at every level of government ignored warning signs, and the city fed the frenzy by selling medallions and promoting them in ads as being “better than the stock market.”

The price of a medallion rose to more than $1 million before crashing in late 2014, which left borrowers with debt they had little hope of repaying. More than 950 medallion owners have filed for bankruptcy, (p. A20) and thousands more are struggling to stay afloat.

For the full story, see:

Niraj Chokshi. “New York’s Top Lawyer Begins Inquiry Into Reckless Taxi Loans.” The New York Times (Tuesday, MAY 21, 2019): A1 & A20.

(Note: ellipsis added.)

(Note: the online version of the story has the date MAY 20, 2019, and has the title “Inquiries Into Reckless Loans to Taxi Drivers Ordered by State Attorney General and Mayor.” Where the online version includes a few extra words, or slightly different wording, the quotes above follow the online version.)

Environmentalist Regulations Inspire Vigilantes to Destroy Fairy Houses

(p. A10) Monhegan and a growing number of other environmentally conscious locales are fighting the scourge of fairy gardens, miniature habitats built by children and young-at-heart adults to attract tiny mythical creatures.

Typically they include a pint-size house with a path leading to its entrance and surrounded with small plants. The houses can range from rustic lean-tos handmade from twigs, bark and pebbles to store-bought plastic castles accompanied by LED lights, artificial plants, colorful glass beads and a family of fairy figurines.

On Monhegan, it is easy to run afoul of the regulations, which forbid picking living plants or using anything brought from the shore. No items are to be used “from your pockets,” including coins, food and anything plastic.

It is also easy to run afoul of Ms. Durst, a retired computer consultant who, like several other like-minded vigilantes, calls herself a “stomper” and has crushed many a fairy house over the years.

. . .

Julie Cole, . . . , is something of a scofflaw. She oversees a 5,564-member fairy-garden discussion group on Facebook, sells fairy furniture online and teaches fairy-gardening classes near her home in Jefferson, Ohio. “It’s a true taste of serendipity to be along a trail and see a little fairy door on a tree,” says Ms. Cole. “I can’t imagine anyone not liking that, but there’s always someone.”

For the full story, see:

Ellen Byron. “‘Fairy Houses’ Are Violating Building Codes.” The Wall Street Journal (Thursday, July 18, 2018): A1 & A10.

(Note: ellipses added.)

(Note: the online version of the story has the date July 17, 2018, and the title “Hey Tinkerbell, Get Your Fairy House Up to Code or It’s Coming Down.”)

“If You Do No Harm, Then You Do No Harm to the Cancer, Either”

(p. B16) James F. Holland, a founding father of chemotherapy who helped pioneer a lifesaving drug treatment for pediatric leukemia patients, died on Thursday [March 22, 2018] at his home in Scarsdale, N.Y.

. . .

“Patients have to be subsidiaries of the trial,” he told The New York Times in 1986. “I’m not interested in holding patients’ hands. I’m interested in curing cancer.”

He acknowledged that some patients become guinea pigs, and that they sometimes suffer discomfort in the effort to eradicate tumors, but he said that even those who die provide lessons for others who will survive.

“If you do no harm,” Dr. Holland said, “then you do no harm to the cancer, either.”

. . .

Dr. Holland acknowledged that while experimenting with drug treatment sometimes amounts to trial and error, the primary killer is typically the disease itself.

“The thing to remember,” he said, “is that the deadliest thing about cancer chemotherapy is not the chemotherapy.” Continue reading ““If You Do No Harm, Then You Do No Harm to the Cancer, Either””

“If You Lower the Hurdles to Innovation . . . , You’ll Get More of It”

(p. A2) You’d think from the debate raging in Washington that taxes are the key to economic growth. They aren’t. In the long run, innovation matters way more, and that depends on inspiration, experimentation and luck, not tax-law changes.

Yet presidents matter for promoting innovation even if it’s less glamorous than taxes. Their support often takes the form of directing money toward basic research or favored industries such as defense or renewable energy.

Under President Donald Trump the place to look is the regulators. Two of his appointees in particular, Food and Drug Administration Commissioner Scott Gottlieb and Federal Communications Commission Chairman Ajit Pai, have prioritized reducing regulatory hurdles to private investment as a way of boosting innovation. It’s too early to gauge their success, but the efforts merit more attention at a time when the growth debate is focused on steep, deficit-financed tax cuts.

. . .

At the FCC, Mr. Pai has targeted the “digital divide,” the gap in broadband access between some communities, especially in rural areas, and others. The share of U.S. households with a fixed broadband connection has stalled at roughly a third in recent years. Mr. Pai thinks the solution is “setting rules that maximize private investment in high-speed networks.”

Controversially, that includes a proposed rollback of his predecessor’s imposition of utility-like regulation so that internet service providers (ISPs) adhere to “net neutrality”—charging all content providers the same to access their networks. Without those limitations, he reckons ISPs will have more incentive to expand capacity and thus access; critics worry this will favor rich, established content providers over innovative newcomers.

. . .

. . . , Mr. Gottlieb’s and Mr. Pai’s theory is that if you lower the hurdles to innovation in specific sectors, you’ll get more of it. It offers a potentially more tangible payoff than fiddling with the tax code.

For the full commentary, see:

Greg Ip. “CAPITAL ACCOUNT; Why Innovation Tops Tax Cuts.” The Wall Street Journal (Thursday, October 26, 2017): A2.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Oct. 25, 2017, and the title “CAPITAL ACCOUNT; Trump’s Regulators Aim to Boost Growth by Lowering Hurdles to Innovation.”)

To Be Dangerous with Crispr Takes a Lot of Genetics Knowledge

(p. A11) “I frankly have been flabbergasted at the pace of the field,” says Jennifer Doudna, a Crispr pioneer who runs a lab at the University of California, Berkeley. “We’re barely five years out, and it’s already in early clinical trials for cancer. It’s unbelievable.”

. . .

Scientists have fiddled with genes for decades, but in clumsy ways.

. . .

Crispr is much more precise, as Ms. Doudna explains in her new book, “A Crack in Creation.” It works like this: An enzyme called Cas9 can be programmed to latch onto any 20-letter sequence of DNA. Once there, the enzyme cuts the double helix, splitting the DNA strand in two. Scientists supply a snippet of genetic material they want to insert, making sure its ends match up with the cut strands. When the cell’s repair mechanism kicks in to fix the cut, it pastes in the new DNA.

. . .

A . . . Crispr worry is that it makes DNA editing so easy anybody can do it. Simple hobby kits sell online for $150, and a community biotech lab in Brooklyn offers a class for $400. Jennifer Lopez is reportedly working on a TV drama called “C.R.I.S.P.R.” that, according to the Hollywood Reporter, “explores the next generation of terror: DNA hacking.”

Ms. Doudna provides a bit of assurance. “Genetics is complicated. You have to have quite a bit of knowledge, I think, to be able to do anything that’s truly dangerous,” she says. “There’s been a little bit of hype, in my opinion, about DIY kits and are we going to have rogue scientists—or even nonscientists—randomly doing crazy stuff. I think that’s not too likely.”

For the full interview, see:

Peterson, Kyle, interviewer. “THE WEEKEND INTERVIEW; The Gene Editors Are Only Getting Started; Would you eradicate malaria-carrying insects? Change your baby’s DNA? Scientists soon may have the power to do both.” The Wall Street Journal (Saturday, July 8, 2017): A11.

(Note: ellipses added.)

(Note: the online version of the interview has the date July 7, 2017, and the same title as the print versio.)

Doudna’s book, mentioned above, is:

Doudna, Jennifer A., and Samuel H. Sternberg. A Crack in Creation: Gene Editing and the Unthinkable Power to Control Evolution. New York: Houghton Mifflin Harcourt, 2017.

“Freakin’ Ridiculous” Regulation

(p. A1) REHOBOTH BEACH, Del.—Capt. Kent Buckson’s radio crackled with word of a situation on the beach. A lifeguard had spotted a large canopy amid the sea of umbrellas. That meant one thing. Time for a takedown.

“We’ve got to get to that one,” said Mr. Buckson, the soft-spoken beach patrol boss. He and his deputy, Aaron Tartal, jumped into an all-terrain vehicle and headed over. Mr. Tartal, shirtless and in red swim trunks, strode over to the canopy owner.

“Good morning, sir. I’ve got bad news,” Mr. Tartal told the man. Then he laid out the new law on the two-mile beach. No tents or canopies allowed, except baby tents up to 3 feet high, wide or deep.

“Freakin’ ridiculous,” groused the man, who declined to give his name, as he dismantled the black 8-by-10-foot canopy he had just erected.

“New city ordinance, it’s a little bit of a learning curve,” Mr. Tartal gamely replied, pointing out the nearby shacks that rent umbrellas for $12 a day.

. . .

(p. A14) . . . , the 25-year-old Mr. Tartal, who is a lifeguard in addition to Capt. Buckson’s beach patrol deputy, told Marjorie Danko, a receptionist from Hershey, Pa., that the $40 three-sided tent she bought for her grandchildren didn’t pass muster, either.

“I don’t understand this,” she said. “I think umbrellas are much more dangerous. What kind of ordinance is that? I mean, really dumb.”

Mr. Tartal apologized but didn’t debate her. “We don’t write the ordinances,” he said, “we just enforce them.”

Clutching some cash, Ms. Danko marched off to go rent an umbrella.

For the full story, see:

Scott Calvert. “Beach Patrol Draws a Line In the Sand: No More Tents.” The Wall Street Journal (Wednesday, July 5, 2017): A1 & A10.

(Note: ellipses added.)

(Note: the online version of the story has the date July 4, 2017, and the title “Beach Patrol Confronts a New Menace: Oversize Tents.”)