Muyembe Had Knowledge of an Ebola Cure Before Clinical Trial

(p. A1) In a medical breakthrough that compares to the use of penicillin for war wounds, two new drugs are saving lives from the virus and helping uncover tools against other deadly infectious diseases. They were proven effective in a gold-standard clinical trial conducted by an international coalition of doctors and researchers in the middle of armed violence.

. . .

(p. A10) Dr. Muyembe set out on his path to an Ebola treatment during the 1995 outbreak. He transferred blood from five survivors to eight patients, hoping that the antibodies that kept some people alive would keep others from dying. Seven of the patients who received the blood transfusion recovered.

He published the results in a scientific journal in 1999. Other researchers said the study was small and had failed to include a control group, a comparison set of patients who weren’t given the treatment, to fully test its efficacy.

For the full story, see:

Betsy McKay. “From a War Zone Came an Unexpected Cure for Ebola.” The Wall Street Journal (Thursday, October 31, 2019): A1 & A10.

(Note: ellipsis added.)

(Note: the online version of the story has the date Oct. 30, 2019, and has the title “‘Ebola Is Now a Disease We Can Treat.’ How a Cure Emerged From a War Zone.”)

Stents Do Not Reduce Heart Attacks or Deaths

(p. A17) The findings of a large federal study on bypass surgeries and stents call into question the medical care provided to tens of thousands of heart disease patients with blocked coronary arteries, scientists reported at the annual meeting of the American Heart Association on Saturday [Nov. 16, 2019].

The new study found that patients who received drug therapy alone did not experience more heart attacks or die more often than those who also received bypass surgery or stents, tiny wire cages used to open narrowed arteries.

That finding held true for patients with several severely blocked coronary arteries. Stenting and bypass procedures, however, did help some patients with intractable chest pain, called angina.

. . .

Stenting costs an average of $25,000 per patient; bypass surgery costs an average of $45,000 in the United States. The nation could save more than $775 million a year by not giving stents to the 31,000 patients who get the devices even though they have no chest pain, Dr. Hochman said.

. . .

But getting a stent does not obviate the need for medical therapy, Dr. Boden noted. Since patients with stents need an additional anti-clotting drug, they actually wind up taking more medication than patients who are treated with drugs alone.

About a third of stent patients develop chest pain again within 30 days to six months and end up with receiving another stent, Dr. Boden added.

For the full story, see:

Kolata, Gina. “Drugs Are Shown to Reduce Need For Surgery to Fix Blocked Arteries.” The New York Times, First Section (Sunday, November 17, 2019): A17.

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

(Note: the online version of the story has the date Nov. 16, 2019, and has the title “Surgery for Blocked Arteries Is Often Unwarranted, Researchers Find.” The online version says that the page number of the New York print edition was A19. The page number of my National edition was A17.)

Rapamycin Will Be Tested to Extend Lifespan of Dogs

(p. 1A) SEATTLE (AP) — Can old dogs teach us new tricks? Scientists are looking for 10,000 pets for the largest-ever study of aging in canines. They hope to shed light on human longevity too.

The project will collect a pile of pooch data: vet records, DNA samples, gut microbes and information on food and walks. Five hundred dogs will test a pill that could slow the aging process.

“What we learn will potentially be good for dogs and has great potential to translate to human health,” said project co-director Daniel Promislow of the University of Washington School of Medicine.

. . .

(p. 2A) Dogs weighing at least 40 pounds will be eligible for an experiment with rapamycin, now taken by humans to prevent rejection of transplanted kidneys. The drug has extended lifespan in mice. A small safety study in dogs found no dangerous side effects, said project co-director Matt Kaeberlein of the University of Washington.

For the full story, see:

Carla K. Johnson of The Associated Press. “Needed: 10,000 Dogs for Project That Could Also Benefit Humans.” Omaha World-Herald (Thursday, Nov. 15, 2019): 1A-2A.

(Note: ellipsis added.)

(Note: the online version of the story has the date Nov. 17 [sic], 2019, and has the title “Old dogs, new tricks: 10,000 pets needed for science.”)

“Rejuvenate Bio” Startup Succeeds in Using Gene Therapy to Fight Age-Related Diseases in Mice

The online PNAS article mentioned below includes the information that one of the article’s referees was Aubrey de Grey, Cambridge scientist, and co-author of The End of Aging. Aubrey de Grey has been arguing for many years that anti-aging research will only take-off when proof-of-concept is achieved with mice. The PNAS article summarized below, appears to provide that proof-of-concept.

(p. A13) North Grafton, Mass.

A Cavalier King Charles spaniel named Shadow was at the front lines of a new approach to gene therapy.

Earlier this month, 7-year-old Shadow was the first dog to be screened at Tufts University for a pilot study attempting to use gene therapy to treat a type of heart disease that often afflicts aging cavaliers.

It’s part of a novel approach to gene therapy that has successfully treated age-related ailments in mice. Now it is being studied in dogs, with eventual hopes to test it in humans.

Researchers reported their success in mice in a study published Monday [Nov. 4, 2019] in the journal PNAS. They treated four age-related diseases in mice using genetic therapy: heart and kidney failure, Type 2 diabetes and obesity. On average, the mice experienced a 58% increase in heart function, a 75% reduction in kidney degradation, and normalized weight and blood-sugar levels in mice fed a high-fat diet, the study found.

. . .

What’s interesting about the new research in mice is that it is broader—targeting not a single rare defect, but common age-related ailments. The experiments injected mice with DNA to create an extra copy of a healthy gene, expressing more healthy material in cells linked to common diseases of aging.

The goal of the biotech company behind the mice study, Rejuvenate Bio —which sprang from research out of the lab of Harvard geneticist George Church, who is a co-founder—is to treat multiple aging-related diseases in dogs. It recently started working with Tufts University’s Cummings School of Veterinary Medicine on the dog pilot. If successful in dogs, the company hopes to treat similar human diseases but says that will take a lot more resources and time.

The firm says it expects the cost of dog genetic therapies would be similar to dog cancer treatments, including surgery, which range from about $500 to $8,000.

. . .

Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City, praised the PNAS study as a proof of concept . . .

For the full story, see:

Sumathi Reddy. “YOUR HEALTH; Gene Therapy Targets Aging.” The Wall Street Journal (Tuesday, Nov. 4, 2019): A13.

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

(Note: the online version of the story has the date Nov. 4, 2019, and has the title “YOUR HEALTH; A New Approach to Gene Therapy—Now In Dogs, Maybe Later In Humans.”)

The PNAS article, summarized in the passages quoted above, is:

Davidsohn, Noah, Matthew Pezzone, Andyna Vernet, Amanda Graveline, Daniel Oliver, Shimyn Slomovic, Sukanya Punthambaker, Xiaoming Sun, Ronglih Liao, Joseph V. Bonventre, and George M. Church. “A Single Combination Gene Therapy Treats Multiple Age-Related Diseases.” Proceedings of the National Academy of Sciences (PNAS) (Nov. 4, 2019): https://doi.org/10.1073/pnas.1910073116.

The book co-authored by Aubrey de Grey, and mentioned way above, is:

de Grey, Aubrey, and Michael Rae. Ending Aging: The Rejuvenation Breakthroughs That Could Reverse Human Aging in Our Lifetime. New York: St. Martin’s Press, 2007.

New York City Regs Force Arthritic Woman to Push Cart to Laundromat Instead of Using Her Laundry Room

(p. A1) When Jean Harrow got a ticket in 2016 for unauthorized renovations to her Queens home, she thought it was a misunderstanding. Yes, she had put a powder room in her basement without realizing she needed a permit. But surely, she said, she wasn’t responsible for the washer and dryer a previous owner had installed downstairs — illegally, according to the $1,600 citation. She would simply explain that at her hearing.

As she waited to do just that, Ms. Harrow got a second ticket — for “failure to comply” with the first. In the 14 months after the original citation, she received five others for the same issue: $15,600 in additional fines. Each meant another hearing, and although she never missed a court date, the tickets kept coming.

Thousands of small property owners in New York City have been hit with a similar pileup of fines, an unintended result of a decade-long crackdown set off by fatal construction accidents. In recent years, the city’s Buildings Department has hired hundreds of new inspectors and doled out harsher penalties for violators. But rules introduced as a safeguard have become a costly trap for ordinary people, The New York Times found.

. . .

(p. A23) Ms. Harrow admits she made a mistake: She should have sought a permit to install the toilet and sink that piggybacked on plumbing already in her laundry room. But, she said she told the inspector, “I didn’t run those pipes — I bought it like this.”

To correct the violation, Ms. Harrow needed to have the unauthorized plumbing removed. Before she could get the permit, however, she had to pay a $1,500 civil penalty.

Pulling the money together took months. The receipt for the payment was lost, then found. Her permit request was rejected several times, because of errors a plumber had made on the application. She received another fine during this period.

At Ms. Harrow’s final hearing, the agency lawyer reduced two fines imposed after the permit came through. But Ms. Harrow was on the hook for the rest. Besides losing the bathroom, she would be out $13,100 in fines plus interest, as well as permit costs, plumbers’ fees, two taxi fares, and a washer and dryer. A different permit would have allowed her to keep the laundry room, but the process would have been even more expensive.

“Now I have to be pushing a cart to go to the wash,” she said. “I have rheumatoid arthritis.”

Ms. Harrow said she tried to put $50 a month toward the fines. “But sometimes, to tell you the truth, I can’t make it.”

For the full story, see:

Grace Ashford. “Snowballing Tickets Bury Homeowners in Debt.” The New York Times (Monday, September 9, 2019): A1 & A22-A23.

(Note: ellipsis added.)

(Note: the online version of the story has the same date as the print version, and has the title “The Law Was Aimed at Deadly Machinery. It Hit Her Washer.”)

Medical Paperwork Wastes Resources and Burns Out Physicians

(p. A23) Consider the use of medical scribes, who complete doctors’ electronic paperwork in real time during patient visits. The American College of Medical Scribe Specialists reported that 20,000 scribes were working in 2014, and expects that number to climb to 100,000 in 2020.

I have heard doctors say they need a scribe to keep up with electronic medical records, the mounting demand of which is driving a burnout epidemic among physicians. Scribes allow doctors to talk with and examine patients without having a computer come between them, but at base they are a workaround for the well-known design flaws of electronic medical records.

As a nurse, when I first learned about scribes, I was outraged. On the job, nurses hear repeatedly how health care companies can’t afford to have more nurses or aides to work with patients on hospital floors — and yet, money is available to pay people to manage medical records. Doctors who use scribes tend to see their productivity and work satisfaction increase, but the trade-off is still there: Scribes demonstrate the extent to which paperwork has become more important than patients in American health care.

For the full commentary, see:

Theresa Brown. “Our Jury-Rigged Health Care.” The New York Times (Friday, September 6, 2019): A23.

(Note: the online version of the commentary has the date September 5, 2019, and has the title “The American Medical System Is One Giant Workaround.”)

Physician-Scientists Should Be Allowed to Discover Cures

(p. A27) Time and again, physician-scientists have changed the history of medicine by identifying a problem in the clinic and taking to the lab to address it. Alexander Fleming watched men die of sepsis during World War I while serving in the Royal Army Medical Corps, then returned home to create penicillin. Sidney Farber, a young physician at Children’s Hospital in Boston, committed himself to finding treatments for childhood leukemia, and laid the foundation for modern cancer chemotherapy.

In the 1970s, the physicians Michael Brown and Joseph Goldstein set out to understand how a young child’s arteries could be as clogged as those of an overweight septuagenarian. This patient-inspired research led to the discovery of LDL-cholesterol receptors, and paved the way for the statin drugs that are taken by millions of people every year in the United States alone.

And more recently, the research efforts of two physicians, Brian Kobilka and one of us, Dr. Lefkowitz, seeking to understand how hormones conferred their biological effects, led to the discovery of a large family of receptors that have formed the basis for the development of hundreds of F.D.A.-approved medications.

. . .

Unfortunately, the career path of the physician-scientist has become longer and a lot less appealing. In the United States, about 20,000 graduates emerge from medical school each year, many with significant debt. Many physicians are well into their 30s by the time they complete their clinical training. Doctors who decide to take the research path face the daunting prospect of many more years struggling to win grants and establish a lab. According to N.I.H. statistics, researchers with medical degrees on average receive their first major N.I.H. grant only at age 45.

. . .

We need to ensure that the brightest young doctors can contribute to further advancements in their field, or we risk stalling the engine that consistently delivers better medicine, longer lives and a stronger economy for Americans and people around the world.

For the full commentary, see:

Mukesh K. Jain, Tadataka Yamada and Robert Lefkowitz. ” More Doctors Should Do Research.” The New York Times (Tuesday, Sept. 24, 2019): A27.

(Note: ellipses added.)

(Note: the online version of the commentary has the date Sept. 23, 2019, and has the title “We Need More Doctors Who Are Scientists.” The online version says that the commentary appeared on p. A29 of the New York print edition. The commentary appeared on p. A27 of my National print edition.)

World Child Mortality Cut in Half

(p. A1) Two decades ago, nearly 10 million children did not live to see a 5th birthday.

By 2017, that number — about 1 in every 16 children — was nearly cut in half, even as the world’s population increased by more than a billion people.

. . .

From 2000 to 2017, all but one of the 97 low-to-middle-income countries that account for the vast majority of deaths of young children lowered their child mortality rates, according to a report released Tuesday [Sept. 17, 2019] by the Bill and Melinda Gates Foundation, along with a research team at the Institute for Health Metrics and Evaluation at the University of Washington, led by Stephen Lim, the institute’s senior director of science and engineering.

For the full story, see:

Alicia Parlapiano, Josh Katz, and Margot Sanger-Katz. “Fewer of the World’s Children Are Dying, but Many Remain at Risk.” The New York Times (Wednesday, Sept. 18, 2019): A1 & A12.

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

(Note: the online version of the story has the date Sept. 17, 2019, and has the title “Almost Everywhere,Fewer Children Are Dying.” In the last paragraph quoted above, the wording follows the online version, and not the print version. The order of the authors’ names in the online version is: Josh Katz, Alicia Parlapiano and Margot Sanger-Katz.)

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. )

How Drinking Coffee Makes Us Younger and More Open-Minded

(p. C2) . . . , if a baby monkey heard a new sound pattern many times, her neurons (brain cells) would adjust to respond more to that sound pattern. Older monkeys’ neurons didn’t change in the same way.

At least part of the reason for this lies in neurotransmitters, chemicals that help to connect one neuron to another. Young animals have high levels of “cholinergic” neurotransmitters that make the brain more plastic, easier to change. Older animals start to produce inhibitory chemicals that counteract the effect of the cholinergic ones. They actually actively keep the brain from changing.

. . .

In the new research, Jay Blundon and colleagues at St. Jude Children’s Research Hospital in Memphis, Tenn., tried to restore early-learning abilities to adult mice. As in the earlier experiments, they exposed the mice to a new sound and recorded whether their neurons changed in response. But this time the researchers tried making the adult mice more flexible by keeping the inhibitory brain chemicals from influencing the neurons.

In some studies, they actually changed the mouse genes so that the animals no longer produced the inhibitors in the same way. In others, they injected other chemicals that counteracted the inhibitors. (Caffeine seems to work in this way, by counteracting inhibitory neurotransmitters. That’s why coffee makes us more alert and helps us to learn.)

In all of these cases in the St. Jude study, the adult brains started to look like the baby brains.

For the full commentary, see:

Alison Gopnik. “MIND & MATTER; How to Get Old Brains to Think Like Young Ones.” The New York Times (Saturday, July 8, 2017): C2.

(Note: ellipses added.)

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

The article co-authored by Jay Blundon and mentioned above,is:

Blundon, Jay A., Noah C. Roy, Brett J. W. Teubner, Jing Yu, Tae-Yeon Eom, K. Jake Sample, Amar Pani, Richard J. Smeyne, Seung Baek Han, Ryan A. Kerekes, Derek C. Rose, Troy A. Hackett, Pradeep K. Vuppala, Burgess B. Freeman, and Stanislav S. Zakharenko. “Restoring Auditory Cortex Plasticity in Adult Mice by Restricting Thalamic Adenosine Signaling.” Science 356, no. 6345 (June 30, 2017): 1352-56.

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.”)