Dr. Ralph M. Steinman

Mike Groll/Associated Press; Pascal Disdier/CNRS, via Associated Press; Mike Groll/Associated Press

 

 

 

The New York Times, GoogleNews.com, October 3, 2011, by Lawrence K. Altman and Nicholas Wade  —  Three scientists shared the Nobel Prize in medicine yesterday, October 3rd,  for their discoveries about the immune system.  From left, Dr. Bruce A. Beutler, Dr. Jules A. Hoffmann and Dr. Ralph M. Steinman.  Dr. Steinman died on Sept. 30.

 

The Nobel Prize committee said Monday that it would stick with its decision to award a medicine prize to Dr. Ralph M. Steinman, an immunologist at Rockefeller University in Manhattan, even though he died on Friday.

 

As a rule, Nobel Prizes are not awarded posthumously, and the Swedish committee in charge of the selections said it had not been aware of Dr. Steinman’s death when it chose the winners.

On Monday, after news of his death was made public by Rockefeller University, the Nobel committee, at the Karolinska Institute in Stockholm, first said it would study the rules of the prizes and figure out what to do next. By mid-afternoon Eastern time, the committee said it would proceed with its plan to bestow the award on Dr. Steinman. The presentation ceremony is Dec. 10.

Dr. Steinman was awarded one-half the prize. The other half went to Dr. Bruce A. Beutler of the Scripps Research Institute in La Jolla, Calif., and Dr. Jules A. Hoffmann of France. All three scientists were recognized for advances in immunology.

They are being honored for discoveries of essential steps in the immune system’s response to infection. Dr. Steinman received a diagnosis of pancreatic cancer four years ago and had devised a treatment for himself based on his discovery, according to Rockefeller University.

The university, which has close ties with the Karolinska Institute, did not know of Dr. Steinman’s death until Monday morning, said Joseph Bonner, a spokesman for the school. The president of Rockefeller, Marc Tessier-Lavigne, immediately called the chairman of the Nobel prize committee to inform him.

To Susumu Tonegawa of the Massachusetts Institute of Technology, who won the prize for his work in immunology in 1987, the decision was a wise one. “All I can say is that the work deserved the prize, and it will be nicer if they make some adjustment,” he said.

In 1973, Dr. Steinman discovered a new class of cell, known as dendritic cells, which are key activators of the adaptive immune system. The dendrites engulf pathogens and display parts of them to the T cells of the immune system. The T cells then proliferate and destroy cells infected by the pathogen.

His work on dendritic cells faced considerable skepticism at first because the number of cells in the bloodstream seemed far too few to activate the T and B cells of the immune system, said Richard M. Locksley, an immunologist at the University of California, San Francisco. But Dr. Steinman persisted, and researchers later came to realize that many more dendritic cells lay outside the bloodstream in the body’s tissues.

A practical consequence of Dr. Steinman’s work is that dendritic cells have begun to be used as adjuvants in vaccines and in the treatment of certain cancers, Dr. Locksley said.

As for the other prize winners, Dr. Hoffmann in 1996 discovered the cell receptors in laboratory fruit flies that are activated by pathogenic bacteria or fungi. Two years later, Dr. Beutler identified the cell receptors in mice that respond to a substance in the coat of bacteria and that can trigger septic shock if over-stimulated. These receptors turned to be made by the same family of genes as those in the fruit fly, known as Toll-like receptor genes.

The Toll-like receptor genes are part of the immune system’s first line of defense against invaders, a generic response known as innate immunity. In the second line of defense, known as adaptive immunity, the body mounts a specific attack on the invading cells and lays down a memory so as to react more quickly to any second encounter.

American scientists have long dominated the Nobel prize honors and this year’s medicine award, though not a clean sweep, shows no sign that this strength is fading, contrary to frequent predictions. Dr. Steinman was born in Canada but worked at Rockefeller University for most of his career. Dr. Beutler is American and Dr. Hoffmann is French.

 

Blanca Nelly Betancur bathes her husband, Carlos Alberto Villegas, in Medellin, Columbia. The family is participating in a potentially groundbreaking assault on Alzheimer’s to see if giving treatment before dementia starts can lead to preventing Alzheimer’s altogether.
Todd Heisler / The New York Times

 

 

 

The New York Times, By PAM BELLUCK and SALVADOR RODRIGUEZ

Published: October 3, 2011

 

For the Betancur family, it was a kind of pilgrimage, an act of faith in science.

The Vanishing Mind

War on Dementia

Articles in this series are examining the worldwide struggle to find answers about Alzheimer’s disease.

 

Fear Grips a Family

In September, four family members traveled from Medellin, Colombia, to the Banner Alzheimer’s Institute in Phoenix, along with eight distant relatives. There are many more where they came from, about 5,000 — all members of the largest extended family linked to an inherited form of Alzheimer’s disease.

“There’s no words to describe seeing a loved one decay to the point where you no longer recognize them,” said Blanca Nelly Betancur, 43, whose mother and, so far, three siblings have inherited the disease. “To see them as a cadaver.”

Banner’s researchers and a Colombian neurologist are studying the extended family, planning a clinical trial to determine whether Alzheimer’s can be prevented by giving drug treatment years before dementia begins.

The Colombian relatives are considered ideal for testing preventive treatments, because scientists can tell which family members will develop Alzheimer’s and approximately when. Those getting the disease carry a genetic mutation causing memory loss in their early to mid-40s and often loss of most cognitive functions by their early 50s.

The trial is not expected to begin until 2012 because researchers are applying for federal financing and have not yet decided which drug to test. Testing will occur in the region where most relatives live, Antioquia, which includes Medellin and many isolated mountain villages.

But last month, 12 relatives visited Phoenix so scientists could conduct PET scans that can show whether their brains have the characteristic amyloid plaques of Alzheimer’s disease. Altogether, these scans will be performed on 50 family members this fall, some with Alzheimer’s already, some with the mutation that will cause it, and some who have no mutation and will not get the disease.

The snapshots of amyloid in family members with and without the gene, and with and without symptoms, will help focus the drug-testing study so researchers can better understand whether the drug is staving off Alzheimer’s, said Dr. Eric Reiman, the Banner Institute’s executive director.

“We need to find out when these amyloid plaques accumulate, how advanced they are by the time they enter the prevention trial,” Dr. Reiman said. “This information will provide a foundation for knowing how much these brain changes have occurred roughly at the time people at their age will enroll in the trial.”

The drug trial will test a treatment that attacks amyloid, most likely a drug already tried unsuccessfully in people with Alzheimer’s symptoms. Many scientists now believe it is possible that drugs have failed so far because once symptoms begin, the brain is already badly damaged.

Initially, the project plans to enroll 100 relatives with the mutation who will receive the drug, plus 100 mutation carriers and 100 noncarriers who will receive a placebo. Participants will not be told whether they have the mutation or are receiving the drug.

Ms. Betancur’s family is in an especially difficult position because she married a distant cousin, Carlos Alberto Villegas, and the mutation runs in both sides of the extended family. Her mother, who was living with them, died last year of Alzheimer’s; a sister with early symptoms now lives with them, too. Mr. Villegas, 54, once a vibrant livestock trader, has Alzheimer’s that is progressing so rapidly that in just the last year he has lost all ability to speak and walk.

“Psychologically it’s very tough,” said their daughter Natalia Agudelo, 24, who also traveled to Phoenix.

“After they lose memory, what remains are their instincts like animals,” she said, adding that her father can still chew and make other instinctive movements. “Until his last moment, we’ll be there seeing what more we can do to help, what more we can do to love.”

Natalia and her younger brother and sister may have inherited the mutation from their father or, if their mother is a carrier, from her as well. As a result, Natalia has decided not to have children.

“I love babies, and I’d be so happy with children, but having a child isn’t just ‘Oh, how cute,’ ” she said. “You have to be realistic and be clear that the disease is very tough. They say in Medellin, ‘Don’t go spreading the Alzheimer’s around.’ ”

Joining them in Phoenix were the elder Ms. Betancur’s brother, William, 50, and her sister Estela, 46, both with symptoms.

William, who quit his job as a bus driver because he could not remember the stops, knows he is losing his mind. He is so enthusiastic about the research that when asked into which arm he preferred the intravenous tube, he said, “Anywhere! With William, you guys have no problems at all!”

But Alzheimer’s makes him frustrated, irritable and “sad that my kids might eventually get the disease,” said William, who had a vasectomy after his third child because of that risk. “I would almost prefer that I not have grandchildren. Or at least only a few.”

When the relatives picked up their passports for the Phoenix trip, William got lost for an hour in the government building. He has no memory of the huge celebration his family threw in May for his 50th birthday. Asked his age, he still thinks he is 49.

“What’s the point of doing these things for him if he doesn’t even remember?” asked his wife, Elida Castrillón.

“Because he feels the love,” Natalia said.

Estela said she had not been told if she has Alzheimer’s, but believes she does, “because I begin to forget things.”

She cries often and is lonely because her husband is estranged, and her daughter is busy with work and school. She hopes researchers might find a cure in time to benefit her.

These days, she is halfway through a book called “A Pesar de Todo, Que Linda Es la Vida” — “Despite Everything, Life Is Beautiful.”