By GINA KOLATA
A number of years ago, five families in Brooklyn who had had babies
with a devastating disease decided to try what was
then nearly unthinkable: to eliminate a terrible genetic disease from the planet.
The disease is Tay-Sachs, a progressive, relentless
neurological disorder that afflicts mostly babies, leaving them mentally
impaired, blind, deaf and unable to swallow. There is no treatment, and most children with the disease die by 5.
The families raised money and, working with geneticists, began a program
that focused on a specific population, Ashkenazi
Jews, who are most at risk of harboring the Tay-Sachs gene. The geneticists offered screening to see whether family members
carried the gene.
It became an international effort, fueled by passion and involving volunteers who went to synagogues, Jewish community centers, college Hillel houses, anywhere they might reach people of Ashkenazic ancestry and enroll them in the screening and counsel them about the risks of having babies with the disease. If two people who carried the gene married, they were advised about the option of aborting affected fetuses. Some matchmakers advised their clients to be screened for the gene, and made sure carriers did not marry.
Thirty years later, Tay-Sachs is virtually gone, its incidence slashed more than 95 percent. The disease is now so rare that most doctors have never seen a case.
Emboldened by that success and with new technical tools that make genetic
screening cheap and simple, a group is aiming even
higher. It wants to eliminate nine other genetic diseases from the Ashkenazic population, which has been estimated at 10 million,
in a worldwide screening. The groundwork is laid, the group says. Its members — genetic counselors, geneticists and pediatricians at the New York University School of Medicine, the Montefiore Medical Center and the Albert Einstein College of Medicine — point out that the genes for the major recessive diseases that afflict Ashkenazim have been isolated. New technology allows screening for all those diseases, plus Tay-Sachs, at once.
That, some geneticists say, is what the Human Genome Project has promised,
an ability to scan a person's genes and find those
that can cause disease. Critics say such projects are just what worry them about the genome project. People will receive a flood of genetic information that may be difficult to understand and interpret about diseases, unlike Tay-Sachs, that can have courses that are impossible to predict.
Some see the project as a test case.
"It is a model for delivering these genetic services," said Dr. Michael M. Kaback, a geneticist at the University of California at
San Diego. "That is why it is important."
Dr. Kaback, an architect of the Tay-Sachs screening, emphasized that worldwide screening for 10 diseases would be difficult,
requiring careful attention to detail and to assessing the project as it starts. But, he said, "It could work."
The project ethicist, Nancy Neveloff Dubler, who directs the bioethics program at Montefiore, said the effort could show the
positive side of screening. "These are largely diseases that take a terrible toll early in life," Ms. Dubler said. "We could save
families from sorrow and children from suffering. That's a tremendously important goal."
Some experts, however, worry about stigmatizing Jews. "It's a dilemma,"
said Jayne C. Gershkowitz, director of the National
Tay-Sachs and Allied Diseases Association.
Ms. Gershkowitz fears that Jews will be seen as a people uniquely afflicted
with 10 genetic diseases. In fact, most diseases occur
in the general population, too, although the genes are much less prevalent.
Other ethnic groups have their own genetic diseases. For example, people
of Mediterranean ancestry may have genes for an iron
storage disease, beta-thalassemia, and blacks and Mediterraneans may have genes for sickle cell disease.
Others worry about how people will use the screening information and whether or not they should.
Lori B. Andrews, a professor of law and an ethicist at the Chicago-Kent
College of Law, said the screening might be the start of
a troubling era, as people receive information they may not be prepared to handle about diseases that may or may not prove
"How much information do we want, and what do you do with it?" Professor
Andrews asked. "This is not like other medical
areas, where there is a clear treatment. This has an impact on self-concept and on relationships with others. It is not a simple
As many as one in three Ashkenazim has one of the genes, but those carriers
are fine. The disease occurs just when a child
inherits a gene from each parent. If two carriers of a mutated gene have children, each baby has one chance in four of inheriting
the mutation from each parent, giving rise to the disease.
Not every disease is like Tay-Sachs. Others affect some people who inherit
two copies of the mutated gene and spare others,
with no way of knowing who will be ill.
Yet, the Tay-Sachs history has shown what is possible, said Dr. Harry
Ostrer, a project leader. Dr. Ostrer, also the director of
the Human Genetics Program at N.Y.U., said that before the Tay-Sachs screening began in the 1970's couples had no idea that
they might have a child with the disease until it was diagnosed. The experience of watching babies suffer and slowly die was so
sad that many of the parents never had other children.
The screening changed that. Now, Dr. Ostrer said, the number of babies
in the United States with Tay-Sachs has dropped, from
50 a year to 5, and most of those are born to couples who are not Jewish and but happen to have the mutated gene.
Many scientists assumed that the next steps would be straightforward.
Just find the genes for the other major recessive diseases
in the Ashkenazim, and those diseases, too, would die with screening.
The genes were found. In some cases, parents of affected children raised the research money themselves.
But, said Dr. Susan J. Gross, a geneticist at Montefiore and Albert
Einstein, which began a Tay-Sachs program in the 70's,
nothing happened. Dr. Gross and others watched with dismay as babies continued to be born to couples who had no idea that
they carried aberrant genes. Doctors were either unaware of the tests or were not offering them to their patients. Jews were
unaware that they were at risk or did not ask for or receive testing.
"The current medical model is not working," Dr. Gross said.
She decided that the solution was to offer testing to the world's Jews
rather than wait for people to ask for it. "I can't see any
other way to get this fixed," Dr. Gross said.
The group worked with the Trust for Jewish Philanthropy, which convened
experts on genetic disease research and testing and
asked them for advice.
"The opinion I had was, `Why not?' " said Dr. Charles R. Scriver, a
geneticist at McGill University in Montreal. In previous
decades, Dr. Scriver directed screening in Montreal to identify carriers of Tay-Sachs and beta-thalassemia, a genetic disease
that causes severe anemia.
High school students were told about the diseases and offered an opportunity
to be tested and given information about the
results. Although those who chose to be tested learned about their genes, no one else could see their results.
"The Tay-Sachs and thalassemia carrier screening programs over their
30-year existence in Montreal have resulted in an almost
complete absence of new cases of these two diseases," Dr. Scriver said.
Some critics ask about ensuring that people understand more complicated
Jewish diseases, which may be more typical of genetic
diseases in general. In Gaucher's disease, people can have a serious illness starting in infancy with anemia, bone pain and
enlarged livers and spleens. While there is an effective treatment, it has cost as much as $150,000 a year. Half the people who
inherit two copies of the mutated gene have no symptoms at all until their mid-40's, and some may never develop symptoms at
"You cannot predict who will have the severe disease," said Dr. Arno
G. Motulsky, a geneticist at the University of Washington
and a member of the advisory board to the group that wants to screen for the 10 disease genes. "This becomes a very tricky
issue. How should you counsel?"
A similar problem occurs with cystic fibrosis, another of the 10 diseases,
Dr. Kaback said. One child will be severely ill, and his
brother, who inherited exactly the same disease-causing genes, may have nothing wrong except, perhaps, the absence of the vas
deferens, which carries sperm from the testes.
Ms. Dubler, not overly concerned, said: "It's not that complicated.
We have taught people about health issues that are much
more difficult. It's a matter of finding the messages that people listen to most easily and the metaphors. We can do that."