For years, researchers have looked for gene mutations that cause disease. Two scientists who started The Resilience Project
have flipped that effort upside down and started looking for gene
mutations that protect against disease. Discovery of such positively
deviant genes paves the way for drugs that mimic the protective
A New York Times story by Gina Kolata
tells the story of a Port Orchard, Washington, man who has a gene for
early onset Alzheimer's. The man's older brother, mother, nine of his
mother's siblings, and six cousins began showing symptoms in their 40s,
and most died in their 50s. The man, now 65, has no signs of the illness,
and researchers are trying to learn whether he has a genetic mutation
that is counteracting or substantially delaying the horrifying impact of
the Alzheimer's gene that he has.
of trying to fix things that are broken, let's look at people where
things are broken but nature finds a way around it," Dr. Eric E. Schadt, director of the Icahn Institute, a medical research institute at Mount Sinai Hospital in New York, said in an interview with the Times.
have found many gene mutations that cause disease or predispose a
person to an illness, and those seem to be considerably more common than
the beneficial mutations. However, with today's fast and relatively
inexpensive methods of sequencing DNA, and the ever-growing databases of
study subjects whose genomes have been sequenced, scientists can begin
to look for the positive mutations. Dr. Schadt and Dr. Stephen H. Friend, director of Sage Bionetworks,
a nonprofit research organization in Seattle, are searching databases
that hold clinical and genetic information. They are looking for people
who, despite having mutations for fatal diseases that strike early in
life, have remained healthy far past the age when the illness should
have appeared. They have analyzed data from more than 500,000 people,
and found only 20 in which a good gene mutation appears to have blocked a
bad one. But because no names are attached to the data, the scientists
can't contact those people. So they contacted researchers studying
extended families with severe genetic illnesses, and they found the
Some amazing beneficial gene mutations have already been discovered. One prevents HIV from entering cells and causing AIDS, and that discovery has enabled scientists to treat HIV positive patients by directly editing their cells. Discovery of another gene alteration that prevents build up of LDL cholesterol
led to discovery of a drug that is now in the final stage of testing.
Researchers using genetic databases have also found mutations in some
genes that confer partial protection against heart disease, osteoporosis and Type 2 diabetes.
Washington man who seems to have defied his dangerous Alzheimer's gene
retired recently. He told the Times his life's work now is to help
scientists understand the treacherous disease that claimed the lives of so
many members of his family.