2 TEXAS DOCTORS CELEBRATE NOBEL MEDICINE PRIZE AT MIT
Author: By Judy Foreman, Globe Staff
Date: Tuesday, October 15, 1985
Page: 1
Section: METRO
Two Texas doctors won the Nobel Prize in Medicine yesterday for their
discovery of how cells in the body pull cholesterol out of the blood, an
understanding that is already paving the way for new drugs to retard the
often-fatal buildup of cholesterol.
Drs. Michael S. Brown and Joseph L. Goldstein from the University of Texas
Health Science Center in Dallas celebrated their surprise victory in Cambridge
yesterday morning with those who know their work best, other scientists
attending a conference on membrane receptors at the Whitehead Institute for
biomedical research at the Massachusetts Institute of Technology.
From the first excited telephone calls early yesterday morning, to a
hastily arranged champagne breakfast, to a mid-morning press conference and
noontime dash to the airport chauffeured by Whitehead chief David Baltimore,
himself a Nobel Prize winner, Brown and Goldstein expressed "surprise" and
''shock" at winning the prize, which this year carries a record $225,000
award.
Brown is director of the department of genetic diseases and Goldstein is
chief of molecular genetics.
Their work has "revolutionized our knowledge about the regulation of
cholesterol metabolism and the treatment of diseases caused by abnormally
elevated cholesterol levels in the blood," said the Karolinska Institute in
Stockholm, which awards the Nobel prizes.
In 1973, Brown and Goldstein discovered a protein receptor on the surface
of cells that grabs cholesterol out of the blood, where it is carried around
by a substance called low density lipoprotein, or LDL.
The LDL receptor on cell membranes pulls the cholesterol inside the cell,
where it is used to make hormones, the cell membrane itself, vitamin D and
other products.
But when a person has too few LDL receptors, not enough cholesterol is
removed from the blood. The cholesterol then builds up as plaque on blood
vessel walls, eventually clogging them so badly that heart attacks and strokes
result. Indeed, half of all deaths in the United States result from this
process, called atherosclerosis.
In most people, it takes time to acquire a deficiency of these receptors,
most likely, the researchers said, through a complex feedback system in which
high levels of dietary cholesterol signal cells not to make any more
receptors.
But one in 500 people with high blood cholesterol levels are born with only
half the normal number of receptors, said Brown, 44, and Goldstein, 45, who
studied familial hypercholesterolemia, the genetic tendency to have too few
receptors. This inherited disease accounts for about 5 percent of all people
who have a heart attack under age 60.
The most dramatic illustration of the doctors' work came two years ago when
they helped treat Stormie Jones, now 8, who had a heart attack at age 6.
Having inherited a receptor deficiency from both parents, she had virtually no
way to rid her body of cholesterol, and had blood levels of cholesterol of
about 1200 milligrams, almost five times the safe level, according to a
science center spokesman in Dallas.
Stormie received the first double organ transplant - a heart to replace
her damaged one, and a liver which, unlike her own, possessed the normal
number of cholesterol receptors. Today, she is in nearly normal health.
Brown and Goldstein mused that someday new drugs based on their work might
conceivably mean Americans could "have their steak and eat it, too," but they
were careful to urge people to follow the low-fat, low-cholesterol dietary
recommendations of the American Heart Association.
Although they have developed a skin test for patients born with too few
cholesterol receptors, there is no similar test yet for acquired receptor
deficiency, they added.
A number of drug companies, however, are working on drugs to increase the
number of receptors, and several drugs already used to reduce blood
cholesterol levels are now believed to work by increasing receptors, the
doctors added.
After finding the LDL receptor itself, Brown, Goldstein and their
colleagues have spent a dozen years understanding and finally, identifying the
gene for that receptor.
Brown, Goldstein and their colleagues in Dallas, Richard Anderson, David
Bilheimer, David Russell and Kenneth Luskey, are now working on other pieces
of the cholesterol puzzle, including how cholesterol builds up on blood vessel
walls and the workings of an apparently opposite receptor, for high density
lipoprotein.
FOREMA;10/14,12:56 NKELLY;10/16,10:47 NOBEL15
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