Genetically engineered insulin

The invention: Artificially manufactured human insulin (Humulin)
as a medication for people suffering from diabetes.
The people behind the invention:
Irving S. Johnson (1925- ), an American zoologist who was
vice president of research at Eli Lilly Research Laboratories
Ronald E. Chance (1934- ), an American biochemist at Eli
Lilly Research Laboratories
What Is Diabetes?
Carbohydrates (sugars and related chemicals) are the main food
and energy source for humans. In wealthy countries such as the
United States, more than 50 percent of the food people eat is made
up of carbohydrates, while in poorer countries the carbohydrate
content of diets is higher, from 70 to 90 percent.
Normally, most carbohydrates that a person eats are used (or metabolized)
quickly to produce energy. Carbohydrates not needed for
energy are either converted to fat or stored as a glucose polymer
called “glycogen.” Most adult humans carry about a pound of body
glycogen; this substance is broken down to produce energy when it
is needed.
Certain diseases prevent the proper metabolism and storage of
carbohydrates. The most common of these diseases is diabetes mellitus,
usually called simply “diabetes.” It is found in more than seventy
million people worldwide. Diabetic people cannot produce or
use enough insulin, a hormone secreted by the pancreas. When their
condition is not treated, the eyes may deteriorate to the point of
blindness. The kidneys may stop working properly, blood vessels
may be damaged, and the person may fall into a coma and die. In
fact, diabetes is the third most common killer in the United States.
Most of the problems surrounding diabetes are caused by high levels
of glucose in the blood. Cataracts often form in diabetics, as excess
glucose is deposited in the lens of the eye.
Important symptoms of diabetes include constant thirst, excessive urination, and large amounts of sugar in the blood and in the
urine. The glucose tolerance test (GTT) is the best way to find out
whether a person is suffering from diabetes. People given a GTT are
first told to fast overnight. In the morning their blood glucose level
is measured; then they are asked to drink about a fourth of a pound
of glucose dissolved in water. During the next four to six hours, the
blood glucose level is measured repeatedly. In nondiabetics, glucose
levels do not rise above a certain amount during a GTT, and the
level drops quickly as the glucose is assimilated by the body. In diabetics,
the blood glucose levels rise much higher and do not drop as
quickly. The extra glucose then shows up in the urine.
Treating Diabetes
Until the 1920’s, diabetes could be controlled only through a diet
very low in carbohydrates, and this treatment was not always successful.
Then Sir Frederick G. Banting and Charles H. Best found a
way to prepare purified insulin from animal pancreases and gave it
to patients. This gave diabetics their first chance to live a fairly normal
life. Banting and his coworkers won the 1923 Nobel Prize in
Physiology or Medicine for their work.
The usual treatment for diabetics became regular shots of insulin.
Drug companies took the insulin from the pancreases of cattle and
pigs slaughtered by the meat-packing industry. Unfortunately, animal
insulin has two disadvantages. First, about 5 percent of diabetics
are allergic to it and can have severe reactions. Second, the world
supply of animal pancreases goes up and down depending on how
much meat is being bought. Between 1970 and 1975, the supply of
insulin fell sharply as people began to eat less red meat, yet the
numbers of diabetics continued to increase. So researchers began to
look for a better way to supply insulin.
Studying pancreases of people who had donated their bodies to
science, researchers found that human insulin did not cause allergic
reactions. Scientists realized that it would be best to find a chemical
or biological way to prepare human insulin, and pharmaceutical
companies worked hard toward this goal. Eli Lilly and Company
was the first to succeed, and on May 14, 1982, it filed a new drug application
with the Food and Drug Administration (FDA) for the human insulin preparation it named “Humulin.”
Humulin is made by genetic engineering. Irving S. Johnson, who
worked on the development of Humulin, described Eli Lilly’s method
for producing Humulin. The common bacterium Escherichia coli
is used. Two strains of the bacterium are produced by genetic engineering:
The first strain is used to make a protein called an “A
chain,” and the second strain is used to make a “B chain.” After the
bacteria are harvested, the Aand B chains are removed and purified
separately. Then the two chains are combined chemically. When
they are purified once more, the result is Humulin, which has been
proved by Ronald E. Chance and his Eli Lilly coworkers to be chemically,
biologically, and physically identical to human insulin.
Consequences
The FDA and other regulatory agencies around the world approved
genetically engineered human insulin in 1982. Humulin
does not trigger allergic reactions, and its supply does not fluctuate.
It has brought an end to the fear that there would be a worldwide
shortage of insulin.
Humulin is important as well in being the first genetically engineered
industrial chemical. It began an era in which such advanced
technology could be a source for medical drugs, chemicals used in
farming, and other important industrial products. Researchers hope
that genetic engineering will help in the understanding of cancer
and other diseases, and that it will lead to ways to grow enough
food for a world whose population continues to rise.