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14 November 2008

Abortion pill

The invention:
RU-486 was the first commercially available drug that prevented fertilized eggs from implanting themselves in the walls of women’s uteruses.
The people behind the invention:
Étienne-Émile Baulieu (1926- ), a French biochemist and endocrinologist Georges Teutsch, a French chemist
Alain Bélanger a French chemist
Daniel Philibert, a French physicist and pharmacologist



Developing and Testing

In 1980, Alain Bélanger, a research chemist, was working with
Georges Teutsch at Roussel Uclaf, a French pharmaceutical company.
Teutsch and Bélanger were interested in understanding how
changes in steroids affect the chemicals’ ability to bind to their steroid
receptors. (Receptors are molecules on cells that can bind with
certain chemical substances such as hormones. Receptors therefore
act as connecting links to promote or prevent specific bodily activities
or processes.) Bélanger synthesized several steroids that bonded
to steroid receptors. Among these steroids was a compound that
came to be called “RU-486.”
Another member of the research project, Daniel Philibert, found
that RU-486 blocked the activities of progesterone by binding tightly
to the progesterone receptor. Progesterone is a naturally occurring
steroid hormone that prepares the wall of the uterus to accept a fertilized
egg. Once this is done, the egg can become implanted and
can begin to develop. The hormone also prevents the muscles of the
uterus from contracting, which might cause the uterus to reject the
egg. Therefore RU-486, by acting as a kind of shield between hormone
and receptor, essentially stopped the progesterone from doing
its job.
At the time, Teutsch’s group did not consider that RU-486 might
be useful for deliberately interrupting human pregnancy. It was
Étienne-Émile Baulieu, a biochemist and endocrinologist and a consultant
for Roussel Uclaf, who made this connection. He persuaded
the company to test RU-486 for its effects on fertility control.
Many tests were performed on rabbits, rats, and monkeys; they
showed that, even in the presence of progesterone, RU-486 could
prevent secretory tissue from forming in the uterus, could change
the timing of the menstrual cycle, and could terminate a pregnancy—
that is, cause an abortion. The compound also seemed to be
nontoxic, even in high doses.
In October of 1981, Baulieu began testing the drug with human
volunteers. By 1985, major tests of RU-486 were being done in
France, Great Britain, The Netherlands, Sweden, and China. When a
relatively low dose of RU-486 was given orally, there was an 85 percent
success rate in ending pregnancy; the woman’s body expelled
the embryo and all the endometrial surface. Researchers found that
if a low dose of a prostaglandin (a hormonelike substance that
causes the smooth muscles of the uterus to contract, thereby expelling
the embryo) was given two days later, the success rate rose to 96
percent. There were few side effects, and the low doses of RU-486
did not interfere with the actions of other steroid hormones that are
necessary to keep the body working.
In the March, 1990, issue of The New England Journal of Medicine,
Baulieu and his coworkers reported that with one dose of RU-486,
followed in thirty-six to forty-eight hours with a low dose of prostaglandin,
96 percent of the 2,040 women they studied had a complete
abortion with few side effects. The women were monitored after receiving
the prostaglandin to watch for side effects, which included
nausea, vomiting, abdominal pain, and diarrhea. When they returned
for a later checkup, fewer than 2 percent of the women complained
of side effects. The researchers used two different prostaglandins;
they found that one caused a quicker abortion but also
brought about more pain and a longer period of bleeding.

Using the Drug

In September, 1988, the French government approved the distribution
of RU-486 for use in government-controlled clinics. The next
month, however, Roussel Uclaf stopped selling the drug because
people opposed to abortion did not want RU-486 to be available and
were threatening to boycott the company.
Then, however, there were threats and pressure from the other
side. For example, members of the World Congress of Obstetrics
and Gynecology announced that they might boycott Roussel Uclaf
if it did not make RU-486 available. The French government, which
controlled a 36 percent interest in Roussel Uclaf, ordered the company
to start distributing the drug once more.
By the fall of 1989, more than one-fourth of all early abortions in
France were being done with RU-486 and a prostaglandin. The French
government began helping to pay the cost of using RU-486 in 1990.
Testing for approval of RU-486 was completed in Great Britain
and The Netherlands, but Roussel Uclaf’s parent company, Hoechst
AG, did not try to market the drug there or in any other country outside
France. (In the United States, government regulations did not
allow RU-486 to be tested using government funds.)
Medical researchers believe that RU-486 may be useful not only
for abortions but also in other ways. For example, it may help in
treating certain breast cancers and other tumors. RU-486 is also being
investigated as a possible treatment for glaucoma—to lower
pressure in the eye that may be caused by a high level of steroid hormone.
It may be useful in promoting the healing of skin wounds
and softening the cervix at birth, easing delivery. Researchers hope
as well that some form of RU-486 may prove useful as a contraceptive—
that is, not to prevent a fertilized egg from implanting itself in
the mother’s uterus but to prevent ovulation in the first place.

Impact

Groups opposed to abortion rights have spoken out against RU-
486, while those who favor the right to abortion have urged its acceptance.
The drug has been approved for use in China as well as in
France. In the United States, however, the government has avoided
giving its approval to the drug. Officials of theWorld Health Organization
(WHO) have argued that RU-486 could prevent the deaths
of women who undergo botched abortions. Under international
law,WHOhas the right to take control of the drug and make it available
in poor countries at low cost. Because of the controversy surrounding
the drug, however,WHOcalled for more testing to ensure
that RU-486 is quite safe for women.

                                             Étienne-Emile Baulieu


 Étienne-Émile Baulieu was born in Strasbourg, France, in
1926. He moved to Paris for his advanced studies at the Faculty
of Medicine and Faculty of Science of Pasteur College. He was
an Intern of Paris from 1951 until he received a medical degree
in 1955. He passed examinations qualifying him to become a
teacher at state schools in 1958 and during the 1961-1962 academic
year was a visiting scientist in Columbia University’s
Department of Biochemistry.
In 1963 Baulieu was made a Doctor of Science and appointed
director of a research unit at France’s National Institute of
Health and Medical Science, a position he held until he retired
in 1997. He also served as Head of Service of Hormonal Biochemistry
of the Hospital of Bicêtre (1970-1997), professor of
biochemistry at University of Paris-South (1970-1993), and consultant
for Roussel Uclaf (1963-1997).
Among his many honors are the Gregory Pincus Memorial
Award (1978), awards from the National Academy of Medicine,
the Christopher Columbus Discovery Award in Biomedical Research
(1992), the Joseph Bolivar DeLee Humanitarian Award
(1994), and Commander of the Legion of Honor (1990). Although
busy with research and teaching duties, Baulieu was on
the editorial board of several French and international newspapers,
a member of scientific councils, and a participant in the
Special Program in Human Reproduction of the World Health
Organization.

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