It also may be that no other pill has the power to force a global reckoning on the ties between a mother's well-being and a woman's reproductive rights.
In the lead-up to this week's G20 and G8 summits in Southern Ontario, where maternal health is a key focus, Stephen Harper's Conservative government worked to separate the two issues. Canada has pledged new money and rallied international commitment to improve the health of mothers worldwide, but Ottawa says it will not support any initiative that involves abortion. Recent polling by Nanos Research suggests that Canadians disagree; 67.7 per cent said women in countries receiving aid from Canada should have access to safe abortions.
Unsafe abortions account for 13 per cent of maternal deaths. Postpartum bleeding accounts for 25 per cent, meaning a largely preventable condition still stands as the lead cause of maternal mortality.
In many ways, the story of misoprostol exposes the minefields in maternal health, and why progress, even on the most lethal front, moves at a glacial pace.
The manufacturer had no incentive to conduct trials to establish safe doses for obstetrics, says Dr. Winikoff, founder and president of Gynuity Health Projects, a non-profit research group that works to improve access to safe reproductive technologies. “It was ‘Don't ask, don't tell,'” she says. “They could still profit and they didn't have to advertise or train doctors in its use.”
So, as non-profit researchers figured out dosages, black markets blossomed, doctors and hospitals picked it up as a multipurpose, off-label obstetrics drug. But the data vacuum eventually proved deadly.
Inducing labour requires just 25 micrograms of misoprostol every four to six hours – a dose so small that a woman “only has to look at the drug” for contractions to start, Dr. Potts says. Yet the pill comes in tablets containing eight to 24 times that dose, which can rupture the uterus late in a pregnancy.
“Doctors were cutting it up with razor blades,” Dr. Potts says, some of them simply eager to have babies born during office hours. There were abuses and mistakes. Overdoses killed women and babies around the world.
Lawsuits were filed, fingers pointed and in August, 2000, G.D. Searle (which was taken over by Pfizer Inc. two years later) sent a letter warning U.S. doctors how deadly Cytotec could be in pregnancy.
Some hospitals stopped using it, but many medical bodies disagreed. The American College of Obstetricians and Gynecologists, for instance, sent out a letter stressing evidence that showed misoprostol to be safe for abortions, inducing labour and after miscarriages, if taken correctly, and the WHO eventually added misoprostol, with medical supervision, for incomplete miscarriage, abortion and labour induction to its List of Essential Medicines.
While the controversy played out in the U.S., Dr. El-Refaey continued work on the drug. In the mid-1990s, he had moved to the University College London where, one day, he passed the portrait of John Chassar Moir, the famous British surgeon who changed childbirth forever with his 1935 discovery of ergometrine, the first drug used to contract the uterus and combat postpartum bleeding.
Dr. El-Refaey knew too well that Dr. Moir's advance had not reached poor regions, including his own. It was why he had chosen his specialty – hoping to make motherhood the happy experience he saw in the West. As he gazed at the portrait, it occurred to him that perhaps misoprostol could force contractions postpartum, perhaps it too had the power to stop a hemorrhage.
In 1996, he and colleagues published evidence of its use against PPH in The Lancet. Then he boarded a plane to see the WHO in Geneva.
Excitement flowed like a spring creek: a cheap and easy pill to combat the biggest mother killer of all time. Within a year, the WHO had co-ordinated a massive trial involving 18,500 women in nine countries to compare misoprostol for PPH against oxytocin, the gold-standard treatment in industrialized countries.
Misoprostol first hit the market as a gastric ulcer drug in the 1980s. Manufactured by the U.S.-based G.D. Searle & Co. under the brand name Cytotec, it was approved for that purpose in 85 countries. But like many drugs, it was found to have other uses.
Cytotec's packaging warned pregnant women against taking it, but by the early 1990s, women in Brazil were doing just that to induce safe abortions. “It spread like bushfire when women figured it out,” Dr. Gülmezoglu says. “Then scientists and researchers picked it up.”
Dr. El-Refaey was one of them. While working on his postdoctoral thesis at Aberdeen University in Scotland, he established the safe dose for an abortion, and found that the drug could be administered vaginally, as well as orally. He also showed that taking misoprostol as a follow-up to mifepristone, now standard practice, made the highly controversial abortion pill RU-486 more effective.
His studies convinced Dr. El-Refaey that misoprostol is unique. “To have so many purposes, at different doses, it's the most important development in women's health for decades.”
The drug is a synthetic prostaglandin, which is a hormone-like messenger found in both sexes that acts on stomachs, kidneys, blood vessels and the uterus. While the online grapevine spread its use as an abortion drug, doctors discovered that misoprostol also could clear the uterus after a miscarriage, sparing women from invasive procedures, and induce labour.
“It became more and more widely used,” says Beverly Winikoff, a New York public-health scientist who has researched misoprostol for 20 years.