12:00 PM Aug, 10, 2006
CHENNAI, India -- Medical staff who helped deliver a one-eyed child born here last week believe the mother may have been given an experimental anti-cancer drug, according to an internal hospital report seen by Wired News.
The report, from Kasturba Gandhi Hospital for Women and Children in Chennai, cites two potential causes for the birth defect: Either it was the result of an undetected chromosomal disorder or the mother was exposed to Cyclopamine, a drug that is being researched by a number of U.S. pharmaceutical companies as a potential cancer treatment.
There is no reference in the report on how Cyclopamine became listed as a possible cause.
The report states the child's parents turned to an unnamed fertility clinic after failing to have a child after six years of marriage. The treatment the mother received is unknown, but it appeared to work as she soon became pregnant. Then, late in her third trimester, she had her first ultrasound and it showed the child had serious problems. Too late to abort, she was rushed to the hospital for an induced labor.
The child was diagnosed with a rare chromosomal disorder, known as cyclopia. She was born with a single eye in the center of her forehead, no nose and her brain fused into a single hemisphere. With such severe deformities, it was a miracle that the girl survived even a few minutes after delivery. Yet now, 11 days later, she has lived significantly longer than other cyclopean cases.
"We were all shocked. My first reaction was to feel very sorry for the mother who had waited so long for her child," said Dr. Sathya Latha, head of pediatrics at the hospital.
The cause of the girl's deformity is still undetermined. But the hospital report's listing of Cyclopamine offers a tragic reminder of concerns over the state of Indian medical regulations, including lax oversight of fertility clinics and low barriers of entry for human drug trials.
Quacks here routinely advertise medical treatments with posters on the backs of buses, and roadside billboards offer cures for everything from infertility to AIDS. One particularly memorable sign reads, "Got AIDS, No Problem."
While some fertility clinics offer useless treatments, others may offer discounts for patients who agree to enroll in illegal clinical trials, according to Dr. Chandra Gulhati, editor of the Monthly Index of Medical Specialties and one of India's leading experts on medical ethics.
"There is no central registry of ongoing clinical trials, so it is almost impossible to check a master list to see what is going on," said Gulhati in an interview with this reporter in March.
Cyclopia affects about one child in a million. It can occur when a mother suffers from extremely low cholesterol or diabetes, or a foreign agent is introduced during pregnancy.
The active ingredient in Cyclopamine was discovered in 1957 when a batch of sheep in Idaho who had been grazing on wild corn lily gave birth to multiple one-eyed kids. Medical experts at the U.S. Department of Agriculture discovered that toxins in the corn lily are powerful teratogens that alter fetal development. The scientists named the toxin Cyclopamine after the one-eyed sheep.
After its discovery the toxin became little more than a footnote in medical textbooks until Philip Beachy, a research scientist at Johns Hopkins University, discovered that it had anti-carcinogenic properties. He showed that when applied correctly the toxin was capable of stopping several types of the most aggressive cancerous tumors that account for 25 percent of cancer deaths. Cyclopamine blocks an essential gene for embryonic development called Sonic Hedgehog. In a happy coincidence of nature, the gene is also a culprit for deadly cancers in the pancreas, thyroid, prostate, skin and esophagus.
In a series of e-mail exchanges, Beachy said he was baffled about how the drug could have appeared on the child's medical chart. Cyclopamine has no documented fertility benefits, and the known risk of birth defects would seem to absolutely rule out its use for that purpose, he said.
"There are trials of drugs related to Cyclopamine in the planning stages, but I am skeptical that the woman was given Cyclopamine in a quantity that would have caused this birth defect because of the lack of known fertility benefits and because it would be difficult and expensive to get enough of the drug to have an impact on a human patient. In fact, it would have been irresponsible to try to treat a woman trying to conceive with it," he wrote.
Responsibility has not always been a hallmark of drug trials in India. In 2000, a researcher at Johns Hopkins gave an anti-cancer agent to 26 patients in the South Indian state of Kerala without first going through animal testing. In another highly publicized incident three years later, two Indian pharmaceutical companies gave the anti-cancer drug Letrozole to more than 400 women as a fertility treatment in what was actually a clinical trial.
Johns Hopkins has given the Boston-based pharmaceutical company Curis an exclusive license to develop Cyclopamine and its structurally related derivatives. Curis has, in turn, licensed Cyclopamine to the San Francisco-based Genentech.
According to a press release, a collaborative clinical trial between Genentech and Curis for a treatment of basal-cell carcinoma related to Cyclopamine was halted in January after "clinical activity was far less than anticipated."
In an e-mail, Curis spokesman Michael Gray said that the company is "not conducting any clinical trials in India and has not sent any Cyclopamine to India." He added that Cyclopamine "is a publicly available compound -- anybody can buy it. Our scientists advise me that you can buy gram-quantities of Cyclopamine from major catalogues."
A representative for Genentech also said the company does not run clinical trials in India.
There are a number of possible explanations for the child's deformity that do not involve Cyclopamine. Though rare, cyclopia occurs naturally in about one in a million live births. It is also possible that a combination of chromosomal disorder and a fertility treatment came together if the mother was prescribed a drug like DES, a synthetic estrogen banned in the United States that prevents miscarriages and could have enabled a nonviable embryo to come to term.
Adding to the uncertainty of causes is that the hospital knows very little about the mother's medical history, what fertility clinic she went to, or what medication she was prescribed.
According to Dr. S. Dhanalakshmi, the superintendent of the hospital, the mother had never been to the hospital before and came with instructions from a sonogram operator to induce her into labor after an abnormal ultrasound.
"She was in such a confused state that she couldn't remember what clinic she had gone to or what medication they had prescribed," said Dhanalakshmi.
Although the baby is still at the hospital, the mother was discharged before doctors collected a complete medical history.
Gulhati, the medical ethicist, said such an oversight is inexplicable given the circumstances of the birth. "It just doesn't sound right," he said. "I think they know more than they are telling."
Under normal circumstances the child's deformities could be caught and the fetus terminated at an early stage of pregnancy. But after a rash of abortions in some parts of India after women discovered they were going to have a girl, the government made it illegal to determine the gender of a child during ultrasound tests. While the gender ratio is balancing out, another result has been that far fewer prospective parents are opting for prenatal care.
For now, the child continues to breathe and, like any other infant, responds to stimuli and occasionally cries when the nurses wheel her from one room to another or administer her feeding tube.
"We don't know how long she will live. We will do all we can for her until God calls her back," said Dhanalakshmi.
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