What the Dog Saw: And Other Adventures

countered the stimulating effects of estrogen. But in breast cells, Pike believed, progestin wasn’t the solution; it was one of the hormones that caused cell division. This is one explanation for why, after years of studying the Pill, researchers have concluded that it has no effect one way or the other on breast cancer: whatever beneficial effect results from what the Pill does is canceled out by how it does it. John Rock touted the fact that the Pill used progestin, because progestin was the body’s own contraceptive. But Pike saw nothing “natural” about subjecting the breast to that heavy a dose of progestin. In his view, the amount of progestin and estrogen needed to make an effective contraceptive was much greater than the amount needed to keep the reproductive system healthy – and that excess was unnecessarily raising the risk of breast cancer. A truly natural Pill might be one that found a way to suppress ovulation without using progestin. Throughout the 1980s, Pike recalls, this was his obsession. “We were all trying to work out how the hell we could fix the Pill. We thought about it day and night.”

4.

Pike’s proposed solution is a class of drugs known as GnRHAs, which has been around for many years. GnRHAs disrupt the signals that the pituitary gland sends when it is attempting to order the manufacture of sex hormones. It’s a circuit breaker. “We’ve got substantial experience with this drug,” Pike says. Men suffering from prostate cancer are sometimes given a GnRHA to temporarily halt the production of testosterone, which can exacerbate their tumors. Girls suffering from what’s called precocious puberty – puberty at seven or eight, or even younger – are sometimes given the drug to forestall sexual maturity. If you give GnRHA to women of childbearing age, it stops their ovaries from producing estrogen and progestin. If the conventional Pill works by convincing the body that it is, well, a little bit pregnant, Pike’s pill would work by convincing the body that it was menopausal.

In the form Pike wants to use it, GnRHA will come in a clear glass bottle the size of a saltshaker, with a white plastic mister on top. It will be inhaled nasally. It breaks down in the body very quickly. A morning dose simply makes a woman menopausal for a while. Menopause, of course, has its risks. Women need estrogen to keep their hearts and bones strong. They also need progestin to keep the uterus healthy. So Pike intends to add back just enough of each hormone to solve these problems, but much less than women now receive on the Pill. Ideally, Pike says, the estrogen dose would be adjustable: women would try various levels until they found one that suited them. The progestin would come in four twelve-day stretches a year. When someone on Pike’s regimen stopped the progestin, she would have one of four annual menses.

Pike and an oncologist named Darcy Spicer have joined forces with another oncologist, John Daniels, in a startup called Balance Pharmaceuticals. The firm operates out of a small white industrial strip mall next to the freeway in Santa Monica. One of the tenants is a paint store, another looks like some sort of export company. Balance’s offices are housed in an oversized garage with a big overhead door and concrete floors. There is a tiny reception area, a little coffee table and a couch, and a warren of desks, bookshelves, filing cabinets, and computers. Balance is testing its formulation on a small group of women at high risk for breast cancer, and if the results continue to be encouraging, it will one day file for FDA approval.

“When I met Darcy Spicer a couple of years ago,” Pike said recently, as he sat at a conference table deep in the Balance garage, “he said, ‘Why don’t we just try it out? By taking mammograms, we should be able to see changes in the breasts of women on this drug, even if we add back a little estrogen to avoid side effects.’ So we did a study, and we found that there were huge changes.” Pike pulled out a paper he and Spicer had published in the Journal of the National Cancer Institute, showing breast X-rays of three young women. “These are the mammograms of the women before they start,” he said. Amid the grainy black outlines of the breast were large white fibrous clumps – clumps that Pike and Spicer believe are indicators of the kind of relentless cell division that increases breast-cancer risk. Next to those X-rays were three mammograms of the same women taken after a year on the GnRHA regimen. The clumps were almost entirely gone. “This to us represents that we have actually stopped the activity inside the breasts,” Pike went on. “White is a proxy for cell proliferation. We’re slowing down the breast.”

Pike stood up from the table and turned to a sketch pad on an easel behind him. He quickly wrote a series of numbers on the paper. “Suppose a woman reaches menarche at fifteen and menopause at fifty. That’s thirty-five years of stimulating the breast. If you cut that time in half, you will change her risk not by half but by half raised to the power of 4.5.” He was working with a statistical model he had developed to calculate breast-cancer risk. “That’s one-twenty-third. Your risk of breast cancer will be one-twenty-third of what it would be otherwise. It won’t be zero. You can’t get to zero. If you use this for ten years, your risk will be cut by at least half. If you use it for five years, your risk will be cut by at least a third. It’s as if your breast were to be five years younger, or ten years younger – forever.” The regimen, he says, should also provide protection against ovarian cancer.

Pike gave the sense that he had made this little speech many times before, to colleagues, to his family and friends – and to investors. He knew by now how strange and unbelievable what he was saying sounded. Here he was, in a cold, cramped garage in the industrial section of Santa Monica, arguing that he knew how to save the lives of hundreds of thousands of women around the world. And he wanted to do that by making young women menopausal through a chemical regimen sniffed every morning out of a bottle. This was, to say the least, a bold idea. Could he strike the right balance between the hormone levels women need to stay healthy and those that ultimately make them sick? Was progestin really so important in breast cancer? There are cancer specialists who remain skeptical. And, most of all, what would women think? John Rock, at least, had lent the cause of birth control his Old World manners and distinguished white hair and appeals from theology; he took pains to make the Pill seem like the least radical of interventions – nature’s contraceptive, something that could be slipped inside a woman’s purse and pass without notice. Pike was going to take the whole forty-year mythology of natural and sweep it aside. “Women are going to think, I’m being manipulated here. And it’s a perfectly reasonable thing to think.” Pike’s South African accent gets a little stronger as he becomes more animated. “But the modern way of living represents an extraordinary change in female biology. Women are going out and becoming lawyers, doctors, presidents of countries. They need to understand that what we are trying to do isn’t abnormal. It’s just as normal as when someone hundreds of years ago had menarche at seventeen and had five babies and had three hundred fewer menstrual cycles than most women have today. The world is not the world it was. And some of the risks that go with the benefits of a woman getting educated and not getting pregnant all the time are breast cancer and ovarian cancer, and we need to deal with it. I have three daughters. The earliest grandchild I had was when one of them was thirty-one. That’s the way many women are now. They ovulate from twelve or thirteen until their early thirties. Twenty years of uninterrupted ovulation before their first child! That’s a brand-new phenomenon!”

5.

John Rock’s long battle on behalf of his birth-control pill forced the Church to take notice. In the spring of 1963, just after Rock’s book was published, a meeting was held at the Vatican between high officials of the Catholic Church and Donald B. Straus, the chairman of Planned Parenthood. That summit was followed by another, on the campus of the University of Notre Dame. In the summer of 1964, on the eve of the feast of St. John the Baptist, Pope Paul VI announced that he would ask a committee of Church officials to reexamine the Vatican’s position on contraception. The group met first at the Collegio San Jose, in Rome, and it was clear that a majority of the committee were in favor of approving the Pill. Committee reports leaked to the National Catholic Register confirmed that Rock’s case appeared to be winning. Rock was elated. Newsweek put him on its cover, and ran a picture of the Pope inside. “Not since the Copernicans suggested in the sixteenth century that the sun was the center of the planetary system has the Roman Catholic Church found itself on such a perilous collision course with a new body of knowledge,” the article concluded. Paul VI, however, was unmoved. He stalled, delaying a verdict for months, and then years. Some said he