After 2 children via IVF, pair faced stem cell issue

Boston GlobeApril 2004

WEYMOUTH — When the letter arrived last spring at this gray-shingled house by the water, it was a reminder of some of the most joyous moments, and some of the most heartsick, that Marie Dooley had ever known.

The letter was from Boston IVF, the clinic that had helped Dooley and her husband, Tom, conceive two children after an emotionally wrenching struggle with infertility. Just seeing the logo on the envelope was a surprise, because she never expected to hear from the clinic again. As she tore the envelope open in her kitchen, she worried it was bad news. What it said was more complicated than she had imagined.

“Our current inventory of cryopreserved embryos shows that you have a total of 4 embryos,” the letter began.

It had been three years since the clinic had created a set of in vitro embryos to help the Dooleys bear children. Her insurance would no longer pay to keep the unused embryos in the freezer. What, the letter asked, did she want to do with them?

“I felt sick over it,” she recalled. “Am I going to give these embryos a life?”

And so, on that spring day, Dooley unexpectedly found herself in the quiet center of one of the most difficult ethical debates of our time. Unneeded embryos like the Dooleys’ are the foundation of an entirely new field of science.

Every experiment using embryonic stem cells — and every argument about their morality — ultimately begins with one of these embryos, about the size of the dot of an “i,” conceived for a couple trying to build a family. About 400,000 sit in freezers around the country, awaiting a decision.

It was a decision that Dooley, who is Catholic, did not begin to know how to make. She had thought she was done having children, but now she began to wonder whether she should use the embryos to try for more. She could have the embryos thrown away by a lab technician, or she could donate them to research. Under these last two choices, an embryo’s potential to become a child would be extinguished.

In political debates, the argument about embryonic stem cells often falls into easy certainties: An unwanted embryo is either a ball of cells useful for medical research or a human life deserving of legal protection.

But for the parents who created it, an embryo is not a simple thing. When Marie Dooley, 37, received her letter, she had long since stopped thinking about her leftover embryos. But she knew they were far more than balls of cells. Two embryos from that clinic had become her children — a 5-year-old daughter, Ava, who went out in a blue-and-silver Cinderella dress last Halloween, and a 3-year-old son, Harry, who gets into new mishaps daily.

Marie’s husband, Tom, suggested that they pay the $500 to keep them frozen for another year. But Marie knew that was just a way to delay an inevitable choice. It felt a little wrong to make such a decision at all, she said, but it felt more wrong to shirk the responsibility.

“I had the power to decide whether to bring a child into the world,” Dooley said. “It was a huge burden.”

Stem cell work at Harvard Just 13 miles away from the Dooley home, in a cramped basement laboratory on the campus of Harvard University, scientists were taking in human embryos, growing them, and trying to pluck out the powerful embryonic stem cells contained inside.

One of several universities conducting this research, Harvard has pushed ahead despite federal restrictions. In 2001, President Bush stopped federal funding for any experiment involving new embryonic stem cells. Later this month, Harvard will publicly launch what could be a $100 million initiative to perform the research without government money.

Harvard scientists would be unable to create new lines of embryonic stem cells without donated embryos supplied by Boston IVF. To interested couples, Boston IVF sends a four-page consent form, which outlines “a research project to establish human embryonic stem cell (hES) lines.”

There would be no way to know it from that spare, clinical description, but the scientist in charge of Harvard’s embryonic cell research, Douglas Melton, is driven by personal reasons. A little more than a decade ago, Melton was a highly successful biologist exploring early frog development when his 6-month-old son, Sam, was diagnosed with type-1 diabetes. So Melton decided to shift all his research into a singular goal: finding a cure for diabetes. To succeed, Melton became convinced he would need stem cells from human embryos.

If anything in science can be considered magical, it is these cells, formed a few days after conception. Over the course of nine months, they will generate every living cell in the body. By studying this mysterious process, Melton and other researchers hope to be able to grow cells that produce insulin for Sam and other diabetics, or find ways to cure any number of other diseases.

Four years ago, at a friend’s barbecue in Lexington, Melton ran into Douglas Powers, Boston IVF’s scientific director, and began talking excitedly about the rapid progress he and another researcher, Harvard’s Andrew McMahon, were making using stem cells from mice. Melton asked Powers whether he would be interested in collaborating on future experiments. Boston IVF, he knew, had many patients who would never use the embryos they had frozen.

After consulting with ethicists, Boston IVF agreed to join the project. Up to then, couples at Boston IVF could either discard their leftover embryos or try to bring them all to term. Now they had another option.

When does life begin? Answering the question about whether these embryos are human lives is beyond the realm of science, at least for now. From the moment of conception, a fertilized egg has the potential to be a child. Yet there is no clear, scientifically agreed upon moment at which a human life can be said to begin.

Legally, the rights to an embryo belong to the couple who created it — and whose feelings about it have been shaped by the dark journey through infertility.

Marie Dooley’s journey began in 1996. The youngest of five children, she always knew she wanted a family. But she was diagnosed with a disease called polycystic ovarian syndrome, and doctors told her it would be difficult to have children without medical help.

As she and her husband began trying to have children, she watched friends and sisters get pregnant, seemingly effortlessly, while month after month, she could not. She thought of all the teen mothers who have children and don’t want them. To her, it didn’t seem fair. Every time she got a phone call from her doctor’s office, she would go into mourning, she said. For days after, she fell into fits of uncontrollable crying. Tom couldn’t console her.

“It’s me,” Marie recalls telling him. As much as she loved her husband, she could not help but feel that her body, at some physical level, was rejecting him, and their love.

To create the embryos, Marie had to endure regular shots to increase her egg production, and Tom had to learn how to give them, using oranges to practice his technique. The night before she was scheduled to have some of her eggs removed, the two of them had to wake in the middle of the night to prepare an injection delivered at precisely 2 a.m. Three times they went through that routine.

Under such procedures, once the eggs are removed and fertilized with the husband’s sperm, each resulting embryo is remarkably delicate. To keep embryos growing outside the womb, Boston IVF lab technicians place them in a dish filled with nutrients, and then store them in a wall of humming incubators that maintain a steady temperature and constant levels of oxygen and carbon dioxide. The lights in the laboratory are even kept low, creating an environment as similar to the womb as possible.

A few days later, several of the developing embryos are placed back in the woman, in the hopes that one will take. Dooley remembers the drive home in 1997, a few days after Christmas. She had just had embryos implanted and worried about every bump.

“I know it sounds pathetic, but I was worried they would fall out,” Dooley said. Nine months later, she had Ava.

In another two years, she and Tom went through much the same ordeal to have Harry. This time there were several good embryos left over.

Whether to expand family The vast majority of the country’s excess embryos are discarded: removed from their freezer, dropped into an orange biohazard bag with the day’s used pipettes and Petri dishes, and thrown out with the day’s medical waste.

For Marie Dooley, that was never an option with her embryos. She thought of all the work that went into creating them — her own ups and downs, the “humiliation” of her husband going into a room with adult magazines, even the hours her father spent waiting for her in the parking lot for clinic visits.

“It just seemed like such a waste to throw them away,” Dooley said.

Dooley opposes abortion but believes it should be the woman’s choice. One option advocated by antiabortion groups — offering the embryos for adoption — is surrounded by difficult legal questions in Massachusetts, and felt impossible to Dooley to pursue. “I was looking at my children and thinking, `that is like giving you away to a stranger,’ ” she said.

The choice that really weighed on her was whether to have more children. For a week she struggled with this. If she did try to get pregnant again, it would be emotionally difficult. Even if the embryos were implanted, there was no guarantee they would lead to a pregnancy, a hard lesson she had learned from previous failures.

Statistics show that fewer than one in four implanted frozen embryos leads to a full-term pregnancy. On the other hand, there was the new life that her children had brought her and her husband. In addition to the two children she has from IVF, Ava and Harry, she has a 18-month-old daughter, Lila, conceived naturally.

“You go and look at your children and say, `What would my life be without you?’ ” she said.

Then there were the practical considerations, such as whether the house had enough room for a fourth child — or a fifth, too, because twins are common in IVF patients.

Tom manages properties for Chestnut Hill Realty, which allows Marie to stay home and care for the children. She worried a lot about the cost of schools. They hope to send all their children to the private high school Tom attended, and of course there is college. That, she said, is was what drove her decision. “As gross as it sounds, it was the price of education,” Dooley said.

Last May, about a week after the first letter arrived, Tom signed the release form, “Consent to Donate Human Embryos and Embryonic Cells for Research.” He headed off to work. After thinking about it a little more, Marie signed it quickly and put it in the mail, eager to move on with her life.

When patients’ embryos are used for the Harvard project, a scientist removes the plastic vials containing the embryos from the main storage containers. She carefully thaws the embryos and places them in petri dishes. She then puts these inside a portable incubator, a silver box about the size of a car battery, and drives them to Melton’s Cambridge lab in her navy Subaru Outback.

Last month, Melton announced that his laboratory, using 344 donated embryos, had managed to create 17 new lines of embryonic stem cells. In the small, highly charged world of stem-cell science, it was the most successful effort to date, doubling the number of lines that researchers around the world have to work with. Melton plans to give the samples free to any scientist who wants them.

Melton’s announcement marked a tiny step toward his goal of curing diabetes, and now the stakes are even higher for him: a few years ago, his daughter Emma, now 17, was also diagnosed with the disease.

Marie Dooley cannot know the fate of her own embryos. The experiment in Melton’s lab was set up so that the cells can’t be identified with the donors. The embryos may have died when they were thawed or failed to develop into a healthy blastocyst. They may have survived to become one of the world’s few healthy lines of embryonic stem cells. They may remain at the clinic, frozen in a separate tank, awaiting a new experiment.

A year after getting the letter from Boston IVF, Dooley says she feels happy with her decision. Dooley voted for President Bush in the last election, and she plans on voting for him again, despite his opposition to the work Melton is doing. The embryos don’t have a heartbeat, she says, and deciding what to do with them was an intensely personal choice.

As she has watched the political battle over stem cell research unfold, she has sometimes thought of sending the president pictures of her family.

“Science gave me a gift,” she said, as her children circled around the dining room table. “I felt I should give back.”