Making goats, history

It could have been a scene from a science-fiction movie.

The year is 1984. Two young scientists burn the midnight oil in a Cambridge laboratory. They are brainstorming cheaper ways to produce human proteins, a key ingredient in many life-saving drugs.

Talk turns to the latest biochemistry buzzword: transgenics, transferring the DNA of one species to another.

The lightbulb flashes. What if they could use an animal, rather than a factory, to manufacture human proteins? Say, alter the genes of cows or goats so that a specific drug could be extracted from their milk?

Looking back on the eureka moment, Harry M. Meade (no relation to this reporter) recalled being so excited that when he got home at 2 a.m., he woke up his wife to tell her the news. Accustomed to her husband's odd hours, she wasn't upset about being awakened, but she wasn't too pleased with his ideas about tinkering with nature, Meade said.

She was just the first in a long line of people Meade would have to win over. But for the next two decades, he held fast to his dream, and today the Newton resident is on the verge of making pharmaceutical history.

Meade, 60, senior vice president of research and development at Framingham-based GTC Biotherapeutics, led a team that transferred human DNA into goat embryos. The company now has a herd of 1,200 hybrid animals on its farm in Charlton.

They look like typical goats, but the females produce milk containing a human protein missing in people who suffer from a rare blood-clotting disorder, antithrombin deficiency, that can complicate surgery or childbirth.

Last month, a drug made from the goat milk, ATryn , was endorsed by a key advisory panel of the European Union. Regulators could approve it for sale in Europe as early as September.

If so, ATryn would be the first drug ever produced from the milk of transgenic animals, said GTC spokesman Thomas E. Newberry .

And at the center of the effort is a guy who shows up at work in a Hawaiian shirt and khakis, whose left ear is pierced, and who -- appropriately enough -- wears a goatee.

That the crowning achievement of Meade's career is grazing on a central Massachusetts farm is fitting. He grew up on a dairy farm in Pennsylvania, and while he leaves the goat tending to others, Meade's tenacity at the lab bench owes much to lessons he learned as a child.

Just as a farmer faces down drought and blight, a scientist endures false leads and fickle investors.

``Growing up on a farm really prepares you," said Meade. ``The beginning part of the year, everything is so beautiful and green. Then the weather turns."

Meade the scientist has seen more than his share of turns.

The first in his family to go to college, Meade said he earned ``gentleman's C's" as a chemistry and electrical engineering major at Union College in New York. He never expected to go on to graduate school. But a professor urged him to further his education.

They were studying a tumor virus that is found in the milk of mice. Meade had to learn how to milk mice, a process that involves a women's breast pump, a pulsating vacuum, and a tube with tiny needles that attach to the teat (mice have hundreds of them, but milking takes only 15 minutes). The project would not only help Meade gain entrance to a doctoral program at MIT, but it equipped him with valuable skills for his drug research down the road.

Meanwhile, at home, Meade and his wife, Erica Schwartz , had their first baby. ``It was hard, economically and every other way," said Schwartz.

The couple met when they were both 18, marrying about a decade later. Schwartz grew up on Long Island and was the first to show Meade the ocean. She said she was attracted by Meade's seemingly dual personality: He was wild and crazy socially, but serious and intense when it came to science.

They had their second child 14 months after the first. Schwartz worked part time in social services. The MIT doctoral student supported his young family by moonlighting as a trash collector for a friend who owned a Sherborn waste collection business. ``That was our food money," Schwartz said.

In 1984, after Meade and colleague Nils Lonberg celebrated their eureka moment, they faced the daunting task of winning over their employer, Biogen Inc. The company's CEO, Walter Gilbert, who won the 1980 Nobel Prize in chemistry for his work in DNA sequencing, told the pair they could devote a fifth of their workweek to the project.

They started out small, tapping Meade's mice-milking experience from college. Their goal was to show that it was possible to produce a protein in milk that is not found naturally. Loosely speaking, they were like software writers. But instead of programming a computer, they were programming an animal -- writing genetic code to be inserted into an embryo -- to produce a protein needed by humans.

They had to come up with DNA sequences that would direct the production of the protein in the mouse's mammary gland.

But while they made progress coaxing genes, they had less success winning the support of their colleagues. At Biogen, the emphasis was more on producing drugs for market than on devising scientific processes with an uncertain future. Meade discovered that being a brilliant researcher wasn't enough. He also needed to get investors on board.

``You could make the argument that people go into science because they don't like to interact with other people," he said, but the cost of high-tech research has changed the formula for success. ``The interaction is almost as important as the science."

Meade said he has since honed his communication skills, discovering that the key is enthusiasm. And, indeed, even a layman can't help but become excited as Meade's eyes light up when he marvels about such arcane matters as the mammary gland's phenomenal ability to manufacture proteins. But for the scientist-turned-salesman -- since featured in Business Week, Scientific American, and The New York Times -- realizing his dream was still decades away.

Frustrated with the constraints on his time at Biogen, Meade left the company in the early 1990s to lead the microbiology research for the transgenic group at Genzyme Corp. Lonberg had already moved on to study transgenics at the Memorial Sloan-Kettering Cancer Center in New York.

Genzyme had just acquired another biotech firm that was researching ways to produce medications in goat milk. Goats start producing milk at a much younger age than cows, making the shaggy animals more appealing to researchers.

Meade's team spun out from the parent company in 1993 to form Genzyme Transgenics Corp., which evolved into GTC Biotherapeutics in 2002. The new company catered to pharmaceutical companies looking for new ways to produce medicines.

At home, Meade told his wife about his dreams of one day using transgenics to treat cancer and HIV. As a mental health and substance abuse counselor, she could see its benefits for AIDS patients, though she was realistic about how long the process might take.

``He'd get me excited about something," Schwartz said. ``When something didn't work, he'd have to figure it out all over again."

In the mid-'90s, the German pharmaceutical firm Behringwerke hired Meade's team to find a treatment for antithrombin deficiency. The project set the researchers on the path that would lead to the groundbreaking drug ATryn -- a path with many turns, not always in the right direction.

Though Meade had frequently helped out on the family farm in Pennsylvania, he spent little time on the company goat farm in the town of Charlton; he was too busy in Framingham with his team doing the genetic research work.

To prepare the embryos, veterinarians peered through a microscope while using a very fine needle to inject the revamped DNA into their nuclei. The embryos were then implanted in a female goat. Then came the seven-month wait for the kid to be born, and hormonally induced to produce enough milk for testing.

In the beginning, only about 10 percent of the goats produced milk containing the desired protein, but after more than five years of experimenting, the scientists hit on a process that yielded nearly a perfect success rate, said Newberry, the GTC spokesman.

Once the proteins are in the milk, they are isolated from the milk to produce the drug, which is administered to humans through a drip bag.

While the news from the farm was good at the start of the decade, the word from Germany was devastating: Behringwerke, in the midst of a corporate merger, abruptly pulled the plug on the project before the drug could undergo clinical trials. Other investors, including Genzyme, also started to pull out.

``That was a dark time for us," said Meade.

After Behringwerke backed out, GTC Biotherapeutics gained ownership of the process of developing ATryn -- and the challenge of courting enough investors to cover the research costs.

Last winter, the company was ready to go to market. Its first stop was London, home of the advisory committee for the European Medicines Agency, the top drug regulator for the European Union. The company was confident, touting the success of its clinical trials.

But the advisory panel rejected the drug, saying not enough patients had been tested.

``It was a really cold day in London," said Meade, and on Wall Street, where shares in the company fell by half, $58 million in paper value up in smoke.

Meade returned to Framingham and motivated his staff in the one way he knew best: He got ``back on the bench," said Suzanne Groet , GTC's vice president of therapeutic protein development, who has worked with Meade on the project since the late 1980s.

``Scientists by nature have to be patient," said Groet. ``Drug development, by its nature, takes a long time. But when you start adding a new technology, that takes an extremely long time. They really have to persevere."

Meade admits that his confidence in himself has alternately soared and plummeted with the roller coaster ride of the project.

``Sometimes you think you're going out and doing something that no one else can do. Other times you think you're doing it because you can't do what everybody else does," he said. ``You always have to second-guess yourself."

Less than six months after it was rebuffed, GTC Biotherapeutics was back before the panel in London. This time, it offered results from a broader pool of patients. And this time it won the panel's endorsement. Europe could give its final OK in September; Meade said clinical trials for Food and Drug Administration approval of US sales should be completed by the end of next year.

GTC officials said producing its drug with goat milk is far more efficient than relying on human plasma, the most common source. Every person in the United States would have to donate blood to derive the supply of the protein produced each year by 150 hybrid goats, according to Newberry.

ATryn treats a rare disorder, but its approval could pave the way for drugs derived from transgenic animals to treat a broad variety of problems. Meade said his next challenge is choosing which avenues to explore.

Despite the media attention, and Meade's potential status as the brains behind a revolution in pharmaceutical production, friends and neighbors know him as the ``nice guy" who clears their driveways with his snow blower, said his wife.

Still, the man known to the neighborhood kids as ``H-bones" can't completely shake the local celebrity. January's splash in Business Week included a photo of Meade on the Charlton farm, hamming it up with one of his four-legged factories.

``I went to the gym," Meade said, ``and one of the guys said, `Are you the one kissing the goat?' "