Ten years ago, a young doctor came into Melissa Moore’s hospital room at Beth Israel Deaconess Medical Center and asked whether she would participate in a study of a common complication of pregnancy called preeclampsia.
Moore, 30 weeks pregnant and there for an early delivery due to the potentially life-threatening condition, said yes — if the doctor would explain what caused it. Dr. Ananth Karumanchi launched into the stripped-down summary he typically gives patients, but Moore interrupted him. She was a scientist. She wanted details.
Moore studies RNA, a multipurpose molecule that regulates gene activity. Karumanchi, a kidney specialist, sees patients and does disease research. Preeclampsia, it turned out, lay at the intersection of their two areas of expertise. They talked about working together. Then they lost touch.
It was the first in a series of near-misses more typical of a romantic comedy than the formation of a fruitful scientific partnership. Fate kept throwing Moore and Karumanchi together until they finally decided to team up. Last week, the pair received a $1 million grant from the Bill & Melinda Gates Foundation to fund the development of a novel, RNA-based therapy for preeclampsia.
Universities strive to spur incidental interactions between people in different fields, starting institutes and building common spaces in the hope that scientists will discover common ground. But Moore and Karumanchi’s collaboration developed organically, following a plot that could unfold only in an area like this, with its concentration of world-class research institutions and hospitals.
“That can only happen in Boston — you can go to a birthday party and the mom of a child is the world’s expert in RNA,” Karumanchi said. “I don’t think you could plan for something like this — it just happens.”
Preeclampsia, marked by high blood pressure and the buildup of protein in the urine of pregnant women, can cause kidney failure, seizures, and death, and it frequently requires babies to be born prematurely. As many as 8 percent of pregnant women in the United States develop the condition, but the disorder’s toll is greatest in developing countries, where prenatal medical care is less available. It is thought to cause the deaths of 76,000 mothers and half a million infants each year.
Karumanchi’s work in the early 2000s had begun to reveal what went wrong at the molecular level. A particular protein involved in inhibiting blood vessel formation spiked in preeclampsia and appeared to play a key role in the disorder. Administering that protein to rodents, Karumanchi had found, was one way to trigger the symptoms.
Those insights were new when Moore and Karumanchi had their first hospital room meeting in 2003, and they turned a previously mysterious medical disorder into one that Moore could help solve. But life carried them in separate directions. Moore gave birth to a girl named Anna, who spent 17 days in the neonatal intensive care unit but is now fine. Moore moved her laboratory to the University of Massachusetts Medical School from Brandeis University. She moved to Brookline.
In 2007, at a children’s birthday party at a gymnasium, Moore saw another parent reading scientific journals and approached him.
“What are you reading?” she asked, Karumanchi recalls. Moore realized he looked familiar, but couldn’t quite place him. Gradually, they figured out that the last time they spoke about science, Moore had been wearing a hospital gown. In the meantime, their young daughters, Anna and Anya, had become friends at the same preschool.
Moore and Karumanchi discussed their different research projects and expertise. Karumanchi went home and researched Moore’s publications, realizing she was a star in her field. Again, they lost touch.
Three years later, Karumanchi gave a talk in Virginia at the annual meeting of a group of elite scientists who receive open-ended funding from the nonprofit Howard Hughes Medical Institute. Karumanchi had recently been added to its roster, and Moore, who had been a Howard Hughes scientist for years, was there.
“We said, ‘This is crazy,’ ” Moore said. They decided they must work together.
Moore was codirector of an institute at UMass focused on developing therapies based on the rapidly evolving knowledge about how short, specially designed strands of RNA could be used to turn genes on and off, a technique known as RNA silencing. Her colleague Craig Mello had recently shared the Nobel Prize for his discoveries in this area, and UMass was amassing a roster of some of the world’s top scientists in the field.
As she and Karumanchi had discussed several times, one of the key problems in preeclampsia was an overabundance of a particular protein. RNA silencing therapy might be a powerful way to lower levels of that protein, Moore suggested. It was an approach very much out of the box for Karumanchi, who had been more focused on traditional drugs.
They began collaborating through video conference calls. With an initial grant from the Gates Foundation, they were able to show that they could use the RNA technology to decrease the levels of the protein in a mouse, with no discernible side effects on mouse pups.
This month, they received a second grant to refine the therapy and ultimately test it in baboons, a necessary step before trying it in women. Their hope is that the approach can eventually be especially useful in developing countries.
Dr. James N. Martin, professor of obstetrics and gynecology at the University of Mississippi Medical Center, said that approaches to prolonging pregnancy by lowering levels of the protein, including through RNA silencing, are promising.
It is still unknown whether such therapies will work and be safe, he said, but greater understanding of preeclampsia has allowed scientists to come up with a slew of ways to attack the condition. Other approaches being developed include traditional drugs and a system that works like dialysis to remove the protein from the blood. “My guess is that at the rate we’re going, we’re going to crack this thing within the next decade,” Martin said.
Many hurdles lie before Moore and Karumanchi, but now that they’ve joined forces, they are committed to seeing their project succeed.
“It’s near and dear to my heart. It’s my pet project,” Moore said. “One of the wonderful things about being a scientist and being involved in research is when things affect you, you can go after them.”