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Unfortunately, her first year of school was 1936—the start of the Spanish Civil War. “She had a very hard time,” says Massagué. “She went back to her village to find her father and brother gone and did not know if they were alive.” She lived with her mother for a time, until her mother was jailed. After the war, the family reunited, and Massagué's mother, with a doggedness she'd pass on to her son, returned to Barcelona and her studies.
That's how she met Massagué's father. They married and passed along their love of science and learning to Massagué, the eldest of their six children. “I had a natural inclination for natural sciences as a kid,” says Massagué. “I loved butterflies. I fell in love with minerals. I like bird watching. Botany. Sociology. Everything.”
And when the opportunities came his way in the United States, his parents were supportive. “They never asked, 'Why are you hanging so long in the U.S.? When are you coming back?'” he says. “It was, 'Go for it. This is lovely. Don't worry about the rest, the pharmacy, others can run it.'”
He could have spent the rest of his scientific days as the TGF beta guy. But around 2000, Massagué got the itch for a new problem to solve.
Going back to Spain was an option, but he was already back several times a year, to visit family and to help Barcelona expand its research capacity. Since 2005, he has been adjunct director of the new Institute for Research in Biomedicine in Barcelona, whose director is Joan J. Guinovart, Massagué's Ph.D. thesis advisor. That, he says, allows him to cultivate his life “as a man from New York and Barcelona.”
Characteristically, the new problem he chose was the toughest in cancer biology: metastasis, the process by which cancer cells leave the tumor of origin and take root in other parts of the body.
Metastasis was recognized as far back as ancient Egypt. But it's still a huge problem, perhaps the problem of cancer. “All the chemotherapy, or the bulk of it, and the radiation, after the surgeon is done, is to prevent metastasis,” says Massagué. “If it were not for metastasis, cancer would be a minor fraction of the problem it is today. You'd just go to the O.R., have the lump taken out, and go home. It would be little more than going to the dentist.”
To find the key controls for cancer's spread, Massagué had to think up a novel way to collect the cells that had the knack both to metastasize and to successfully set up shop. Not easy; cells aren't very efficient at the whole metastasis game. Primary tumors shed millions of cells into the bloodstream every day. “And yet,” says Massagué, “if we die of metastasis, we don't die of millions of metastases.” Which cells were the right ones to study?
He used cells taken from the tumor of a woman who had died of breast cancer and injected them into immunodeficient mice. Then he collected those that traveled to the bone—a common site of metastasis for breast cancer—and injected them into yet another batch of mice. In those mice, bone tumors developed in half the time, indicating that Massagué has recruited the worst offenders.