The Stanford University human geneticist identified the genes and genomic abnormalities underlying numerous rare diseases, including Rett syndrome, and advanced the field of molecular diagnostics.
By Anna Azvolinsky | May 1, 2018
Before moving her lab from the University of California, San Diego (UCSD), to Yale University in 1978, Uta Francke learned how to fly. “I thought, where could you go from New Haven if you are very busy and don’t have much time? It’s hard to do with a car and even the train, so I got a license to fly a small plane and joined a flying club in New Haven,” says the professor emerita of genetics and pediatrics at Stanford University School of Medicine.
In her Piper Comanche plane, Francke would zoom off to Martha’s Vineyard or Nantucket for weekend excursions or to institutions in the northeast to give invited seminars on her research. “I would agree to give talks if the institution was within flying distance. And then the researchers would take me out to dinner, and what they mostly wanted to do was talk about my flying the airplane,” she says.
But Francke had much to discuss in addition to her experience as a pilot. She trained as a physician in Germany, initially driven by her interest in pediatrics. In the U.S., she entered—and helped define—the new field of medical genetics, becoming an expert in human cytogenetics and pioneering molecular diagnostics techniques.
Her scientific accomplishments include being among the first to map specific genes to their chromosomal locations and, with that information, contribute to a detailed map of the human genome. Francke and her team also found the genes responsible for Prader-Willi and Rett syndromes, laying the foundation for investigators to discover genes responsible for other rare genetic disorders.
Francke’s research helped set the stage for the Human Genome Project (HGP) that began in the 1990s. What is underappreciated today, according to Francke, are the efforts by researchers like herself—who had generated detailed maps of each human chromosome—that greatly facilitated stitching together the sequences generated by the HGP.
But before molecular diagnostics and her discovery of variants responsible for rare diseases, Francke was a sharp student growing up in wartime Germany with parents who initially discouraged her from following her academic talents.
From her father’s death, an opportunity
Francke was born in 1942 in a small town just north of Frankfurt, Germany. Her father, who had a law degree, fought for Germany in World War II, and her mother was an elementary school teacher. Her parents did not think she and her sister should attend the local school that would put them on a path to a university education, as neither of her parents thought that girls needed much in the way of career options. Instead, the girls went to a local middle school that would direct them to become secretaries or technical assistants.
Then, when Francke was 12, her father suffered what was assumed to be a heart attack at age 46. “It was a total shock for us. I realized that things can change suddenly, that nothing is truly stable,” says Francke.
After her father’s death, Francke informed her mother that she wanted to switch schools, and her sister followed suit. From then on, Francke’s mother let her choose her own way. She chose a science track in which she was the only girl. “I didn’t feel out of place at all,” she says.
After high school, Francke pursued a career in medicine. She had volunteered at a hospital, doing the unglamorous work of changing patients’ bedpans and sheets, and found the tasks gratifying. “I loved taking care of patients. I wanted to go into medicine because it was immediately useful to people,” she says. At the University of Marburg, Francke settled into a cozy student life of coursework and singing in a choir. But after two years, she realized that small-town life wasn’t preparing her well for the “real world,” so she transferred, in 1963, to the University of Munich, where she completed her clinical training.
Attaining her medical degree required Francke to write a thesis, and she initially inquired about bacteriophage research at the Max Planck Institute of Biochemistry in Munich, where her first husband, whom she’d met in medical school, was working on his thesis. But a professor at the institute discouraged her from molecular genetics work, Francke recalls, likely because she was a woman. Instead, she was advised to pursue a clinically focused thesis. She followed up with patients who had been diagnosed with an appendix tumor to see whether the cancer—identified incidentally by a pathologist when they’d had their appendices removed—progressed in subsequent years. Francke and her surgeon collaborator found that the tumors were not likely to recur or metastasize.
New country, new profession
Francke completed medical school in 1967, followed by two years of postgraduate rotations in various specialties. In 1969, she applied for a pediatric fellowship at the Children’s Hospital of Los Angeles. She wanted additional pediatric training, and her husband was starting a postdoc at UCLA. The Children’s Hospital took a chance on Francke, she says, as she didn’t know much English and didn’t have a US license to practice. “I knew so little about America. I remember calling a lab and asking someone there to send me test results. After saying, ‘Thank you,’ the person replied, ‘You’re welcome.’ And I thought, ‘I should write down their number, I am welcome there!’ I didn’t know about this expression and many others.”
After that residency, Francke was ready for a change and applied for a new medical genetics fellowship at UCLA. In 1970, she was among the first fellows in the program, making the rounds in the hospital to identify patients with potential genetic anomalies that could be studied. Back at the lab, Francke sat at the microscope manually counting the number of chromosomes in patient samples to spot abnormal karyotypes with more or fewer than 46 chromosomes. In 1971, she found out about a new technique, developed in Sweden, in which chromosomes are stained with a fluorescent dye, quinacrine mustard, resulting in distinct chromosomal banding patterns that allowed for the identification of individual chromosomes.