• 2009 Spring/Summer Paths of Progress

    Honoring her daughter
    Edited by Debra Bradley Ruder

    Megan HannaA portrait of her late daughter Molly, taken the summer before she died, helps motivate Megan Hanna in her work as a data analyst at Dana-Farber's Center for Cancer Genome Discovery. (Molly is at left in the portrait. 

    When Megan Hanna sits at her desk in Dana-Farber's Center for Cancer Genome Discovery, the nearby portrait of her daughter Molly offers more than a photographic tie to her family. It represents Hanna's inspiration for her second career.

    Molly Hanna was a beautiful, kind, strong-willed, and optimistic young woman who died in February 2002 at age 18 after three-and-a-half years of treatment for neuroblastoma, a rare cancer of the nervous system. During that time, her mother stayed by her side, researching treatment options and accompanying her to appointments and procedures at Dana-Farber's Jimmy Fund Clinic, Children's Hospital Boston, and around the country.

    Some of the scientific material was baffling to Hanna, who was then a graphic designer. In her overwhelming grief after Molly's death, Hanna went back to school to better understand the biology and chemistry behind the illness that claimed her middle child. Today, she is a data analyst at the genome center, where she works with clinicians and researchers who are seeking to mine genetic data from tumor samples for various studies. In October, Hanna contributed to a significant paper in the journal Nature about a newly discovered set of genetic mutations in neuroblastoma patients.

    "Megan's experience shows that if you have the motivation, you can do something pretty extraordinary professionally," says center Co-director Matthew Meyerson, MD, PhD, who hired Hanna as a summer intern five years ago and then brought her on full time. "She's a great biological data analyst, and she is very highly motivated to help people with neuroblastoma and all cancers. She's driven forward a lot of our work on neuroblastoma."

    Hanna's desire to advance the cause also inspires her to ride in the Pan-Massachusetts Challenge bike-a-thon for Dana-Farber and its Jimmy Fund. This past year, Hanna and Molly's father (Megan's ex-husband), Doug, raised $20,000 to support neuroblastoma research at the Institute.

    Paths of Progress writer Debra Bradley Ruder sat down with Megan Hanna last fall at her research group's high-tech offices at the Broad Institute of MIT and Harvard in Cambridge, Mass. Her story follows on the next few pages.

    Meagan and team membersAt Dana-Farber's Center for Cancer Genome Discovery, Megan Hanna (foreground) works closely with (left to right) Heidi Greulich, Laura MacConaill, Matthew Meyerson, and William Hahn. 

    November marks the 10th anniversary of Molly's diagnosis, so I've been thinking about it a lot lately. She was diagnosed because she had a bike accident and landed on her head. We got to Mount Auburn Hospital [in Cambridge, Mass.] and they did a CT scan. All of a sudden, they put us in an ambulance and sent us to Children's [Hospital Boston]. Before the morning came they were saying things like 'tumor' and 'oncologist,' but they still didn't know what kind of cancer it was. It took another two weeks, until Friday the 13th, for them to diagnose it as neuroblastoma because it was so unexpected in a child her age. Even her pediatrician had seen only one neuroblastoma in his entire career. It's very rare, 600 a year in North America, and most patients are below the age of 5. While I was taking biostatistics, I calculated the likelihood of a 14-year-old getting neuroblastoma: one in 13 million.

    Molly had five or six rounds of chemotherapy at Dana-Farber and Children's and surgery at Children's that winter in preparation for a double stem cell transplant. However, she didn't respond well, and we had to figure out what other treatment options were available. There are only a handful of centers across the country that treat neuroblastoma, and each one offers a different approach. Molly did an experimental protocol in New York involving a couple rounds of super high-dose chemotherapy, then nine months of monoclonal antibody therapy. She responded well, but a few months later the disease was back. The next winter she enrolled in a clinical trial of the radioactive drug MIBG in Philadelphia, followed by a stem cell transplant in Los Angeles. Again, the disease came back with a vengeance within a few months, and she died the following February.

    "It's hard to explain, but my grieving was so extreme that immersing myself in something completely foreign and incomprehensible was in some way a respite."

    When she was diagnosed, I began to try to understand the disease and read journal article after journal article, but an art school diploma does not prepare you well for this at all. After Molly died, there were still some questions in my mind. I wanted to know what a kinase was, for example, and what a ligand was. I'd read the definitions over and over again, but I didn't grasp what happens inside and outside a cell. I took an intensive general chemistry class at Boston College over the summer. I flunked it, but I was intrigued enough to want to learn more. I decided to take cell biology next, and the logical companion to that was organic chemistry. A friend tried to talk me into it, and I thought, "What, am I crazy? How could I possibly understand organic chemistry?" But nothing else in my life made sense, so I enrolled. That semester I took organic chemistry and cell bio, followed by more organic chemistry and biochemistry.

    It's hard to explain, but my grieving was so extreme that immersing myself in something completely foreign and incomprehensible was in some way a respite. Meantime, I couldn't manage appointments and sometimes I'd forget to pay my bills; my marriage had broken up, and my life was disintegrating around me. Most days, all I wanted to do was to go to bed, but the studying drove me.

    I loved organic chemistry and did very well, and I even did well in biochemistry. So I thought, what the heck, I'll apply to graduate school. I applied to one program and didn't tell my friends and family because I was sure I wouldn't get in (because who would accept someone with an undergraduate degree from an art school?), but then I did. The program was a master of science in bioinformatics at Northeastern University. I don't think there was a person less prepared for that program than me, but I jumped in and somehow got through it. My older daughter Bridget was away at college, but my son Willy – who is four years younger than Molly – suddenly had to cope with a mother in graduate school. He learned how to cook, and most evenings were spent together doing our homework.

    Molly Hanna, her brother and sisterMolly Hanna (at left) was a high-school student, writer, and artist who was devoted to her siblings, Bridget and Will. 

    One day, Matthew [Meyerson] called and asked if I would like to interview for a part-time summer internship reviewing sequence traces (the patterns in DNA that encode genetic information) looking for mutations in tumors. It's incredibly boring and meticulous work, but it was the perfect starter job for me: being in cancer research but doing something basically visual. There were more than a million traces to be reviewed manually.

    The mutation review took a long time, and then I stayed on. It has been incredibly hard getting here, both personally and professionally. And yet I always found the work that was happening around me so exciting and compelling that I never would have chosen otherwise.

    I became a co-author on the neuroblastoma paper in Nature  this way: Matthew knew my story, and we wanted to work on neuroblastoma genomics. I knew a couple of possible funding sources – funding for research on rare diseases is always difficult – and I ended up applying for a genomics grant from Alex's Lemonade Stand Foundation for childhood cancer research. The grant was funded for $160,000, with Matthew as principal investigator. Our collaborators Rani George, MD, PhD, and Tom Look, MD, PhD, working with funding from the Friends for Life organization, had some results suggesting that the ALK gene might be important in neuroblastoma, so we sequenced ALK in a large sample set. I coordinated the sequencing and did the mutation analysis. Looking for mutations is like looking for a needle in a haystack, but the ALK mutations seemed exciting from the start. They had all the hallmarks of important mutations, and they were not previously known variations in the human genome. Rani and Takaomi Sanda, MD, PhD, tested several drugs against the mutations [which are associated with tumor growth] with promising results, and the hope now is that these drugs might work in neuroblastoma patients who carry this mutated gene.

    With Molly I always knew that it was just a race against time. She lost the race, but maybe the next child won't.

    The care at the Jimmy Fund Clinic and Children's was spectacular. There was something about the clinic that felt like being at home; Molly would walk in and people would take care of her. One time, she'd lost her hair again and really wanted a wig, but couldn't leave the clinic because she was getting blood and platelet transfusions. She was so tall that it took the better part of a day to get transfused. So she sent me up to the Friends Boutique, and I brought down a big stack of wigs. Dr. Sam Volchenboum was a pediatric oncologist there at the time. It was late in the day and the other patients had gone, and he parked himself on the end of Molly's bed while she tried on wig after wig. After a while other people wandered in, and soon everyone was trying on wigs and laughing. She got a dark one that suited her and a long blond wig just for fun.

    We laughed at everything because it was so awful. You just had to make the best of it.

    I never left Molly's side during those years. Maybe if I'd made a different decision, things might have been easier for the whole family, but I don't regret a moment of it. I made sure she got the best care she could. Living without her in the world has been very hard. You go through that experience together and you become best friends – so you don't just lose your daughter, you lose your best friend, too. But I feel like Molly's proud of me for doing this work, and that what I do honors her.

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