Fred Hutch’s Drs. Fred Appelbaum, Kiranjit Dhillon, Denise Galloway, Kathi Malone and Matthias Stephan swap stories about the struggles and thrills of conducting lifesaving research.
How did each of you get started in research?
DR. KIRANJIT DHILLON: I originally wanted to go into medicine. To get clinical experience, I ended up working in a hospital as a phlebotomist for a couple of years. One of the things that it made me aware of really quickly was I wasn’t sure how I liked being around sick people, which is a really horrible thing for a physician. But I loved studying human disease. So to me the obvious choice was research, and that took me down this path. I wanted to help people. Ultimately that’s what drives all of us. With research, we hope that instead of working with one patient at a time, we might contribute to something that might have a broader impact.
DR. DENISE GALLOWAY: It’s funny, I started doing phlebotomy also when I was in college. Then I started taking some classes and found I really liked working in the lab, trying to make discoveries, little minute discoveries, one at a time. I just found the lab was the right environment for me.
DR. KATHI MALONE: I might have taken the most circuitous route to research. My parents didn’t believe girls should go to college, and there were also financial barriers. When the nun who taught Latin at this all-girls school heard that I wasn’t going to college and [that] I was a National Merit semifinalist, she went to my parents and basically said, "This is crazy." So I was allowed to go to college. Then when I went to college, it was like, what were the professions women go into? Teaching, nursing, social work. So I thought, "Social work." And the day I graduated, I thought, "Oh, this is so not what I want to do." I was sort of in love with medicine, but at a distance. So I went the pre-med route. I was taking history of medicine, and this instructor starts showing all these slides of correlations between exposures and disease, and that was the most fun I’d had in a long time. I said, "I’d love to do this for a living." He said, "Have you heard the word ‘epidemiology’?" And that changed everything for me. Now I would do this for free. And I actually think all of you would too.
Researchers ranging from veterans to early-career investigators, left to right:
Dr. Matthias Stephan (arrived in 2012) is an expert in immunobioengineering, an emerging field that blends immunology and engineering to make materials used in treatments for cancer and other diseases.
Dr. Denise Galloway (1978), whose research, which demonstrated the link between human papillomaviruses (HPV) and genital-tract cancers, paved the way for the HPV vaccine.
Dr. Fred Appelbaum (1978), Fred Hutch deputy director and executive vice president,
is a world authority on blood cancers.
Dr. Kathi Malone (1993) is an epidemiologist who studies the origins and outcomes of
Dr. Kiranjit Dhillon (2008), a postdoctoral fellow in Fred Hutch’s Taniguchi Lab, focuses on why tumors become resistant to chemotherapy.
Photos by Robert Hood / Fred Hutch
DR. FRED APPELBAUM: [pretending to write] “I would do this for free.” I’ll be sure to mention it to [Hutch President and Director] Gary [Gilliland] so he’ll know.
MALONE: At the end of the day, it’s problem-solving, it’s The New York Times crossword puzzle seven days a week.
APPELBAUM: I was a sophomore in medical school. I had been looking at the brain stem and memorizing where each of the cranial nerves came out. I was bored and started leafing through journals. It was 1970, and there was [Fred Hutch stem cell transplant pioneer] Don Thomas’ first attempt to use bone marrow transplant to cure leukemia. It just seemed like the most amazing thing I could imagine. I was taking a course in immunology from one of the great old immunology professors, so I took the paper to Prof. [Robert] Schwartz, and I said, “Is this something that’s possible?” It was like that
scene from “The Graduate”: plastics. He took a cigar out of his mouth and said, “Fred, this could really be important.”
I was lucky enough to apply and get a position at the National Institutes of Health to work in a lab that was doing basic immunology transplantation. One day the phone rang and it was Don, saying,
“I read a few of your papers, and we have a position in Seattle and wondered if you’d be interested.” It was like the heavens opening and God looking down.
DR. MATTHIAS STEPHAN: I was brought up in a small village, very Catholic, [to believe] that you have to make sure your life has a purpose. When I was about 12 or 13, it was the first HIV case. I [thought] “Oh, I’ll find a cure for HIV.” And then I became aware of the whole cancer field, and so I couldn’t decide, do I want to cure HIV or cancer?
When I went to medical school, I worked with HIV patients. I didn’t ultimately go into HIV research because it was just too complicated. It was a rotation, so we started seeing cancer patients. Back then gene therapy was a big field, and I felt there was more potential for developing gene therapy for cancer.
APPELBAUM: AIDS was too complicated so you picked gene therapy for cancer? Just checking.
What challenges did you face when you were starting out, compared to now?
GALLOWAY: When I look back, the challenges were technical. You just couldn’t do many of the things you can do today. You had an idea of something you would like to investigate, but you didn’t have the tools to do it. Now it’s a completely different set of challenges. It’s hard to get a job. It’s hard to get funded.
STEPHAN: Did you know back when you started about the whole funding issue?
GALLOWAY: I never really worried about money, until recently. I just thought, “Ah, top 30 percent, I can end up there.”
What percentage of grant applications get funded now?
GALLOWAY: Seven or 8 percent is the funding level for cancer.
APPELBAUM: In some ways, it was the best of times and the worst of times. People have said, “Could Don have invented transplantation if he had to do it today, with the regulatory environment, with how hard it is to write a clinical trial, the number of committees it has to go through?” On the other hand, our patients were so sick. It was just emotionally so hard to put them through the pain and suffering of the transplants at that time. Imagine trying something and it failing 10 times in a row. It was easier to write the trials, it was easier to get them going, it was easier to get funding, but it was devastatingly hard to conduct them.
MALONE: You probably didn’t have the kind of supportive measures for the patients that could make the experience less horrible.
APPELBAUM: One of the reasons that survival in treating leukemia has improved is we have antiemetics [anti-nausea medicine]. Back then when you’d give chemotherapy to a patient with acute myeloid leukemia, they would be vomiting their guts out for days. If you’re older and weak and you’re throwing up constantly, you aspirate, you get pneumonia, and that can be fatal. It’s not any picnic today, but it’s much easier. Supportive measures have come from other disciplines — antiemetics, pain medications, anti-infectives, antivirals, antifungals. Funding is a lot harder. But there are things that are a lot better, too.
STEPHAN: One of the questions I have is, in public health, when you publish something, say a correlation between a particular diet and cancer risk, do people listen, do they change their diet?
MALONE: Overcoming behavior challenges in humans is not an easy thing. Much more work is needed to identify effective strategies.
GALLOWAY: One of the things about doing basic science is when you make these [discoveries] and then a company develops a vaccine, you think, that’s fantastic. Problem solved. Well, the problem is that people don’t take the vaccine. And that’s totally out of my realm where I can do anything about it. It’s so frustrating that logically you have such a great vaccine and now you have to deal with human nature and with the lack of a single-payer system in the U.S., all the problems of the real world.
Photos by Robert Hood / Fred Hutch
Which leads me to the question:
How do you deal with setbacks and disappointments?
DHILLON: You brought up this question at an interesting point. We were looking at a set of ovarian tumors that we got from a clinical collaborator, trying to identify some kind of pattern that we can associate with [treatment] resistance. And there’s so much noise [irregularities that muddy the real data] in the clinical samples, that it’s just devastating — personally devastating — that we can’t use this set. We’re scientists, we’re not supposed to think too much about this, but it breaks my heart to think about the 40 women who donated these samples.
MALONE: Is this related to how they were processed? I’m trying to understand what the noise means.
DHILLON: It’s got to be some kind of technical thing. We’re trying to identify the source. We’ve spent months on this.
APPELBAUM: In laboratory research particularly, I would do the same experiment one day and the next day and the next, and my media wasn’t quite right, or I didn’t pick the right pH, or my culture got infected. It was just so frustrating.
MALONE: We have the equivalent of that in my world — like, we didn’t ask the survey question the right way.
GALLOWAY: There’s part of lab work that’s just a slog. You have to do it over and over and over.
DHILLON: But when it finally works, there’s nothing like it. And that keeps you going for a long time.
What gets you up in the morning? What are you waking up excited about coming in and doing?
GALLOWAY: The HPV vaccine is currently given as three doses. The World Health Organization has just recommended that you could reduce that to two doses. There really aren’t a lot of studies that tell you whether that’s adequate or not. We’re looking at the memory B cells that are made in response to vaccination. If we can learn about the immune response, we could address the question whether or not two versus three [doses] give you the same immune memory. I’m really excited to know the answer to that.
APPELBAUM: The thing that I’m so excited about is to see if we really can take what now appears to be our ability to engineer T cells and combine it with things that take the brakes off the immune system to make a difference in solid tumors. I am really hopeful that immunotherapy is going to be the mainstay of cancer treatment in 10 years for metastatic cancer because it’s so much safer, so much less toxic. And some of the responses that we’re seeing in melanoma — and in some cases of lung cancer and bladder cancer — are truly enduring. These patients may well be cured or enjoy very long remissions. I’m not doing the work myself; I’m trying to facilitate it, so that it can happen. It just gets me up every day.
MALONE: The area that’s been getting me up in the morning is looking at outcomes after breast cancer, specifically recurrences and second primary cancers. Sixteen percent of the cancers reported in the national SEER system [Surveillance, Epidemiology and End Results Program of the National Cancer Institute] are second primaries.
APPELBAUM: Sixteen percent now? Wow.
MALONE: Some of that is because, as survival has improved, people now have longer lives and the opportunity to get second cancers. If you know that certain modifiable lifestyle factors could reduce your risk of that second primary — and we’re pretty sure that’s true — being a cancer patient might put you in a better position to [make changes]. This gets back to the question [Denise] raised: How do you get people to make changes?
STEPHAN: I’m excited about developing techniques to apply T-cell therapy, make it affordable so it can be developed and produced and distributed just like chemotherapy [rather than] customized for every patient. I know that every field has a certain time when it’s hot. We probably have 10 years to convince the world that we can get it to work and that it actually has a solid effect on a variety of tumors and we can produce it at a reasonable cost. It’s a race. But I like the thrill.