Photo by Robert Hood / Fred Hutch News Service
If you ask biologist Dr. Wenying Shou about her favorite moment in her lab, she’ll pull up gorgeous fluorescent images of red, green and blue cells and explain to you how those photos revealed how cooperating cells fend off cheaters.
But if you ask her about the most incredible experiment she’s ever seen, she’ll describe a different scene: an elderly man, very sick, lying in a hospital bed in a room by himself. She watches him through a leaded window that shields her from the radioactivity coursing through his blood.
And she sees her father’s swollen neck, where his lymph nodes bulge from his advanced non-Hodgkin lymphoma, shrinking before her eyes.
“I do a lot of experiments and the experiments I’ve done are beautiful,” Shou said. “I never expected something that beautiful could happen to a human being.”
In the 10 years since Shou launched her basic science laboratory at Fred Hutchinson Cancer Research Center, that one day when her father, Zhonghao Shou, received an experimental treatment developed by her colleagues in the Hutch’s Clinical Research Division ranks as the highlight.
There have been low points in that decade too, of course. When her father was first diagnosed with stage 4 lymphoma while visiting her in Seattle, just a year after she’d joined the Hutch. When his oncologist told him his cancer was incurable and he likely had only two years to live. And when, after her father had beaten the odds and was in remission five years past his diagnosis, her mother, Lingyan Fang, was diagnosed with rectal cancer.
Fang and Zhonghao Shou now live in Seattle with their daughter and granddaughter, 6-year-old Eureka. Their home is just half a mile from Dr. Wenying Shou’s Fred Hutch lab and the Hutch’s clinical care partner, Seattle Cancer Care Alliance, where the two were treated.
Both went through several types and rounds of treatment, some of them incredibly taxing. Both of them are now in remission and consider themselves cured. But it’s there that the similarities end.
“They are dramatically different stories of cancer treatment,” Shou said. “My dad is more like the rosy side, my mom is the darker side.”
A basic scientist’s new view of clinical research
For Shou, both stories point to the importance of developing better, more targeted treatments for cancer.
Her father benefited from one such approach: an experimental radioactive antibody developed at the Hutch that homes to cancerous cells in the blood, causing less damage to healthy tissues compared with total-body radiation. Zhonghao Shou had relatively few side effects.
These targeted therapies were not available for Fang. Because of the size and placement of her tumor, she had to have large sections of her colon and rectum removed. That procedure and the subsequent chemotherapy left her with long-lasting pain and chronic difficulties controlling her bowel functions that disrupt her sleep on a regular basis.
Even though Dr. Wenying Shou’s own research is not directly related to cancer — she studies how complex communities of different microbes can either cooperate or compete to get ahead — her family’s experiences also underscore the importance of basic science. Work like hers is how you understand how living systems function in great detail, she said, be it in a collection of bacteria or how fundamental processes go awry in one person’s tumor. It provides the foundation on which targeted treatments and other clinical advances can be built.
“If we really understood how things work, we might be able to design much more specific drugs that work much more potently, with much fewer side effects,” Shou said.
Shou’s Fred Hutch colleague, Dr. Ajay Gopal, a clinical researcher who led the trial her father participated in, echoed Shou’s sentiments.
“The work that she’s doing, a lot of these fundamental discoveries do translate into therapies, albeit it might be decades later,” Gopal said. “You don’t want to put people’s lives in terms of basic science experiments, but we are trying to replicate the science that one does in the laboratory in the clinic so we can advance the field, with all the compassion and consent that we must do in the clinic taking care of people’s loved ones.”
Her parents’ cancer stories — especially that of her father, a participant in a Fred Hutch clinical trial — also changed how Shou views clinical research.
With a background in both molecular biology and mathematics, Shou likes research where she can control the system precisely. Unlike genetically engineered bacteria and single-celled fungi, humans are too messy to study, she said. Even in the most well designed clinical trial, there are too many unknowns.
Or so she thought before that day in the hospital, watching her father receive an experimental therapy born of clinical research. It turned out her professional views as a scientist didn’t hold up in the face of a loved one suffering with a disease.
Photo by Robert Hood / Fred Hutch News Service
“Because [my own work] involves well-controlled experimental systems, we can gain a very mechanistic and quantitative understanding with error bars marked everywhere,” Shou said. “In my dad’s case, I no longer care that much about exactly how a drug works or error bars. I just care that his lymph nodes shrink rapidly and thoroughly. I was amazed by how my view about science has changed.”
Two parents diagnosed
Zhonghao Shou’s cancer story is inextricably tied up in science — his own, his daughter’s, and the research that spawned the treatments that sent him into remission.
Now 78, he is a self-trained geologist whose education was cut short in his native China by the communist government. He was in the middle of writing and publishing a research paper on earthquake prediction when he was first diagnosed with lymphoma in 2008. He’d been having sharp stomach pains for a while, but on a trip from his home in California to Seattle to visit his daughter, they got so bad that the two went to the emergency room.
He was diagnosed with stage 4 mantle cell lymphoma, a type of non-Hodgkin lymphoma, and stayed in Seattle to be treated at SCCA by oncologist Dr. Michael Linenberger. The doctors told him he probably had about two years left.
Zhonghao Shou’s first thought was of his research.
“I felt lost, but I was not afraid of death,” he said, his daughter translating his native Mandarin into English. “My work on earthquake prediction would have to be stopped.”
Fang’s first symptoms appeared in 2013 when she started noticing blood in her stool. One day she was washing dishes and blood just started gushing out, she said. It was confusing and terrifying.
Shou took her to the doctor, where they did a colonoscopy and found four tumors in her rectum.
Fang, now 70, was physically healthy her entire life, she said, also speaking through Dr. Wenying Shou to translate. She never even got colds, but she suffered from lifelong depression.
She was born in Shanghai at the dawn of the communist-led People’s Republic of China. From the beginning, her life under the communist regime was incredibly hard, she said. Her father was a well-known artist who was targeted by the government during the Cultural Revolution. He committed suicide.
Zhonghao Shou was from a poor family in a village in Zhejiang Province and was something of a child prodigy, his daughter said. He was the top student in China’s most selective high school. But then government officials asked him to plant evidence to frame his math teacher for a crime. He refused and was denied entrance to college. He was assigned to work as a security guard at a storage facility instead, Shou said, but studied math and science on his own time and eventually got promoted to work as a chemist.
Later in life, he devised a theory of earthquake prediction. Though controversial — many academic geologists don’t believe earthquake prediction is possible — his work has drawn attention.
Multiple treatments, one lasting side effect
After his diagnosis, he received the standard chemotherapy combination for his lymphoma, known as R-CHOP. The tumors shrank, but not enough. So his doctor recommended the clinical trial.
“I was somewhat afraid, but I felt I really had no choice, because there was not a complete response” he said. “It was an experiment.”
Zhonghao Shao was one of 36 participants in that trial, and one of the slightly more than half who went into long-term remission. His cancer stayed at bay until 2011, when he noticed double vision and a lump in his eye. The cancer was back — not unusual for mantle cell lymphoma, which has a high rate of relapse. He was treated with another combination of aggressive chemotherapies, and the cancer was beat back once again.
When Fang, Shou’s mother, was diagnosed with cancer, her first thought was that she did not want to be treated. She had suffered enough in China, she said. But her husband talked her into it.
“Because I live to support my family’s career, my husband’s career, I will get treatment,” she said. “If I were living alone, I would never have gone for this.”
She had surgery to remove the tumors — and much of her colon and rectum as well. The doctors gave her a synthetic rectum, to avoid the need for a lifelong colostomy bag, but because it does not absorb water like natural tissues and because so much of her colon is missing, Fang’s bowel movements are now much more frequent and it’s harder for her to control them.
Her doctor warned her that she might have bowel movements five or six times a day after the surgery. She thought she could handle that, but it turned out to be a vast underestimate in her case, she said.
Her frequent needs disrupt her sleep every night. In combination with her chronic depression, the sleep deprivation has been incredibly difficult.
“I don’t have this basic function of a normal human,” Fang said. “I feel very down.”
She quickly pointed out she doesn’t blame her doctors for her problems. They did the best they could for her, she said. Both Zhonghao Shou and Fang said they are grateful to their doctors and caregivers at SCCA, who went above and beyond to do their best for them.
Zhonghao Shou said he feels healthy and lucky to be alive. He was not afraid of dying, he said, but if he’d died without finishing his research projects — and the book he published just last year, with his wife and daughter’s help — he would have died with regret. Now he can die with peace, he said.
Fang, too, was not afraid of dying. But now, because of her debilitating side effects, she wishes she were dead, even though her cancer is gone.
‘The willpower came from our work’
Although Fang is not a scientist, she, too, had work that helped sustain her during treatment. Earlier in her life, she’d been a writer in China, following her father’s artistic path. She’d published a story that was included in a Chinese textbook as an example of a unique style of writing, her daughter said.
When she was going through treatment, her editor in China contacted her to propose that she write down her life story — the story of her childhood in China, her move to the U.S. with her husband and daughter, her cancer. His encouragement meant a lot, Fang said.
“It transformed me,” she said. “I started writing. I tried to ignore the numbness of my fingers and the pain from the chemotherapy.”
She finished the memoir, which she titled “Escape.”
“For both my husband and I, if we don’t have this goal to finish something, we probably wouldn’t have been doing nearly as well,” Fang said. “For both of us the willpower came from our work.”
A community of research — and treatment
For Dr. Wenying Shou, her mother’s story doesn’t hold as many clear-cut revelations as that of her father. She recognizes how much her mother has been through. But she is grateful that she chose to be treated, and that her cancer was cured.
“Even if she wishes she was dead, to me of course her being alive is a gift. She is so important to me and taking care of my daughter and the entire family,” Shou said. “I just wish the side effects of cancer treatment were not that long lasting.”
When Shou chose to start her lab at the Hutch, she came for the center’s track record in basic science. But the fact that her new lab was on the same campus as a top-notch cancer treatment facility turned out to be more than just a perk. That connection saved her career, she believes.
Acting as both caregiver and backup translator for her father (and later, for her mother) as she was also trying to launch her research career, she would often see him settled in the waiting room at SCCA, then run down to her lab to start some experiments, and run back up to the clinic when her father called her to say the doctor had arrived.
She’s not sure she would have made it through the grueling early years of establishing her own laboratory without that flexibility, she said. But that benefit pales in comparison to the work of her colleagues — clinical researchers and oncologists — that saved her parents.
“I just feel so lucky that I have the Hutch on my side,” she said. “I owe the Hutch my parents’ lives.”
Proceeds from this year’s IN for the Hutch, the signature, sell-out event of the Innovators Network, will benefit basic science at Fred Hutch, like that of Dr. Wenying Shou. Want to support basic science at the Hutch but can’t come to the event? Make a donation online.
Rachel Tompa is a former staff writer at Fred Hutchinson Cancer Research Center. She has a Ph.D. in molecular biology from the University of California, San Francisco and a certificate in science writing from the University of California, Santa Cruz. Follow her on Twitter @Rachel_Tompa.
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