Dr. Barry Stoddard is developing tools that could revolutionize treatment for cystic fibrosis, sickle-cell anemia and Parkinson’s disease. He’s a leader in his field and has a 20-year track record of success. But the current National Institutes of Health funding climate, compounded by sequestration, is so bad that one of his key projects is in jeopardy and Stoddard thinks there’s a 50-50 chance he’ll be forced to give up his academic research at the end of next year.

“If I can’t find funding, I’ll go find a new career,” he says.

Stoddard’s story illustrates how NIH cuts are hitting home for even the most established researchers, endangering discoveries that could spark the next generation of lifesaving treatments.

Dr. Barry Stoddard

His lab is developing what Stoddard calls “molecular guided missiles” – molecules that zero in on a gene mutation that’s causing a disease, cut around it, and insert new instructions. Those instructions make the gene behave normally and eliminate the disease.

The field’s Holy Grail is to develop molecules so precise that they write over a single genetic sequence without affecting any others. Stoddard and his colleagues have accomplished this feat in preliminary experiments and are poised to do it on a much larger scale. But their funding is running dry.

Last fall, Stoddard applied for an NIH grant that would bring in $250,000 a year for four years, covering about half of his lab’s annual budget. The NIH scored his application in the 16^th percentile, meaning it was stronger than 84% of the applications submitted. But that wasn’t good enough, even though Stoddard has previously received funding for grants scored in the 20^th to 25^th percentiles.

He says this is a sign of how the NIH is cranking back on funding to accommodate its budget, which has been flat for years and now has been cut by roughly five percent due to the federal budget sequester.

“At any point in the last two decades of my career, a grant in the 16^th percentile would have been funded almost automatically,” Stoddard says.

He rewrote and resubmitted his grant based on the NIH’s feedback, but there’s no guarantee it will get a better score. And he can’t resubmit it again if it doesn’t get funded this time.

Stoddard is scrambling to find a foundation or other outside source to fund his work. But those sources are few and far between and typically don’t cover the costs required to power, light and maintain laboratory space.

“I’m writing grant applications as fast as I can, but it feels a little like blasting at the sky with a shotgun and hoping for something to fall out,” Stoddard says.

He fears that federal cuts to research funding could have a chilling effect. If the sequester isn’t replaced by a more sensible approach, Stoddard expects medical research to dramatically contract. That means giving up not only on new discoveries and medical treatments, but also on the companies and jobs they spawn. Stoddard’s own work has been the foundation for two private companies including Seattle-based Pregenen.

“The amount of money we spend on research is a tiny fraction of the federal budget,” Stoddard says. “The tragic thing about these cuts is that they’re so unnecessary.”

Visit our sequestration page for the latest news on how budget cuts impact Fred Hutch and cancer research nationwide.

A Seattle Visit

Many times I’ve driven past the Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance campus and wondered how I would react to seeing those bright brick buildings after Jenny had died. Would I be overcome with grief? Frustration? Anger? Would I have to look away?

Happily, none of the above. And quite the opposite—I now get a strong sense of joy, of promise and of reflection on so many days of Jenny’s treatment when we were strong and Jenny was making it her workplace—the foundry of her remaining days.

Jenny

Yesterday, I took the opportunity to visit SCCA and have lunch with Dr. Bill Bensinger and Dr. Zandra Klippel, Jenny’s oncology team. Dr. Bensinger oversaw Jenny’s treatment for myeloma after her transplants and guided us through numerous clinical trials. As you read his bio you will understand his stature in the myeloma world. We enjoyed him thoroughly and he guided us well.

The confidence that he inspired in Jenny was, I believe, a strong factor in her strength and determination. Dr. Klippel worked most closely with Jenny as a post-doctoral fellow under Dr. Bensinger and spent the most time with us over the last year in the clinic.

Zandra is blessed with deep compassion and empathy for her patients, an ability to go well beyond symptoms and treatments and find the whole patient. She is also a gifted researcher, spending her non-clinic hours working on emergent therapies for myeloma that will, we hope, extend the lives of many future patients.

The lunch gave me an opportunity to share Jenny’s final days with them and perhaps give them the comfort of knowing that their work was not in vain—that they furnished the gift of time that let us prepare for Jenny’s death with acceptance and the knowledge that she and I did our best.

Like all of us, they miss Jenny. They each reflected on her contributions to their day to day, her contributions to myeloma research and her example to other patients and families. We spoke of the wealth of data Jenny left through her participation in clinical trials. We reflected on her presence at clinic, her humor, her scarves.

A few months ago, while I was searching myeloma clinical trials, I encountered an abstract of a paper reporting a novel therapy under trial in Denmark and Boston. The experiment involved the use of a human antibody. I mentioned the trial to Zandra, who hadn’t heard of it. She mentioned it to Dr. Bensinger, who was immediately enthusiastic about its potential—for Jenny—and others with the risk factors that made her disease so lethal.

At the time, Zandra cautioned that, even if they could participate in the trial, it would take time. Perhaps too much time to benefit Jenny. Yesterday, Dr. Bensinger confirmed that he has had discussions with the pharmaceutical company that produces the antibody and has been asked to develop a research proposal to explore its potential. He has asked Zandra to co-lead the project with another Hutch researcher.

I couldn’t be more gratified.

Jenny’s and my journey into the strange territory of cancer brought us to remarkable experiences, unforgettable people, and emotional growth that was unimaginable. We made that odyssey with so many others—patients who have passed before, patients surviving now and the cancer patients of the future. We were accompanied by doctors and nurses and technicians and researchers—a long line reaching from the past toward the future.

Brilliant minds and bright hearts. And nothing about that progression was stationary. We moved among this pilgrimage. And Jenny helped move this collective effort with her example and her effort.

The journey brought us also to a place. A city within a city. Bright brick buildings teeming with people dedicated to healing others and being healed themselves.

A place of sacrifice and frequent disappointment. But also a place of promise and example. Of the best of the best of compassion and the applied power of human intelligence.

No. I don’t have a problem driving past the site. I do shed tears, but not of loss or regret. I feel joy. I feel deep connection to Jenny and to the good that happens at Fred Hutch and SCCA.

Dr. Kathi Malone, a Fred Hutch epidemiologist, has spent her career studying what causes breast cancer and predicting the impact of those factors—including genetic history. In the wake of Angelina Jolie’s decision to have her breasts surgically removed to diminish her 87 percent risk of breast cancer due to her BRCA1 gene mutation, Malone shares her expertise in genetic determinants of breast cancer:

Who would you encourage to seek genetic testing for BRCA1 and BRCA2?

Dr. Kathi Malone

There are two main groups of women we recommend who should consider genetic counseling: those who have been diagnosed with certain types of cancer and/or those with certain patterns of cancer among their blood relatives.

Women with a personal history of breast cancer at an early age (before age 50 is a common cutoff), those who have had bilateral breast cancer, and women who have had ovarian cancer all fall into groups at higher risk of carrying a BRCA1 or BRCA2 mutation and thus should consider genetic counseling.

What if I’ve never had cancer but there’s some family history of it?

There are groups of women without a personal cancer history but with specific patterns of cancer in their family whom we encourage to seek genetic counseling and possible BRCA1/BRCA2 mutation testing. These include women who have:

• a first-degree relative (mother or sister) affected with breast cancer before age 50 or with bilateral breast cancer
• a first- or second-degree relative (aunt or grandmother) who had both breast and ovarian cancer
• multiple relatives affected with breast or ovarian cancer
• a male relative with breast cancer

Also, BRCA1/2 gene mutations have been observed to be more prevalent in individuals of Ashkenazi Jewish descent. Therefore, women with Ashkenazi ancestry who have a positive but less pronounced family history profile may still benefit from genetic counseling.

If I fall into one of these high-risk categories, do I need to take action?

Yes, being a carrier of a BRCA1 or BRCA2 gene mutation presents a lot of complexities and challenges. Women who carry one of these mutations have a much higher than average lifetime risk of developing breast and/or ovarian cancer and cannot afford to ignore the genetic side of things. They need information on their potential options for risk reduction, surveillance and risk management.

What should other women do to lower their breast cancer risk?

For other women, it is probably reasonable to focus on understanding their risk profile (calculate your risk) and assess whether there are modifiable risk factors they might change, like weight, activity level, tobacco use, etc.

For those like Jolie who have an inherited genetic mutation, how many choose to remove their breasts and/or ovaries? 

There are not a lot of data available on the proportions of BRCA1 or BRCA2 mutation carriers who move forward with risk-reduction surgery (like preventative mastectomy or oophorectomy). The decision to have risk-reduction surgery in high-risk women varies considerably across countries and within countries, and is influenced by a variety of factors such as age, childbearing status and plans, clinician views, perception of risk, and so on.

There are some indications that the rates of these procedures have been increasing over time. A recent report shows that women may initially, upon learning of their high-risk status and the options for risk reduction, opt out of risk reduction surgery but then may proceed with surgery years later. It is worth noting that risk reduction surgeries are not the only options: increased screening for cancer and the use of certain medications such as tamoxifen are some of the other options available.

Dr. Kathi Malone

By Colleen Steelquist, Hutchinson Center Science Editor

Angelina Jolie’s disclosure in today’s New York Times of her recent preventive double mastectomy made headlines around the world. Her celebrity spotlight illuminates the decisions faced by many women who share a similar family history of breast and/or ovarian cancer.

Jolie learned she carried a mutation in BRCA1, which along with BRCA2, are genes that act as tumor suppressors. For most people who develop cancer, cancer-causing gene mutations happen over the course of a lifetime, leading to cancer later in life. But some people are born with a gene mutation inherited from their mother or father. The risk of developing breast and/or ovarian cancer is greatly increased in women like Jolie (and men) who inherit these mutations.

We all, of course, want to reduce our risk of getting cancer. But it’s important to remember that genetic testing isn’t recommended for everyone—only about 5 percent to 10 percent of breast cancer cases are thought to be hereditary. It’s better to start by evaluating your risk with your doctor than rushing for genetic testing.

According to population research led by Fred Hutch’s Dr. Kathi Malone,  among breast cancer cases with a family history of ovarian cancer, 14 percent were found to carry a BRCA1 mutation. Among those who had a family history of both breast and ovarian cancer, 27 percent carried the mutation.

Fred Hutch researcher Dr. Julie Gralow, who directs the Breast Medical Oncology program at Seattle Cancer Care Alliance, said testing should be considered in families that have faced multiple cases of breast and ovarian cancer, young ages at diagnosis (40 or younger), male breast cancer incidence, and multiple cancers in the same family member.

Dr. Julie Gralow

And it’s optimal to test the family member who has cancer, Gralow said. “Otherwise, a negative result could mean either no gene mutation in the family or a family with a gene mutation that the tested person didn’t inherit,” she said.

For a BRCA1 or BRCA2 carrier, removing the ovaries is definitely recommended after childbearing and by age 40. “We don’t find ovarian cancer early or treat it well,” Gralow explained.

However, for women with either mutation, a double mastectomy is an option, but it’s not a solid recommendation, according to Gralow. “Mastectomy reduces risk for developing breast cancer, but because we would follow such a patient closely, we’d likely find a cancer early and it wouldn’t impact her survival,” she said.

Genetic tests are available to check for BRCA1 and BRCA2 mutations and genetic counseling is recommended before and after these tests through a clinic like SCCA’s Breast and Ovarian Cancer Prevention Program.

For the vast majority of people who face breast cancer, their risk stems from being female and getting older. Second to those, an individual’s reproductive history—childbearing, breastfeeding, age of first menstruation and menopause, use of hormone replacement therapy—plays a role.

The good news: Many Fred Hutch research studies show factors we can control, like our weight, activity levels and alcohol consumption, also impact our risk.

And as Gralow is quick to point out, even if there is controversy about the age to start them and how often to get them, mammograms save lives.

Read more about how to reduce your risk of breast cancer on our website.

When a major global vaccine alliance announced today that it had struck an agreement with two pharmaceutical companies to drastically reduce the price of human papillomavirus (HPV) vaccines in poor countries, there was plenty to celebrate at Fred Hutch.

Fred Hutch, via Dr. Denise Galloway and colleagues, made major breakthrough contributions to the vaccine that prevents HPV.

Their work showed that HPV is associated with nearly all genital-tract cancers and with many head and neck cancers. Her team also played a pivotal role in identifying how HPV causes cancer.

Cervical cancer used to be one of the most common causes of cancer death among American women, but thanks to widespread use of the Pap test, early detection and the introduction of the HPV vaccine, it’s no longer one of the biggest cancer threats.

“In just 25 years, we went from not having any idea what viruses were involved in these cancers to having a vaccine,” Galloway said in a previous interview about her work. “That’s amazingly fast.”

Dr. Denise Galloway

However, Galloway has often said it is imperative to take the vaccine into low-income countries, where HPV is a major killer of women, and where a vaccine would do the most good.

The price of the vaccine, which is about $300 for the three needed doses in the U.S. and other developed nations, is out of reach for poor women in Africa, Asia, Latin America and other parts of the world.

And yet, according to the World Health Organization, cervical cancer remains the second most common cancer in the world, with more than 500,000 new cases and 275,000 deaths each year—virtually all linked to HPV. More than 85 percent of cervical cancer deaths occur in developing countries.

This is why the agreement reached by the Global Alliance for Vaccines and Immunization with Merck, the maker of Gardasil vaccine, and GlaxoSmithKline, the maker of Cervarix, is so important.

Both companies have agreed to sell their vaccines in poor countries for under $5 per dose.

It’s certainly a transformational moment—a cause for celebration here and around the globe as research continues to move forward against cancer.

“My team made a discovery that improved outcomes for kids with brain tumors from 55 percent to 70 percent,” he said. “Without federal funding, research like this may never see the light of day.”

Olson’s comments came during a recent roundtable discussion with Sen. Patty Murray, who visited Fred Hutch’s campus to get a firsthand view of sequestration’s potential impact. Along with more than a half-dozen researchers from Fred Hutch, Seattle Children’s Research Institute, UW Medicine and the Pacific Northwest Diabetes Research Institute, Olson painted a bleak picture.

The two recent cuts were to grants Olson was promised by the National Cancer Institute. These funding reductions weren’t directly tied to sequestration but Olson believes they reflect a new caution among grant makers adapting to the changing fiscal landscape.

Dr. Jim Olson

In an ironic twist, these budget cuts can be self-defeating by imperiling projects that could save the government money. For instance, Olson’s team is developing federally-funded technology that determines which cancer treatments will be effective in particular patients.

At a time when the government is trying to reduce health care costs, “the last thing you want to do is spend $100,000 giving someone medicine that doesn’t have a chance of helping them,” Olson said.

Another key worry: sequestration might draw private dollars away from innovative new projects. Private philanthropy traditionally provides seed money that lets researchers test cutting-edge ideas and generate the results they need to apply for large federal grants.

“I’m afraid those philanthropic donations will be used to backfill projects where NIH funding is pulled out,” Olson said. “That could cost us a generation of new science.”

Sequestration could also translate into fewer jobs. Fred Hutch has already indicated that sequestration will trigger layoffs, and Olson sees a similar impact in his lab and at two companies he founded to improve cancer treatment.

These companies, Presage Biosciences and Blaze Bioscience, receive significant federal funding and have created 33 jobs in the past three years. Olson said they could create up to a thousand more. But the two recent grant cuts cost him money he had planned to spend on six new salaries. He also recently had to let his lab’s most senior researcher leave for another job after 13 years.

“I couldn’t match the offer they got without knowing what my own funding was going to be,” Olson said.

Several years ago, my father, René, took a job with one of the most heinous schedules that could be imposed on a human being: a regular morning start for a week, followed by a swing-shift week, and finally, a week of work deep into the night, when everyone else was sleeping.

The three-week cycle went on and on, very quickly turning my father into a zombie. It didn’t take long for the brutal schedule to start affecting his health. Of course, it sure seemed to put a damper on his social life as well. And talk about making him grumpy!

Today, we know a lot more about the detrimental effects of working through the night. And with continued research, the case against working instead of sleeping only gets stronger.

A recent study, for example, found a strong connection between lost sleep and weight gain. Just losing a few hours of sleep over a few nights in a row was enough to trigger weight gains.

At Fred Hutch, researchers have been looking at the connection between late-night work and cancer, specifically among women. A study released in 2005 suggested a link between late-night shifts and an increased risk of breast cancer.

At the time, Fred Hutch researchers believed night-shift work could alter hormonal levels in women, exposing them to a greater cancer risk.

Another Fred Hutch study, published in the April issue of the journal Occupational and Environmental Medicine, reports that night-shift work may be linked to increased ovarian cancer risk.

The Fred Hutch team, led by Dr. Parveen Bhatti, of the Center’s Public Health Sciences Division, found that night shifts were associated with a 24 percent increased risk of invasive epithelial ovarian cancer and a 48 percent increased risk of borderline disease compared with those who only worked daytime hours. They also found that women ages 50 and above were significantly more likely to develop ovarian cancer if they had worked at night.

Fred Hutch’s Dr. Parvin Bhatti

No wonder the International Agency for Research on Cancer classifies shift work that disrupts circadian rhythms (the body’s normal time clock) as a cancer-causing agent.

What is causing this increased risk? Bhatti and his co-authors, Drs. Mary Anne Rossing and Kristine Wicklund, speculate the increased risk could be linked to melatonin, a powerful hormone that is normally produced at night. Melatonin regulates reproductive hormones, including estrogen, and it scavenges harmful free radicals and boosts production of other antioxidants in the body. However, melatonin production is suppressed by ambient light.

Expect to hear more in the near future about melatonin, late-night shifts and increased risk of cancer. For now, getting a good night’s sleep can’t hurt at all. If anything, it might just keep those grumpy feelings from bubbling to the surface—and that potential extra weight at bay.

If you’re a cyclist, we have something entirely new to keep you motivated all the way through summer: the first-ever Obliteride, a community-wide bicycle event with a powerful purpose.

Obliteride is a fundraising bike ride to benefit lifesaving cancer research at Fred Hutch. To be held on Aug. 9-11, it will feature an entire weekend of cycling, celebrations and concerts. Don’t ride much, you say? There’s an easy 25-mile ride, followed by 50-, 100- and 180-mile rides for the more experienced set.

In case you didn’t know this, we are quite fortunate to have one of the top cancer research centers in the world right here in our Northwest community. By participating in Obliteride, you can help make a real difference here and with far-reaching impacts around the world.

Thanks to Obliteride sponsors, 100 percent of every dollar raised will directly benefit lifesaving cancer research at Fred Hutch.

There’s an opportunity for everyone to get involved. Volunteering or fundraising provide great alternatives to riding while clearly contributing to and participating in this new community effort. Sign up to ride, volunteer, or fundraise at obliteride.org. Route maps are now available at obliteride.org/ride and short highlight videos of each route are at obliteride.org.

Science For Life