Many of us around the globe know the repeat offender under his lens too well—if not by sight then by deed. It has forced Bloom to play multiple roles in the lab—historian, forensic pathologist and, ultimately, evolutionary biologist—as he seeks to understand what makes it tick.

On the bottom of a petri dish, it doesn’t look that formidable. But this particular strain of influenza, which traces its lineage to a single progenitor dating back to 1968, killed as many as 1 million people in what came to be known as the Hong Kong flu pandemic of 1968-69.

Since then, the virus, now called H3N2, has amassed an impressive number of mutations in a very short window of time, sickening untold numbers of people along the way. In less than 40 years, it has undergone 39 mutations in a single gene, explaining why it’s so difficult to fight the flu. If this rate of evolution doesn’t sound too impressive, consider that millions of years would have to go by to see a similar change in a human gene. We are but mere tortoises in a race against the viral cheetahs of the world.

But what if we can figure out how this strain will evolve next, as Bloom is seeking to do, long before it does? If we uncover its most guarded secrets—jump a couple of steps ahead of its evolution—we might be able to stop it before it catches a ride into our bodies on a sneeze or cough.

Dr. Jesse Bloom

This is a big idea, the kind of thinking that’s nurtured at the Hutchinson Center, where basic scientists are seeking answers to the most fundamental and vexing questions in science: Why are some of us more susceptible to cancer? How does HIV so easily strip naked our most powerful immune defenses? How do cells communicate with one another?

Why, of all things, would our bodies attack their own cells? At the Hutchinson Center, evolutionary biologist Dr. Harmit Malik and his colleagues think that when it comes to autoimmune diseases such as lupus, we may be looking at the remnants of lost evolutionary arms races.

“We want to determine whether autoimmunity—when the body’s immune system turns against itself—results from an evolutionary arms race between ancient parasitic genes and the defense mechanisms that control them, which could provide a new model for understanding what causes lupus,” Malik said.

Dr. Harmit Malik

The human genome is littered with parasitic “jumping genes,” or endogenous retroelements, which can replicate and re-insert themselves into DNA. During millions of years of evolution, most of these genes have lost their ability to jump, but a tiny fraction are still capable of becoming active.

Recently, it was discovered that some people with lupus carry a mutation in the TREX1 gene, which inhibits their body’s ability to recognize and attack these jumping genes when they become active. This led Malik and colleague Dr. Richard McLaughlin to theorize that autoimmunity may arise when cells can no longer recognize these jumping genes, or retroelements.

Malik recently received a $300,000 grant from the Lupus Research Institute to study the potential role of “genetic conflicts” in the development of lupus.

“The Lupus Research Institute grant will allow us to test this theory for the first time by analyzing genetic variation in the TREX1 gene and active retroelements, and look for evidence that each has influenced the evolution of the other,” Malik said.

The odds of becoming an actual donor are not very high because finding a perfect match is rare. But for this Scottish firefighter, it was the right thing to do.

The call came much sooner than expected—only a year after signing up with the international bone-marrow registry. Across the Atlantic and the continental U.S., in a tiny town in Eastern Washington, a man suffering from a fatal bone marrow disorder needed her desperately.

The match was so nearly perfect that Wilkie thought she and Ryan Kilbury could be related. Today, in many ways, they are.

Bone marrow recipient Ryan Kilbury and his donor, Joanne Wilkie.

Five years ago, doctors harvested Wilkie’s marrow cells and gave them to Kilbury, a young Pasco, Wash., father suffering from leukemia.

The transplant was successful, and Kilbury and his wife went on to have another child. Meeting his donor was always on his mind, but it’s also rare for donors and recipients to meet, especially when life-saving cells travel across the world. But this winter, Wilkie traveled to Seattle to meet the Kilburys and the Hutchinson Center transplant team.

It was the kind of joyous day doctors and caregivers rarely experience—the meeting between a once-dying father of two and the donor whose gift enabled him to become the thriving father of three.

“We suspect that somewhere, you’ve got some Scottish blood in you,” Dr. Hootie Warren told Kilbury. “There is no chemotherapy for Ryan’s
variety of leukemia, no treatment. There really was only one option—transplantation,” said Warren, who led Kilbury’s life-saving team.

Transplantation with unrelated donors was once extremely uncommon. Today, while the procedure is common, matches for genetic compatibility can be hard to find, especially for racial and ethnic minorities, who tend to be under-represented in donor registries.

That’s why on separate continents, Wilkie and the Kilburys now work to increase awareness of the need for more donors, and encourage people of all ethnic groups to participate in the registry.

In the U.S. alone, there are more than 10,000 individuals right now with a life-threatening blood disease who need a bone marrow or stem cell transplant but lack a related donor.

Even though they may be continents apart, it takes people like Wilkie and Kilbury to show us when it comes to fighting disease, we’re all part of one huge global family.

For more information on how to register as a donor, visit www.marrow.org

In a span of just three decades, two of our three Nobel laureates have received the prize for their breakthrough research in basic science, while seven of our basic scientists have been elected to the National Academy of Sciences, one of the nation’s highest honors bestowed on a scientist.

I write about these accolades not to boast of our successes but to emphasize to our friends and supporters how critical basic research is to our mission to prevent, detect and treat cancer and other life-threatening diseases. Nearly every important drug and breakthrough therapy succeeds because it is based on our understanding of basic science. Without this knowledge, conducting medical research becomes more of a walk through a maze rather than an extension of scientific concepts and principles.

Answering science’s most fundamental questions requires a creative, tenacious and fearless group of people—out-of-the-box thinkers. And because the Hutchinson Center nurtures this kind of risk-taking scientific culture, we are able to recruit the world’s best basic scientists.

Consider Dr. Sue Biggins, the first researcher in the world to figure out exactly how to isolate a “molecular machine” that helps cells divide correctly. Her research is important not only because it gives us a deeper understanding of how cells work but also because it may lead to potential new targets for cancer therapies.

Our Basic Sciences Division also includes Dr. Mark Roth, who has found lifesaving applications for suspended animation, once the sole province of science fiction. Roth is now perfecting his techniques so that soon, we can lengthen storage time of human organs, extending transplantation to more people and buying time for trauma patients who have suffered severe blood loss or a heart attack.

We need basic scientists and we need their expertise. Without them, we have nowhere to go—no foundations upon which to build new strategies to fight cancer and other diseases, no new knowledge to expand upon what we already have learned. That’s why our basic science researchers remain passionate about their work. Their commitment has made us one of the most forward-looking research institutions in the world.

Our researchers will be quick to tell you their successes have been made possible by a unique atmosphere at the Hutchinson Center that encourages scientific cooperation where helping one another with investigations is the norm. Think of the innovations Bell Laboratories made to our life styles and culture: the transistor, the laser, the solar cell and the initiation of digital communications and cable communications.

It is this sustained commitment to intellectual curiosity that provides the milieu to bring new ideas into existence and allow their translation into improved human health.

In that spirit of cooperation, we hope you will partner with us to continue funding basic science research at the Hutchinson Center. We have accomplished a great deal, but we need your help to fuel a new era of lifesaving medical advances.

Cordially,

Dr. Larry Corey
President and Director

Collectively and individually, they continue to increase our knowledge of how our bodies work and how disease enters the picture. Some of their many seminal contributions to science have led to new drugs and cancer treatments.

Dr. Irwin Bernstein

Dr. Irwin Bernstein developed a laboratory method for expanding the number of stem cells in a unit of cord blood by manipulating genes in blood-forming stem cells. This fundamental work is now being used by Dr. Colleen Delaney to make umbilical cord blood transplants effective for patients with leukemia.

Dr. Colleen Delaney

This work is groundbreaking because donor umbilical cord blood doesn’t need to be as stringently matched to a patient, making transplants available to patients with rare blood types or mixed race backgrounds for whom finding a match is very difficult.

Bernstein and colleagues also discovered an antibody that led to the first antibody-targeted chemotherapy, Mylotarg®, for advanced acute myeloid leukemia. The treatment directly targets tumor cells while sparing healthy cells from collateral damage, making it less toxic and more effective.

Dr. Linda Buck was the first to identify a family of genes that control the olfactory system, a complex network that governs our sense of smell. She was awarded a Nobel Prize for her work. The genes are blueprints for a family of smell-receptor proteins in the nose that work in different combinations so that the brain can identify a nearly infinite array of odors—much like when the letters of the alphabet are combined to form different words.

Dr. Linda Buck

Uncovering how this system works has been fundamental to understanding the machinery that controls the relay of sensory signals from the world around us to the central nervous system. This work also has important implications for understanding how the sense of smell may be altered in patients undergoing cancer therapy. Reducing the sense of smell often reduces their ability to eat, and strategies to improve smell/taste may be important in maintaining nutrition for patients.

By careful study of how oncogenic proteins are regulated and how they influence cell division, Dr. Jonathan Cooper and colleagues found how a protein called Src, which is activated in the majority of

Dr. Jonathan Cooper

epithelial cancers, is held in check in normal cells and tissues. They also study the normal function of Src in regulating brain development. Src regulates cell migrations in both the developing brain and in cancer. These findings could lead to a better understanding of neurological development and, possibly, cancer metastasis.

Dr. Robert Eisenman is a world leader in the field of oncogenes, aberrantly regulated genes that cause cancer. His studies on a gene known as Myc—which is found in an abnormal state in virtually all cancers—are seminal to scientists’ understanding of how normal cells progress to cancer cells. Eisenman’s work has paved the way for the discoveries of other oncogenes. His work now is looking for strategies to target Myc for potential cancer therapy.

Almost everything we know about cells—how they grow and divide, how they express their genetic information, and how they use and store energy—has come from studying these tiny critters.

At the Hutchinson Center, basic scientists rely on viruses, bacteria, yeast, flies, worms and even fish to study life’s processes, such as cell division, evolution, wound healing, fertility and metabolic hibernation.

We turn to them because studying humans is usually not the best way to successfully tackle the most interesting research questions. And these miniature lab partners—better known as model organisms—are well suited for the job. Model organisms are selected for their rapid growth, abundant reproduction and ability to tolerate genetic manipulation. Being inexpensive and non-demanding wins high marks, too.

Over decades of research, we have ascertained that all living organisms—including us—pretty much operate the same way. So, to shed light on a biological process in people, we turn to flies or yeast.

So, why study one model organism over another? It depends on what researchers are studying.

At the Hutchinson Center, “Team Yeast” loves to point out that they can see the results of genetic manipulation of Saccharomyces cerevisiae, baker’s yeast, in a mere two hours, the time it takes the cells to divide once.

Yeast is easy to grow and extremely flexible—whether it sits in a toasty incubator to reproduce rapidly or goes dormant in a freezer for 30 years. Ever resilient, yeast bounce right back and start to reproduce after thawing out. Genetically, yeast cells are also highly modifiable.

Dr. Lee Hartwell, Hutchinson Center director emeritus, relied on yeast to help him with his research into the inner workings of cells. He discovered the genes that control the cell cycle in yeast and malfunction in tumor cells exist in more or less the same capacity in human cells.

He also learned which genes regulate which parts of the cell cycle. In cancer cells, mutations behave like stuck accelerators and broken brakes, leading to out-of-control cell growth and reproduction. His discoveries earned him a Nobel Prize in 2001.

The discovery could lead to a biomarker-based test for diagnosing facioscapulohumeral muscular dystrophy (FSHD), and the findings have implications for developing future treatments as well as for cancer immunotherapies in general. The findings were reported earlier this year.

The work establishes a viable roadmap for how the expression of the DUX4 gene can cause FSHD. Whether this is the sole cause of FSHD is not known; however, the latest findings “are about as strong of evidence as you can get” of the genetic link, said corresponding author Dr. Stephen Tapscott, a member of the Center’s Human Biology Division.

Dr. Stephen Tapscott

Tapscott and colleagues sought answers to the questions about what the DUX4 protein does both normally in the body and in the FSHD disease process. In the latest study, they identified that the DUX4 protein regulates many genes that are normally expressed in the male germ line but are abnormally expressed in FSHD muscle. Germ line cells are inherited from parents and passed down to their offspring.

“This study is a significant step forward by solidifying that the DUX4 transcription factor causes this disease, while offering a number of viable mechanisms for why the muscle is damaged,” Tapscott said.

Transcription factors are tools that cells use to control gene expression. Genes that are “turned on” in the body are “transcribed,” or translated, into proteins.

Now that scientists know that targets for DUX4 are expressed in skeletal muscle, an antibody- or RNA-based test could be developed to diagnose FSHD by examining muscle tissue from a biopsy, Tapscott said. Such biomarker-based tests also could be used to determine how well new treatments are working to suppress FSHD.

Ultimately, these markers may lead to the development of a urine test that could complement prostate biopsy for predicting disease aggressiveness and progression.

“Prostate biopsies are invasive and don’t always pick up all of the cancer. Post-digital-rectal exam urine collection is much less invasive. If a urine-based diagnostic test was developed that could help predict aggressive disease or disease progression, that would be ideal,” said Dr. Daniel Lin, the study’s principal investigator.

Dr. Daniel Lin

Lin leads a nationwide consortium of eight institutions called the Canary Prostate Active Surveillance Study, an endeavor dedicated to identifying and validating biomarkers of high-risk prostate cancer.

“The ultimate goal is that men on active surveillance could use a test based on these biomarkers or others to complement biopsy and PSA data to indicate or rule out the presence of an undetected aggressive cancer or future development of aggressive cancer,” said Lin, who cautioned that these initial results, while promising, need to be confirmed in a larger study.

The Canary Foundation and the Early Detection Research Network of the National Cancer Institute funded the study.

Dr. Jihong Bai
Charting the brain’s intercellular highway

Before they had illustrations of human organs to guide them, medieval surgeons were left to hack their way through the body like sailors sent to sea without a map.

Like an early anatomist, Center neurobiologist Dr. Jihong Bai is pioneering a map of the brain’s intercellular highway, pinpointing how brain cells target and communicate with each other.

“Back when people were dissecting and drawing organs, they didn’t know what it would be used for, but they were building fundamental understanding,” he said. “That’s what we’re doing here—we’re building a foundation of knowledge.”

Dr. Jihong Bai

Using the miniscule roundworm C. elegans, the Harvard-trained scientist is coaxing the brain’s nerve cells—neurons—to give up their secrets. He wants to know how neurons talk. Where’s the volume dial that makes cells shout or whisper to one another? What makes neurons speed up their communication or have a more leisurely conversation?

The answers lie within the roundworm’s 302 neurons, a highly similar but petite nerve neighborhood compared to the human brain’s 100 billion neurons.

Bai uses behavioral, genetic, biochemical, imaging and electrophysiological techniques to better understand the molecular underpinnings of brain signaling, work that could have a broad impact in understanding the physiology of the brain. Such a map could lead to better strategies for treating psychological and
neurological diseases like schizophrenia, Alzheimer disease or epilepsy.

“People here are doing incredible things,” he said. “It’s a great place to be curious and creative.”

Dr. Sue Biggins
Unraveling the mysteries of cellular machinery

As a newly minted researcher a decade ago, Dr. Sue Biggins chose the Hutchinson Center—as have many top researchers—because of what it isn’t: It isn’t about playing it safe or working alone. It isn’t about empire building. It’s not full of policies and politics to trip over. It’s all about having the scientific freedom, she said, to do the best, most unconventional research possible.

“Good basic science is inherently risky,” Biggins said.

The geneticist’s most recent success involved kinetochores, molecular machines that play a critical role during cell division. For decades, researchers tried and failed to isolate or assemble whole, functioning kinetochores to better understand how they help chromosomes separate and end up in the correct daughter cell. If this goes awry, entire chromosomes are gained or lost, a hallmark of most cancer tumors, hereditary birth defects and miscarriages.

Biggins’ team—stepping away from genetic methods and borrowing from the biochemistry playbook—for the first time succeeded in separating the
kinetochores from dividing yeast cells and studying them in test tubes. During cell division, kinetochores act like handles on chromosomes and are under tremendous pressure as fibers pull on these handles to move the chromosomes within the dividing cell.

Dr. Sue Biggins

If chromosomes fall off in the midst of this process, they don’t end up in the daughter cell. Biggins and colleagues found the harder the kinetochores are pulled, the harder they attach, like a finger trap toy. This counterintuitive characteristic explains why the process works correctly so often.

What’s true in yeast is also true in human cells, so Biggins’ accomplishment could lead to ways to correct kinetochore defects in cancer cells or to therapies that target cells with the wrong number of chromosomes.

Biggins’ breakthrough came with help from fellow researcher Dr. Toshio Tsukiyama, who broke from his own research to teach her new techniques.

“I had absolutely no experience with biochemistry, but it was clear to me that for the field to progress, someone had to figure out how to pull the kinetochore out of the cell. I’m surrounded by unselfish colleagues willing to make other labs as successful as their own.”

Last May, the HIV Prevention Trials Network study, known as HPTN 052, showed that the early use of antiretroviral drugs reduced heterosexual HIV transmission to uninfected sexual partners by 96 percent. More than 1,700 couples in which one partner is HIV positive and the other is HIV negative from nine countries on four continents participated in the study.

The Center’s Dr. Ying Chen was the lead statistician for the study and the second author of the paper, both led by Dr. Myron Cohen of the University of North Carolina at Chapel Hill. Drs. Thomas Fleming and Lei Wang at the Center also contributed.

Dr. Ying Chen

The HPTN 052 team helped design the study and develop its blueprint with the principal investigators. They worked with an independent data and safety monitoring board as it reviewed the study’s safety and efficacy data twice yearly.

Since the study began participant enrollment in 2005, the team processed almost 518,000 forms containing the study volunteers’ medical data, conducted the interim analysis and provided all of the statistical support for the paper.

This data crunching, attention-to-detail role is crucial to forming accurate conclusions and study results.

“In combination with other promising clinical trials, the results have galvanized efforts to end the world’s AIDS epidemic in a way that would have been inconceivable even a year ago,” wrote Dr. Bruce Alberts, editor-in-chief of Science, in his editorial about the breakthrough.

“This is not to say that we can abandon the search for an AIDS vaccine. Nor will profound change come overnight from the promise of using treatment as prevention. But for its role in making success conceivable, we have chosen the results of this trial as our breakthrough of the year.”

And she will be there again this year to cheer them on during the 35th anniversary of the Shore Run/Walk—whose proceeds benefit the Survivorship Program at the Hutchinson Center.

Annette is among several women who have poured their hearts and souls into the race since its beginning. And runners and walkers have returned their affection, making the event one of the most beloved in the Seattle area.

For Annette, the race is a celebration of life, a happy and upbeat event that has helped many cancer survivors and their families cope with life’s ups and downs.

“I have run it a couple of times. I had cancer myself—two bouts of breast cancer,” she said. “My treatments were successful, and I’m very thankful. Being involved in this race, giving back to the community, is very healing.”

Over the past 34 years, the race has become a gauge on the war on cancer, she said, showing enormous progress in a tangible, very visible, way.

“Over the years, I have seen many, many more survivors participating in the race, and more and more people celebrating survivorship,” Annette said. “Cancer touches all of our lives, and it’s great to see so many people coming together to fight this disease.”

As a longtime firefighter in one of the nation’s largest airports, he often delivered first aid to sniffly travelers who exposed him to viruses.

He also dismissed his cough as a byproduct of Seattle’s long and dank winter. It was his foot doctor, of all people, who off-handedly remarked, “Still got that pesky cough? Maybe you should go see someone about that.”

Terry Stoltenberg

It’s pneumonia, another doctor told him after looking at a chest X-ray. Antibiotics followed but the cough did not go away. Finally, a CT scan unveiled a more ominous diagnosis last spring: A tumor in the lower lobe of his left lung. Stoltenberg was shocked by the diagnosis. He had never smoked and here he was, facing a tumor that could kill him very quickly.

Thousands of Americans face a similar crisis each year, even though many have never smoked. As many as 25 percent of all lung cancers are not due to smoking, making lung cancer in nonsmokers the seventh most common cause of cancer deaths worldwide.

Overall, lung cancer remains the leading cause of cancer death in the United States. Last year, it killed 157,300 men and women, more than breast, prostate, colon, liver and bladder cancers combined. Within this group, about 15,000 died from lung cancer even though they had never smoked.

EMPHASIS ON EARLY DETECTION, STATE-OF-THE-ART DIAGNOSIS

While these are certainly grim statistics, the outlook is improving for lung cancer patients as researchers make unprecedented strides in the diagnosis and treatment of lung tumors.

Fred Hutchinson Cancer Research Center and its treatment partner, Seattle Cancer Care Alliance, are leading the way in a number of key research areas, from landmark biomarker discoveries for early detection to precise screening techniques and targeted therapies.

Just a few short years ago, Stoltenberg’s treatment choices would have been severely limited. But thanks to a team of Hutchinson Center and SCCA lung cancer experts armed with the most advanced technology, his malignancy was diagnosed and the fist-sized tumor removed, using the least invasive and most precise methods—methods perfected over the last decade with the help of Hutchinson Center and SCCA clinicians.

“Ten or 20 years ago, it’s safe to say that Terry’s lung cancer would have been found much later in its development, and his treatment options would have been limited. His prognosis for survival would have been poor,” said Dr. David Madtes, a pulmonary researcher at the Hutchinson Center and director of SCCA’s Lung Cancer Early Detection and Prevention Clinic. “The new treatments he received here have given him the best possible chance for long-term survival and possibly for a cure.”

Madtes’ specialized, three-year-old multidisciplinary clinic is one of only a few in the country that assesses people’s risk of lung cancer and expedites evaluations of suspicious findings, using state-of-the-art diagnostic techniques. The clinic’s emphasis on early detection—including a new CT screening program—and prevention through smoking cessation help make the clinic a unique resource in the region.

Many older and medically sicker patients could not tolerate the standard, more toxic, high-dose regimens used to prepare patients for transplantation. For many years after the Hutchinson Center pioneered bone marrow and stem cell transplantation, people over 40 were generally not eligible for either procedure, but thanks to work by Hutchinson Center researchers, that age limit started moving up.

The most dramatic shift came after Center researchers, led by Dr. Rainer Storb, developed what came to be known as the mini-transplant, a “kinder, gentler” form of allogeneic (donor cell) stem cell transplantation.

Today, according to a new study, age alone no longer should be considered a defining factor for older patients seeking stem cell transplantation. “Age is no longer a barrier to allogeneic transplant,” said the Center’s Dr. Mohamed Sorror, lead author of the study.

This is an important finding, the authors said, because more than 20 percent of the U.S. population will be 65 or older by 2030, with an expected 77 percent increase in the number of blood cancers for this population in the next two decades. However, many eligible patients are not being treated with stem cell transplants to treat their blood cancers.

“These statistics clearly highlight the reluctance of providers in offering allogeneic stem cell transplantation to the elderly,” Sorror said. “Little is known about the reasons behind the low referral rate of older patients to transplant or how mini-transplant outcomes compare to those of conventional therapies. We are initiating a multicenter study designed to follow patients from the time of diagnosis to answer both questions.”

Sorror and colleagues found that the five-year rates of overall and disease-progression-free survival among mini-transplant patients were 35 percent and 32 percent, respectively.

Patients in three age groups—60 to 64, 65 to 69 and 70 to 75—had comparable survival rates, which suggested that age played a limited role in how patients tolerate the mini-transplant, researchers said.

The mini-transplant, known in medical circles as nonmyeloablative transplantation, relies on the ability of donor immune cells to target and destroy the cancer—without the need for high-dose chemotherapy and radiation. Instead, low-dose radiation and chemotherapy is used to suppress the immune system rather than destroy it. This helps the body accept the donor stem cells, which then go to work to attack cancer cells—called the graft-vs.-leukemia effect—and rebuild the immune system.

But he chooses to stand behind a podium and talk about what happened to him as a 10-year-old because he knows his ordeal carries certain lessons about the early detection of cancer, the importance of research and perseverance.

“I don’t think I have ever made it through one of his speeches without getting teary-eyed and upset,” said Paula, his adoring mom. As she listens to him, she relives his experience—the family’s experience—all over again. But it’s a small price to pay if her son’s 108 visits to the hospital, 14 rounds of  chemotherapy, six trips to the emergency room, dozens upon dozens of blood draws, 27 X-rays and seven CT scans will inspire someone to donate to research.

Certainly, this is just a partial list of what it took to remove a softball-size tumor from his chest. There’s no math that can calculate the emotional toll on Gary and his family.

Cancer makes you grow up pretty fast. Just ask Gary. Recently, he spoke at a formal event to raise funds to support early cancer detection research at the Hutchinson Center.

He doesn’t change the speech much. What is written is what is true.

“I try to keep my speech straightforward,” said Gary, who was treated for bone cancer. “Not totally sad or happy. The honest truth is that going through all the experiences was very difficult, but as long as you have family and friends around you, you can keep your spirits up.”

About the speech: “I’m not a great writer in particular, and I’m trying to get better at English. My mom helped me with the speech.” No shame in that, of course. Mom helped him with a lot more than stringing sentences together.

Most freshmen also don’t call themselves cancer survivors. Gary became one at age 10. Cancer is certainly a major part of his life experience, but he likes to stress to everyone that he is a happy kid, healthy and active—a defender on his soccer team. His cancer, he knows, was caught early enough so something could be done about it.

And as he grows older, he wants to do his part. Today it’s speeches. A few years down the road, it might be something else.

“I know that research is very important. This is how we find ways to detect cancer much earlier. And this is how we learn how to fight it best,” he said.

“I don’t know if I’ll become a researcher some day. But I do know that I want to do something that is helpful to the world. It is my way of paying back.”

In the process, they discovered a number of potential key drivers—recurrent genetic mistakes—common to advanced prostate cancer that may contribute to disease progression.

The researchers also have identified several instances of genetic “hypermutation,” an excess of single-letter DNA “spelling errors” that could cause the cancer to become resistant to therapies commonly used to slow the progression of advanced prostate cancer, such as androgen-blocking drugs and surgical castration.

Dr. Peter Nelson

“The most interesting finding to come out of our DNA sequencing project was the discovery of three aggressive tumor types that had 10 times the number of mutations compared to the other advanced prostate cancers we studied,” said the Center’s Dr. Peter Nelson, one of the authors of the study.

“That was very surprising and unusual. We don’t know the cause of these hypermutated tumors, but the frequency of the mutations suggests these tumors might evolve very rapidly to develop resistance to therapies,” he said.

The discovery of these genetic mutations should provide clues to illuminate why some prostate cancers are lethal, and potentially could be used to develop screening tests for early detection or drug targets to slow or halt cancer growth, Nelson said.

This is why our solid tumor program is a growing component of our research, and why many of our investigators remain focused on the tasks at hand: advance our knowledge of solid tumors; garner support for new clinical trials; develop effective tools to detect cancers much earlier, when they’re most treatable; save more lives from the anguish of cancer.

This issue of Quest focuses its attention on lung cancer, which remains the leading cause of cancer deaths in the United States. Globally, lung cancer has become a major health burden. But as you’ll read in our article, smoking is not the sole cause of all these cancers. Lung cancer in nonsmokers is the seventh most common cause of cancer in the world.

Many of our researchers focus their energies on lung cancer, from creating unique quitting programs for smokers to increasing our knowledge of the biology of lung cancer. Consider recent findings by Dr. Samir Hanash and his team. In September, they announced the discovery of proteins in the blood that are associated with early lung cancer development.

A key goal of such a study is to develop a blood test for the early detection and diagnosis of lung cancer. New imaging technologies coupled with state-of-the-art surgical techniques, and a better understanding behind genetic mutations that lead to lung cancer, are also helping us get a better grasp on this disease.

As a leading cancer research center, we have many supporters—people who have been touched by our mission to eliminate cancer and related diseases as causes of human suffering and death and want to do their part. Some of these supporters are volunteers—dozens upon dozens of people who help raise private funds to support our research and reach out to our patients during the most trying of times.

In this issue of Quest, we write about five of our volunteers, a dedicated group of people who have given us thousands of hours of their valuable personal time in support of our cause.We couldn’t do it without them. And we can’t do it without your help. We hope you’ll continue to support the Center and its mission.

• Patients diagnosed with chronic bronchitis or emphysema before their cancer diagnosis are about 30 percent more likely to develop lung cancer than those without such a diagnosis, according to a study led by Dr. Alyson Littman and her Center colleagues. The risk associated with a form of the disease known as squamous cell carcinoma was even higher, at about 50 percent. These findings are important because they may help doctors identify patients who are most likely to get lung cancer.
• Current and former heavy smokers may reduce their risk of getting lung cancer as well as any kind of cancer by increasing the amount that they exercise, Center researchers found. Results varied by age group and gender.
• Dr. Michael Mulligan, an SCCA physician and University of Washington researcher, is a national leader in minimally invasive surgical techniques that get lung cancer patients back on their feet more quickly. By inserting a tiny camera through a millimeters-long incision, the surgeon can see inside a patient’s chest and operate with less trauma to surrounding tissue that occurs with traditional, open-chest surgery. The technique, known as video-assisted thoracic surgery, is well suited to removing early stage lung cancer.

Foamy viruses are not known to cause disease currently, but they’re important to study partly because of the story of HIV, which originated from a family of viruses, called retroviruses, that are nonpathogenic in their natural hosts. The viruses that led to HIV bear some similarities to foamy viruses.

Dr. Maxine Linial

Although Linial and her colleagues have found key differences between foamy viruses and retroviruses like the one that led to HIV, parallels with important health implications may also exist.

“By the time HIV was understood it was too late,” Linial said. “Here we have a chance to get ahead.”

This is basic science at its best, with researchers such as Linial seeking to extricate secrets from things that most people would not even notice, but with tremendous implications to our well-being.

That’s why there was something special about the scientific talk Linial gave to her Hutchinson Center colleagues earlier this year after an extended absence. Linial is proud of her work, and was once accustomed to designing beautiful PowerPoint presentations that made her data pop. This time, she used no slides.

Nor did she refer to notes. She operated only from memory and her deep knowledge base. Afterward, audience members said it was the best talk the veteran microbiologist had given in a decade.

In some ways, the talk was Linial’s own state of the union—a declaration that her scientific contributions are as strong now as they were before an accident last spring that left her severely injured and hospitalized for months. And it spoke to her own work: We need to know everything we can about foamy viruses.

Although her body has since healed in many ways, she operates under a challenging new reality: A damaged-beyond-repair optic nerve left her without sight.

“People just have to realize I’m trying my best,” said Linial, one of the Center’s longest-serving faculty members. “I’m still very committed to the research in my lab.”

Linial’s lab leads several projects designed to learn more about how foamy viruses replicate and change their genetic structure. They’re also collaborating with University of Washington researchers on a large study in Bangladesh of monkey-to-human transmission of foamy viruses.

In this South Asian nation, where humans settled on land once dominated by primates, the two species come into contact with regularity, which may have implications for how the virus moves between them.

The five-year initiative will also study the underlying behavioral causes of obesity and ways to prevent it, particularly among children, cancer survivors and others at high risk.

“The idea (is) to attack the problem of obesity and cancer with teams of researchers from many scientific fields, such as nutrition science, molecular epidemiology and behavioral science,” said Dr. Mark Thornquist, principal investigator of the initiative’s coordinating center. “By approaching the problem
from many directions and collaborating across studies, we hope to make scientific progress faster than more narrowly focused research. The coordinating center helps to tie all of these researchers together and enables us to collaborate more effectively,” he said.

The National Cancer Institute “is very concerned about the epidemic of obesity and its implications for cancer,” said Dr. Robert Croyle, director of the NCI’s division of Cancer Control and Population Sciences. “This investment reflects the urgency of the problem and the need to accelerate scientific progress to inform cancer-control strategies.”

The American Cancer Society estimates that about 30 percent of cancer deaths are due to poor nutrition, excess weight and lack of exercise.

“This consortium will aim to understand the link between cancer and obesity at a fundamental, biologic level,” Thornquist said.

Ugandan Vice President Edward Ssekandi plants a tree to mark the future site of the Uganda Cancer Institute/Fred Hutchinson Cancer Research Center Clinic and Training Institute in Kampala.

“Through the collaboration between the Hutchinson Center and the Uganda Cancer Institute, we hope to develop new, low-cost prevention and treatment strategies that will not only stem the rising burden of cancer in sub-Saharan Africa but will benefit millions of people worldwide,” said Dr. Larry Corey, president and director of the Hutchinson Center.

“Our commitment in Uganda is to increase survival rates for common infection-caused cancers from 10 percent to 90 percent over the next three years while pursuing a unique research opportunity to find new ways to prevent infection-associated cancers, which will benefit cancer patients both in resource-poor and resource-rich regions,” he said.

The building will be the first comprehensive cancer center jointly constructed by U.S. and African cancer institutions in sub-Saharan Africa. The new facility will extend patient access to cancer diagnosis and research-based treatment. It will allow further study on the links between infectious diseases, such as HIV and Epstein-Barr virus, and cancers such as Kaposi sarcoma and the most common life-threatening malignancy among Ugandan children, Burkitt lymphoma.

“Cancer is increasingly recognized as an enormously important global health problem that kills more people worldwide than HIV, tuberculosis and malaria combined, and nearly two-thirds of these deaths are in the developing world,” Corey said.

“Sub-Saharan Africa has among the highest cancer rates in the world, and these rates appear to be increasing in association with the HIV epidemic,” he said.

“For a lot of us, the Hutchinson Center is just that huge complex by the side of the freeway,” said Matt Logue. “We see it every day, but we don’t know how relevant it is to our lives.”

“I was diagnosed with leukemia four years ago. It opened my eyes to the cancer side of the world. And I discovered the Hutchinson Center. The people who pioneered bone marrow transplants are right here in my backyard. I take a lot of comfort in that knowledge,” he said.

Today, Logue is a key volunteer at the Center. He is raising funds for innovative research but he also wants people to know that this is not simply a huge medical research complex—that first and foremost, it’s a place that truly cares about people. And so, he champions the researchers who continue to make strides against deadly diseases.

As a cancer survivor, he also understands all too well what the Center means to people struggling with cancer and other diseases.

The Center prizes volunteers such as Logue for multiple reasons. They’re often a direct link to patients who are treated at Seattle Cancer Care Alliance—the treatment arm of the Hutchinson Center; they stuff envelopes and staff events; they help raise funds to support research and they write plenty of thank you notes to donors and friends of the Center.

If you talk to volunteers, they will tell you that they prize their involvement with the Hutchinson Center for many reasons, from a desire to help advance science to helping patients who are undergoing a difficult time in their lives.

“The Hutchinson Center has saved the lives of so many of our friends,” said Karen Leslie, who spends several hours volunteering at the Center each week with her husband, David Hopkins.

“We volunteer because we love it. It gives us a purpose, and it’s given us a pretty rich life,” she said.

Here are the stories of a few of our volunteers, who tell us why they choose to spend their valuable time helping the Hutchinson Center.