How researchers turn ideas into groundbreaking cancer treatments

It often takes a leap of faith to advance science—and plenty of professional risk

Editor’s note: This is the first posting of a four-part series by science writer Justin Matlick, who has become fascinated by cancer research at the Hutchinson Center. The series follows Dr. Colleen Delaney’s trajectory at the Hutchinson Center—and her attempts to bring better cancer therapies to her patients. In his second posting, Justin talks about Delaney’s challenges in the lab.

Part 1: Pursuing a breakthrough

By Justin Matlick, Hutchinson Center science writer

It seems like barely a week goes by without news of a laboratory discovery that could revolutionize cancer treatment. For people who aren’t immersed in research, it’s easy to think it’s only a matter of time before these discoveries become lifesaving therapies. But the laboratory work is just the first step in a process that not only can take years and cost millions of dollars, but also is fraught with potential pitfalls and dead-ends.

Here at the Hutchinson Center, this translational process is a key part of our work. It’s also one of the least understood. So we decided to take readers on a step-by-step journey through the process of turning one of our discoveries into a potentially groundbreaking treatment.

Dr. Colleen Delaney

The series focuses on Dr. Colleen Delaney’s breakthrough work to expand the number of stem cells in a unit of umbilical cord blood, opening the door to more widespread use of cord blood transplants to treat leukemia and other blood cancers.

Since cord blood transplants don’t require the close genetic matching needed for more conventional bone marrow transplants, they are an option for the thousands of patients each year who can’t find a suitable donor. But the small number of cells in each unit of cord blood limits their use, especially in larger children and adults. This is the challenge addressed by Dr. Delaney’s work.

Our first post focuses on Delaney’s difficult decision to take on the project. From there, we’ll take readers through the steps leading up to the fateful day when Delaney delivered a batch of cells to her first patient and then waited to hear whether the therapy worked.

“It was one of the most exciting and nerve-wracking times in my life,” she recalled. “I don’t think I slept for a week.”

 An intriguing opportunity

When Dr. Colleen Delaney arrived at the Hutchinson Center in 2000, she didn’t plan to spend her career as an oncologist in the lab. She had finished medical school and her residency; her goal was to spend two years in the lab as part of a fellowship program and then go back to clinical practice as a fully trained pediatric oncologist.

“My main passion is caring for patients,” she said, “and my plan was to get good research training and spend my career at the bedside.”

Then, while working in Dr. Irwin Bernstein’s lab, Delaney encountered an intriguing opportunity that had the potential to save the lives of cancer patients worldwide.

Dr. Irwin Bernstein

Bernstein and his colleagues had just published a paper outlining a potential breakthrough. By advancing the understanding of how blood stem cells renew themselves, the researchers had developed a system that could potentially increase the number of stem cells in a unit of cord blood. If Delaney could further perfect Bernstein’s method and use it in patients, it could improve the outcome of cord blood transplantation for the large number of patients with blood cancers—including about 95 percent of racial minority patients—who can’t find a genetically-matched bone marrow donor.

At first blush, it sounds like an easy decision: How often do you get the chance to take on a potentially revolutionary project? But Delaney was torn. She was already getting job offers as a clinical pediatric oncologist. Taking on Bernstein’s project would postpone her plan by at least two years. And she knew that the project—like all laboratory discoveries—wasn’t a sure thing.

“It was clear you could grow these cells in the lab,” Delaney said, “but even for me it was a little hard to believe this might actually end up in people.”

Refining a discovery

To understand the opportunities and challenges Delaney faced, it helps to get a clearer view of Bernstein’s discovery. Like bone marrow, stem cells from cord blood can give rise to all types of cells of the blood and immune systems, and can be used as the source of stem cells for transplants that combat leukemia and other blood cancers.

The problem is, a single unit of cord blood contains relatively few stem cells. That means it takes much longer for the transplant to take hold—around 25 to 28 days, vs. roughly 15 to 18 days for conventional bone barrow transplants. This leaves patients at an increased risk of contracting life-threatening infections.

Bernstein had figured out how to break through this barrier. He and his colleagues had pieced together a way to manipulate stem cells with the goal of increasing their numbers. If they could produce enough of the cells in the lab, and if those multiplied cells could take hold in patients in less time, they could dramatically reduce the up-front risk of infection. This could change the way transplantations are performed and make cord blood a more viable alternative to bone marrow. But they needed someone to refine their discovery.

To Delaney, it sounded like a tall order—and an intriguing challenge. For starters, she would have to translate Bernstein’s experiments into processes that could be reproduced on a large scale and could yield cells that are safe and effective in humans.

This could mean years of painstaking refinements that would lead to better scientific understanding of this process, but from a clinical feasibility standpoint, it was only the tip of the iceberg.

The funding conundrum

If things went well, Delaney would also then have to apply to the FDA for permission to test the experimental therapy in people. This would require that all components of this methodology be approved for use in humans. In addition, she would have to write grant proposals and attract hundreds of thousands of dollars in funding. She would have to recruit patients into clinical trials. And she would have to accept the reality that, despite all this effort, the therapy might not work.

That can be a deal breaker for many young researchers. Faced with pressure to rack up publications early in their careers, they often hesitate to take on long-term projects with uncertain prospects. Delaney decided it was worth the risk, especially since she could still become a full-time doctor when the project was over.

“We were able to get two years of funding and I figured that, even if we didn’t get the results we wanted, I would learn some really valuable tools,” she recalled.

“And besides,” she said with a laugh, “it was only two more years.”

That was 11 years ago. And while the intervening years have brought innumerable challenges, they’ve also put Delaney on course to contribute to a therapy that can improve the lives of generations of cancer patients.

“I really didn’t have a sense of what this type of commitment meant, or of how complex it would be,” she said. “But I also didn’t realize how rewarding it would be if it all worked out.