The search for a groundbreaking cancer treatment—Chapter 2 of 4

Editor’s note: This is the second 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 first posting, Matlick explored Delaney’s pivotal decision to dedicate her career to fighting cancer.

Part 2: ‘What am I doing wrong and how can I make this better?’

By Justin Matlick, Hutchinson Center science writer

Science might be thought of as a white-collar pursuit, but it requires a blue-collar work ethic and dedication. That’s certainly true of translational research, which takes breakthrough discoveries and turns them into real-world treatments. So when Dr. Colleen Delaney started developing a new therapy for leukemia and other blood cancers, she knew it was going to be a long, complicated journey.

Dr. Colleen Delaney

Her starting point was a discovery by the Hutchinson Center’s Dr. Irwin Bernstein. Bernstein figured out that, by activating a particular pathway within blood stem cells, scientists could instruct them to multiply into more stem cells. After extensive testing, Bernstein’s approach was used to increase the number of stem cells in a unit of human umbilical cord blood—a discovery that Delaney knew could be of enormous benefit to blood cancer patients.

Stem cells from umbilical cord blood can be a good alternative for patients who need a stem cell transplant but can’t find a matching bone marrow donor. The problem is, cord blood contains relatively few stem cells. This means it takes longer for cord blood transplants to engraft, leaving patients vulnerable to infection. Bernstein’s discovery had the potential to solve this problem.

It was up to Delaney to translate that potential into a lifesaving therapy, and her medium-term goal was to push the technique far enough along to where she could apply to the FDA to start clinical trials. That meant refining the technique until she could prove it was safe and potentially effective. To accomplish that, she had to overcome some big scientific hurdles—hurdles that illustrate just how arduous and rewarding research can be.

Thinking like a factory engineer

Think of Delaney’s first challenge as the scientific version of manufacturing a next-generation sports car. Bernstein’s discovery was akin to unveiling the eye-popping new prototype. Delaney’s job was to figure out how to actually manufacture thousands of those cars to extremely precise standards.

In scientific terms, Delaney needed to develop a standardized process that could be used to increase stem cells in units of umbilical cord blood, over and over again. That process would have to yield cells that were safe to be used in humans. Only then would she be able to apply to the FDA and move forward with clinical trials.

The crux of this process involved unraveling exactly how Bernstein’s process triggered the cells to multiply. The process rested on a protein that, when introduced into a culture with the stem cells, activated the pathway that caused the cells to multiply. Delaney’s team needed to better understand this reaction so they could know how to reliably manipulate the cells.

This is where the painstaking part of laboratory work comes in. Delaney and her colleagues spent two years testing and re-testing specific doses of the ligand and other substances, closely measuring how the stem cells reacted and how many new cells were reproduced. Their goal was to generate the data they needed to move forward with an application to the FDA.

“When you think of people in the lab, you think of them pipetting stuff into Petri dishes,” Delaney said. “And that’s what we were doing, over and over and over again.”

The a-ha! moment

It’s easy to get lost in this process, to get overly obsessive about testing and re-testing. When your goal is to develop a therapy that will be used in people, you want everything to be as predictable and safe as possible. This single-minded attention to detail is part of what makes a good scientist. It also makes it hard to know when to be satisfied with your results and move on to the next stage.

“I’m the type of person who’s always asking ‘What am I doing wrong and how can I make this better?’ And I was focused on those questions even though, in our tests, we almost always got the outcome we wanted,” she said.

Sometimes it takes getting out of the lab to realize just how far your work has come. That’s one reason scientists don’t work in a vacuum. Instead, they gather ideas and feedback from colleagues at their home institutions and from organizations around the world.

So it’s fitting that one of Delaney’s a-ha moments came not when she achieved a particular milestone in the lab, but when she went to a lecture by another researcher who was also working on growing cord blood stem cells in the lab.

The guest lecturer “was excited about how her team was producing a four-fold expansion of stem cells,” Delaney said, “and I was sitting there thinking, ‘Wow, we routinely get 150-fold or 250-fold expansion.”

That’s when Delaney knew it was time to stop deliberating and take the final steps toward applying to the FDA to conduct clinical trials.

“Until then, I don’t think I realized how good our results were or how robust our system was,” she said. “At the lecture, I realized, ‘Now is the time.”