For Renowned Researcher, Seeing Basic Science Turn into Promising Therapies Is the 'Holy Grail' of Oncology

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If you’re not brimming with optimism, you don’t belong in cancer research. Between government cutbacks and NIH funding freezes, it’s getting harder and harder to do our jobs. So you need to believe that by spending long hours in the lab, something good for mankind will come out of it.

— Owen N. Witte, MD

“From bench to bedside” is a phrase that captures the essence of modern oncology: Researchers at the bench seek to solve the biologic puzzles of cancer that can translate into the development of therapeutics delivered at the bedside. Owen N. Witte, MD, has spent most of his career as a basic bench researcher, deciphering these oncologic riddles with great success.

Dr. Witte was born in Brooklyn, but he grew up in the suburban Long Island town of Levittown. He said it was a fifth grade teacher, coincidently named Mrs. Levitt, who first sparked his passion for science. “She had a real hands-on approach that engaged you in a way that made science fascinating. She also recommended a great book called Microbe Hunters [by Paul de Kruif]. My friends and I read the book over and over. It really had a profound influence on my relationship with science,” said Dr. Witte.

Fascination with Immunology and Cancer

The future researcher’s interest in science grew more intense during his high school years, and he completed his undergraduate studies at Cornell University in Ithaca, New York. “This was during the Vietnam War, and I certainly wanted to stay out of it. After graduating Cornell, I headed to Stanford to get my medical degree. Through a whole bunch of happenstances, I ended up in the lab of Dr. Irv Weissman, who is now the Director of the Stem Cell Institute at Stanford. He became a terrific mentor and a personal friend,” said Dr. Witte.

“I began working with Irv on viruses that cause certain types of leukemia in mice. It was an eye-opening experience at the interface of immunology and cancer. After I graduated medical school, I dipped my toe in clinical medicine during an internship and realized I really didn’t like it. The clinic was not where I was going to make my stand,” said Dr. Witte. “So I went back to research, doing a postdoctoral at MIT with David Baltimore, PhD,” he continued.

Breakthrough Research in Tyrosine Kinase Activity

Once again at the interface of immunology and cancer, Dr. Witte studied a virus that had been isolated a few years earlier by Herbert Abelson, MD. “My work essentially helped characterize a protein produced by a gene in the Abelson virus. I also discovered the unique enzymatic activity in the gene, which is a tyrosine kinase. At the time, nobody knew what the discovery meant,” explained Dr. Witte. Further experimentation gave a clue. “We were quite sure that the kinase activity was linked to the biological activity, but at that point we had no idea about these kinase networks, and how the signaling integrated, creating this master driver of the cancer cell.”

In 1980, Dr. Witte left MIT and joined the faculty at UCLA. He stayed in contact with Drs. Weissman and Baltimore, two great influences on his career with whom he would collaborate over the years.

“At UCLA, a graduate student of mine named James Konopka, made an observation that changed my life. He discovered the abnormal tyrosine kinase in human leukemia we now call Bcr-Abl. This was the work that really defined how a common gene in mouse and human leukemia works by a similar genetic activation mechanism. And of course that storyline led to the development of imatinib (Gleevec), in which many people played important roles,” said Dr. Witte.

Dr. Witte has always been a scientific explorer, looking for new challenges. In the 1990s, his research led to the discovery of Bruton’s tyrosine kinase enzyme, which is required for normal B-lymphocyte development. “That gene, as it turns out, was responsible for a genetic defect in the immune system called Bruton’s X-linked agammaglobulinemia. It basically means that you don’t make B cells and you don’t make immunoglobulins,” said Dr. Witte.

From this work, it became apparent that Bruton’s tyrosine kinase would be an important drug target for treating immune disorders and certain lymphomas and leukemia. “And that target has been realized and used to produce therapies. In fact, there are new drugs, including ibrutinib, coming out this year in which Bruton’s tyrosine kinase is the target. So this is a consistent theme of my career, trying to understand the basic biology and genetics of the system—be it B-lymphoid system or chronic myeloid leukemia—and define what the key target is,” said Dr. Witte.

More recently, he has turned his attention to prostate cancer and the role of tissue stem cells in cancer progression.

Keeping an Eye on the Pipeline

In addition to running his own research laboratory of nearly 25 individuals, which is made of equal parts technical staff, graduate students, and post-docs and clinical fellows, Dr. Witte also has a major administrative role as Director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. “That role helps to coordinate something that I believe is very important: pushing basic science through the translational pipeline and into the clinic. I spend a lot of time organizing research efforts between and among groups, essentially making sure these important efforts have the resources they need to move their research ahead,” commented Dr. Witte.

He stressed, “It is very difficult and expensive to transition an idea into a clinical trial. We’ve even built our own good manufacturing process facility to buttress our efforts. And the good news is that all the hard work is paying off with exciting new cellular therapies under development.”

Dr. Witte remains enthusiastic about his continuing work ushering discoveries from the laboratory into the pipeline. In this veteran scientist’s view, what is an essential attribute for a researcher coming into the field to have? Optimism, he says.

“If you’re not brimming with optimism, you don’t belong in cancer research. Between government cutbacks and NIH funding freezes, it’s getting harder and harder to do our jobs. So you need to believe that by spending long hours in the lab, something good for mankind will come out of it,” said Dr. Witte.

Dr. Witte says that it reenergizes him to try something new in the lab. Like space, the world of genetics and microbiology remains a limitless frontier of unending exploration. Dr. Witte has never looked back at his decision to pursue a career in the laboratory instead of the clinic. “To me, the Holy Grail is seeing basic science turn into new and hopeful therapeutics entering the field of cancer care.”

To relax, Dr. Witte takes spin classes, considering himself a borderline “exercise nut.” He also likes to cook. “I love to experiment with different recipes. In fact, at one point in my youth I toyed with the idea of becoming a professional chef,” said Dr. Witte, adding with a laugh, “But that’s way too much work.”

His suggested reading for young students? You guessed it, a book called Microbe Hunters. ■