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Aug. 25, 2011 Volume 33, No. 1

MU scientist’s uncommon research takes on common cancers

Fred Hawthorne

REACHING FOR A CURE M. Fred Hawthorne will lead clinical trials of a procedure that targets cancer tumors with experimental boron compounds. Shane Epping photo


Therapy could shrink tumors without tissue damage

M. Frederick Hawthorne has a personal interest in the small-animal trials his research team is conducting on cancerous tumors.

Hawthorne supported his wife, Diana, as she successfully battled breast cancer in 1977. Then, in 2008, he too experienced the trauma of surgery, chemotherapy and radiation to treat the oral cancer that took half of his tongue.

Now Hawthorne will lead clinical trials of a procedure called boron neutron capture therapy (BNCT) that he and his team believe will irradiate and shrink tumors more selectively than current treatments without affecting healthy tissue.

Testing at the University of Missouri Research Reactor (MURR) and MU’s International Institute of Nano and Molecular Medicine will begin in early September and continue for about two years.

“This therapy should improve the cancer survival rate,” Hawthorne says. “Head and neck, prostate and breast cancers may be the most treatable,”

In the trials, Hawthorne and team will follow the health of mice that have cancerous murine breast tumors induced by grafted tumor cells. Researchers will anesthetize the mice and inject each animal with tumor-targeting boron compounds that travel through the blood to bind with tumors and provide targets in diseased cells for neutrons. Hawthorne expects his six experimental boron compounds to more effectively reach tumors than previously tested compounds.

Researchers will then expose the mice to neutron radiation for 20 minutes, creating a reaction with the boron that Hawthorne describes as a “little nuclear explosion,” which should kill the cancer cells.

“After the mice wake up, we will observe them for weeks and measure the size of their tumors. The mice should all survive the compound and the radiation, and the tumors should shrink,” Hawthorne says.

As researchers finish testing the mice, they will begin a two-year clinical trial of the same compounds on larger animals. Clinical trials on human volunteers could begin in about five years.

At a later date, Hawthorne’s group also plans to test the procedure as a possible treatment for rheumatoid arthritis. In a similar fashion to the cancer research, injections of boron compounds will mark the synovium — the inflamed tumor-like mass — before irradiation.

The University of Missouri holds Hawthorne’s patents and patent applications on the boron target compounds, which are produced in his laboratories. The team will continue to make new drugs with improved performance.

In a related study, a group of researchers with the Argentine Atomic Energy Commission in Buenos Aires is using Hawthorne’s boron compounds in trials on hamsters with head and neck tumors. Those researchers are sharing data with the MU group.

Even as a youngster growing up in Kansas and Missouri, Hawthorne believed chemistry was his future. He set up his first lab, making new polymers, at age 12. He wrote his first paper at 16, which has expanded to his current 550 papers. He has 35 patents and pending patents.

Hawthorne’s schooling didn’t exactly meet the norm. Because his father’s civil engineering job required frequent moves, he attended 20 different schools before high school.

At 16, Hawthorne left Rolla High School to study chemical engineering after passing entrance exams at Missouri School of Mines & Metallurgy in Rolla. He transferred to Pomona College in Claremont, Calif., for a bachelor’s degree in chemistry and completed graduate studies with a 1953 doctorate at UCLA, mentored by future Nobel Laureate Donald Cram.

Before moving into academic research, Hawthorne worked on rocket propellants for Rohm and Haas Company in Huntsville, Ala., and later in Philadelphia, Pa. It was at Rohm and Haas that he found his research niche – borane-cluster chemistry.

The major honors for Hawthorne’s lifetime work reflect his status in the scientific community. In 1973 at age 44, he earned a coveted membership in the U.S. National Academy of Sciences. For 31 years, from 1969 to 2000, he served as editor-in-chief of the journal Inorganic Chemistry. And he won the 2009 American Chemical Society Priestley Medal — the society’s highest award — for pioneering work in boron chemistry.

There are many other awards he considers favorites as well, including a 1994 Willard Gibbs Medal from the Chicago section of ACS; a 1988 ACS Award for Distinguished Service in the Advancement of Inorganic Chemistry; and a $200,000 King Faisal International Prize for Science (2003 co-winner) for achievements having a profound effect on cancer therapy.

Now in his eighth decade, after fighting cancer professionally and personally, and lauded with honors any chemist would covet, Hawthorne continues to search for what he considers the career-defining achievement: a way to combat common cancers.

Hawthorne is credited with the rare achievement of creating a field of research and excelling in it. When he began his career in the chemistry of boron about 50 years ago, there was little existing information about the chemistry of the element.

Hawthorne envisioned boron as the potential basis of new products such as pharmaceuticals and nanomaterials. He took on the goal of using boron combinations — boranes and carboranes — to cure common cancers through targeted anti-cancer drug delivery as well as boron neutron capture therapy.

Positive results in Hawthorne’s early tests years ago at UCLA indicated that mice showed low toxicity to the compounds. But without access to a neutron source, he was unable to conduct clinical trials with irradiation to activate the boron atoms.

That changed in 2006 when Hawthorne retired from UCLA and moved his research laboratory to MU. The move required three 18-wheel moving vans filled with files, chemicals, thousands of pieces of glassware and instruments of all varieties. Joining Hawthorne were UCLA research group faculty members Mark Lee, PhD, and Satesh Jalisatgi, PhD, as well as several doctoral students who were working with him.

Hawthorne was lured back to Missouri by the resources available to help complete his life’s work: a medical school, a veterinary college and the nation’s largest academic research reactor with a neutron beam line dedicated to BNCT. Sealing the deal was the promise of an International Institute of Nano and Molecular Medicine, which Hawthorne founded and now directs.

“Nothing beats this,” he says. “This is the only research site in the United States with that combination of research tools.”

— Nancy Moen

Published with permission of Mizzou Wire