Cancer Fighter

Professor’s personal battle leads to development of new cancer drug

Jonathan Sessler wanted to ignore the pain. After all, his senior year at the University of California at Berkeley gave him plenty of things to take his mind off the persistent aching he felt under his arm. There were exams to study for, chemistry labs to finish and grad school applications to worry about. But Sessler’s older brother Dan, a first-year medical student at the time, would have none of his younger brother’s hemming and hawing and hassled him to get checked out by a doctor.

Sessler finally relented, and a week later he found himself in the hospital minus a spleen and having his upper body blasted with an aggressive radiation treatment for Hodgkin’s lymphoma, a cancer of the lymph system. He’s now thankful for his brother’s insistence. The treatment worked and the cancer went into remission.

Despite the overwhelming stress of cancer treatment and school, Sessler graduated in 1977 with honors in chemistry and began pursuing his doctor’s degree at Stanford University. Then, one frightening day in his third year, Sessler heard something no cancer survivor ever wants to hear: his lymphoma was back.

This time, Sessler received chemotherapy under the care of a young attending physician at Stanford named Dr. Richard A. Miller. Against all odds, he beat his cancer a second time and returned to his research with a challenge issued by Miller that would loop through his brain for years to come.

“You’re a chemist,” said Miller in 1979. “Find new cancer drugs.”

More than 25 years later, Sessler and Miller, co-founders of the company Pharmacyclics, Inc., are riding high on the news of the latest trials of the drug Xcytrin®, based on molecules developed in Sessler’s lab. The drug has shown promise in delaying some symptoms associated with brain cancer that has spread from the lungs. The results are promising enough that Pharmacyclics plans to file a New Drug Application with the U.S. Food and Drug Administration (FDA) this year.

Developing a cancer-fighting molecule

When Sessler arrived in the Department of Chemistry and Biochemistry in 1984, he hadn’t yet found an answer to Miller’s charge.

“As much as I wracked my brains, I just couldn’t figure out a way to make that new cancer drug,” says Sessler, now the Roland K. Petitt Centennial Professor of Chemistry and Biochemistry at The University of Texas at Austin. He’d been studying porphyrins, the highly pigmented molecules that help make up the hemoglobin in red blood cells.

When I arrived in Texas, it became clear that here, everything is bigger. So I had this simple idea to make a bigger version of porphyrins. --Dr. Jonathan Sessler“But when I arrived in Texas, it became clear that here, everything is bigger,” he jokes. “So I had this simple idea to make a bigger version of porphyrins.”

Porphyrins, Sessler knew, concentrate in cancer cells. If he could make one of these molecules large enough to hold a heavy metal like gadolinium, which is commonly used to produce magnetic resonance imaging (MRI) agents, the new molecule could be used to enhance MRIs and in the treatment of cancer.

The young, affable Sessler surrounded himself with extremely talented graduate students such as Greg Hemmi, Tarak Mody and Darren Magda, a postdoctoral fellow named Dr. Toshiaki Murai, and kept working hard. After about five years, he got what he was looking for: a larger porphyrin molecule that can hold a heavy metal at its center. One afternoon during a lab meeting at the Crown & Anchor Pub, the Sessler Lab dubbed the new Texas-sized molecules “texaphyrins.”

From lab bench to bedside

When Miller learned of the new texaphyrins during Sessler’s annual check-up in California in the late 1980s, he immediately suggested they start a company. And that, according to Sessler, is when the hard work began.

“Teaching and research is pure joy,” he says. “The only thing that’s really hard is fundraising.”

Luckily, Miller had a knack for the business, and by 1991, Pharmacyclics, Inc. was born.

Pharmacyclics, in Sunnyvale, Calif., licensed the technology behind texaphyrins from the university and has been developing commercial and medical uses for the molecules. Miller has served as president and CEO of the company since its inception and Sessler’s former students, Hemmi, Mody and Magda, migrated there to work as research scientists.

In conjunction with radiation, Xcytrin enhances cancer cell death. Radiation puts stress on the cells and the drug puts further stress on the cells. Add them together and the cells start to die. --Dr. Jonathan Sessler Without Miller, Sessler is quick to point out that he wouldn’t be here today nor would his science have moved as far as it has into the world of medicine.

“Dr. Miller knows what is and is not important medically,” he says. “We’re the chemists. Without the creative spark between the two, there’s no chance.”

It’s this interplay between medical doctors and scientists that the new Texas Institute for Drug and Diagnostic Development (TI-3D), of which Sessler is a founding member, aims to foster. TI-3D promises to help academic scientists at the university navigate through some of the complicated issues surrounding moving a new molecule or medical diagnostic technique into the medical stream.

Though Sessler didn’t have an organization like TI-3D to help, he holds up Pharmacyclics and the recent successes of Xcytrin as an example of what can happen when academic scientists, entrepreneurs and medical doctors work together.

Fighting cancer with Xcytrin

In recent Phase 3 trials, Pharmacyclics and its collaborators delivered the texaphyrin-based drug Xcytrin (motexafin gadolinium) in conjunction with whole brain radiation treatment to more than 500 patients with non-small cell lung cancer that had spread to the brain. When such cancers begin taking over important centers of function in the brain, people begin to experience changes in muscle strength, vision and mental state, a process called neurologic progression.

In North America, patients receiving Xcytrin plus radiation experienced neurologic progression 16 months later than patients not receiving the treatment. The company announced these promising results at the annual meeting of the American Society of Clinical Oncology in June 2006.

In North America, patients receiving Xcytrin plus radiation experienced neurologic progression 16 months later than patients not receiving the treatment.Sessler says texaphyrins like those used in Xcytrin focus on cancer cells and disrupt cellular metabolism and energy production, weakening or destroying the cells.

“In conjunction with radiation, Xcytrin enhances cancer cell death,” says Sessler. “Radiation puts stress on the cells and the drug puts further stress on the cells. Add them together and the cells start to die.”

Texaphyrins steal electrons from cell-protecting molecules (for example, antioxidants) and produce compounds toxic to cells, like peroxide.

“Texaphyrins steal away the things that could protect a cell and as a result they make more of the very things the cell is trying to protect against,” Sessler explains. “Now this sounds terrible, except that texaphyrins are highly localized in cancer. So you’re going to kill cancer cells. This is devilishly clever.”

And texaphyrins are relatively non-toxic to normal cells, which is a great boon when talking about harsh cancer treatments. Other trials are now underway to test the potential of Xcytrin to act as a stand-alone chemotherapeutic agent or in combination with other known cancer drugs.

By helping develop a new cancer drug that has extended the quality of life of real patients battling a terrible disease, Sessler is closer than he’s ever been to meeting Miller’s challenge. He’s hopeful that the FDA will approve the drug for treating cancer patients.

“I don’t think it’s fair to cancer patients to have to wait through another five years of trials,” he says. “I’m hoping that this will receive a fair hearing at the FDA, and they come to the conclusion that the benefits to patients outweigh any concern.”

Jonathan Sessler’s Website

BY Lee Clippard

Photo of Dr. Sessler: Matt Lankes

Dr. Ruth Sessler Bernstein is an Assistant Professor of Nonprofit Management at the Pepperdine University. She earned an undergraduate degree from Rensselaer Polytechnic Institute and MS from Brown University both in Geology. Subsequently she received a MA in Philanthropy from Indiana University’s School of Philanthropy and a Doctorate of Management from Case Western Reserve University’s Weatherhead School of management. She was an Assistant Professor of Nonprofit Studies at the University of Washington Tacoma (2015-2020). Her publication and research interests focus on (1) diversity and inclusive interactions, and (2) nonprofit governance. In 2021, her book Performance Through Diversity and Inclusion: Leveraging Organizational Practices for Equity and Results was published with co-authors Judy Weisinger and Paul Salipante. Dr. Bernstein is a regular presenter at ARNOVA (Association for Research in Nonprofit Organizations and Voluntary Action) and AOM (Academy of Management). Her publications have appeared in numerous nonprofit and management journals, including Nonprofit Management and Leadership, Equality, Diversity & Inclusion: An International Journal, and Journal of Business Ethics. In her free time, you can find her reading great books, or outside hiking, kayaking, and skiing with family and friends.

To improve on over 60 years of attempts to achieve fairness and performance from diversity, Performance through Diversity and Inclusion: Leveraging Organizational Practices for Equity and Results is aimed at being smarter with our efforts. Based on knowledge from large bodies of research and illustrated with successful cases, the book provides practical guidance for managers, leaders, diversity officers, educators and students to achieve the benefits of diversity by taking advantage of opportunities to create meaningful, inclusive interactions. Implementing inclusive interaction practices, along with accountability practices, enhances performance outcomes for the organization and improves equity for members of historically underrepresented and marginalized groups. The book is available at:

Andy Sessler wins the Presidential Fermi Award, 2014

Andrew Sessler, award-winning theoretical physicist, acclaimed humanitarian, and former director of Berkeley Lab (1973-1980) who founded both the Earth Sciences Division and what is now the Environmental Energy Technologies Division, has been named a recipient of the Enrico Fermi Award by President Obama. One of the federal government’s oldest and most prestigious prizes for scientific achievement, the Fermi Award is administered on behalf of the White House by the U.S. Department of Energy. It carries an honorarium of $50,000 and a medal. Sessler shares this year’s award with chemist Allen Bard of the University of Texas.

“Allen Bard and Andy Sessler have advanced the science and technology frontier throughout their distinguished careers and, in doing so, have contributed greatly to sustained U.S. leadership in research and development,” said Secretary of Energy Ernest Moniz. “I congratulate them for their achievements and hope that the example they set serves as inspiration to future generations of scientists and engineers.”

Sessler was selected for his “outstanding contributions to the establishment of the beam-physics knowledge basis that has underpinned the development of current-generation particle accelerators and storage rings deployed at leading research institutions throughout the world.” Bard was selected for his pioneering contributions to the field of electrochemistry.

“Andy Sessler changed the face and character of Berkeley Lab,” says current Berkeley Lab Director Paul Alivisatos. “He successfully made the case for science to aid our country during its first energy crisis and helped establish the Lab’s efforts that brought about important technologies and standards that have improved the way we conserve and consume energy.”

Sessler, 85, first made his scientific mark in the 1950s with foundational work in particle accelerators that provided the basis for today’s colliders, including the Large Hadron Collider at CERN, synchrotron light sources, such as Berkeley Lab’s Advanced Light Source, and free-electron lasers. In addition, he and collaborator Keith Symon were one of the first to report on stochastic phenomena, or chaos, in particle accelerators.

“I was very fortunate to be a theoretical physicist in the early years of particle accelerators,” Sessler said. “We were able to apply theory to single and multiple particles effects in beams, which taught us how to obtain the intense beams necessary for colliders, synchrotron light sources and free-electron lasers.”

For his physics research, he has received the Lawrence Award and the Wilson Prize.

Sessler was 44 when he became Berkeley Lab’s third director, just two weeks after the start of the 1973 oil embargo, when gas prices soared and gas station lines extended for several blocks. In response, his first action was to establish what was then called the Energy and Environment Division.

“I felt the future of the Laboratory was in other directions as well as high energy physics,” said Sessler, an avid backpacker and skier who often rode a bike to work, in discussing the sea-change at the Laboratory he initiated. “I’d always loved the outdoors, and preserving the environment was a big concern. Seeing that the U.S. was developing a national energy plan, I knew we were one of the few places in the country with the expertise to help.”

In addition to his ground-breaking work in particle accelerator and beam physics, and his leadership in directing the scientific research landscape toward new horizons in sustainable energy and the environment, Sessler is also being recognized for his public advocacy of scientific freedom and other humanitarian causes. During the Cold War era, he was a co-founder of the human rights group “Scientists for Sakharov, Orlov and Sharansky (SOS), scientists who were persecuted as dissidents in what was then the Soviet Union. For this effort, in 1994 he became the first recipient of the American Physical Society (APS)’s Dwight Nicholson Medal for Humanitarian Service.

“I like to think that many physicists look up, on occasion, from their experimental apparatus or computer screen, to see that all is not well with the world, and devote some time, effort, and money to help,” he said, when he received this award. “The opportunities are there, and the need is there, for the struggle for human rights is an eternal one.”

Ximena L. Valdes, M.D. is Dr. Sesser’s wife. Dr. Valdes graduated from the University of Chile Medical School in 1971. A Pediatric residency at Cedars Sinai Medical Center in Los Angeles was followed by a fellowship in Pediatric Cardiology at the University of California in Los Angeles. Dr. Valdes is fluent in Spanish and is Board certified in both Pediatrics and Pediatric Cardiology.

Dr. Valdes practiced Pediatrics and Pediatric Cardiology in Los Angeles for a decade before moving to the San Francisco Bay area, where she joined the Department of Pediatrics of Kaiser Permanente Medical Group for 10 years. She then moved to Louisville, KY where she was Associate Professor of Pediatrics at the Children and Youth Project of the University of Louisville, a comprehensive primary care pediatric clinic serving high-risk patients of the Louisville inner-city. Upon moving to Cleveland, Dr. Valdes joined the Global Child Health program at the University Hospital Rainbow Babies and Children’s Hospital as a Case Western Reserve Associate Professor of Pediatrics, practicing in a Refugee Clinic, assisting during humanitarian emergencies in children and mentoring medical students in rural Peru.

Dr. Valdes is now retired from medical practice and devotes her energy to volunteer activities, serving as docent at the Cleveland Museum of Art and as co-chair of programs for The Print Club of Cleveland. She is also a Trustee of The Temple Tifereth Israel, and a tutor/mentor to children and young adults.