In his cramped fifth-floor office on the University of Texas campus, just down the hall from the lab where he and his colleagues invent molecules, UT’s 2016 inventor of the year wants to talk about the odds of failure.
Jonathan Sessler is a cheerful man who twice survived an aggressive form of cancer. He co-founded a $21 billion biotech company. He is close to fulfilling a promise he made to the doctor who saved his life: to invent a new cancer treatment drug.
But Sessler politely brushes aside the warm-and-fuzzies. He wants to talk about the work that remains. And the lessons that Austin civic leaders could glean from his adventures in the biotech industry. And he wants to talk about a cold, hard reality: The odds remain stacked against him, even after 40 years in labs chasing a molecule he thinks could save the lives of cancer patients.
He puts the odds of that drug being widely used at worse than 1 in 10. Then he shrugs. He wants to talk, most of all, about why a scientist should be willing to toil for decades in search of a breakthrough that will probably never happen.
“I think what people don’t appreciate is how difficult it is to extract secrets from Mother Nature,” Sessler says. “These are incredibly difficult problems.”
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The patient’s chance: 1 in 2
Sessler’s story could start any number of places: a Northern California lab, a cancer treatment center, a UT classroom. Or it could start at the Crown and Anchor Pub.
That is the low-slung patio-and-billiards bar near the UT campus where Sessler and his colleagues often met in the mid-1980s, bouncing around ideas for molecules to create. Sessler had spent years studying porphyrins, a type of ring-shaped molecule that has a tendency to be taken in by cancerous tissues.
Sessler’s idea was to create a porphyrin large enough to carry the metals that are detected in MRI scans. Such a molecule that bonds to cancer cells could make MRIs far more effective in spotting the disease, Sessler reasoned.
The inspiration for making a bigger molecule was obvious, he jokes.
“Everything is bigger in Texas,” he said. “Why not a porphyrin?”
Cancer had been one of Sessler’s preoccupations since his undergraduate days at the University of California, Berkeley. Sessler, as a 19-year-old chemistry major, was diagnosed in 1976 with Hodgkin’s lymphoma, a particularly pernicious kind of cancer. He endured the chemotherapy sessions, the hair loss, the race to get home from the clinic before the vomiting started, the fear that the disease, or its treatment, could kill him. Treatment has improved since then. But research suggests that, at the time, his chance of surviving five years was about 50-50.
“Chemotherapy” Sessler says, “is a race between killing the cancer and killing the patient.”
He beat the cancer. He continued his schooling, moving on to Stanford as a graduate student, but relapsed. He again endured the sickness, the fear, the possibility of death. Again, he beat the cancer. His survival led the oncologist who treated him, Richard A. Miller, to implore of him: “You’re a chemist. Find new cancer drugs.”
That quest eventually led Sessler to UT, where he took a job as a professor and researcher, and to the meetings at the Crown and Anchor. Over beer, he and the graduate students and postdoctoral candidates working with him hashed out ideas, taking the joke about a drug as big as Texas even farther. The molecule would be the biggest porphyrin the world had ever seen. It needed a worthy name.
What else could it be but Texaphyrin?
The founder’s chance: 1 in 10,000
Sessler, now 60, was named UT’s inventor of the year largely for the progress he has made in creating Texaphyrin. The award also cites Sessler’s 75-plus patents and his role in co-founding Pharmacyclics, a biotech company that made such a remarkable breakthrough that it sold for $21 billion in 2015.
The company history comes with a twist, though. Texaphyrin, the idea on which the company was founded, was a failure — at least officially. It illustrates a conundrum of medical research: Numerous promising ideas compete for limited dollars, but the desire to heal can be derailed by government safety regulations designed to protect people from harm.
Sessler’s oncologist had kept in touch with him. As it turned out, Miller was not just a clinician, but also a highly regarded researcher and entrepreneur. He was intrigued by Sessler’s idea of using a porphyrin as a new cancer-treating molecule. They tailored a Texaphyrin to treat brain cancer.
But all such inventions are unlikely to succeed. Most research puts the odds of taking a compound from idea to market at somewhere between 1 in 5,000 and 1 in 10,000 — far less likely than dating a millionaire, writing a best-selling novel or discovering your child is a genius, and about as likely as being seriously injured by a toilet.
Early clinical trials were successful, according to the Economist. The magazine noted that of the 60 patients treated to that point, “over three-quarters have had their brain-tumor load halved” and “have also survived longer than would be expected with conventional radiotherapy.”
But the short version of a long tale is that Texaphyrin failed the trials. Sessler says that is because clinical investigators in France waited too long to apply the treatment to patients, whose cancer was therefore too far along for the drug to be effective. The assessment is partially confirmed by a University of Chicago Law School analysis of the testing methods, which found the investigators did wait too long, though noting the error is not proof of the drug’s usefulness.
Whatever the merits of the testing, regulators with Food and Drug Administration said they could not deviate from the agency’s rigid testing protocols.
Texaphyrin never got to the market.
Sessler absorbed a crushing failure.
Then he went back to the lab.
“You can go home, collapse on the floor and cry” in such circumstances, he says. “Or you can go home, collapse on the floor and cry, then pick yourself up again and get back to work.”
As the company he co-founded struggled and convulsed and tried to keep its footing, Sessler sold his share of its stock, a bit at a time. He made enough to live well, he said — his kids were taken care of, a divorce did not ruin him financially, he bought a lake house, he kept his job at UT — but founding the company did not make him rich.
Sessler said a sense of humor helps. He has a husky voice, a dislike for ties and a penchant for testing out Aggie jokes in the classroom.
That Pharmacyclics was founded on a failed idea is the wrong way to view the company, Sessler says. The company pivoted to a different cancer treatment drug, Ibrutinib. That drug — someone else’s — hit big. The company sold for the eye-popping total, becoming a well-publicized example of the wild world of biotech research.
Sessler’s advice to those interested in establishing a vibrant biotech industry in Austin: Consider the drama at Pharmacyclics a natural part of the business.
“Being 1 for 2 in this field is remarkable,” he says.
As to what the community can expect, in terms of successes and failures, he added: “There is no normal in biotech. Maybe the one norm is that (a company’s) founding technology is not the technology that makes a company successful.”
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The inventor’s chance: 1 in 10 (or worse)
Sessler’s research has led him to think Texaphyrin could be used for more than MRIs or brain cancers.
He is trying to develop a drug to deliver the platinum derivatives used to kill many cancers. He is the co-founder of Cible — French for target, as in targeting cancer cells — a company trying to bring this new version of Texaphyrin from promising lab results to clinical trials.
One of Sessler’s business partners, fellow UT chemist Jonathan Arambula, likens this iteration of Texaphyrin to a tow truck: It takes a platinum molecule, hauls it to a cancer and drops off the metal — a far more precise way of delivering treatments than simply flooding someone’s body with a stream of toxic platinum agents that will mostly miss the target and sicken a patient in the process, Arambula said.
The odds remain against them, though. Research suggests the odds of bringing a drug to the market are 1 in 10 after preclinical trials begin. And Sessler, “a wannabe entrepreneur,” notes that he needs to raise money before even reaching the preclinical trial stage.
In considering those odds, and the possibility of failure, Sessler hearkens back to one of his mentors, Max Perutz, whom some consider the father of molecular biology.
Perutz would tell Sessler “apocryphal stories about how no one thought he had a chance of solving the X-ray structure of hemoglobin,” which is about 100 times larger than any molecule that had been analyzed at the time. “When (Perutz) arrived in Cambridge … he was told by Sir W. Lawrence Bragg something to the effect of, ‘The chances of your success are zero, but the importance is infinite; therefore, I support you.’ ”
“These tales stuck with me,” Sessler says. “As a cancer survivor, I have no choice. I must try.”
But he cautions against seeing his life as a story motivated by a tragic event like cancer. Perhaps, he said, his insights are instead rooted in simple curiosity. Or stubbornness. Or other qualities humanity possesses in abundance, qualities that drive not only scientists but poets, painters, coders, composers and others who attempt to create.
Sessler talks a lot about gratitude, particularly toward taxpayers: “It is of towering importance to me that they are getting the service they deserve.” And he talks a lot about motivation as a counterpoint to disappointment: the real reason, when the pretensions are stripped away, that someone pursues a dream. Is it the acclaim that success brings or the work itself?
To underscore his point, he notes that the lab he oversees at UT is about more than curing cancer. It’s about making “really cool molecules” of all types, a fascination of his long before the cancer. He talks at length about how a student just invented a “Bevoligand,” a molecule with no particular use, other than the amusement it creates when people realize how closely it resembles the Longhorn mascot.
That sort of creation, interesting but far from world-changing, might be the most significant breakthrough a scientist makes, Sessler says — if there are any breakthroughs at all.
“These are really low odds,” Sessler says. “We balance those low odds with an appreciation for the chance to explore things that really excite us. And, if we are lucky, help people.”