UT’s in­ven­tor of year chal­lenges slim odds

‘As a can­cer sur­vivor, I have no choice,’ says chemist. ‘I must try.’

Austin American-Statesman - - FRONT PAGE - By Marty Toohey mtoohey@states­man.com

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 has 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.”

The pa­tient’s chance: 1in2

Sessler’s story could start in 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 his on­col­o­gist, 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 was 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 Texa­phyrin to treat brain can­cer.

But 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 does not prove 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 neck­ties and a pen­chant for test­ing 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 that eye-pop­ping sum, 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.”

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.

The in­ven­tor’s chance: 1 in 10 (or worse)

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 “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.”



Jonathan Sessler was named UT’s 2016 in­ven­tor of the year in part for Texa­phyrin, a mol­e­cule he cre­ated that bonds to can­cer cells. He is work­ing on a new ver­sion that can de­liver platinum de­riv­a­tives that can kill can­cers.

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