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Ambition

G W R E S E A R C H • f A l l 2 0 1 1 29

The spell of restless nights had fallen,like clockwork, upon Ferid Murad duringthe early days of October 1998.

It had been this way each October fora couple of years, ever since the murmursbegan that his name was on the lips ofhis peers at such an auspicious point onthe calendar.

For the biochemist, who at the timewas a professor and department head atthe University of Texas Health ScienceCenter at Houston, sleep simply wasn’tin the cards.

So Dr. Murad was awake when thephone rang at 4 a.m.

“I’m sorry to disturb you,” the caller said.It was Nils Ringertz, from the Nobel

Assembly, with news that most peoplewouldn’t mind being disturbed for.“Congratulations,” he said. “You got theNobel Prize.

“Please don’t tell anybody for the next30 minutes,” he said, “until we make thepress release here in Stockholm.”

“And I thought to myself,” Dr. Muradrecalls, “Who am I going to call at 4o’clock in the morning?”

Not that he had time, anyway. Dr.Murad scrambled into the shower andinto a suit. Within an hour media beganto gather outside his door, touching offa deluge of interviews and flower deliv-eries and emails and phone calls.

“That first day was pretty wild,” he says.It’s a whirlwind that has been blowing

now for more than a decade.Within just the first year his audiences

included President Bill Clinton, SupremeCourt Chief Justice William Rehnquist,and Palestinian leader Yasser Arafat.He was feted at medical conferences, heserved as grand marshal of a July Fourthparade in his hometown of Whiting, Ind.,and in Macedonia he met for the firsttime a small army of relatives.

“It’s been amazing,” he toldthe Houston Chronicle of that first year ofNobel status. “You don’t have a lot oftime to savor it.”

In the years since, the invitations tolecture, to meet, to consult, to dedi-cate buildings continued. He’s beento dozens of countries, some so manytimes he has lost count, traveling whathe estimates to be in the ballpark of1.5 million miles. (That would put himon par with the recently retired spaceshuttle Discovery, which traveled tospace and back 39 times.)

It’s a long journey that once again haslanded Dr. Murad in Washington, D.C.,this time to stay.

This spring he joined the faculty ofGW’s School of Medicine and HealthSciences with the rare designation ofuniversity professor—GW’s highest

AmbitionNobel

For new GW facultymember Ferid Murad,

winning the biggestprize in science has

meant dedicating himselfto fostering future

laureates. And if he winsa second medal along

the way, all the better.B y d a n n y f r e e d m a n

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30 G W R E S E A R C H • f A l l 2 0 1 1

academic rank. At the announcementin January, GW Provost Steven Lermansaid Dr. Murad’s presence on campus “isan honor that elevates both the statureof his department and the prestige of theentire university.”

Within the Department ofBiochemistry and Molecular Biology, Dr.Murad is establishing a new lab that willhave in its crosshairs at least three bigscientific questions, the kinds of ques-tions which, successfully answered, mayeven be Nobel-worthy … again.

Never mind that no one has evergarnered two Nobels in the area of medi-cine. As Dr. Murad says: “Wouldn’t it benice to be first?”

t the heart of all thisactivity is one doozy ofa molecule.

Nitric oxide was,for decades, considered

merely an environmental hooligan—anunstable no-goodnik of a chemical. Born of

vehicle exhaust, smoke stacks, and burningcigarettes, this toxic gas was known to havea hand in smog, acid rain, and possibly thedepletion of the ozone layer.

“[T]his gas,” noted a 1992 article in thejournal Science, “had a bad reputation.”

But by the 1980s it had become clearto scientists that nitric oxide was far morethan a mere troublemaker. If it has anugly side—and it does—nitric oxide alsois strikingly important to the inner work-ings of the human body. And beyond that,it is a molecule that heals.

In naming it “Molecule of the Year”in 1992, Science dubbed the changing faceof nitric oxide no less than a “Cinderellastory,” offering “a classic example ofnature’s continuing power to surprise.”

It was in the labs of Dr. Murad andthe two other pharmacologists withwhom he shared the 1998 Nobel Prizein Physiology or Medicine—RobertFurchgott and Louis Ignarro—that amore complete picture of nitric oxidewas assembled.

Over the course ofmore than a decade,their work revealed nitricoxide as a gas gener-ated by the body to helptransmit signals betweencells in the cardiovascularsystem—in this case,flipping the switch thatallows smooth musclecells (muscles that workinvoluntarily) to relaxand dilate the bloodvessels, which increasesblood flow and relievesblood pressure.

The fact that nitricoxide does its work byleaving its cell of originto penetrate and regulateother cells represented“an entirely new principlefor signaling in biologicalsystems,” according tothe Nobel Assembly.Today it remains the onlygas known to act as a

messenger in the body.At the front end of this effort, in

the mid-1970s, Dr. Murad solved thecentury-old riddle of how the drugnitroglycerin and others that alsocontain nitrogen work as treatmentsfor angina pectoris—chest pains oftencaused by clogged arteries that arebeginning to choke off blood supply tothe heart.

The answer, Dr. Murad eventu-ally found, was that these drugs areconverted in the body to nitric oxide. Allthat nitric oxide, in turn, stimulates anenzyme and initiates a chain reaction torelax smooth muscle cells.

“For more than a hundred years it wasused as a vasodilator [to increase bloodflow],” Dr. Murad says. “But nobodyknew precisely how it was working.”

(Alfred Nobel—as in the NobelPrizes—was so wary of nitroglycerin asa treatment for his heart disease that in1890 he refused when a doctor recom-mended it. The inventor of dynamite

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G W R E S E A R C H • f A l l 2 0 1 1 31

was no stranger to the volatile ingredientthat also gives dynamite its punch. “Isn’tit the irony of fate that I have beenprescribed [nitroglycerin], to be takeninternally!” he wrote to a colleague.)

Dr. Murad’s findings in 1977 onthe beneficial role of nitric oxide, andhis suggestion that the body may evenproduce the gas itself, created a scientificstir and several years of disbelief. “Evenmy closest friends and colleagues wereskeptical,” he remembers.

Nonetheless, he pressed on.Meanwhile, efforts by Drs. Furchgott andIgnarro to identify an unknown signalmolecule produced by the body led tothe realization that it was actually nitricoxide, validating Dr. Murad’s speculation.

The findings “triggered an explo-sion in the nitric oxide field, openingthe floodgates of discovery,” celebratedscientist Joseph Goldstein noted whenpresenting Drs. Murad and Furchgottthe 1996 Albert Lasker Basic MedicalResearch Award, often consideredAmerica’s version of the Nobel Prize.

Or as Dr. Murad puts it: The fieldfrom that point has just “gone bananas.”

Researchers have generated morethan 130,000 scholarly articles on thesubject, he says, and nitric oxide now hasat least one scientific journal solely dedi-cated to understanding its work.

The reach of nitric oxide, scientistsnow know, extends far beyond thecardiovascular system. In the nervoussystem, it helps control disparate func-tions, from memory to vision, and it’s aweapon in the immune system’s arsenalagainst bacteria, parasites, and tumors.Its role in the body also has helpedinform doctors’ understanding of a rangeof diseases and conditions, from diabetesand arthritis to septic shock and cancer.

In the area of drug development,premature newborns who are not gettingenough oxygen, known as “blue babies,”can be given nitric oxide gas to aid themovement of blood; and enhancingnitric oxide’s effect on blood flow inthe penis is the magic behind the block-buster Viagra.

“There are very, very few biologicalprocesses that won’t be regulated bynitric oxide,” Dr. Murad says. “So it’s gota lot of potential.”

he butterflies didn’tstand a chance.

Dr. Murad recallsgoing as a preteen tocatch butterflies with

friends in his hometown along LakeMichigan, south of Chicago. The planwas to mount the insects in a home-made display, but he knew that exces-sively handling them could ruin theirprismatic wings.

He figured the answer—and hereis where a budding scientist of somerenown might stand out in a crowd ofyoungsters—was to poison them withcyanide gas. “So I went to the localpharmacist and I said: ‘Could I havesome potassium cyanide and hydro-chloric acid to kill butterflies?’ And hegave it to me.”

“That’s when I became interested inchemicals,” he says with a laugh.

He would follow that curiosity,as well as interests in medicine andteaching, all the way to a PhD inpharmacology, a medical degree, anda career spent mentoring students inacademic centers.

Of course, ittakes much morethan smarts(and access totoxic chemicals)to propel achild to success.The rest—discipline, hardwork, deter-mination—Dr.Murad wouldlearn earlyon inside thebubble of hisfamily’s smallrestaurant.

His parents both were runaways:his father from a family of Albanianshepherds living in Macedonia, hismother from a large, hard-luck familyin Illinois. They married in 1935 andraised three boys in a small apartmentbehind the family business.

“When we were able to stand ona stool to reach the sink we washeddishes,” Dr. Murad wrote in an autobio-graphical essay for the Nobel website,“and later when we could see over thecounter, we waited tables and managedthe cash register.”

He made sport of memorizing aroomful of orders and tallying bills in hishead. The regulars, he says, ranged frombankers and businessmen to laborersand his teachers from school. “Manyof them became very close friends and,really, advisers,” he says.

Between school and the restaurant, hefound time to letter in track and cross-country, among other sports, as well as singin the chorus and play the lead in operettas.

His parents “always would stress theimportance of education,” Dr. Muradrecalls. “If you wanted to do somethingand not work so hard as us, they wouldsay, then go to school. And we did.”

He was the first in his extendedfamily to go to college. Both of hisyounger brothers would follow his lead

into graduate programs, one more

chemicals)

success.

into graduate programs, one

(Right) Dr. Murad’s Nobel diploma.

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32 G W R E S E A R C H • f A l l 2 0 1 1

becoming a dentist and the other ananthropologist.

Dr. Murad attended DePauwUniversity, in Indiana, and left therewith a fiancée, Carol Ann Leopold. Shewas studying English and Spanish atDePauw, though the pair met a thousandmiles away in Fort Lauderdale, Fla., overspring break.

“Within a month we were pinned andsix months we were engaged,” says Dr.Murad. The next summer they wed, just ashe prepared to begin a combined MD/PhDprogram at Western Reserve University(now Case Western Reserve), in Ohio.

And just as he left college with afiancée, Dr. Murad completed graduateschool with a family—four girls. (Ason would come along, too, before hefinished medical residency.)

His experience at graduate schoolwould also give him something of aNobel pedigree. One of his mentors inthe laboratory there, Earl W. SutherlandJr., would later win a Nobel Prize in1971. And Dr. Sutherland had come upthrough the lab of husband-and-wifeduo Carl and Gerty Cori, who both wonNobel Prizes in 1947.

The years that followed found Dr.Murad swinging among the top rungsof the ladder for science and medicine,holding positions as a researcher, physi-cian, or administrator at MassachusettsGeneral Hospital, the NationalInstitutes of Health, the University ofVirginia, Stanford University, AbbottLaboratories, Northwestern University,and, most recently, the Universityof Texas Health Science Center atHouston.

Along the way, he carried with him anattribute picked up from his mentors inthat graduate school lab: a willingness totake research into the murky unknown,even if it means failure.

“There’s no way to do researchwithout going down blind alleys,” hesays. And that will mean sometimesgiving up and retreating.

“But if you give up,” he says, “maybeyou can come back a few years later when

you’ve got the technology to readdressthe question.”

n the case of cancer “afew years” has meanta few decades for Dr.Murad’s lab, but the timefinally seems right.

“We gave up because we didn’t have thetools, we couldn’t answer the questions,”Dr. Murad says of his efforts to mitigatecancerous tumors in the mid-1970s.Instead, he turned to nitric oxide and thework that would win him a Nobel Prize.

But by the early 2000s, with thedevelopment of new tools and techniques,the blind alley from the 1970s began tolook navigable.

“We’ve come back sort of full circlenow,” he says. In recent work, Dr. Muradsays, his lab has found that the growth ofsome cancer tumors—in particular glio-blastoma, a very aggressive type of braincancer—can be suppressed in the lab bymanipulating the work of nitric oxideand another messenger molecule that hadhelped lead to the nitric oxide discovery,called cyclic guanosine monophosphate (orcyclic GMP).

When those tumors are put in thebrains of mice and the messenger path-ways are similarly altered, Dr. Muradsays, the mice have lived up to four timesas long—84 days, up from 21. Whetherthat will work in humans it’s too soon tosay. But it’s one of the big questions he’llbe taking up from his new lab at GW.

“If we could make any impact whatso-ever, it’d be a big advance,” he says of glio-blastoma. “I don’t think we’re going to curethe disease but maybe we can add somemonths to the life expectancy.”

Similar manipulations, his team hasfound, may be capable of influencing thegrowth and differentiation of human andmouse embryonic stem cells in the processof changing them into heart cells andpossibly even brain cells.

“What do we have to do now to takethose cells and begin to use them fortransplantation to treat Parkinson’s,or Alzheimer’s, or myocardial infarc-

tion [heart attack], or people with liverfailure?” he says.

The answer, for now? A heck of lot ofwork over the next two or three decades,as Dr. Murad sees it. However, that kind ofmedicine is certainly coming, he says. “It’sonly a matter of time.”

Meantime, Dr. Murad also plans towork toward development of a drug thatwould block some of the crippling andeven lethal bouts of diarrhea caused eachyear by cholera infection and one type ofE. coli bacteria.

Cholera kills more than 100,000 peopleeach year and affects perhaps 5 millionoverall. As for that particular type of E. coli,Dr. Murad is targeting one of two toxins itproduces that together kill at least as manyas cholera and strike millions more as amajor cause of travelers’ diarrhea and diar-rheal disease.

That research relates back to the samemessenger molecule, cyclic GMP, whichis increased as the infections over-stim-ulate the intestines. Dr. Murad says histeam has recently identified a chemicalcompound that would block that chain ofevents, relieving many from this Third-World scourge.

There is lab work yet to be done beforeit can move into clinical trials, though, andmuch money to be raised to get to thatpoint—on the order of a million dollars,he estimates.

And though Dr. Murad worries whetherfunding sources will be interested ininvesting money in “new ideas and risk,”he does not sound daunted. After all, hehas met skepticism before and walked awaywith a Nobel Prize.

So he plans to continue swinging for thefences. “I think that’s the only way to doresearch,” he says.

As he does, Dr. Murad also will befocused on endowing students with thewealth given to him by his mentors—asense of adventure in problem-solving andthat Nobel pedigree. “One of my goals is toidentify that next generation here at GeorgeWashington,” he recently told faculty andstaff. “So I want all your best students tocome knocking on my door.”

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