A SUPPLEMENT TO THE YALE BULLETIN & CALENDAR — 2009

Translating basic research into new tech-nologies that advance our health and wel-fare has been part of Yale’s “DNA” for cen-

turies, and the pace of innovation at the Universitycontinues to accelerate dramatically.Today’s Yale inventors are helping to lead the

way in science, medicine and engineering.Withplans in place for new research institutes on theWest Campus, Yale is on the cusp of becoming aneven greater incubator of new ideas andmethodsfor exploring key scientific questions.Supporting its faculty and student innovators,

and helping to bring the fruits of their inventive-ness to people around the world are important ini-tiatives at Yale. Its Office of Cooperative Researchis working to shepherd discoveries by Yale facultyto the marketplace through university-industrypartnerships and start-up ventures, while the YaleEntrepreneurial Institute is helping student withideas for unique products and services to launchtheir own businesses.This special section highlights some—but by

nomeans all — of the Yale faculty whose researchis helping to address important health and quality-of-life issues, and the students whose creative ideasare fueling newmarketplace ventures.

YALE INNOVATORSTheir Inventions Today Are Shaping the World of Tomorrow

Yale Discoveries AdvancingHealthAndWelfare in the 21st Century

University Programs Are Nurturing an‘Entrepreneurial Mindset’ in Students

In the past decade, Yale University hasmade a concerted effort to supportstudent entrepreneurs.In both courses that deal with intrica-

cies of business start-ups and organiza-tions geared to support students withcommercial ideas, the culture of entrepre-neurship has taken deep root throughoutthe Yale community.“Our faculty and students show a nat-

ural interest in, and inclination for, entre-preneurial development, which is verymuch in line with the nature of engineer-ing,” says T. Kyle Vanderlick, dean of theYale School of Engineering and AppliedScience (YEAS).“We certainly understand the impor-

tance of supporting entrepreneurship,knowing that without it, some of thegreatest technological advancements ofour time would be sitting in a labunused,” adds Vanderlick.The YEAS course “Creativity andNew

ProductDevelopment,” for example, pro-vides an overview of the stages of productdevelopment in a competitivemarketplaceby simulating the process in class.

Another school where would-beentrepreneurs can learn the busi-

ness of business is the Yale School ofManagement (SOM).Sharon M. Oster, dean of SOM and

the Frederic D.Wolfe Professor ofMan-

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From the Submarine to the Artificial Heart, Invention Is a Centuries-Old Tradition at Yale

Yale’s tradition of staking out the fore-front of invention and innovation

began with some of its earliest graduatesand faculty.Dotted with water-powered mills and

rich in craftsmen with mechanical skills— clock and instrument makers, black-smiths, iron workers, shipwrights andgunsmiths — Connecticut was a centerof the Industrial Revolution in theUnited States. So it was not surprisingthat Yale produced inventors and entre-preneurs who helped forge the newnation’s technological and scientificadvances.David Bushnell, studying at Yale Col-

lege, built the first combat submarine in1775 during the Revolutionary War. Hisvessel, the Turtle, could move underwa-ter but failed in its mission to attach amine to a British warship in New Yorkharbor.

One of the best-known innovatorswho studied at Yale created his

invention at the end of the 18th century,and he was, literally, an Eli. Eli Whitney, who graduated from Yale

College in 1792, is credited with creat-ing the first cotton gin, a device toremove the seeds from cotton, a processthat previously relied on manual labor.He received a patent in 1794. Whitney, who is less known for

improving a system of interchangeableparts for making firearms, was one of (Continued on page 7)

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early America’s most important figures inadvancing industry through technology.Perhaps his greatest contribution was adeveloping a system of manufacturingthat employed an assembly line, a con-cept later perfected by Henry Ford.

In the 19th century, Whitney’snephew, Eli Whitney Blake, perfected

a stone-crushing machine for macadamroads. Blake, who graduated from YaleCollege in 1816, was inspired to createhis invention when he observed workersbreaking stone with a hammer whilebuilding a road near New Haven. Heformed a company to produce themachines, and hundreds were in use bythe late 1870s. This rock crusher becamethe model for similar machines now in

(Continued on page 7)

To showcase all the Yale researchers who are developing innovative solutions to problems in thesciences, medicine and engineering would take far more space than can be accommodated inthese pages. These are just a few of Yale’s 21st-century innovators.

Repairing the ‘Fabric of Thought’ With Drugs That De-Stress the Brain

As Amy Arnsten puts it, the prefrontal cortex is the Goldilocks of the brain: “It needs everything just right.”

When working properly, this most evolved part of the brain allows people to planahead, make complex decisions, organize and multi-task. But under stress, the prefrontalcortex can malfunction — as chemicals are unleashed, stopping cells from communicatingproperly and hampering the cells from regulating thought and behavior.Arnsten has devoted much of her work to developing medications that allow the brain

cells in the prefrontal cortex to talk with each other more easily, thereby reducing or pre-venting the effects of stress or harmful genetic alterations.In recent years, she made key discoveries of substances for treatment of mental disor-

ders involving this area of the brain.Shire Pharmaceuticals is developing Arnsten’s discovery of the use of guanfacine for

treatment of attention-deficit hyperactivity disorder (commonly known as ADHD) andother similar disorders. The FDA has ruled Shire’s New Drug Application “approvable,”and the compound is undergoing final safety testing.Yale’s Office of Cooperative Research (see related story, page 8) is working with Arnsten

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2 YALE INNOVATORS

to find a company to develop her discovery of the use of chelerythrine for treatment ofschizophrenia, bipolar disorder, post-traumatic stress disorder and other related conditions.A professor of neurobiology and psychology, Arnsten credits a pivotal moment while

she was still studying neuroscience in college with putting her on her path to discovery.It was summer, and she volunteered in

her home state of New Jersey in a mentalhospital that housed thousands of patients.Medications available then were inade-quate, and Arnsten saw a need for neuro-scientific insights into crippling mental ill-nesses. There were only two psychiatristson staff, one with a penchant for adminis-tering painful electro-convulsive therapy— which today is still used to treat severedepression but has been improved so as tobe painless.One day back then, Arnsten was having

a lucid conversation about astronomy witha patient who had been a physicist, whenthat doctor’s name came up. The commenttriggered an immediate negative response:The man’s speech became disordered and incoherent, barely making sense.“It was such a huge clue,” Arnsten said, “that stress can neuro-chemically alter the fab-

ric of thought. It was a big clue in the treasure hunt that’s become my career.”

Mining Ancient Chinese Remedies For Cutting-Edge Therapies

Put simply, Yung-chi Cheng’s work in pharmacology has had a profoundly positive effecton human health. He is one of Yale’s more prolific inventors, with several drug-related

patents and applications that have been the basis for groundbreaking therapies to treat dis-eases that afflict millions. Drugs he has invented are routinely used to treat cancer,HIV/AIDS and hepatitis B. Yale and Cheng, together with Scheer and Co., founded Achillion Pharmaceuticals, a

New Haven-based company that is working on improved antiviral compounds. The com-pany is developing a drug invented by Cheng called elvucitabine, aimed at combatingHIV/AIDS and hepatitis B. It is now in phase II clinical trials, on track for FDA approval.He also invented a drug called clevudine, for treatment of hepatitis B, which each year

causes hundreds of thousands of deaths worldwide. The drug is already being sold inKorea by Seoul-based Bukwang Pharmaceutical Company. Pharmasset Inc. is developing

the drug for the U.S. market, andit is in phase III trials.Cheng’s research has long

been on the cutting edge of phar-macology, but one of his latestpursuits is going back to thefuture — way back. He’s created a botanical drug,

PHY906, based on traditionalChinese herbal medicine. It’s aformulation of four herbs that hasbeen used to alleviate commonstomach ailments for nearly 2,000years.Along with Yale, Cheng co-

founded Phytoceutica to developsuch traditional Chinese medi-cines. Dr. Ed Chu, chief of med-ical oncology at Yale Cancer Cen-ter, his colleagues and other

universities are studying the clinical potential of PHY906 and other Chinese herbal medi-cines.Known to his friends and colleagues as Tommy, Cheng has developed this botanical

prescription drug to reduce the toxic effects of chemotherapy cancer treatments and toenhance the therapeutic effects of a broad spectrum of anti-cancer treatments.Together with the National Cancer Institute, Cheng’s lab is exploring PHY906’s

mechanisms of action. The studies are essential not only for assessing PHY906 but areexpected to establish a new paradigm for future drugs — what Cheng calls poly-chemicalmedicine with “systems biology” in mind.Early in his Yale career, he developed 3TC for use against hepatitis B, and is responsible

for a slew of Yale-developed compounds. Cheng says he chose to study at Yale, arrivingfrom Brown in the early 1970s to start postdoctoral work, because pharmacologistWilliam Prusoff was here (see related story, page 3).Cheng says he considers Prusoff a giant in the field, and his role model.

Turning Nature’s ‘Garbage Disposals’ Into Promising Cancer Treatments

One person’s castoff is another’s treasure. That’s certainly true for Craig Crews and hisresearch on a chemical from a microorganism — a proteosome inhibitor — that he

turned into a promising new treatment for cancer.Yale filed for patents on the discovery, and Crews started a company, Proteolix, to

develop it. The company is now conducting the second round of clinical studies towardFDA approval.Crews and his colleagues routinely scan the literature for reports of biologically active

compounds found in nature. Many of these natural products were identified in drugscreens but weren’t pursued as pharmaceuticals because firms couldn’t figure out howthey work. Not knowing the mechanism of action, the government won’t approve thembecause unforeseen drug interactions could spell problems.Crews studies these small molecules, not necessarily to find new drugs but to under-

stand how they act on the cellular machinery so they can be used as research tools.“One stood out,” Crews said, recalling when he noticed a compound that looked

promising because it could kill tumor cells. After identifying that this compound inhibits the proteosome, his lab synthesized sev-

eral more potent derivatives. “Wewere improving on nature if youwill,” he said. Proteosomes are the garbage

disposals of cells. Crews’ researchdemonstrated that if you stop acancer cell from getting rid of itswaste, the cell kills itself. Thuscancer cells are more vulnerableto cell death when the proteo-some is inhibited.The drug appears to be prom-

ising for treatment of relapsedcases of myeloma, a type of bloodcancer. Cells that survive initialtreatment can become resistant tofront-line drugs. “It’s impor-tant,” Crews said, “for oncolo-gists to have a plan B, or depth onthe bench.”

Helping Golfers Perfect Their Game With the Sound of Swing

Neither of Bob Grober’s parents were into golf, but he took to the game as a boy andhas been swinging a club ever since. He’s quick to admit his invention — a club that

tells golfers when their swing is smooth and rhythmic by emitting pleasing musical sounds— was born of a desire to improve his game. “If I was to tell you that this is about anything other than making me a better golfer I’d

be lying,” he said.The Yale applied physics professor and former college golfer invented Sonic Golf,

which went on the market in December. Yale patented the invention and licensed it to acompany Grober launched to make the product entirely in Connecticut. A sensor in the shaft of the club transmits wirelessly to a headset as the motion of the

swing is converted to musical tones.“With audio, you can understand the motion of the golf swing in real time and make

adjustments immediately,”Grober said. “That’s turned outto be profound.” The musical biofeedback

allows golfers to hear and simul-taneously feel what a good swingis like — in a way that’s not possi-ble from watching videos. Thattraditional method of instructiontends to be static, point to point,as instructor and student breakthe swing down and analyze itscomponents.Several pro golfers and instruc-

tors are singing the praises ofSonic Golf. Vijay Singh got onelast June from one of Grober’sfriends and went on to win severaltournaments. Singh says theinvention has helped him tremen-dously by making his swing a lot more consistent. His version allows him to choose amusical tone from among 10 different instruments. The rock organ is Grober’s favorite.The Yale golf teams were given a Sonic Golf system, and they’ve just started using it.Raised in upstate New York, Grober went to Vanderbilt University, part of a strong

NCAA golf conference, partially on a scholarship from the Westchester Golf Association.He worked as a caddy on numerous courses to make money. “I lived Caddyshack,” hesaid. Now he’s a professor, inventor and entrepreneur.

Tapping the Genetic CodeTo Predict Blindness and Other Diseases

Josephine Hoh set out to find the genes that predispose people to age-related maculardegeneration, the leading cause of blindness in the elderly in the United States and anailment that afflicts tens of millions worldwide. The young researcher from Taiwan achieved not only that discovery but pioneered a

new, more efficient way of identifying the genes involved in such diseases.Hoh, a mathematical statistician turned genetic epidemiologist, managed to pave the

way for researchers to see the value of using her visionary genome-wide association studytechnique for many other common diseases — hypertension, diabetes, schizophrenia andheart disease among them.In 2005, just two years after arriving at Yale, she identified DNA variants in Comple-

ment Factor H, as well as variantsin other genes as major risk fac-tors for developing age-relatedmacular degeneration.Yale has filed patents on these

inventions and has worked with alocal entrepreneur, David Scheer,to launch Optherion (www.optherion.com), a New Haven-based biotechnology firm thatseeks to develop both therapiesand diagnostics for age-relatedmacular degeneration. Hohprefers to focus on her ownresearch and is not involved in themanagement of the company. An associate professor in the

Yale School of Public Health,

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Hoh brings to her research not only her talents as a numbers-crunching statistician andvisionary geneticist, but a never-give-up attitude. Rejected initially for funding by theNational Institutes of Health — because her proposal was judged “a fishing expedition”and “over-ambitious” — she convinced the Raymond and Beverly Sackler Foundation forArts and Sciences to support her work.Since she and her colleagues published their groundbreaking findings in “Science” mag-

azine in April 2005, the article has been cited by other scientists hundreds of times. Thejournal recognized her research as one of the top 10 scientific breakthroughs of the year.

Building Ever-Greater Memory Capacity For Ever-Smaller Digital Devices

When you buy a laptop, you get to decide how much memory to pack into your com-puter. The same kind of memory, known as DRAM (dynamic random access mem-

ory), is in your cell phone or PC.As consumers expect lighter products with greater memory, industry faces a mounting

challenge to fit the more powerful memory devices — including a transistor and a storagecapacitor — into smaller spaces. Enter T.P. Ma, a Yale electrical engineering professor whose work is known to virtually

every semi-conductor and computer hardware company in the world. One of his inven-tions is an improved DRAM that major corporations see as a promising technology tosolve this problem. His invention eliminated the need for a storage capacitor; it’s built into the transistor,

thus solving the space problem. It also dramatically increases the intervals between whichthe memory has to berefreshed — another majoradvance. Yale has patented thetechnology, and Ma expects itwill be a couple of years beforeit arrives on the market.“Several major companies

are talking to us and will wantto do some prototyping,” hesaid. “What we have done onthe university scale they willwant to do on the demonstra-tion scale, for production.”Ma has served as principal

investigator on joint researchand development projects withnumerous companies. Theyinclude Motorola, GeneralElectric, Hughes, Rockwell, Phillips, Siemens, Hitachi, Toshiba, Mitsubishi, Intel andIBM, where Ma worked for three years after receiving his Yale doctorate. His studentshave gone on to leadership roles at high-technology companies.He first arrived at Yale as a graduate student from Taiwan, not because of some grand

plan but because of the vagaries of graduate school applications. Completing requiredmilitary service, he had little time to write essays — in English — for his applications.Other top schools called for five-page essays, but Yale asked for only two pages. Thus, Yalebecame his first choice, quipped Ma.At Yale, Ma’s earlier research papers helped lay the foundation for flash memory, which

can be electrically erased and reprogrammed in many devices. He recently won the Connecticut Medal of Technology, the state’s highest honor for

technological achievement. In bestowing the award, the chair of the board of governorsof higher education said it’s not often that basic academic research leads to widespreadapplications: “But the next time you answer your cell phone, take a digital picture, or tuneinto your iPod, know that its flash memory is in large part made possible by the pioneer-ing work of T.P. Ma.”

Harnessing the Power of Osmosis To Create Clean Water Affordably

Rob McGinnis was in a chemistry class at a community college when he hit on the idea of using a new twist on an old technology to address the world’s growing need for

affordable clean water.McGinnis, now a Yale doctoral

student in environmental engi-neering, and his adviser, ProfessorMenachem Elimelech, havedesigned systems that harness thepower of osmosis to producefreshwater from seawater orindustrial waste water — using a10th of the energy needed inconventional desalination systemsthat rely on reverse osmosis.The new technology employs

“forward osmosis,” whichexploits the natural diffusion ofwater through a membrane. Theprocess draws pure water from itscontaminants to a solution ofsalts that can be removed easilywith low heat treatment — effec-tively desalinating or decontami-nating water with little energy input.Yale, which funded the research, has filed for patents on the technology and is commer-

cializing it through a startup company called Oasys Water Inc. The firm just secured $10 million in venture capital in its first round of financing. (See related story, page 8.)“Within the next year,” McGinnis said, “we expect to have a demonstration system at a

customer’s location.”In addition, the researchers say it’s possible to produce electricity economically from

sources such as industrial waste heat, using a related method — pressure treated osmosis.As water moves into a pressurized draw solution, the pressure of the expanded volume is

released through a turbine to generate electrical energy.McGinnis is a former Navy bomb squad member. Figuring out how to defuse bombs

— with all sorts of mechanical devices, chemical hazards and electronic circuitry — wasgreat training for a future engineer, he said, but after the Navy and pre-med studies at thecommunity college in California, he was ready for something totally different when hetransferred to Yale as a junior. He majored in theater studies and thought he’d be a writer.He still wanted to pursue forward osmosis even though he wasn’t studying engineer-

ing, he said, and was “overjoyed” when the Yale College Dean’s Office came up withfunding. By the time he received his bachelor’s degree in 2002, he had worked out thebasic principles. He expects to receive his Ph.D this spring, and plans to work for Oasys.

Forging a Potent Weapon In the Battle Against HIV/AIDS

Apotent anti-HIV/AIDS drug called Zerit® has prolonged the lives of hundreds of thousands of patients suffering with the disease.

William Prusoff and his late colleague Tai-Shun Lin developed the drug, d4T, in thelate 1980s. The compound, Prusoff explains, was first synthesized by Dr. Jerome Horwitzin Detroit as an anti-cancer drug but it was not very effective. Prusoff and Lin, however, discovered it was very effective at slowing HIV. The drug

worked by incorporating itselfinto HIV’s DNA and shuttingdown the reproductive mecha-nism.Yale licensed the discovery to

Bristol-Myers Squibb, whichbegan selling Zerit® in 1994.(See related story, page 8.) Underpressure to make it available topoor patients in Africa, the com-pany agreed in a landmark 2001decision to offer it at no profit insub-Saharan Africa.Zerit® became an essential

part of a widely prescribed anti-HIV cocktail, and has earnedYale, Lin and Prusoff millions ofdollars in royalties. But Prusoff,who is professor emeritus of phar-macology, has given away much of the money to charities like Doctors Without Borders.A child of Russian immigrants who ran a grocery store, Prusoff said his greatest satisfac-

tion was that his discoveries helped people. “It’s a terrific kick for one’s ego,” he said. “Dr.Lin and I got tremendous satisfaction from knowing that what we had produced was ofbenefit to society.”Though Prusoff is best known for the anti-HIV drug, his drug inventions began much

earlier. His work in the 1950s at Yale led to the first antiviral compound approved by theFDA. Called idoxurine, it’s an analog of thymidine, and is used to treat herpes eye infections.Prusoff plays down the fact that he is generally regarded as the father of antiviral

chemotherapy. He likes to say he’s simply been lucky to pursue his passion for more than50 years. “I don’t consider it work,” he said. “My work is my hobby.”At 88, he’s semi-retired, but still trying to come up with improved antiviral com-

pounds. He continues to study the complexities of thymidine, the molecule that’s beenhis lifelong interest. “They prolong life,” he said of antiviral compounds for HIV, “but they’re not cures.

We still need a cure for AIDS.”

Halting Tumors’ Growth by Targeting Their ‘Achilles Heel’

Joseph Schlessinger is one of the world’s leading cellular biologists and cancer-treatmentinventors.Widely known for pioneering studies of how cells grow and divide, and how aberrant

cell signals can lead to cancer, he has made discoveries that have led to an entire field ofcancer research, producing a new class of targeted anti-cancer drugs — multi-kinaseinhibitors — that combat the disease by retarding both tumor growth and blood supply.Before coming to Yale in 2001, Schlessinger invented a treatment for various types of

deadly cancers; it was called SU11248, or Sutent. He co-founded a company and theFDA approved the drug in 2006 to treat gastrointestinal and kidney cancers. Pfizer Inc.ultimately acquired the firm, and Sutent is now is being tested for other types of cancer. More recently at Yale, where he is chair of pharmacology at the School of Medicine, he

invented a novel approach for development of antibody drugs to treat cancers that haveescaped conventional therapies. His discovery was the basis for a New Haven company he founded with Yale called

Kolltan Pharmaceuticals, which recently secured $35 million in financing. (See relatedstory, page 8.) Kolltan is developing monoclonal antibodies against various cancers thatthe company hopes to move rapidly into human clinical trials toward FDA approval. Schlessinger’s latest breakthroughs were the result of painstaking research into cellular

signals that switch on the growthof tumors — and how to stop thatgrowth. “When you really under-stand how these receptors work,you can find new Achilles’ heelsthat you can use in order to blockactivity in cancer and other dis-eases,” he said.By targeting these sites, drugs

can block receptors and overcomeresistance that develops whenpatients undergo lengthy treat-ment with current cancer drugs. Schlessinger, who has turned

down offers to run drug compa-nies, savors the freedom of acade-mia. “I think you have to use yourimagination and come up with

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Discoveries (Continued from page 2)

3YALE INNOVATORS

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the big questions,” he said, “and then try to answer them.”Known to friends and colleagues as “Yossi,” Schlessinger said he has been fascinated by

science since boyhood but remains haunted by war. Born in the former Yugoslavia at thevery end of World War II, his parents were Jewish partisans fighting the Nazis. Many ofhis extended family members were murdered, he noted. His parents fled communism with him after the war and settled in Israel, but there was

no escape from conflict, said Schlessinger. He was an officer in Israel’s elite Golanibrigade, laying or removing mines in the 1967 Six-Day War, the 1973 Yom Kippur Warand the 1982 invasion of Lebanon.

Creating a Quantum Computer,One Artificial Atom at a Time

Robert Schoelkopf and Michel Devoret are creating basic building blocks for a future quantum computer.

These computers of tomorrow, researchers say, will store, process and transfer hugeamounts of information unimaginably quickly and in spaces that are almost inconceivablysmall — visible only with an electron microscope.The two applied physics professors are among an elite group of experimentalists, work-

ing at the level of single microwave photons, tiny packets of light energy.Schoelkopf is a former NASA

engineer who earned his doctor-ate at Caltech, and Devoret was adirector of research at the FrenchAtomic Energy Commissionbefore moving to Yale. Devoret isalso a member of the prestigiousCollege de France.At Yale, Schoelkopf and

Devoret are combining novelnew designs for superconducting“artificial atoms” with tiny super-conducting cavities to create elec-trical circuits that realize“microwave quantum optics on achip,” said Steven Girvin, a Yaletheoretical physicist who collabo-rates on their project.The two scientists have man-

aged to squeeze the tiny photonsinto ultra small cavities on a chip, akin to a regular computer microchip. They’ve alsosqueezed “artificial atoms” that can act as quantum bits — units to process and store quan-tum information — into the ultra small cavities. The tiny packets of energy from themicrowaves interact with these small atoms a million times more strongly than if the atomshad been in a standard bigger cavity.The cavity acts as a “quantum bus” allowing quantum information to be sent from one

atom to another, forming the basis of a new architecture, the beginnings of what somedaythe researchers expect will be a huge integrated circuit of quantum bits.Traditional computers use and store information as zeros and ones, or open and closed

switches. In quantum computing, information will be processed as zeros and ones simul-taneously — allowing for exponential advances.The pioneers of traditional computers had to go from mechanical relays to vacuum

tubes to transistors and finally to giant integrated circuits. Quantum computing pioneers,as Girvin puts it, are still in the equivalent of the transistor stage.But the potential is real enough for the U.S. Department of Defense and the National

Security Agency to fund research, expecting to develop quantum computers for nationalsecurity purposes, such as cryptanalysis. “If quantum computers can be built,” Girvin said, “they can very efficiently break cer-

tain types of codes.” � �

Eliminating the ‘Guesswork’ in Developing More Effective Antibiotics

When first developed, antibiotics were hailed as godsends, treating infections byinhibiting biological

processes — including jammingthe machinery that makes pro-teins in bacterial cells. Problemshave arisen, however, as resistanceto the widely prescribed drugs hasgrown dramatically.The work of two Yale profes-

sors — Thomas Steitz in molecu-lar biophysics and biochemistryand Peter Moore in chemistry —initially had nothing to do withthe design of new drugs. Theirseminal studies illuminated thebasic structure of the ribosome,the protein-making machinery inall cells. In particular, Steitz andMoore detailed the structure ofthe larger of two parts of the ribo-some, the 50S subunit. That ribosomal subunit also happens to be a major target of antibiotics. Their discover-

ies have led to a novel approach to the design of new classes of antibiotics active againstresistant strains of bacteria. In a nutshell, these drugs hit and bind to the target better thanthe old versions because they were designed to remove the guesswork.The information has been licensed by Yale to a New Haven-based startup company,

Rib-X Pharmaceuticals, that the two researchers helped found in 2001. To date, Rib-Xhas raised more than $173 million in four rounds of venture financing.The company has developed a compound using this structure-based approach that

already has passed phase II clinical trials. It will combat Methicillin-resistant Staphylococ-cus aureus, or MRSA, a particularly tough bacteria that kills 19,000 people each year in

U.S. hospitals alone. By illuminating the ribosomal subunit’s structure, the researchers were able to view the

mechanism of action of the antibiotics from a closer vantage point. “What we were able todo is find how several dozen antibiotics bind to the ribosome,” Steitz said. “Without thestructure, you wouldn’t know what to tie to what to make a new drug.”They began their search not to help drug makers produce better antibiotics, but to

understand the ribosome, because it is so fundamental to the function of cells. It’s thelargest “machine” in the cell. Their research “showed that the RNA part of the ribosome isthe catalytic component,” Steitz said, “and that has evolutionary implications, because itshowed that the ribosome started out entirely [composed of] RNA. The RNA came first.”It is a very important discovery about the evolution of life, said Steitz. “The fact that we

can use it to make antibiotics is exciting too.”

Using a Microchip To Analyze The ‘Blueprint’ of Proteins

The word “protein” comes from the Greek word for “primary.” Indeed, proteins arevital to living organisms, as they take part in every process within cells.

Michael Snyder, who won the 2007 Connecticut Medal of Science, the state’s highesthonor for scientific achievement, has earned a reputation as one of the world’s leadingpioneers in the study of proteins. In several pivotal studies, Snyder and his team demonstrated that it was possible to ana-

lyze thousands of genes and proteins at once.The head of the Yale Center for Genomics and Proteomics, Snyder helped develop the

first method for the global analysis of transcription factors. These are proteins that bind tospecific sequences of DNA, thereby controlling the transfer of genetic information fromDNA to RNA. Transcription factors read and interpret the genetic “blueprint” in the DNA, and regu-

late gene expression. By controlling gene expression, transcription factors control theidentity of cells and how they divide and grow. Understanding the transcription factors’work is crucial for understanding human disease.Prior to this work, researchers analyzed targets of transcription factors one at a time,

and thus had an incomplete picture of how they worked. In 2001, Snyder led a Yale team that created the first microchip able to analyze virtually

all yeast proteins, allowing research on a scale many scientists believed was not possible.A Yale-licensed company, Protometrix, commercialized the microchip technology. The

firm has since been acquired by aCalifornia-based firm, Invitrogen,now called Life Technologies.Snyder has used this microchip

to study how proteins work andhow they are regulated. Mostrecently, he has applied this tech-nology to try to identify earlymarkers for ovarian cancer, a lead-ing cause of death for manywomen, as it is often diagnosedwhen the disease is quite advanced. His laboratory has found that

patients with ovarian cancer oftenhave antibodies directed to cer-tain proteins. The researchershope that this might someday beused in a test for the disease.Recently, Snyder also has

focused research on humanembryonic stem cells. He and his team discovered a novel signaling pathway that is essen-tial for the self-renewal of embryonic stem cells. They then used the information to createone of the first media for cell growth that is free of any non-human animal components, astep that is very important to the future use of human embryonic stem cells for therapy.

Unleashing the Power of Nature To Further Genetic Research

Mutant mice sounds like the title of a B-movie. Multiply them by tens of thousands,and you’ve got a mutant mouse factory.

That’s exactly what geneticist Tian Xu has established, and when he talks about hismice he might as well be referring to the Oscars: In his ambitious vision, he sees medicalresearch gold.Early in life, Xu escaped the repression of the Chinese Cultural Revolution and ulti-

mately landed in New Haven. He now runs genetics labs at Yale and at his Chinese almamater, Fudan University in Shanghai.He and his team plan to identify many of the genes responsible for human diseases, by

generating and studying mutant mice. Xu aims to establish a center for genetic models of diseases that will attract researchers

from across the globe. He expects the researchers to use the mutant animals to create thefirst functional map of the mammalian genome. “It will,” he said, “greatly advance ourunderstanding of human biologyand disease and our ability todevelop new diagnostics and ther-apeutics.”His innovation is on an epic

scale: He intends to produce amillion mutant mice in the Yale-Fudan facility in China to comeup with 100,000 new strains ofmice, each with a disrupted geneor genetic element.Xu unleashed the power of

nature and engineered a piece ofmoth DNA called the piggyBactransposon to become a “jump-ing gene” in the mouse. Thisgene makes the mouse a mutantfactory. When the animal breeds,

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Discoveries (Continued from page 3)

4 YALE INNOVATORS

the modified transposon causes random genetic mutations in the mouse’s offspring —one gene per mouse is disabled. Making experimental mice this way is much quicker andless expensive than current methods, said Xu.More than 99% of mouse genes have counterparts in humans, so these mice will pro-

vide the first glimpse of the functions of many of our genes, most of which remain myster-ies nearly a decade after the human genome project catalogued their existence, Xu adds.By systematically mutating every gene and screening the mice for defects, Xu plans to

identify the genes responsible for most diseases. “If you know the genetic basis of thesediseases in mice, you can go up stream to humans and verify,” he said. “Then you have adiagnostic base and the animal model and target for studying disease mechanisms and fordeveloping therapeutics.”

Tuning Up the Internet To MakeIt Run Smoother and Faster

If you’ve ever been frustrated at how long it takes to download something from theInternet, the team of Y. Richard Yang and Avi Silberschatz may have just the cure.The two computer scientists have engineered a system to make the Internet work more

smoothly and efficiently.The problems with the Internet have arisen because its basic core hasn’t changed since

its beginnings 40 years ago, they explain. The goals then were modest: Connect somemilitary installations and a handful of universities, mostly for electronic mail traffic andterminal access.It simply was not designed to do all of the things people do with it today, and layer

upon layer of ad hoc fixes have been applied, according to Silberschatz and Yang.In the current landscape, companies that provide customers access to the Internet —

both Internet Service Providers (or ISPs) and individual users connected to each other

directly using peer-to-peer soft-ware (or P2Ps) — are not workingcooperatively enough to ensuresmooth, rapid flow of informa-tion, said the Yale scientists.Information exchange schemes

among the users are inefficientand costly, like dialing long dis-tance to call a neighbor, theynote.In recent tests on some of the

largest ISPs, the Internet archi-tecture engineered by the Yaleteam has produced significantspeed boosts for P2P informationtransfer — for example, an 80% speed increase for Comcastcustomers.The Yale team’s innovation,

P4P, which stands for “provider portal for P2P applications,” has the potential to reducecosts for ISPs while also improving performance of P2Ps. It works by allowing seamlesscommunications between the two.Yale is actively working with a variety of partners to make the system an Internet stan-

dard. “We are very pleased that Verizon is already running our system in production,”Yang said. If every major service provider employs it, as Yang and Silberschatz hope, theinnovation will be ubiquitous yet invisible to end users. “It will be like a car hummingmuch better, without you knowing exactly what they’ve done in the engine to make it runbetter,” Silberschatz said.“If we manage to have P4P under the hood in most of the Internet applications, we’ll

be more than delighted,” he said. “We’ll consider it a huge success.”

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Discoveries (Continued from page 4)

Every day brings Yale researchers closer to new breakthroughsin medicine, science and engineering. The following is a brieflook at some of the Yale scientists whose discoveries may soonyield treatments and products for people around the world.

New Class of AntibioticsRon Breaker, professor of molecular, cellular and devel-opmental biology, and professor of biophysiology and bio-chemistry: After imagining and “inventing” riboswitches,RNA sequences that can bind and act as sensors in variousmolecules, Breaker discovered natural riboswitches in thegenomes of microorganisms. Riboswitches act as majorcontrol elements for gene expression. Yale startup BioRe-lix was established to use these genetic elements fordesigning a new class of antibiotics.

Genome Analysis for Brain AneurysmDr. Richard Lifton, chair of genetics, professor of medi-cine and of molecular biophysics and biochemistry: Liftonis one of the world’s leading advocates of genome-wideanalysis of human populations to find genetic links to dis-eases. For example, Yale neurobiologist Dr. Murat Guneland Lifton recently discovered a genetic link to brainaneurysms, and their findings could lead to new tests tospot those at greatest risk.

RNA Snippets and Stem CellsHaifan Lin, director of Yale’s Stem Cell Research Center:Lin is among the world’s leading investigators of how tinysnippets of RNA can have profound effects on physiologi-

cal activity in organisms. His lab has studied how stem cellsrenew themselves in sex cells, and his work on various so-called small RNAs has many medical applications.

Improved VaccinesRuslan Medzhitov, professor of immunobiology: Thefocus of Medzhitov’s research is the innate immune sys-tem, which alerts the host to infectious assaults and trig-gers a cascade of responses — known as the adaptiveimmune response — that is the basis for vaccine activity.Improved vaccines could be developed by introducing theimmune system with disease antigens that are physicallylinked to particular polypeptide activators of the innateimmune response. A Yale startup, VaxInnate, is developinga high-throughput screening platform to identify theseactivators.

Amorphous MetalsJan Schroers, professor of mechanical engineering:Schroers and his team have been exploring a class of mate-rials called amorphous metals or bulk metallic glasses,BMGs, that can be molded like plastics and are moredurable than silicon or steel. He has created a process formaking computer chips at the nano-scale that may revolu-tionize such production by exploiting these novel metals.

Biomarkers for Disease RiskFrank Slack, professor of molecular, cellular & develop-mental biology, and Joanne Weidhaas, professor of thera-peutic radiology: The Yale Cancer Center researchers dis-

covered a potential diagnostic test to pinpoint genetic bio-markers to help identify those individuals who are mostpredisposed to lung cancer, ovarian cancer and other typesof the disease.

Spinal Cord Injury TreatmentStephen Strittmatter, professor of neurology: Strittmat-ter helped discover the existence of a molecule, calledNogo, that shows incredible promise in animal models fortreating spinal cord injury, for which there is no currenteffective treatment.

New Class of SemiconductorsHong Tang, professor of mechanical engineering andelectrical engineering: While the force of light is too weakto be used to power devices in everyday use, he and hisengineering team have found that it can be harnessed todrive machines — when scaled to nano-proportions. Thisresearch is opening the door to a future new class of semi-conductor devices operated by the force of light.

Electrodes To Predict Epileptic SeizureHitten Zaveri, associate research scientist in neurology,and Dr. Dennis Spencer, chair and the Harvey and KateCushing Professor of Neurosurgery: These two scientistsare creating wireless electrodes for detecting epilepsy andmore accurate ways of measuring epileptic seizure onset.Spencer pioneered new surgical treatments for the disor-der that have been adopted by medical centers aroundthe world.

Looking to the Future: Promising Research on the Horizon

5YALE INNOVATORS

Yale College and the University’s graduateand professional schools are already home

to more than 800 science, math and engineer-ing labs. But Yale’s science research footprintis about to grow much larger. Two years ago, the University acquired a

136-acre pharmaceutical research park,located on the border of the neighboringcommunities of West Haven and Orange,Connecticut. The West Campus includes more than

500,000 square feet of research laboratories,which will eventually house five interdiscipli-nary institutes that will share core facilities.“Yale is already in the midst of a boom in

the expansion of its science and medical facili-ties,” said Yale President Richard C. Levin,when announcing the University’s acquisitionof the West Campus space. “The addition of this ready-made, state-of-

the-art research space will allow that growthto accelerate at an unprecedented level —potentially making it possible for Yale scien-tists to develop new discoveries, inventionsand cures years earlier,” he added.

Yale’s West Campus Will Enable Research To Advance at ‘Unprecedented’ Pace

In the past year, Yale senior Henry Finkel-stein explored career opportunities withlarge corporations and start-up companies.Responses, much less job offers were scarce,but Finkelstein landed on his feet.Finkelstein and three fellow students are

partners in a new venture called CampusKings, which this spring will sell canvaswalking shoes and aesthetic basketballshoes that carry the Yale logo and an imageof Harkness Hall floating safely encasedbetween the shoes’ inner and outer soles.Finkelstein’s decision to become an

entrepreneur was born of both a personalpassion and a poor business climate, whichin many ways, he says, made his decision tohelp launch a business much easier. Despitean academic and professional resume thatincluded an internship at a top manage-ment consulting firm in San Francisco,Finkelstein attracted little interest fromcompanies that a few years earlier wereoffering large salaries and incentives forYale graduates to join their firms.

Instead, he and three friends approached Yale about the project and then closed a deal tomanufacture Yale-branded shoes made in China — thus, Campus Kings was born. (Seecompany profile, below.) They are now negotiating a licensing agreement with Yale.“I’m not stupid. I read the papers and hear what venture capitalists are saying, that the

river has dried up,’’ says Finkelstein, a skateboarder who hails from San Diego. “But thatjust made this decision easier to make. I don’t have the same choices any more. I don’thave as much to lose.”Yale is seeing a sharp uptick in students launching similar ventures. Sometimes a stu-

dent’s commercial ambitions may get anudge in classes that explore the nuances ofbusiness start-ups. Sometimes their ideasare nurtured within student entrepreneurialsupport groups. If students are ready tolaunch a company, they can get help fromthe Yale Entrepreneurial Institute (YEI),which was launched by Yale more than twoyears ago to keep promising student-gener-ated companies in New Haven.

And sometimes, the impetus comes from a dismal economy. “It used to be

the plan was to get the internship at theinvestment bank because that leads to a jobafter graduation,” says Shana Schneider,deputy director of YEI. “Now the conversa-tion I hear is that, ‘I don’t have to go thatway any more, I can work on my businessidea now and work on my business aftergraduation.’ More students are seeingthose options on a par, now that one is nota sure bet anymore.”The evidence of an entrepreneurial surge

at Yale can be found in many places. YEI has seen an increased number of applications forits summer program, where students stay on campus to work on business ideas. At least ahalf dozen of those students had planned to pursue careers in corporate America. The stu-dent-run Yale Entrepreneurial Society (YES) this year has also seen an increase in numbersof applications for its annual contest, as well. Alina Wang, a Yale College junior and incoming president of YES, is hearing the same

story from her peers as Schneider.“Being an entrepreneur means more than starting abusiness, it is an attitude you can bring to school, to life,” says Wang. “It is an action-ori-ented state of mind.”

Increasingly, Yale Students Launching Their Own Companies

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Student Ventures Making a Mark on the MarketplaceThe following are among the many student-run businessesthat have taken launch with the aid of the Yale Entrepre-neurial Institute (YEI).

Using Behavioral Science To Promote Good Causes

Both of Emily Yudofsky’s parents are psychiatrists, soher interest in behavioral science is no surprise. The Yale College junior started a neuromarketing com-

pany, Applied Resonance Research, and plans to specializein research that involves public service advertising andnon-profit organizations’ ad campaigns. In high school, Yudofsky participated in research of per-

sonality disorders while a study of neuroimaging and brand-ing was under way. Regions of the brain were activatedwhen consumers were exposed to Coke images but dor-mant for Pepsi images. Now she wants to use that kind ofknowledge to help create smoking-cessation or anti-drunkdriving campaigns that make a difference. She launched herfirm through the YEI Summer Fellowship Program.

Monitoring Glaucoma Via an Eye Implant

The standard monitoring of people suffering from glau-coma, a leading cause of blindness, relies on outdateddevices that provide only a momentary snapshot of thepatient’s condition. Paul Di Capua, a joint degree student at the Schools of

Medicine and Management, along with Dr. Vicente Diaz’05 M.B.A. and Dr. Amir Cohen are working with the YEIto obtain a patent for a monitor that would be painlesslyimplanted in the eye to measure intra-ocular pressure, akey metric for devising more effective, individually-tai-lored therapies.The Yale student-startup expects to have aprototype device by the end of the year.

Ringing In the New Day With More Energy

Arun Gupta first thought of inventing a way to wake upat just the right time while attending high school, when hewas alert some days and groggy on others. He learned thatthose who wake during REM sleep were more likely tostart the day feeling energetic.

The Yale College stu-dent and a partner fromBoston College devel-oped a wristband thatmonitors hand move-

ments during sleep and relays the information via Blue-tooth to a cell phone alarm. The alarm will sound duringthe optimal REM-sleep time in a 20-minute window. The business plan and prototype were developed during

YEI’s Summer Fellowship Program.

Reducing Bad Vibrations in TurbinesYulee Newsome, a Yale School of Management student

who previously was a nuclear engineer on a Navy subma-rine, founded a company that expects to market its tech-

nology to the military and commercial aviation. It’s a system to monitor turbine vibration, meant to

increase turbine efficiency and reduce maintenance costs.

Turning Electronic Recyclables Into Cash

Rich Littlehale and Bob Casey had a bunch of old elec-tronics and no easy way to recycle them. While the deviceswere no longer of any use to them, they thought the itemscould still be worth money. So the two Yale College jun-iors hit on the idea of a website to enable people to getpaid quickly to recycle their electronic stuff.Their aim was to avoid the usual hassles associated with

selling used items online, such as opening an account andproviding credit card information. On YouRenew.com,

consumers search fortheir kind of device,answer a few questionsabout its condition andreceive an offer price. Ifthey accept, customerscomplete the transac-

tion through a quick checkout process and get a free ship-ping label for sending the device. Users can be paid by checkor PayPal or donate proceeds to a non-profit organization.YouRenew.com is a service of TwigTek LLC, based in

New Haven, with offices in the YEI Incubator.

Taking Cyberspace Advertising to the Next Level

A group of Yale and Harvard students founded a com-pany called PaperG as a sort of virtual bulletin board forlocal online advertisements. Businesses can place their poster-sized flyers on PaperG’s

Flyerboard, which converts them into interactive ads withfeatures including e-mail-sharing, social networking andonline maps. The company — led by Victor Cheng ’08, KaMo Lau ’08 and Victor Wong ’10 — moved into the YEI’sIncubator Space last year and raised venture capital.

Putting Your Foot Where Your School Spirit Is

Tim Kau ’09 and Christopher Chau ’10 were in a HongKong market filled with American goods during the sum-mer of 2008 and thought a Yale-branded shoe wouldsurely sell well. The idea has taken hold, and the two students are in the

process of negotiating an agreement with Yale licensingstaff and a Chinese shoe manufacturer to make a canvaswalking shoe and a more high-tech style basketball shoe.Besides the Yale logo, the shoes are expected to feature animage of Harkness Hall embossed between the clear insoleand outsole.The partners — who include marketing director Henry

Finkelstein ’09 and chief executive officer Stephen Cam-mock ’09 — are taking the idea to the licensing offices ofother Ivy League institutions such as Harvard.When theyvisit China again in a few years, Kau and Chau hope to seethe Campus King Yale brand on the feet of passers-by.

Campus Groups Help Unite and Support

Business-Minded Students

Yale has a diverse group of organizations dedicated tohelping students who want to learn more about theworld of business or to start their own ventures. Theseinclude the following:

Yale Entrepreneurial Institute (YEI): Founded by the Uni-versity in 2006, the YEI helps undergraduate and graduatestudents start new ventures. Yale was one of the first universitiesin the country to launch such an institute, and since its inceptionas a crash summer program, YEI has grown into a year-roundUniversity department that acts as a base for entrepreneurshipon campus, with events that serve the interests of students andthe New Haven community. (http://www.yale.edu/yei)

Yale Entrepreneurial Society (YES): Now celebrating its10th anniversary, YES is run by students who offer educationaland networking opportunities to foster new venture creationand economic development. YES organizes campus andregional events and conferences to encourage entrepreneur-ship at Yale and in the community. It also sponsors the Y50Kcompetition, in which top business leaders evaluate studentbusiness plans competing for $50,000 in venture capitalmoney. (http://yesatyale.org)

School of Management (SOM) EntrepreneurshipClub: Organized and run by SOM students, this club works to facilitate graduate student start-ups and develop alumni support for them, and to promote interest in entrepreneurialaffairs both within the SOM community and beyond.(http://students.som.yale.edu/sigs/entrepreneurship)

Yale Biotechnology and Pharmaceutical Society(YBPS): The YBPS is a University-based organization thatlinks people and groups in the Yale-New Haven communityand beyond with an interest in biotechnology and pharmaceu-ticals. The group was founded in 1997 by a team of businessand graduate students; it has over 1,200 members and coordi-nates a plethora of biotechnology- and pharmaceutical-related activities in the Yale-New Haven community andbeyond. (http://www.yale.edu/ybps)

Yale Law & Business Society (YLBS): An organizationdedicated to promoting the interaction between law, policyand business, YLBS serves as a center for members of the LawSchool community who are interested in business issues,including those affecting business startups. (http://www.law.yale.edu/stuorgs/ylbs.htm)

6 YALE INNOVATORS

Medical Student’s Desire To Boost Study Habits Spawns Interactive Learning System

Elliot James Rapp does not have a photographic mem-ory — a quality that might have come in handy in

2006, his first year as a Yale medical student, when he waslooking for ways to learn the difference between the“pons” and the “medulla oblongata” and thousands ofother medical facts. Fortunately for himself and, ulti-mately, for the Yale School of Medicine, what Rapp doeshave is a skill for programming.The former Microsoft software engineer has developed a

new interactive program that is already being used by med-ical school students to learn about the wonders and com-plexity of the human body in new and collaborative ways.On April 22, Rapp’s concept was recognized as best

business plan in the Yale IDEA (Innovation in DigitalEnvironments Award) competition, a new contestdesigned to support new talent and new digital projectswithin the Yale community.Rapp, now 30, began his first career at an enterprise soft-

ware company in Austin, Texas, and later went to work forMicrosoft where he helped develop their advanced Webservices platform. Then he decided to go to medical school.“I always loved programming and technology, but I

learned that I care even more about what the final productis being used for,” Rapp says.

While he loved Yale’s open learning policy, whichemphasizes learning for the sake of learning over

tests and examinations, Rapp was frustrated by what hesaw as inefficiencies in the learning process and how littlemedical students interacted in their study habits.

In 2007, he developed a desktop application calledLiKiRi (Learn It, Know It, Recall It) Knowledge. The pro-gram encourages students to take notes in a format thatallows them to test their own progress. It also identifiesareas where they are weak and encourages collaborationand sharing among classmates.Here’s an example of how it works, explains Rapp: He and

7YALE INNOVATORS

agement and Entrepreneurship, says theheads of large corporations are in as muchneed of entrepreneurial skills as those ofyoung start-up companies.“The abilities to think creatively and

articulate a vision, to advocate for a productor a point of view, to develop a business caseand a funding strategy, and to work effec-tively with a variety of constituencies are allpart of the entrepreneurial mindset,” shenotes.In addition to holding workshops for

business executives from around the world,SOM courses offers students opportunitiesto learn-by-doing by tackling real-worldproblems in their classes. One course,“Global Social Entrepreneurship,” offers alittle of both. The class brings social entre-preneurs and mission-driven entrepreneursfrom around the world, who work with Yalefaculty and students in the class to address aspecific problem in their organizations. Inits first year, the course focused on leaders ofnon-governmental organizations (NGOs)from India.

“Global Social Enterprise (GSE),” astudent club that evolved to

include a for-credit course, is anotherunique offering at SOM. Founded in 2004,GSE allows students to put their classroomknowledge to practical use and gain hands-on experience in the areas of internationaldevelopment and social enterprise. Duringthe 2009 spring break trip, GSE participantsworked in small groups to provide pro bonoconsulting services to private and non-profitsocial enterprises in Thailand.

three other students formed a study group to solidify theirknowledge of human anatomy after the first year of medicalschool. They each created LiKiRi notes on their region of thebody and then presented the information to the other mem-bers of the group using the application. At the end, they eachhad a knowledge base that covered the entire body. Further-more, LiKiRi Knowledge allowed them to test their reten-

tion of the information and identify weak areas.From user surveys, Rapp estimates that more than 30%

of first- and second-year medical students now use theapplication. “I knew if I spent hundreds of hours creating aprogram for myself I would want other students to use it aswell,” he says.The program has improved considerably with several

version releases over the last two years, Rapp notes. In addi-tion, it now has a companion web application called LiKiRiCommons. Users with an account at LiKiRi Commons areable to access their LiKiRi Knowledge notes from any loca-tion at any time. If they wish, they can also establish sharingand collaborative preferences. These specify who has accessto their learning material — be it their study partners,friends, classmates or even complete strangers.

In between developing products and undertaking a rig-orous medical school curriculum, Rapp has developedplans to bring the LiKiRi Learning System to otherschools. The system is applicable not only to medicalschool students, but all learning environments, he believes.“Having seen the current version of LiKiRi, we were

immediately struck by the opportunity to scale the plat-form,” says James G. Boyle, director of Yale the Entrepre-neurial Institute, a University-operated agency dedicatedto helping students create their own businesses. (Seerelated story, page 6.) “I’d go as far as saying that it couldbe a disruptive technology [i.e., an unexpected technolog-ical innovation] for the education sector.”

“Ten years from now I see LiKiRi Learning as a plat-form that provides students one place to store and accesstheir knowledge no matter if the content is self-generatedor provided by teachers, classmates or publishing compa-nies,” Rapp says. “They will be able to create, modify andreview this knowledge much more efficiently than is possi-ble with today’s tools. Schools will put entire curriculumsinto LiKiRi.”

use around the world.Yale became an early center for science

education in the 19th century, thanks to astring of pioneering professors who drewsome of the brightest science students of theday to the University.In 1804 the Yale Corporation gave Pro-

fessor Benjamin Silliman a year’s leave tostudy chemistry and geology in Europe and$10,000, a princely sum at the time, to pur-chase books and scientific equipment tobring back to Yale. Silliman taught chemistryand natural history for 51 years, and is nowrecognized as a father of American science.

One of Silliman’s students, JamesDwight Dana, became one of the most

important geologists and naturalists of thecentury. He served as a scientist on theWilkes Expedition, the first great Americanvoyage of exploration in the Pacific. Hiswork on the taxonomy of corals still stands.Dana taught at Yale for more than 40 years,until shortly before his death in 1892.Dana also is credited with helping to per-

suade Josiah Willard Gibbs, one of thecountry’s most renowned scientists, fromleaving Yale for Johns Hopkins when thelatter was founded. Gibbs earned the firstengineering doctorate in the United Statesin 1863. His insights into thermodynamicsrevolutionized the field. He was appointed

professor of mathematical physics in 1871,the first such professorship in the country,and he held that post nearly until his deathin 1903. He was the country’s premier sci-entific intellect at the end of the 19th cen-tury, and helped to build Yale’s reputationfor science achievement.In the 20th century, other Yale graduates

and faculty made transformative scientificdiscoveries and technological advances. Forexample:• Lee DeForest, who earned a bachelor’s

degree in 1896 and a Ph.D in 1899, was apioneer in radio waves and was considered a“Father of the Electronic Age.” As anundergraduate, he tapped into the Univer-sity’s electrical system and blacked out thecampus. In 1906, he invented the triode, orAudion, radio vacuum tube, which allowedfor amplification for radio reception. Twoyears later, for the French war ministry, hedemonstrated a system of wireless telephonyfrom the Eiffel Tower. In 1910, he broad-cast the first “Live from the Met” opera per-formance, featuring Enrico Caruso. Publicreceivers were set up in New York, JerseyCity and Bridgeport, because no one yethad a radio. • Yale School of Medicine student

William H. Sewell Jr. in 1949 built amechanical pump to reroute blood flow toand from the heart using parts of a child’s

Erector Set — the kind of building toy heplayed with as a boy (and which, inciden-tally, was the brainchild of Yale alumnusA.C. Gilbert ’09 M.D.). Sewell graduatedwith the Class of 1950 and won the covetedthesis prize for his work. Today the pump,the forerunner of the artificial heart, is dis-played at the Smithsonian Institution• Joshua Lederberg, who earned a Yale

Ph.D. in 1948, became one of the century’sleading scientists. His work in bacterialgenetics had important medical implicationsand led to his sharing the Nobel Prize forMedicine in 1958. His work at StanfordUniversity with Edward Tatum and GeorgeBeadle — the discovery that genes regulatespecific chemical processes — made him oneof the youngest Nobelists. He helped lay thefoundations for today’s biotechnology rev-olution. • Sidney Altman, now a Sterling Profes-

sor of Chemistry at Yale, shared the NobelPrize in chemistry with Thomas Cech of theUniversity of Colorado in 1989, for whatthe committee called one of the two “mostimportant and outstanding discoveries inthe biological sciences in the past 40 years.”They discovered that RNA, in addition toserving as the transmitter of genetic infor-mation inscribed in DNA, could also serveas an enzyme, or bio-catalyst. This abilitywas previously believed to reside solely inproteins. RNA thus can possess, in a singlemolecule, two of life’s most fundamentalchemical capabilities. Cech coined the word“ribozyme” to describe all-RNA enzymes.

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Yale’s Tradition of Invention (Continued from page 1)

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Entrepreneurial Minds(Continued from page 1)

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At the Office of Cooperative Research

Since its founding 27 years ago, Yale’sOffice of Cooperative Research (OCR)

has built a significant portfolio of inventionsand patents — and has grown into anengine of regional economic development.Its mission is to facilitate the translation ofresearch from Yale’s labs into products andservices that benefit society.Dozens of companies have been started

with Yale research as their foundation. InNew Haven alone, about 30 companieshave sprouted from Yale innovations. Located at the foot of Science Hill on

Temple Street, OCR is recognized as a lead-ing force for catalyzing economic growth byidentifying, counseling and nurturing earlystage technologies and guiding the transi-tion into robust companies. As managing director of the office for the

past 10 years, Jon Soderstrom has presidedover numerous marriages between Yaleinventions and private investments. In thattime, the office has helped in the formationof about 40 companies that have collectivelyattracted more than $450 million in venturecapital financing.

It wasn’t always this way. Until the late1970s, academic leaders on campus didn’tconsider it their jobs to patent Yale inventions. In the 1950s, William Prusoff, professor

emeritus of pharmacology, who is widelyviewed as a father of antiviral chemotherapy,struck upon the therapeutic value of idox-uridine against herpes infections that causedblindness. In the 1960s, this became thefirst antiviral compound approved by theFDA. But Yale didn’t protect this intellec-tual property.“Yale didn’t want to deal with patents at

the time,” he recalled. “It was pure aca-demic research.” In the first decade after the Office of

New VenturesUsing Yale TechnologyIn the past five years, the Office of Coop-erative Research has helped launch 21new companies to commercialize tech-nologies discovered in Yale laboratories.These are the companies, their productand their websites (where available):

OASYS WaterCleantech for seawater desalinationhttp://www.oasyswater.com

Kolltan PharmaceuticalsCancer therapeuticshttp://www.kolltan.com

Affomix (2008)Antibody screening technologyhttp://www.affomix.com

3PrimiRCancer diagnostics

New Haven PharmaceuticalsTherapeutics for depression andGI disordershttp://newhavenpharma.com

CardioPhotonicsMonitor for blood volume status

ExperimedPeptide drug discovery platform

OptherionTherapeutics and diagnostics for age-related macular degenerationhttp://www.optherion.com

Helix TherapeuticsGenetic repair therapieshttp://helixtherapeutics.com

Carigent Drug delivery technologyhttp://www.carigent.com

BioRelixAntibiotic discovery http://www.biorelix.com

JS GeneticsGenetic tests

CoolSpine LLCCooling cathether for use in cardiothoracic surgery

Vidus Ocular (now part of OPKO) Device to treat glaucoma http://www.opko.com

Vascular Insights LLCClariVein catheter for treating varicose veinshttp://vascularinsights.com

Ren PharmaceuticalsBiotherapeutic for renal diseasehttp://www.renpharma.com

Marinus PharmaceuticalsTherapeutics for psychiatric disordershttp://www.marinuspharma.com

Sonic GolfTraining device for golfhttp://www.sonicgolf.com

HistoRxQuantitative histopathology testing anddiagnosticshttp://www.historx.com

Applied Spine TechnologiesSpinal implant devicehttp://www.appliedspine.com

Access ScientificVascular access devicehttp://www.accessscientific.com

Yale’s 10 Highest Royalty Revenue

Generating Licenses*

D4T - Zerit® for HIVDrug$276.7 million

FTC — Emtriva® for Hepatitis BDrug $9.5 million

Modified Nucleotides:Preparation and use research reagent$ 7.5 million

Electrospray Mass SpectrographyMass spectrometry$7.5 million

Lyme Rx© Vaccine for Lyme diseaseVaccine$4.3 million

L-FMAU – Clevudine® for HBVDrug $4.2 million

Cloned Human Tissue FactorDiagnostic$3.1 million

Diagnostic of Genetic and Malignant DiseaseDiagnostic$2 million

“French in Action”Language instruction video/DVD(See related story, this page .)$1.5 million

X-PLOR Software $1.4 million

* As of 2008

Guiding Yale Innovations from the Laboratory to the Marketplace

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Cooperative Research was founded, Yale’sinterest in developing practical applicationsfrom basic research began to change, as didthe research environment in the Universityand the economic environment surround-ing the campus. When Richard Levin became Yale’s pres-

ident in 1993, he challenged the office toenergize the University’s role in buildingties with the private sector and supportingeconomic development. For example, Prusoff and a colleague dis-

covered that a compound called d4T waseffective against HIV, and the Universitypatented that use in 1988. The drug,licensed to Bristol-Myers Squibb and mar-keted as Zerit®, became an integral part ofthe widely prescribed “cocktail” to combatHIV/AIDS.

Yale now makes about $10 million to $20million each year in royalties from the com-mercialization of licensed patents, accordingto OCR. A chief area of growth has been biotech-

nology; more than 30 biotech companieshave sprung from Yale research, attractingmore than $1 billion in equity investmentsand employing hundreds of people in thegreater New Haven area.

Soderstrom says he envisions moregrowth in the long run, despite the eco-

nomic downturn. “In this economic climate,” he said, “you

need to keep your eyes on the future. Thenew ideas and intellectual property are theseeds of tomorrow’s economy and we haveproved that New Haven is fertile groundwhere new businesses can take root.”

Series Explores Challenges Faced by New VenturesThe leaders of local companies that are

using discoveries made in Yale laborato-ries to develop new life science technologiesdiscuss their ventures in the Yale-CUREBiohaven Entrepreneurship Series. Speakers come from the scientific and

business sides of the new enterprises. Pro-grams focus on key factors that drove thesuccess of each company, scientific or tech-nological advantages, business models andlessons learned in starting and developing a

business. The series also offers social net-working opportunities for scientists andresearchers in the Yale community.

Sponsors include: Yale Office of Cooper-ative Research, Connecticut United for

Research Excellence (CURE), Wiggin andDana LLP, Price Waterhouse Coopers andElm Street Ventures.To learn more about the series, visit

www.curenet.org.

8 YALE INNOVATORS

Twenty Years Later, ‘French in Action’ Still a Success

There’s nothing like learning a for-eign language when the words and

phrases can be heard and then repeatedin the context of a simple conversation. Yale innovator Pierre Capretz made

the most of this method when he created“French in Action” more than 20 yearsago as an in-house method for teachingFrench language and culture to Yaleundergraduates.Capretz, director of the Yale Lan-

guage Development Studio at Yale, useda series of continuing conversationsbetween an American student namedRobert and a young French womannamed Mireille to teach French tocountless Americans. The multimediaapproach to language teaching andlearning combines three complementarymedia — print, audio and visual images.“French in Action has been used by

over 2,000 colleges and universities inthe United States alone. Due to its suc-cess, it is one of the top-10 royalty rev-enue generating Yale licenses. (See box,this page.) The learning program alsoinspired a 52-episode “French inAction” PBS television series. The success of “French in Action” has

enabled Capretz to transform other cul-

tural materials into interactive language-learning products, such as an interactiveCD-ROM (pictured above), which isbased on the classic François Truffautfilm “Jules et Jim.”

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