YA L E I N N O V ATO R S

Their Inventions Today Are Shaping the World of Tomorrow

ranslating basic research into new technologies that advance our health and welfare has been part of Yales DNA for centuries, and the pace of innovation at the University continues to accelerate dramatically. Todays Yale inventors are helping to lead the way in science, medicine and engineering. With plans in place for new research institutes on the West Campus, Yale is on the cusp of becoming an even greater incubator of new ideas and methods for exploring key scientific questions. Supporting its faculty and student innovators, and helping to bring the fruits of their inventiveness to people around the world are important initiatives at Yale. Its Office of Cooperative Research is working to shepherd discoveries by Yale faculty to the marketplace through university-industry partnerships and start-up ventures, while the Yale Entrepreneurial Institute is helping student with ideas for unique products and services to launch their own businesses. This special section highlights some but by no means all of the Yale faculty whose research is helping to address important health and qualityof-life issues, and the students whose creative ideas are fueling new marketplace ventures.

To further new discover y, Yale has invested billions of dollars in new research facilities, such as the Center for Microelectronics Materials and Structures Clean Room (right) for building nano-devices.

Yale Discoveries Advancing Health And Welfare in the 21st Century

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

Repairing the Fabric of Thought With Drugs That De-Stress the Brain
As a Yale student during the American Revolution, David Bushnell designed and built the first combat submarine, an under water vessel dubbed The Turtle.

From the Submarine to the Artificial Heart, Invention Is a Centuries-Old Tradition at Yale
ales tradition of staking out the forefront of invention and innovation began with some of its earliest graduates and faculty. Dotted with water-powered mills and rich in craftsmen with mechanical skills clock and instrument makers, blacksmiths, iron workers, shipwrights and gunsmiths Connecticut was a center of the Industrial Revolution in the United States. So it was not surprising that Yale produced inventors and entrepreneurs who helped forge the new nations technological and scientific advances. David Bushnell, studying at Yale College, built the first combat submarine in 1775 during the Revolutionary War. His vessel, the Turtle, could move underwater but failed in its mission to attach a mine to a British warship in New York harbor.

early Americas most important figures in advancing industry through technology. Perhaps his greatest contribution was a developing a system of manufacturing that employed an assembly line, a concept later perfected by Henry Ford.

n the 19th century, Whitneys nephew, Eli Whitney Blake, perfected a stone-crushing machine for macadam roads. Blake, who graduated from Yale College in 1816, was inspired to create his invention when he observed workers breaking stone with a hammer while building a road near New Haven. He formed a company to produce the machines, and hundreds were in use by the late 1870s. This rock crusher became the model for similar machines now in
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s 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 plan ahead, make complex decisions, organize and multi-task. But under stress, the prefrontal cortex can malfunction as chemicals are unleashed, stopping cells from communicating properly 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 preventing the effects of stress or harmful genetic alterations. In recent years, she made key discoveries of substances for treatment of mental disorders involving this area of the brain. Shire Pharmaceuticals is developing Arnstens discovery of the use of guanfacine for treatment of attention-deficit hyperactivity disorder (commonly known as ADHD) and other similar disorders. The FDA has ruled Shires New Drug Application approvable, and the compound is undergoing final safety testing. Yales Office of Cooperative Research (see related story, page 8) is working with Arnsten
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University Programs Are Nurturing an Entrepreneurial Mindset in Students

ne of the best-known innovators who 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 creating the first cotton gin, a device to remove the seeds from cotton, a process that previously relied on manual labor. He received a patent in 1794. Whitney, who is less known for improving a system of interchangeable parts for making firearms, was one of

Yale chemistr y professor Sidney Altman (right) received a Nobel Prize in 1989 for his work as codiscoverer of RNAs role as a bio-catalyst.

n the past decade, Yale University has made a concerted effort to support student entrepreneurs. In both courses that deal with intricacies of business start-ups and organizations geared to support students with commercial ideas, the culture of entrepreneurship has taken deep root throughout the Yale community. Our faculty and students show a natural interest in, and inclination for, entrepreneurial development, which is very much in line with the nature of engineering, says T. Kyle Vanderlick, dean of the Yale School of Engineering and Applied Science (YEAS). We certainly understand the impor-

tance of supporting entrepreneurship, knowing that without it, some of the greatest technological advancements of our time would be sitting in a lab unused, adds Vanderlick. The YEAS course Creativity and New Product Development, for example, provides an overview of the stages of product development in a competitive marketplace by simulating the process in class. nother school where would-be entrepreneurs can learn the business of business is the Yale School of Management (SOM). Sharon M. Oster, dean of SOM and the Frederic D. Wolfe Professor of Man(Continued on page 7)

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to find a company to develop her discovery of the use of chelerythrine for treatment of schizophrenia, 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 mental hospital that housed thousands of patients. Medications available then were inadequate, and Arnsten saw a need for neuroscientific insights into crippling mental illnesses. There were only two psychiatrists on staff, one with a penchant for administering painful electro-convulsive therapy which today is still used to treat severe depression but has been improved so as to be painless. One day back then, Arnsten was having a lucid conversation about astronomy with Amy Arnstens experience in a New Jersey mental hosa patient who had been a physicist, when pital inspired her interest in understanding the effects of that doctors name came up. The comment stress on the brain. triggered an immediate negative response: The mans speech became disordered and incoherent, barely making sense. It was such a huge clue, Arnsten said, that stress can neuro-chemically alter the fabric of thought. It was a big clue in the treasure hunt thats become my career.

eral more potent derivatives. We were improving on nature if you will, he said. Proteosomes are the garbage disposals of cells. Crews research demonstrated that if you stop a cancer cell from getting rid of its waste, the cell kills itself. Thus cancer cells are more vulnerable to cell death when the proteosome is inhibited. The drug appears to be promising for treatment of relapsed cases of myeloma, a type of blood cancer. Cells that survive initial treatment can become resistant to front-line drugs. Its important, Crews said, for oncologists to have a plan B, or depth on the bench.

Craig Crews has discovered a promising treatment for cancers that have grown resistant to chemotherapy. His drug prevents cancer cells from disposing of their waste thus killing them.

Helping Golfers Perfect Their Game With the Sound of Swing

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Mining Ancient Chinese Remedies For Cutting-Edge Therapies

ut simply, Yung-chi Chengs work in pharmacology has had a profoundly positive effect on human health. He is one of Yales more prolific inventors, with several drug-related patents and applications that have been the basis for groundbreaking therapies to treat diseases 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 company is developing a drug invented by Cheng called elvucitabine, aimed at combating HIV/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 in Korea by Seoul-based Bukwang Pharmaceutical Company. Pharmasset Inc. is developing the drug for the U.S. market, and it is in phase III trials. Chengs research has long been on the cutting edge of pharmacology, but one of his latest pursuits is going back to the future way back. Hes created a botanical drug, PHY906, based on traditional Chinese herbal medicine. Its a formulation of four herbs that has been used to alleviate common stomach ailments for nearly 2,000 years. Along with Yale, Cheng cofounded Phytoceutica to develop Tommy Cheng has created a botanical drug, which is based on an such traditional Chinese mediancient Chinese remedy for stomach ailments, for use in reducing cines. Dr. Ed Chu, chief of medical oncology at Yale Cancer Centhe toxic effects of chemotherapy. ter, his colleagues and other universities are studying the clinical potential of PHY906 and other Chinese herbal medicines. 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 to enhance the therapeutic effects of a broad spectrum of anti-cancer treatments. Together with the National Cancer Institute, Chengs lab is exploring PHY906s mechanisms of action. The studies are essential not only for assessing PHY906 but are expected to establish a new paradigm for future drugs what Cheng calls poly-chemical medicine 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, arriving from Brown in the early 1970s to start postdoctoral work, because pharmacologist William Prusoff was here (see related story, page 3). Cheng says he considers Prusoff a giant in the field, and his role model.

either of Bob Grobers parents were into golf, but he took to the game as a boy and has been swinging a club ever since. Hes 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 Id 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 a company 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. Thats turned out to be profound. The musical biofeedback allows golfers to hear and simultaneously feel what a good swing is like in a way thats not possible from watching videos. That traditional method of instruction tends to be static, point to point, as instructor and student break the swing down and analyze its components. Several pro golfers and instructors are singing the praises of Sonic Golf. Vijay Singh got one An avid golfer himself, Bob Grober has created a golf club that gives last June from one of Grobers friends and went on to win several audio feedback to players that tells them when their swing is smooth and rhythmic. His Sonice Golf system has been used by pros. tournaments. Singh says the invention has helped him tremendously by making his swing a lot more consistent. His version allows him to choose a musical tone from among 10 different instruments. The rock organ is Grobers favorite. The Yale golf teams were given a Sonic Golf system, and theyve 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, he said. Now hes a professor, inventor and entrepreneur.

Tapping the Genetic Code To Predict Blindness and Other Diseases

Turning Natures Garbage Disposals Into Promising Cancer Treatments

ne persons castoff is anothers treasure. Thats certainly true for Craig Crews and his research 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 toward FDA 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 drug screens but werent pursued as pharmaceuticals because firms couldnt figure out how they work. Not knowing the mechanism of action, the government wont approve them because unforeseen drug interactions could spell problems. Crews studies these small molecules, not necessarily to find new drugs but to understand 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-

osephine Hoh set out to find the genes that predispose people to age-related macular degeneration, the leading cause of blindness in the elderly in the United States and an ailment 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 study technique for many other common diseases hypertension, diabetes, schizophrenia and heart disease among them. In 2005, just two years after arriving at Yale, she identified DNA variants in Complement Factor H, as well as variants in other genes as major risk factors for developing age-related macular degeneration. Yale has filed patents on these inventions and has worked with a local entrepreneur, David Scheer, to launch Optherion (www. optherion.com), a New Havenbased biotechnology firm that seeks to develop both therapies and diagnostics for age-related macular degeneration. Hoh prefers to focus on her own research and is not involved in the management of the company. Once judged a fishing expedition, the method devised by An associate professor in the Josephine Hoh to more efficiently identify genes linked with diseases Yale School of Public Health,
was hailed as one of the top 10 science breakthroughs in 2005.
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Hoh brings to her research not only her talents as a numbers-crunching statistician and visionary geneticist, but a never-give-up attitude. Rejected initially for funding by the National Institutes of Health because her proposal was judged a fishing expedition and over-ambitious she convinced the Raymond and Beverly Sackler Foundation for Arts and Sciences to support her work. Since she and her colleagues published their groundbreaking findings in Science magazine in April 2005, the article has been cited by other scientists hundreds of times. The journal recognized her research as one of the top 10 scientific breakthroughs of the year.

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 was great training for a future engineer, he said, but after the Navy and pre-med studies at the community college in California, he was ready for something totally different when he transferred to Yale as a junior. He majored in theater studies and thought hed be a writer. He still wanted to pursue forward osmosis even though he wasnt studying engineering, he said, and was overjoyed when the Yale College Deans Office came up with funding. By the time he received his bachelors degree in 2002, he had worked out the basic principles. He expects to receive his Ph.D this spring, and plans to work for Oasys.

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

hen you buy a laptop, you get to decide how much memory to pack into your computer. The same kind of memory, known as DRAM (dynamic random access memory), 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 storage capacitor 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 inventions is an improved DRAM that major corporations see as a promising technology to solve this problem. His invention eliminated the need for a storage capacitor; its built into the transistor, thus solving the space problem. It also dramatically increases the intervals between which the memory has to be refreshed another major advance. Yale has patented the technology, and Ma expects it will be a couple of years before it arrives on the market. Several major companies are talking to us and will want to do some prototyping, he said. What we have done on the university scale they will want to do on the demonstration scale, for production. Ma has served as principal The pioneering work done by T.P. Ma has helped revolutionize how diginvestigator on joint research and development projects with ital devices such as cell phones, computers, cameras and iPods store and erase data. numerous companies. They include Motorola, General Electric, Hughes, Rockwell, Phillips, Siemens, Hitachi, Toshiba, Mitsubishi, Intel and IBM, where Ma worked for three years after receiving his Yale doctorate. His students have 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 required military 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, Yale became his first choice, quipped Ma. At Yale, Mas 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 states highest honor for technological achievement. In bestowing the award, the chair of the board of governors of higher education said its not often that basic academic research leads to widespread applications: But the next time you answer your cell phone, take a digital picture, or tune into your iPod, know that its flash memory is in large part made possible by the pioneering work of T.P. Ma.

Forging a Potent Weapon In the Battle Against HIV/AIDS

potent 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 the late 1980s. The compound, Prusoff explains, was first synthesized by Dr. Jerome Horwitz in 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 itself into HIVs DNA and shutting down the reproductive mechanism. Yale licensed the discovery to Bristol-Myers Squibb, which began selling Zerit in 1994. (See related story, page 8.) Under pressure to make it available to poor patients in Africa, the company agreed in a landmark 2001 decision to offer it at no profit in sub-Saharan Africa. Zerit became an essential part of a widely prescribed antiHIV cocktail, and has earned While William Prusoff is best known for his work on the drug Yale, Lin and Prusoff millions of Zerit, part of the anti-HIV cocktail, he also led the research that dollars in royalties. But Prusoff, who is professor emeritus of phar- led to the first-ever antiviral compound approved by the FDA . 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 satisfaction was that his discoveries helped people. Its a terrific kick for ones ego, he said. Dr. Lin and I got tremendous satisfaction from knowing that what we had produced was of benefit 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 the FDA. Called idoxurine, its 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 hes simply been lucky to pursue his passion for more than 50 years. I dont consider it work, he said. My work is my hobby. At 88, hes semi-retired, but still trying to come up with improved antiviral compounds. He continues to study the complexities of thymidine, the molecule thats been his lifelong interest. They prolong life, he said of antiviral compounds for HIV, but theyre not cures. We still need a cure for AIDS.

Halting Tumors Growth by Targeting Their Achilles Heel

Harnessing the Power of Osmosis To Create Clean Water Affordably

ob 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 worlds growing need for affordable clean water. McGinnis, now a Yale doctoral student in environmental engineering, and his adviser, Professor Menachem Elimelech, have designed systems that harness the power of osmosis to produce freshwater from seawater or industrial waste water using a 10th of the energy needed in conventional desalination systems that rely on reverse osmosis. The new technology employs forward osmosis, which exploits the natural diffusion of water through a membrane. The process draws pure water from its contaminants to a solution of A new technology developed by graduate student Rob McGinnis salts that can be removed easily (left) and Professor Menachem Elimelech uses for ward osmosis with low heat treatment effecto produce clean water with very little energy. tively desalinating or decontaminating water with little energy input. Yale, which funded the research, has filed for patents on the technology and is commercializing 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 customers location. In addition, the researchers say its 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

oseph Schlessinger is one of the worlds leading cellular biologists and cancer-treatment inventors. 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 of cancer research, producing a new class of targeted anti-cancer drugs multi-kinase inhibitors 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 the FDA 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 have escaped 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 related story, page 8.) Kolltan is developing monoclonal antibodies against various cancers that the company hopes to move rapidly into human clinical trials toward FDA approval. Schlessingers latest breakthroughs were the result of painstaking research into cellular signals that switch on the growth of tumors and how to stop that growth. When you really understand how these receptors work, you can find new Achilles heels that you can use in order to block activity in cancer and other diseases, he said. By targeting these sites, drugs can block receptors and overcome resistance that develops when patients undergo lengthy treatment with current cancer drugs. Schlessinger, who has turned down offers to run drug companies, savors the freedom of academia. I think you have to use your Joseph Schlessinger has pursued many novel approaches to treatimagination and come up with ing cancer most recently, by focusing on blocking the signals that
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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 the very end of World War II, his parents were Jewish partisans fighting the Nazis. Many of his 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 Israels elite Golani brigade, laying or removing mines in the 1967 Six-Day War, the 1973 Yom Kippur War and the 1982 invasion of Lebanon.

U.S. hospitals alone. By illuminating the ribosomal subunits structure, the researchers were able to view the mechanism of action of the antibiotics from a closer vantage point. What we were able to do is find how several dozen antibiotics bind to the ribosome, Steitz said. Without the structure, you wouldnt 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. Its the largest machine in the cell. Their research showed that the RNA part of the ribosome is the catalytic component, Steitz said, and that has evolutionary implications, because it showed 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.

Creating a Quantum Computer, One Artificial Atom at a Time

Using a Microchip To Analyze The Blueprint of Proteins

obert 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 huge amounts of information unimaginably quickly and in spaces that are almost inconceivably small visible only with an electron microscope. The two applied physics professors are among an elite group of experimentalists, working at the level of single microwave photons, tiny packets of light energy. Schoelkopf is a former NASA engineer who earned his doctorate at Caltech, and Devoret was a director of research at the French Atomic Energy Commission before moving to Yale. Devoret is also a member of the prestigious College de France. At Yale, Schoelkopf and Devoret are combining novel new designs for superconducting artificial atoms with tiny superconducting cavities to create electrical circuits that realize microwave quantum optics on a chip, said Steven Girvin, a Yale theoretical physicist who collaboMichel Devoret (left) and Robert Schoelkopf have created artificial rates on their project. atoms for use in quantum computer,s which will be able to store vast The two scientists have manamounts of information in microscopic spaces. aged to squeeze the tiny photons into ultra small cavities on a chip, akin to a regular computer microchip. Theyve also squeezed artificial atoms that can act as quantum bits units to process and store quantum information into the ultra small cavities. The tiny packets of energy from the microwaves interact with these small atoms a million times more strongly than if the atoms had 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 someday the 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 simultaneously 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 national security purposes, such as cryptanalysis. If quantum computers can be built, Girvin said, they can very efficiently break certain types of codes.

he word protein comes from the Greek word for primary. Indeed, proteins are vital to living organisms, as they take part in every process within cells. Michael Snyder, who won the 2007 Connecticut Medal of Science, the states highest honor for scientific achievement, has earned a reputation as one of the worlds leading pioneers in the study of proteins. In several pivotal studies, Snyder and his team demonstrated that it was possible to analyze 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 to specific sequences of DNA, thereby controlling the transfer of genetic information from DNA to RNA. Transcription factors read and interpret the genetic blueprint in the DNA, and regulate gene expression. By controlling gene expression, transcription factors control the identity 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 a California-based firm, Invitrogen, now called Life Technologies. Snyder has used this microchip to study how proteins work and how they are regulated. Most recently, he has applied this technology to try to identify early markers for ovarian cancer, a leading cause of death for many women, as it is often diagnosed when the disease is quite advanced. His laboratory has found that patients with ovarian cancer often have antibodies directed to certain proteins. The researchers hope that this might someday be Michael Snyder led a Yale team that created the first microchip able used in a test for the disease. to analyze all yeast proteins allowing research on a previously Recently, Snyder also has unprecedented scale. focused research on human embryonic stem cells. He and his team discovered a novel signaling pathway that is essential for the self-renewal of embryonic stem cells. They then used the information to create one of the first media for cell growth that is free of any non-human animal components, a step that is very important to the future use of human embryonic stem cells for therapy.

Eliminating the Guesswork in Developing More Effective Antibiotics

hen first developed, antibiotics were hailed as godsends, treating infections by inhibiting biological processes including jamming the machinery that makes proteins in bacterial cells. Problems have arisen, however, as resistance to the widely prescribed drugs has grown dramatically. The work of two Yale professors Thomas Steitz in molecular biophysics and biochemistry and Peter Moore in chemistry initially had nothing to do with the design of new drugs. Their seminal studies illuminated the basic structure of the ribosome, the protein-making machinery in all cells. In particular, Steitz and Research into the structure of ribosomes by Thomas Steitz (left) and Moore detailed the structure of Peter Moore has led to the development of antibiotics that are effecthe larger of two parts of the ribotive against resistent strains of bacteria. some, the 50S subunit. That ribosomal subunit also happens to be a major target of antibiotics. Their discoveries have led to a novel approach to the design of new classes of antibiotics active against resistant strains of bacteria. In a nutshell, these drugs hit and bind to the target better than the 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-X has 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 Staphylococcus aureus, or MRSA, a particularly tough bacteria that kills 19,000 people each year in

Unleashing the Power of Nature To Further Genetic Research

utant mice sounds like the title of a B-movie. Multiply them by tens of thousands, and youve got a mutant mouse factory. Thats exactly what geneticist Tian Xu has established, and when he talks about his mice he might as well be referring to the Oscars: In his ambitious vision, he sees medical research gold. Early in life, Xu escaped the repression of the Chinese Cultural Revolution and ultimately landed in New Haven. He now runs genetics labs at Yale and at his Chinese alma mater, 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 the first functional map of the mammalian genome. It will, he said, greatly advance our understanding of human biology and disease and our ability to develop new diagnostics and therapeutics. His innovation is on an epic scale: He intends to produce a million mutant mice in the YaleFudan facility in China to come up with 100,000 new strains of mice, each with a disrupted gene or genetic element. Xu unleashed the power of nature and engineered a piece of moth DNA called the piggyBac transposon to become a jumping gene in the mouse. This gene makes the mouse a mutant Tian Xu leads research teams at Fudan University in Shanghai factory. When the animal breeds,
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(background, left) and at Yale University (right). His genetically engineered mice will someday help researchers studying diseases.

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the modified transposon causes random genetic mutations in the mouses offspring one gene per mouse is disabled. Making experimental mice this way is much quicker and less expensive than current methods, said Xu. More than 99% of mouse genes have counterparts in humans, so these mice will provide the first glimpse of the functions of many of our genes, most of which remain mysteries 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 these diseases in mice, you can go up stream to humans and verify, he said. Then you have a diagnostic base and the animal model and target for studying disease mechanisms and for developing therapeutics.

Tuning Up the Internet To Make It Run Smoother and Faster

f youve ever been frustrated at how long it takes to download something from the Internet, 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 hasnt changed since its beginnings 40 years ago, they explain. The goals then were modest: Connect some military installations and a handful of universities, mostly for electronic mail traffic and terminal 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 software (or P2Ps) are not working cooperatively enough to ensure smooth, rapid flow of information, said the Yale scientists. Information exchange schemes among the users are inefficient and costly, like dialing long distance to call a neighbor, they note. In recent tests on some of the largest ISPs, the Internet architecture engineered by the Yale team has produced significant speed boosts for P2P information Internet providers that use the P4P system created by computer sci- transfer for example, an entists Avi Silberschatz (left) and Y. Richard Yang have experienced 80% speed increase for Comcast customers. up to an 80% increase in speed for their customers. The Yale teams innovation, P4P, which stands for provider portal for P2P applications, has the potential to reduce costs for ISPs while also improving performance of P2Ps. It works by allowing seamless communications between the two. Yale is actively working with a variety of partners to make the system an Internet standard. 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, the innovation will be ubiquitous yet invisible to end users. It will be like a car humming much better, without you knowing exactly what theyve done in the engine to make it run better, Silberschatz said. If we manage to have P4P under the hood in most of the Internet applications, well be more than delighted, he said. Well consider it a huge success.

Looking to the Future: Promising Research on the Horizon

Every day brings Yale researchers closer to new breakthroughs in medicine, science and engineering. The following is a brief look at some of the Yale scientists whose discoveries may soon yield treatments and products for people around the world.
New Class of Antibiotics

cal activity in organisms. His lab has studied how stem cells renew themselves in sex cells, and his work on various socalled small RNAs has many medical applications.
Improved Vaccines

covered a potential diagnostic test to pinpoint genetic biomarkers to help identify those individuals who are most predisposed to lung cancer, ovarian cancer and other types of the disease.
Spinal Cord Injury Treatment

Ron Breaker, professor of molecular, cellular and developmental biology, and professor of biophysiology and biochemistry: After imagining and inventing riboswitches, RNA sequences that can bind and act as sensors in various molecules, Breaker discovered natural riboswitches in the genomes of microorganisms. Riboswitches act as major control elements for gene expression. Yale startup BioRelix was established to use these genetic elements for designing a new class of antibiotics.
Genome Analysis for Brain Aneurysm

Ruslan Medzhitov, professor of immunobiology: The focus of Medzhitovs research is the innate immune system, which alerts the host to infectious assaults and triggers a cascade of responses known as the adaptive immune response that is the basis for vaccine activity. Improved vaccines could be developed by introducing the immune system with disease antigens that are physically linked to particular polypeptide activators of the innate immune response. A Yale startup, VaxInnate, is developing a high-throughput screening platform to identify these activators.
Amorphous Metals

Stephen Strittmatter, professor of neurology: Strittmatter helped discover the existence of a molecule, called Nogo, that shows incredible promise in animal models for treating spinal cord injury, for which there is no current effective treatment.
New Class of Semiconductors

Dr. Richard Lifton, chair of genetics, professor of medicine and of molecular biophysics and biochemistry: Lifton is one of the worlds leading advocates of genome-wide analysis of human populations to find genetic links to diseases. For example, Yale neurobiologist Dr. Murat Gunel and Lifton recently discovered a genetic link to brain aneurysms, and their findings could lead to new tests to spot those at greatest risk.
RNA Snippets and Stem Cells

Jan Schroers, professor of mechanical engineering: Schroers and his team have been exploring a class of materials called amorphous metals or bulk metallic glasses, BMGs, that can be molded like plastics and are more durable than silicon or steel. He has created a process for making computer chips at the nano-scale that may revolutionize such production by exploiting these novel metals.
Biomarkers for Disease Risk

Hong Tang, professor of mechanical engineering and electrical engineering: While the force of light is too weak to be used to power devices in everyday use, he and his engineering team have found that it can be harnessed to drive machines when scaled to nano-proportions. This research is opening the door to a future new class of semiconductor devices operated by the force of light.
Electrodes To Predict Epileptic Seizure

Haifan Lin, director of Yales Stem Cell Research Center: Lin is among the worlds leading investigators of how tiny snippets of RNA can have profound effects on physiologi-

Frank Slack, professor of molecular, cellular & developmental biology, and Joanne Weidhaas, professor of therapeutic radiology: The Yale Cancer Center researchers dis-

Hitten Zaveri, associate research scientist in neurology, and Dr. Dennis Spencer, chair and the Harvey and Kate Cushing Professor of Neurosurgery: These two scientists are creating wireless electrodes for detecting epilepsy and more accurate ways of measuring epileptic seizure onset. Spencer pioneered new surgical treatments for the disorder that have been adopted by medical centers around the world.

Yales West Campus Will Enable Research To Advance at Unprecedented Pace

ale College and the Universitys graduate and professional schools are already home to more than 800 science, math and engineering labs. But Yales science research footprint is about to grow much larger. Two years ago, the University acquired a 136-acre pharmaceutical research park, located on the border of the neighboring communities of West Haven and Orange, Connecticut. The West Campus includes more than 500,000 square feet of research laboratories, which will eventually house five interdisciplinary institutes that will share core facilities. Yale is already in the midst of a boom in the expansion of its science and medical facilities, said Yale President Richard C. Levin, when announcing the Universitys acquisition of the West Campus space. The addition of this ready-made, state-ofthe-art research space will allow that growth to accelerate at an unprecedented level potentially making it possible for Yale scientists to develop new discoveries, inventions and cures years earlier, he added.

YALE INNOVATORS

Increasingly, Yale Students Launching Their Own Companies

I
n the past year, Yale senior Henry Finkelstein explored career opportunities with large 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 Campus Kings, which this spring will sell canvas walking shoes and aesthetic basketball shoes that carry the Yale logo and an image of Harkness Hall floating safely encased between the shoes inner and outer soles. Finkelsteins decision to become an entrepreneur was born of both a personal passion and a poor business climate, which in many ways, he says, made his decision to help launch a business much easier. Despite an academic and professional resume that included an internship at a top management consulting firm in San Francisco, Finkelstein attracted little interest from companies that a few years earlier were offering large salaries and incentives for Yale graduates to join their firms.

dents commercial ambitions may get a nudge in classes that explore the nuances of business start-ups. Sometimes their ideas are nurtured within student entrepreneurial support groups. If students are ready to launch a company, they can get help from the Yale Entrepreneurial Institute (YEI), which was launched by Yale more than two years ago to keep promising student-generated companies in New Haven.

nd sometimes, the impetus comes from a dismal economy. It used to be the plan was to get the internship at the investment bank because that leads to a job after graduation, says Shana Schneider, deputy director of YEI. Now the conversation I hear is that, I dont have to go that way any more, I can work on my business idea now and work on my business after graduation. More students are seeing Frustrated at the tight job market, student and skateboarder Henry Finkelstein joined with his friends to launch Camthose options on a par, now that one is not pus Kings, which manufactures shoes bearing the Yale name or the logo. This is one of their prototypes. a 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 for nstead, he and three friends approached Yale about the project and then closed a deal to its summer program, where students stay on campus to work on business ideas. At least a half dozen of those students had planned to pursue careers in corporate America. The stumanufacture Yale-branded shoes made in China thus, Campus Kings was born. (See dent-run Yale Entrepreneurial Society (YES) this year has also seen an increase in numbers company profile, below.) They are now negotiating a licensing agreement with Yale. of applications for its annual contest, as well. Im not stupid. I read the papers and hear what venture capitalists are saying, that the Alina Wang, a Yale College junior and incoming president of YES, is hearing the same river has dried up, says Finkelstein, a skateboarder who hails from San Diego. But that story from her peers as Schneider.Being an entrepreneur means more than starting a just made this decision easier to make. I dont have the same choices any more. I dont business, it is an attitude you can bring to school, to life, says Wang. It is an action-orihave as much to lose. ented state of mind. Yale is seeing a sharp uptick in students launching similar ventures. Sometimes a stu-

Student Ventures Making a Mark on the Marketplace

The following are among the many student-run businesses that have taken launch with the aid of the Yale Entrepreneurial Institute (YEI). nology to the military and commercial aviation. Its a system to monitor turbine vibration, meant to increase turbine efficiency and reduce maintenance costs.

Campus Groups Help Unite and Support Business-Minded Students

Yale has a diverse group of organizations dedicated to helping students who want to learn more about the world of business or to start their own ventures. These include the following:

Using Behavioral Science To Promote Good Causes

Both of Emily Yudofskys parents are psychiatrists, so her interest in behavioral science is no surprise. The Yale College junior started a neuromarketing company, Applied Resonance Research, and plans to specialize in research that involves public service advertising and non-profit organizations ad campaigns. In high school, Yudofsky participated in research of personality disorders while a study of neuroimaging and branding was under way. Regions of the brain were activated when consumers were exposed to Coke images but dormant for Pepsi images. Now she wants to use that kind of knowledge to help create smoking-cessation or anti-drunk driving campaigns that make a difference. She launched her firm through the YEI Summer Fellowship Program.

Turning Electronic Recyclables Into Cash

Rich Littlehale and Bob Casey had a bunch of old electronics and no easy way to recycle them. While the devices were no longer of any use to them, they thought the items could still be worth money. So the two Yale College juniors hit on the idea of a website to enable people to get paid 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 and providing credit card information. On YouRenew.com, consumers search for their kind of device, answer a few questions about its condition and receive an offer price. If they accept, customers complete the transaction through a quick checkout process and get a free shipping label for sending the device. Users can be paid by check or 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.

Yale Entrepreneurial Institute (YEI): Founded by the University in 2006, the YEI helps undergraduate and graduate students start new ventures. Yale was one of the first universities in the country to launch such an institute, and since its inception as a crash summer program, YEI has grown into a year-round University department that acts as a base for entrepreneurship on campus, with events that serve the interests of students and the New Haven community. (http://www.yale.edu/yei) Yale Entrepreneurial Society (YES): Now celebrating its
10th anniversary, YES is run by students who offer educational and networking opportunities to foster new venture creation and economic development. YES organizes campus and regional events and conferences to encourage entrepreneurship at Yale and in the community. It also sponsors the Y50K competition, in which top business leaders evaluate student business plans competing for $50,000 in venture capital money. (http://yesatyale.org)

Monitoring Glaucoma Via an Eye Implant

The standard monitoring of people suffering from glaucoma, a leading cause of blindness, relies on outdated devices that provide only a momentary snapshot of the patients 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 YEI to obtain a patent for a monitor that would be painlessly implanted in the eye to measure intra-ocular pressure, a key metric for devising more effective, individually-tailored therapies.The Yale student-startup expects to have a prototype device by the end of the year.

Taking Cyberspace Advertising to the Next Level

A group of Yale and Harvard students founded a company called PaperG as a sort of virtual bulletin board for local online advertisements. Businesses can place their poster-sized flyers on PaperGs Flyerboard, which converts them into interactive ads with features including e-mail-sharing, social networking and online maps. The company led by Victor Cheng 08, Ka Mo Lau 08 and Victor Wong 10 moved into the YEIs Incubator Space last year and raised venture capital.

School of Management (SOM) Entrepreneurship Club: 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 entrepreneurial affairs both within the SOM community and beyond.

Ringing In the New Day With More Energy

Arun Gupta first thought of inventing a way to wake up at just the right time while attending high school, when he was alert some days and groggy on others. He learned that those who wake during REM sleep were more likely to start the day feeling energetic. The Yale College student and a partner from Boston College developed a wristband that monitors hand movements during sleep and relays the information via Bluetooth to a cell phone alarm. The alarm will sound during the optimal REM-sleep time in a 20-minute window. The business plan and prototype were developed during YEIs Summer Fellowship Program.

(http://students.som.yale.edu/sigs/entrepreneurship)
Yale Biotechnology and Pharmaceutical Society (YBPS): The YBPS is a University-based organization that
links people and groups in the Yale-New Haven community and beyond with an interest in biotechnology and pharmaceuticals. The group was founded in 1997 by a team of business and graduate students; it has over 1,200 members and coordinates a plethora of biotechnology- and pharmaceuticalrelated activities in the Yale-New Haven community and beyond. (http://www.yale.edu/ybps)

Putting Your Foot Where Your School Spirit Is

Tim Kau 09 and Christopher Chau 10 were in a Hong Kong market filled with American goods during the summer of 2008 and thought a Yale-branded shoe would surely sell well. The idea has taken hold, and the two students are in the process of negotiating an agreement with Yale licensing staff and a Chinese shoe manufacturer to make a canvas walking shoe and a more high-tech style basketball shoe. Besides the Yale logo, the shoes are expected to feature an image of Harkness Hall embossed between the clear insole and outsole. The partners who include marketing director Henry Finkelstein 09 and chief executive officer Stephen Cammock 09 are taking the idea to the licensing offices of other Ivy League institutions such as Harvard.When they visit China again in a few years, Kau and Chau hope to see the Campus King Yale brand on the feet of passers-by.

Yale Law & Business Society (YLBS): An organization

dedicated to promoting the interaction between law, policy and business, YLBS serves as a center for members of the Law School community who are interested in business issues, including those affecting business startups. (http://www. law.yale.edu/stuorgs/ylbs.htm)

Reducing Bad Vibrations in Turbines

Yulee Newsome, a Yale School of Management student who previously was a nuclear engineer on a Navy submarine, founded a company that expects to market its tech-

YALE INNOVATORS

Medical Students Desire To Boost Study Habits Spawns Interactive Learning System

lliot James Rapp does not have a photographic memory a quality that might have come in handy in 2006, his first year as a Yale medical student, when he was looking for ways to learn the difference between the pons and the medulla oblongata and thousands of other medical facts. Fortunately for himself and, ultimately, for the Yale School of Medicine, what Rapp does have is a skill for programming. The former Microsoft software engineer has developed a new interactive program that is already being used by medical school students to learn about the wonders and complexity of the human body in new and collaborative ways. On April 22, Rapps concept was recognized as best business plan in the Yale IDEA (Innovation in Digital Environments Award) competition, a new contest designed to support new talent and new digital projects within the Yale community. Rapp, now 30, began his first career at an enterprise software company in Austin, Texas, and later went to work for Microsoft where he helped develop their advanced Web services 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 product is being used for, Rapp says. hile he loved Yales open learning policy, which emphasizes learning for the sake of learning over tests and examinations, Rapp was frustrated by what he saw as inefficiencies in the learning process and how little medical students interacted in their study habits. In 2007, he developed a desktop application called LiKiRi (Learn It, Know It, Recall It) Knowledge. The program encourages students to take notes in a format that allows them to test their own progress. It also identifies areas where they are weak and encourages collaboration and sharing among classmates. Heres an example of how it works, explains Rapp: He and

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 the application. I knew if I spent hundreds of hours creating a program for myself I would want other students to use it as well, he says. The program has improved considerably with several version releases over the last two years, Rapp notes. In addition, it now has a companion web application called LiKiRi Commons. Users with an account at LiKiRi Commons are able to access their LiKiRi Knowledge notes from any location at any time. If they wish, they can also establish sharing and collaborative preferences. These specify who has access to their learning material be it their study partners, friends, classmates or even complete strangers.

I
Elliot James Rapp had a career as a computer programmer before becoming a student at the Yale School of Medicine, where he developed the LiKiRi interactive learning program. The system is being adapted for the broader educational market.

three other students formed a study group to solidify their knowledge of human anatomy after the first year of medical school. They each created LiKiRi notes on their region of the body and then presented the information to the other members of the group using the application. At the end, they each had a knowledge base that covered the entire body. Furthermore, LiKiRi Knowledge allowed them to test their reten-

n between developing products and undertaking a rigorous medical school curriculum, Rapp has developed plans to bring the LiKiRi Learning System to other schools. The system is applicable not only to medical school students, but all learning environments, he believes. Having seen the current version of LiKiRi, we were immediately struck by the opportunity to scale the platform, says James G. Boyle, director of Yale the Entrepreneurial Institute, a University-operated agency dedicated to helping students create their own businesses. (See related story, page 6.) Id go as far as saying that it could be a disruptive technology [i.e., an unexpected technological innovation] for the education sector. Ten years from now I see LiKiRi Learning as a platform that provides students one place to store and access their knowledge no matter if the content is self-generated or provided by teachers, classmates or publishing companies, Rapp says. They will be able to create, modify and review this knowledge much more efficiently than is possible with todays tools. Schools will put entire curriculums into LiKiRi.

Yales Tradition of Invention (Continued from page 1)

use around the world. Yale became an early center for science education in the 19th century, thanks to a string of pioneering professors who drew some of the brightest science students of the day to the University. In 1804 the Yale Corporation gave Professor Benjamin Silliman a years leave to study chemistry and geology in Europe and $10,000, a princely sum at the time, to purchase books and scientific equipment to bring back to Yale. Silliman taught chemistry and natural history for 51 years, and is now recognized as a father of American science. professor of mathematical physics in 1871, the first such professorship in the country, and he held that post nearly until his death in 1903. He was the countrys premier scientific intellect at the end of the 19th century, and helped to build Yales reputation for science achievement. In the 20th century, other Yale graduates and faculty made transformative scientific discoveries and technological advances. For example: Lee DeForest, who earned a bachelors degree in 1896 and a Ph.D in 1899, was a pioneer in radio waves and was considered a Father of the Electronic Age. As an undergraduate, he tapped into the Universitys electrical system and blacked out the campus. In 1906, he invented the triode, or Audion, radio vacuum tube, which allowed for amplification for radio reception. Two years later, for the French war ministry, he demonstrated a system of wireless telephony from the Eiffel Tower. In 1910, he broadcast the first Live from the Met opera performance, featuring Enrico Caruso. Public receivers were set up in New York, Jersey City and Bridgeport, because no one yet had a radio. Yale School of Medicine student William H. Sewell Jr. in 1949 built a mechanical pump to reroute blood flow to and from the heart using parts of a childs

Entrepreneurial Minds
(Continued from page 1)

ne of Sillimans students, James Dwight Dana, became one of the most important geologists and naturalists of the century. He served as a scientist on the Wilkes Expedition, the first great American voyage of exploration in the Pacific. His work 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 persuade Josiah Willard Gibbs, one of the countrys most renowned scientists, from leaving Yale for Johns Hopkins when the latter was founded. Gibbs earned the first engineering doctorate in the United States in 1863. His insights into thermodynamics revolutionized the field. He was appointed

Benjamin Silliman, who taught chemistr y and natural history at Yale for over half a centur y, is widely recognized as one of the fathers of American science.

The cotton gin was invented by Yale alumnus Eli Whitney, who also developed a revolutionary system of manufacturing that is now employed by industries throughout the world.

Erector Set the kind of building toy he played with as a boy (and which, incidentally, was the brainchild of Yale alumnus A.C. Gilbert 09 M.D.). Sewell graduated with the Class of 1950 and won the coveted thesis prize for his work. Today the pump, the forerunner of the artificial heart, is displayed at the Smithsonian Institution Joshua Lederberg, who earned a Yale Ph.D. in 1948, became one of the centurys leading scientists. His work in bacterial genetics had important medical implications and led to his sharing the Nobel Prize for Medicine in 1958. His work at Stanford University with Edward Tatum and George Beadle the discovery that genes regulate specific chemical processes made him one of the youngest Nobelists. He helped lay the foundations for todays biotechnology revolution. Sidney Altman, now a Sterling Professor of Chemistry at Yale, shared the Nobel Prize in chemistry with Thomas Cech of the University of Colorado in 1989, for what the committee called one of the two most important and outstanding discoveries in the biological sciences in the past 40 years. They discovered that RNA, in addition to serving as the transmitter of genetic information inscribed in DNA, could also serve as an enzyme, or bio-catalyst. This ability was previously believed to reside solely in proteins. RNA thus can possess, in a single molecule, two of lifes most fundamental chemical capabilities. Cech coined the word ribozyme to describe all-RNA enzymes.

agement and Entrepreneurship, says the heads of large corporations are in as much need of entrepreneurial skills as those of young start-up companies. The abilities to think creatively and articulate a vision, to advocate for a product or a point of view, to develop a business case and a funding strategy, and to work effectively with a variety of constituencies are all part of the entrepreneurial mindset, she notes. In addition to holding workshops for business executives from around the world, SOM courses offers students opportunities to learn-by-doing by tackling real-world problems in their classes. One course, Global Social Entrepreneurship, offers a little of both. The class brings social entrepreneurs and mission-driven entrepreneurs from around the world, who work with Yale faculty and students in the class to address a specific problem in their organizations. In its first year, the course focused on leaders of non-governmental organizations (NGOs) from India. lobal Social Enterprise (GSE), a student club that evolved to include a for-credit course, is another unique offering at SOM. Founded in 2004, GSE allows students to put their classroom knowledge to practical use and gain handson experience in the areas of international development and social enterprise. During the 2009 spring break trip, GSE participants worked in small groups to provide pro bono consulting services to private and non-profit social enterprises in Thailand.

M O R E I NN OVAT I O N
For information o n futu re gro undbre aking disc over ies by Yale researchers, visit the we bsite at:

http://innovators.yale.edu

YALE INNOVATORS

Guiding Yale Innovations from the Laboratory to the Marketplace

At the Office of Cooperative Research

ince its founding 27 years ago, Yales Office of Cooperative Research (OCR) has built a significant portfolio of inventions and patents and has grown into an engine of regional economic development. Its mission is to facilitate the translation of research from Yales labs into products and services that benefit society. Dozens of companies have been started with Yale research as their foundation. In New Haven alone, about 30 companies have sprouted from Yale innovations. Located at the foot of Science Hill on Temple Street, OCR is recognized as a leading force for catalyzing economic growth by identifying, counseling and nurturing early stage technologies and guiding the transition into robust companies. As managing director of the office for the past 10 years, Jon Soderstrom has presided over numerous marriages between Yale inventions and private investments. In that time, the office has helped in the formation of about 40 companies that have collectively attracted more than $450 million in venture capital financing.

New Ventures Using Yale Technology

In the past five years, the Office of Cooperative Research has helped launch 21 new companies to commercialize technologies discovered in Yale laboratories. These are the companies, their product and their websites (where available): OASYS Water Cleantech for seawater desalination http://www.oasyswater.com Kolltan Pharmaceuticals Cancer therapeutics http://www.kolltan.com Affomix (2008) Antibody screening technology http://www.affomix.com
Jon Soderstrom (left), director of the Office of Cooperative Research, discusses a pending Yale patent with Denny Kalenzaga, director of finance and administration for OCR.

3PrimiR Cancer diagnostics New Haven Pharmaceuticals Therapeutics for depression and GI disorders http://newhavenpharma.com CardioPhotonics Monitor for blood volume status Experimed Peptide drug discovery platform Optherion Therapeutics and diagnostics for agerelated macular degeneration http://www.optherion.com Helix Therapeutics Genetic repair therapies http://helixtherapeutics.com Carigent Drug delivery technology http://www.carigent.com BioRelix Antibiotic discovery http://www.biorelix.com JS Genetics Genetic tests CoolSpine LLC Cooling cathether for use in cardiothoracic surgery Vidus Ocular (now part of OPKO) Device to treat glaucoma http://www.opko.com Vascular Insights LLC ClariVein catheter for treating varicose veins http://vascularinsights.com Ren Pharmaceuticals Biotherapeutic for renal disease http://www.renpharma.com Marinus Pharmaceuticals Therapeutics for psychiatric disorders http://www.marinuspharma.com Sonic Golf Training device for golf http://www.sonicgolf.com HistoRx Quantitative histopathology testing and diagnostics http://www.historx.com Applied Spine Technologies Spinal implant device http://www.appliedspine.com Access Scientific Vascular access device http://www.accessscientific.com
Stories by Daniel Jones and Bill Hathaway; Photo Illustrations by Michael Marsland; Editing and Design by LuAnn Bishop

t wasnt always this way. Until the late 1970s, academic leaders on campus didnt consider it their jobs to patent Yale inventions. In the 1950s, William Prusoff, professor emeritus of pharmacology, who is widely viewed as a father of antiviral chemotherapy, struck upon the therapeutic value of idoxuridine against herpes infections that caused blindness. In the 1960s, this became the first antiviral compound approved by the FDA. But Yale didnt protect this intellectual property. Yale didnt want to deal with patents at the time, he recalled. It was pure academic research. In the first decade after the Office of

Cooperative Research was founded, Yales interest in developing practical applications from basic research began to change, as did the research environment in the University and the economic environment surrounding the campus. When Richard Levin became Yales president in 1993, he challenged the office to energize the Universitys role in building ties with the private sector and supporting economic development. For example, Prusoff and a colleague discovered that a compound called d4T was effective against HIV, and the University patented that use in 1988. The drug, licensed to Bristol-Myers Squibb and marketed as Zerit, became an integral part of the widely prescribed cocktail to combat HIV/AIDS.

Yale now makes about $10 million to $20 million each year in royalties from the commercialization of licensed patents, according to OCR. A chief area of growth has been biotechnology; more than 30 biotech companies have sprung from Yale research, attracting more than $1 billion in equity investments and employing hundreds of people in the greater New Haven area.

Yales 10 Highest Royalty Revenue Generating Licenses*

D4T - Zerit for HIV Drug $276.7 million FTC Emtriva for Hepatitis B Drug $9.5 million Modified Nucleotides: Preparation and use research reagent $ 7.5 million Electrospray Mass Spectrography Mass spectrometry $7.5 million Lyme Rx Vaccine for Lyme disease Vaccine $4.3 million L-FMAU Clevudine for HBV Drug $4.2 million Cloned Human Tissue Factor Diagnostic $3.1 million Diagnostic of Genetic and Malignant Disease Diagnostic $2 million French in Action Language instruction video/DVD (See related story, this page .) $1.5 million X-PLOR Software $1.4 million

he leaders of local companies that are using discoveries made in Yale laboratories to develop new life science technologies discuss their ventures in the Yale-CURE Biohaven Entrepreneurship Series. Speakers come from the scientific and business sides of the new enterprises. Programs focus on key factors that drove the success of each company, scientific or technological advantages, business models and lessons learned in starting and developing a

Series Explores Challenges Faced by New Ventures

oderstrom says he envisions more growth in the long run, despite the economic downturn. In this economic climate, he said, you need to keep your eyes on the future. The new ideas and intellectual property are the seeds of tomorrows economy and we have proved that New Haven is fertile ground where new businesses can take root.

business. The series also offers social networking opportunities for scientists and researchers in the Yale community. ponsors include: Yale Office of Cooperative Research, Connecticut United for Research Excellence (CURE), Wiggin and Dana LLP, Price Waterhouse Coopers and Elm Street Ventures. To learn more about the series, visit www.curenet.org.

Twenty Years Later, French in Action Still a Success

* As of 2008

heres nothing like learning a foreign language when the words and phrases can be heard and then repeated in 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 years ago as an in-house method for teaching French language and culture to Yale undergraduates. Capretz, director of the Yale Language Development Studio at Yale, used a series of continuing conversations between an American student named Robert and a young French woman named Mireille to teach French to countless Americans. The multimedia approach to language teaching and learning combines three complementary media print, audio and visual images. French in Action has been used by over 2,000 colleges and universities in the United States alone. Due to its success, it is one of the top-10 royalty revenue generating Yale licenses. (See box, this page.) The learning program also inspired a 52-episode French in Action PBS television series. The success of French in Action has enabled Capretz to transform other cul-

tural materials into interactive languagelearning products, such as an interactive CD-ROM (pictured above), which is based on the classic Franois Truffaut film Jules et Jim.