by Holly Korschun lmost every day, Emory cardiologist Jonathan Langberg treats patients who have atrial fibrillation, an abnormally fast and irregular heartbeat that causes weakness and shortness of breath and can lead to blood clots. Besides prescribing medication and sometimes shocking a patient's heart into regularity, Langberg uses catheter ablation, a technology he helped pioneer ten years ago to help correct mild atrial fibrillation. He passes a current into a wire threaded through a vessel into the heart and burns a match-sized hole. But Langberg regularly confronts the limitations of his practice. Single-spot ablation cannot cure widespread fibrillation. And measuring the severity of disease in order to plan treatment is largely a guessing game. Several years ago, Langberg and a former colleague decided they could do better. They designed a new diagnostic tool that makes it much easier to predict which patients will respond to medication or to spot ablation. For severe cases of atrial fibrillation, Langberg and his partner created a new nonsurgical technology using catheter ablation to isolate sections of the heart. Two years ago, the researchers founded Atrionix, a medical device company located in Palo Alto, California. Langberg hopes that commercializing his research will allow him to quickly develop his inventions into technology useful in his everyday practice.

angberg joins a growing number of biotech pioneers and entrepreneurs at Emory who are discovering that transferring their ideas from the laboratory to the marketplace may be the most promising route to further their research and bring new discoveries more rapidly to patients. Their inventions have grown into a wide range of diagnostic tools and therapies, ranging from diagnostic software and new treatments for incontinence and depression to growing bone tissue and brain cells, finding new drugs to fight AIDS and HIV, and overcoming phobias. Through re-creating jungle scenes from Vietnam, Emory psychologist Barbara Rothbaum uses virtual reality exposure therapy to treat patients with post-traumatic stress disorder. Her patented system has also helped patients who are afraid of heights and flying. The system was developed in cooperation with the Graphics, Visualization, and Usability Center at Georgia Tech. Since 1990, the US Patent Office has issued Emory 111 patents on pharmaceuticals and technologies. In 1998 alone, Emory filed 50 patent applications, including products that already have resulted in Emory start-up companies or licensed technology. Many technologies discovered by Emory researchers are still awaiting a commercialization opportunity, and Emory's technology transfer office hopes to guide as many of them as possible toward that goal. The researchers, the university, the state, and above all, patients, have a tremendous amount to gain from their success. Since 1991, when Emory first hired a dedicated licensing specialist, the university has been vigorously growing its technology transfer program. In 1993, Emory created the Office of Technology Transfer. Two years later, Emory already ranked 19th among all US universities in generating licensing revenues. This year those revenues are expected to reach close to $5.5 million. Emory is in a unique position among universities to capitalize on a positive local business climate that seems determined to capture biomedical research dollars for Georgia that in the past have gone to just a handful of other states. Nationwide, university technology transfer is booming. According to the most recent survey of the Association of University Technology Managers, the top research universities earned a total of more than $336 million in royalties from licenses on their inventions in 1996 - about 23% more than in 1995. And universities formed 184 new start-up companies in 1996 based on their licensed technology.

Orthopedic surgeon Scott Boden's discovery of a gene that encourages bone growth could potentially eliminate or significantly reduce the need for many of the half a million bone graft surgeries performed annually in the United States. Up to 40% of these spinal fusions fail to form adequate bone.

he 1980 Bayh-Dole Act first gave universities the green light to own and patent inventions resulting from federally funded programs and even encouraged universities to collaborate with commercial concerns. For most of the next decade, however, the vast majority of universities and their faculty did not vigorously pursue commercialization opportunities. Academia traditionally frowned on direct involvement with private-sector, profit-seeking ventures. Such activities carried the onus of conflict of interest: the possibility of corrupting the pure search for knowledge on which academic free inquiry is based. The decade of the 90s has seen a significant shift away from these traditional attitudes as sophisticated conflict-of-interest guidelines have been developed, and as the benefits of carefully structured technology transfer efforts have been realized. Technology transfer begins when a researcher discloses an invention to the university and files a patent application through the US Patent Office, protecting the invention until a patent is either issued or the application is rejected. A patent can be licensed to an existing company or used as the basis for creating a new start-up company. When licensing a patented product or technology to a company, Emory negotiates a complex agreement that may include licensing fees, milestone payments, royalties from the eventual sale of products, or an equity share in the company itself. With equity, Emory benefits from the company's success whether or not its earnings are directly related to Emory discoveries. From the university's point of view, not the least of the possible benefits of technology transfer is potential for additional revenues to support university missions. "The holy grail for most universities is to have one or more of its technologies developed into royalty-bearing products," says Vincent La Terza, former director of Emory's Office of Technology Transfer, noting that probably the most widely known invention was the University of Florida's electrolyte-loaded sports drink, Gatorade. This rare, but achievable circumstance ensures year after year of substantial income. Michigan State has been the beneficiary of this through cisplatin, the chemotherapy drug. Yale has started to receive royalties in excess of $10 million per year on sales of the antiviral compound Zerit. The groundwork has been laid for Emory to join this privileged group of universities. Emory has consistently generated more license revenues than many universities with much larger research programs. The model for a successful Georgia-based and supported biomedical start-up company is Atherogenics. After identifying compounds that help block the progression of cardiovascular disease, cardiologists Wayne Alexander and Russell Medford secured $1 million in seed venture capital from Alliance Technology Ventures (ATV) to found their new company. Atherogenics today has more than $20 million in venture capital funding and is aligning with a larger pharmaceutical company to support further drug development. For the individual researcher or inventor, the excursion into technology transfer can have many consequences, some unforeseen, as was the case with Medford. Although still on the Emory faculty, he became CEO of Atherogenics soon after its founding. His move from researcher to business leader was not by design, but out of necessity. "Typically, scientific founders of companies do not do what I'm doing," he explains. "Usually you want to transfer the technology to a company, then provide input to the scientific progress of that project. In Atlanta, however, we were in the difficult position of having little biotechnology infrastructure. The responsibility fell on me to accomplish many of the tasks necessary to put the company together and represent it to the investor community." Like Medford, other Emory entrepreneurs have also discovered that the process of commercialization can be arduous but well worth it. In September 1997, Emory orthopedic surgeon Scott Boden and his colleagues identified the LMP-1 gene and its protein that can encourage growth of osteoblasts, or bone tissue. In June 1998, Emory licensed exclusive rights to Sofamor Danek Group, Inc., a medical device and biomaterials company, to manufacture and market products related to Boden's genetic discovery. The new technology has enormous potential for treating many orthopedic conditions, including fractures, trauma, infections, and tumors, and eventually perhaps osteoporosis. Sofamor Danek paid Emory $4 million in licensing fees and is scheduled to make milestone payments of millions of dollars over the next several years if Boden meets five research goals. The company will cover the considerable costs of development and clinical trials necessary to gain FDA clearance before marketing products in the United States. If a drug results from the research, Emory will receive royalties on all sales.

eyond earnings potential, technology transfer has accelerated and achieved a higher priority for another reason. Biomedical science is finally reaping what the decades-long national investment in research has sown. The current surge of interest in university technology transfer is fueled both by rapid advances in molecular medicine and by the entry of biotechnology into the traditional practice of medicine. To a large extent, it reflects the National Institutes of Health (NIH) investment in medical research - a relatively young field just now beginning to mature. David Blake, associate director of the Woodruff Health Sciences Center and the key developer of Johns Hopkins' highly successful technology transfer program before coming to Emory, sees a natural and necessary process. "Technology transfer is being done not because universities are looking for new ways to raise capital," Blake says, "and our scientists are not all of a sudden developing new value systems to help them become millionaires. The NIH has invested in basic biomedical research for more than 50 years, not just to create knowledge, but for that knowledge to make a difference in health care. It's not called the National Institutes of Biomedical Research; it's called the National Institutes of Health." As Blake explains it, we have just recently progressed to the point where our knowledge base is strong enough to generate a consistent stream of practical applications. "Until the past ten years, the prospects of that happening with any frequency were low, but things are changing, primarily due to the human genome project. Since all things chemical operate at the molecular level, until your discovery gets to that level, you're working around the edges."

ransferring technology from the laboratory or clinic to the marketplace directs the flow of earnings from commercialized products back into research programs, into departmental budgets, and into the hands of the researchers themselves. It also is an absolute necessity to ensure the survival of most new medical products, La Terza says. "Developing technology in this country has to be done through the commercial sector, and to do it there, you have to know the rules," La Terza says. "The first rule is that you have to own the idea or the discovery. If a scientist were to publish a new technology and not even bother to create a proprietary position through a patent, it would be in the public domain and no company would pick it up. If it were a pharmaceutical, for example, that drug would probably not be developed." "No company would go through the expensive development and regulatory approval processes if another company could also make that compound. If a company can't be offered an exclusive position on a compound or technology, they won't go forward with it." Universities also can incur significant expenses to protect and license their technologies, including the cost of running technology transfer offices and paying attorneys. "If you are not going to create new technologies as a subsidized activity," says La Terza, "you must seek reasonable value for your technologies. You also have to give incentives to the players." When Emory receives a royalty for a product, 40% goes to the inventor (often a team of researchers), and the remaining 60% is allocated among the inventor's laboratory, the department chair, the dean's office, and the university president's office. All these distributions are designed to help provide for continued research and overhead support. It makes sense to generously compensate researchers, La Terza explains. "The heart of the technology transfer program is the investigators. We find that the faculty coming to the tech transfer office are extremely talented, achievement-oriented individuals. They also are amazingly busy. Most have a clinical practice, a research program, and teaching duties. For them, taking the next step and getting involved in technology transfer can entail a lot of risks, in terms of both time and effort. There has to be sufficient reward."

he university's system of checks and balances ensures that while faculty are sufficiently compensated for their work, both they and the university are protected by specific rules relating to conflict-of-interest. Investigators engaged in sponsored research are required to file a conflict-of-interest statement with their dean at least once a year. The dean reviews proposals and financial interests to determine whether they pose a potential or a real conflict of interest. In the School of Medicine, attorney Brenda Seiton oversees all research in which faculty have a personal financial interest. She is the medical school's liaison with the Conflict of Interest Panel, which consists of six to ten faculty members appointed by the provost with the approval of the deans of medicine and the graduate school. Some investigators view Emory's rules, including one requiring disinterested parties outside the university to validate research related to technology transfer, as overly restrictive and an unnecessary hindrance. However, cell biologist Marla Luskin, both a member of the committee and an inventor, says the committee is not trying to be an impediment, but is trying to ensure that nothing backfires for a university investigator because of poor oversight. Most Emory investigators have freed themselves from the idea that technology transfer is in any way a violation of academic ethics. "The notion that being an entrepreneur or being involved with commercialization of technology is somehow corrupt is simply not true," says Langberg. "Taking your research beyond academic recognition provides you with additional motivation. In that sense, it is very positive."

Most of the royalties from cardiac imaging software CEqual, PerfSPECTive, and the Emory Cardiac Toolbox have been funneled back into research and development, says radiologist Ernest Garcia. CEqual alone has sold nearly 3,000 copies, generating $2,500 in royalties per copy.

rnest Garcia, vice chairman for research in the department of radiology and director of the Emory PET (Positron Emission Tomography) Center, was one of the first Emory faculty members to venture into technology transfer 17 years ago, when it was still unexplored territory. Garcia's team developed and licensed the software product CEqual, which generates a two-dimensional polar map of the heart and helps cardiologists monitor blood flow in the heart and diagnose coronary artery disease. CEqual was followed by the three-dimensional imaging software PerfSPECTive, and, more recently, by the Emory Cardiac Toolbox, which includes a half dozen software tools that provide more extensive image interpretation. Another way of working with industry is to sublicense drugs made by large companies and test them in clinical trials for novel indications. In addition to developing its own drugs to treat kidney disease, Renalogics, an Emory start-up biopharmaceutical company, has sublicensed several drugs called FLAP antagonists, developed by Merck & Co. and Bayer, Inc. to stop progression of glomerulonephritis (GN), a serious inflammatory kidney disease. Results of an early clinical trial using one of the new drugs in Emory patients were extremely encouraging. A young woman with lupus nephritis achieved a healthy pregnancy after her symptoms completely subsided following treatment. "This has been a very successful example of cooperation between industry and academic medicine," says Kamal Badr, Renalogics' chief scientific officer, who founded the company with fellow nephrologist Juha Kokko, former chair of medicine. "Most important, we did not have to change our own research in any way. I just continued doing what I was interested in and had been doing for the past 14 years, which is studying GN. Neither of us has paid any price academically. My work continues to be supported by the NIH, but now I also am getting support from a company I founded, which is an easier process. At the same time, Emory stands to benefit tremendously from our success."

In her studies of the function of brain cells and their relationship to neurodegenerative diseases, Emory cell biologist Marla Luskin found that some neurons in the postnatal forebrain can divide and proliferate.

y far the most compelling reason for the upsurge in university technology transfer is the benefit to society of bringing better products and technologies to bear on improving health. Forming partnerships with business sometimes allows investigators to further their research in unexpected directions, benefiting patients in new ways. Recently Emory cell biologist Marla Luskin discovered that a growth factor introduced into the adult brain can greatly increase the number of newly generated neurons and that the neurons can migrate to areas of the brain responsible for movement and for higher mental functions. These dividing cells could be useful therapeutically for treating diseases such as Parkinson's. Almost three years ago, with the help of Emory's Office of Technology Transfer, Luskin filed for patent protection for the method of obtaining these proliferating neurons from the mammalian brain as well as for their therapeutic uses for a variety of purposes. "Our patent lawyers had the foresight to cover almost anything you could imagine," says Luskin. This year Luskin and Emory licensed the technology to Acorda Therapeutics, Inc., a New York-based biotech company working on ways to promote regeneration and repair of the nervous system following injury and disease. The license agreement will help bring Luskin's work to human clinical trials more quickly, an area she had avoided because her basic NIH grants did not cover human investigations. Now she is "cautiously optimistic" that these cells will be among the best available to treat diseases like Parkinson's. She expects her basic laboratory research to proceed in tandem with her new clinically applied research. Although Luskin is pleased by the license agreement, she maintains her focus on her basic research. "The motivation should not be to work with a company," she says. "The motivation should be to do good science and answer important questions because you never know what will lead to the next clinically relevant finding."

ven as these Emory investigators plunge ahead into the new world of technology transfer, the health sciences center plans to boost the efforts of many other budding entrepreneurs through its planned biotechnology development center at "Emory West." Other changes are also in the offing.

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In August, La Terza moved from the academic to the business side of technology. He left Emory to become vice president for business development and general counsel at Octagen Corp., an Emory start-up company that includes licensed technology based on the work of Emory hematologist Pete Lollar. Lollar has discovered how to recombine molecules to encourage blood clotting in hemophiliacs who don't respond to conventional treatments. Nancy Wilkinson, Emory assistant vice president for research and director of Emory's Office of Sponsored Programs, is interim director of technology transfer and heads the search for a new director. Wilkinson plans to make the tech transfer process as smooth and efficient as possible through a reorganized structure that will include proactive interactions with faculty and permanent assignment of each faculty member to one licensing professional. The tech transfer office will have a new web page on-line in early 1999. With that rising level of support, scientists, Emory administrators, and our supporters off campus remain optimistic about the future of tech transfer here. Holly Korschun is science managing editor in the Communications Office of the Woodruff Health Sciences Center at Emory.