118  Pursuing Excellence in Healthcare and Drug Discovery with the goal of linking the medical school with chemists from the pharmacy school to generate innovative drug research. Meanwhile, at Duke, Allen Roses, a former Duke professor, left GlaxoSmithKline after 10 years to head up Duke’s new drug discovery efforts. Roses’ goal is to identify drug research opportunities that the pharmaceutical industry is not pursuing and then to bring them into what is currently a virtual company. Once the new drugs are tested in animal models and humans, he hopes to sell them to pharmaceutical companies that will be able to bring the drugs to market. Duke’s ability to develop potential compounds will be helped by the award of one of the first clinical and translational science awards (CTSAs) from the National Institutes of Health—a grant focused on translating basic sci- ence findings into therapies that will improve health. UPMC has taken a simi- lar approach by entering into an agreement to join Carnegie Mellon University in developing innovative computer and software research and investment in a Carnegie Mellon spin-off that uses software to help organizations in procure- ment deals [32]. Using Academic Laboratories as Incubators Another approach to commercializing discoveries has been to use academic lab- oratories as incubator facilities to pursue industry-sponsored research. Several universities have developed free-standing research institutes or foundations to separate research activities that are industry related. ese include the Draper and Lincoln Laboratories and the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology, the Applied Physics Laboratory at the Johns Hopkins University, and the Wisconsin Alumni Research Foundation of the University of Wisconsin-Madison. ese have proven successful largely due to a mission that is driven by a donor or sponsor (e.g., the need for the applied physics laboratory to carry out classified military research), a clear focus, and careful oversight and management by the associated university. However, using an academic laboratory within the confines of the university to support industry-funded research raises significant concerns. Great care must be taken to ensure that there is no cross-talk between the trainees and person- nel in the laboratory on the university side and those on the corporate side. is becomes a difficult situation when the proximity of the investigators and the common technology of the laboratory result in sharing of reagents, know-how, or technology. It is difficult to protect conflicts of interest, and it is equally dif- ficult to adjudicate conflicts of commitment because of an inherent incentive for both faculty and staff to spend more time on for-profit activities than on fundamental research at a time when federal grant support is increasingly dif- ficult to obtain. Commercializing Research Discoveries  119 How AMCs Can Commercialize Technology in Difficult Economic Times It is important that, at a time when AMCs are financially stressed, they seek new revenue sources; an important one is the commercialization of new technology that comes from the research labs of America’s medical schools. e approaches outlined previously have led to successful financial ventures for a number of different AMCs. As noted, however, each of these approaches has limitations and careful oversight is needed to ensure that conflicts of interest do not impede good judgment on the part of institutions and inventors and that decisions are always in the best interest of patients and subjects of clinical trials. However, in the face of a global financial meltdown, when larger pharmaceutical companies are laying off staff and funding from private equity is decreasing, it is becoming increasingly difficult for AMCs to partner early-stage discoveries or spin off suc- cessful companies for the development of later stage products [33]. In addition, pre-money valuations by venture capital companies are at an all- time low. Some AMCs will simply wait out the storm. However, it may not be advantageous to wait out the current recession because the clock starts ticking once a patent is issued; therefore, long delays may waste substantial portions of the life of a patent, resulting in limited value once it is time to move toward commer- cialization. us, AMCs must seek ways to commercialize their patents even at times of great financial stress in the U.S. marketplace. e suggestions in the fol- lowing sections, based on successful programs at a number of different academic institutions, may be helpful in times of crisis in the global financial markets. Intellectual Property Bundling Intellectual property bundling is the aggregation of intellectual property from multiple institutions for the purpose of optimizing opportunities for licensing to the pharmaceutical or device industry. Although patents encourage commer- cialization by giving the ownership rights to new discoveries to their inventors, the patent process often inhibits the exchange of information needed for the collaborative development of new technology. Because so many processes in drug development require pieces of the new technology to come from the work of independent investigators, biotechnology companies must often deal with multiple patent holders in order to develop a single product. As a result, the “downstream” researchers or biotechnology companies must negotiate licensing agreements with each of the different “upstream” patent holders in order to cre- ate a viable patent portfolio. Unfortunately, the costs of these numerous agreements often become pro- hibitive and sometimes individual institutions are resistant, leading to what is 120  Pursuing Excellence in Healthcare commonly known as “patent thicket.” Pooling allows a group of patents from different institutions to be “bundled” together under the control of a single insti- tution, thereby creating a one-step process for potential licensees at a reason- able cost. Technology bundling also allows institutions without the resources to pursue a large number of technology transfer agreements on their own to work collaboratively with other institutions to pursue joint efforts. Collaboration is important; data show that fewer than half of the research universities actively seeking patents break even from technology transfer efforts and two-thirds of the revenue has gone to only 13 institutions [34]. By defining preexisting guide- lines for patenting, a consortium of institutions can negotiate more effectively. e Larta Institute, a private firm specializing in technology transfer and the Ewing Marion Kaufman Foundation of Kansas City initiated the Technology Bundling Project [35]. After reviewing more than 1,500 inventions from six institutions, the project group was able to identify 41 potential bundles made up of 100 different technologies [35]. A similar approach was taken by a group of organizations in New Mexico, including the University of New Mexico, the National Center for Genome Resources, and other nonprofit institutions in the state, to create the Technology Research Collaborative [36]. One of the fun- damental objectives of this group was to create institutional agreements that would support the ability of the organization to bundle patents and license them through a single entity [36]. However, it must be noted that these types of collaborative activities are not easy. e various partners must negotiate the relative value of each contribu- tion, negotiate in advance how royalty revenues will be distributed, and identify the added value that comes from collaborating. Furthermore, these agreements often require an outside arbiter to set values and to provide unbiased leadership [37]. Nonetheless, in our current fiscal environment, such collaborative activities present an opportunity to overcome existing challenges. Development of Cross-Institutional Collaborations in Technology Transfer Technology transfer has become increasingly sophisticated and complex over the past decade, and AMCs undertaking efforts to commercialize their dis- coveries face some important challenges. As in many businesses, the ability to obtain venture capital financing or to out-license new discoveries requires the talents of individuals who have at some time in their careers been part of the relatively small world of venture capital and/or the drug-development industry and have demonstrated success in their earlier endeavors. Because many venture capitalists pay as much attention to the “jockey” as they do to the “horse” when Commercializing Research Discoveries  121 they make their decisions about which new biotechnology companies they will finance, the experience level of the inventor or the individual chosen to run the new company is also of great importance. Unfortunately, it is difficult to recruit individuals who have been successful in biotechnology venture capital or in the development and leadership of biotechnology companies before they joined academia. Another challenge for AMCs developing technology transfer programs is the inherent cost of the patent process and the need to have attorneys familiar with the many different areas of biotechnology—from the synthesis of small molecules to the identification of the relevance of single nucleotide polymor- phisms in the human genome. Patent attorneys with this type of expertise are neither inexpensive nor readily available, so technology transfer offices often receive advice from less experienced lawyers that leads them to patent a number of products with little commercial value or to pass on patenting discoveries that might later be found to have enormous value. Indeed, few inventors with whom I have spoken thought that their technology transfer offices provided an optimal level of service. Technology transfer offices are undermanned and have excessive overhead. is creates an optimal opportunity for a group of AMCs to partner in devel- oping a first-rate technology transfer program staffed with experts in the phar- maceutical and biotechnology business as well as patent attorneys. Partnering would result in decreased overhead costs. e increased number of patent filings would make it cost effective to hire first-rate patent attorneys on a full-time basis or to outsource patent work to a single, high-quality attorney or firm and to explore the process of patent bundling when appropriate. Indeed, combining patent offices can be just one more part of the collabo- ration among various institutions that is now encouraged by the NIH and it has recently led to pooling of research efforts across all of Harvard’s hospitals and research institutions as well as the efforts of Boston University and Tufts University [38]. At a time when venture capital funding is so difficult to obtain, collaborations among a large group of AMCs may also allow the various schools to contribute to their own venture fund. is would provide small start-up pack- ages to new biotechnology companies and help them until improvements in the markets allow venture capital firms once again to invest actively in early-stage biotechnology at reasonable valuations. Development of Nonprofit Biotechnology Companies e Laboratory for Drug Discovery in Neurodegeneration (LDDN) looks like many other biotechnology start-ups. Located in Cambridge, Massachusetts, with a mission of creating new drugs to treat human disease, the laboratory 122  Pursuing Excellence in Healthcare is quite unique because it is not a biotechnology company but rather a not-for- profit entity that sits under the Harvard Medical School umbrella [39]. LDDN began in 2001 with part of a $37.5 million gift from an anonymous donor. By focusing on drugs that are not blockbusters but rather treat specific diseases that affect a smaller number of patients, the center hopes to gain economic rewards. Because LDDN has no shareholders, it does not have the usual pressures for rapid results and because it is a not-for-profit entity, it can seek collaborative help from the many parts of the Harvard Medical School research enterprise. A unique part of the program is that it funds sabbaticals for Harvard postdoc- toral researchers. is allows them to bring their target proteins or genes to the laboratory and work for a period of 12–18 months to develop small molecules that can alter the function of these proteins. us, they are able to translate their basic research findings into therapeutic compounds. e research is facilitated by the presence of a large library of compounds, robotic screening systems, and medicinal chemists. However, like for-profit biotechnology laboratories, LDDN must raise money to continue to support itself through grants and contracts. Future funding will come from licensing deals and royalty streams. In the meantime, its focus on a sin- gle disease raises enormous opportunities for fundraising from patients and family members. e application of this type of not-for-profit biotech to other medical centers will require the same type of substantive donation or funding that was used to start LDDN. However, this type of facility might be applicable to funding through a collaborative effort of a group of AMCs and their affiliated hospitals. References 1. McLean, J. 1959. e discovery of heparin. Circulation 19:75–78. 2. Marcum, J. A., McKenney, J. B., Galli, S. J., Jackman, R. W., and Rosenberg, R. D. 1986. Anticoagulantly active heparin-like molecules from mast cell-deficient mice. American Journal of Physiology 250 (5 Pt 2): H879–888. 3. Armstrong, M. 2008. 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Lazar, K. 2008. Harvard medical researchers pool work. e Boston Globe, May 30. 39. Alper, J. 2003. Biotech thinking comes to academic medical centers. Science 299:1303–1304. III SPHERE OF ACTION: EDUCATION - Core Mission - Sphere I. Sphere II. Business Structure Sphere IV . Outstanding Care Research Chapter 7: Resolving the Physician Workforce Crisis Chapter 8: e Changing Demographics of America’s AMCs Chapter 9: Te aching Medical Professionalism in the AMC Education Sphere III. 127 7Chapter Resolving the Physician Workforce Crisis In the first place, the small town needs the best and not the worst doctor procurable. For the country doctor has only himself to rely on: he cannot in every pinch hail specialist, expert, and nurse. On his own skill, knowledge, resourcefulness, the welfare of his patient altogether depends. e rural district is therefore entitled to the best trained physician that can be induced to go there. Abraham Flexner 1910 [1] Introduction In 1910, Flexner first noted concerns regarding the size of the physician work- force and the need to ensure that qualified physicians practiced in both small towns and large cities. Today, the United States is facing a shortage of physi- cians that will imperil its ability to care for the ever increasing size of the U.S. population—especially in rural and underserved urban areas [2,3]. ese short- ages come at a time when 20% of Americans live in regions that have already been designated as health professional shortage areas [4,5]. Only recently has the general public begun to become aware of this brewing crisis. For example, in February 2008 USA Today described the plight of Nassawadox, Virginia, where a shortage of surgeons had adversely affected care [4]. [...]... glucose tolerance and a marked increase in cells in the pancreas that make insulin Although he had a novel finding that had the potential to yield substantial gains in the understanding and treatment of diabetes, his pathway to NIH funding was impeded by the fact that he would have to seek funding from an evaluation group at the NIH that was not familiar with him or his work After 3 years of trying for... of improving the number of clinician investigators has been a clinical research loan repayment program that repays educational debts for individuals who spend the majority of their time in clinical research [27] However, the impact of this program is limited by the fact that it only applies to minority candidates, there are far more applicants than funding, and the repayments only cover a part of the. .. is to increase the number of students trained at each of today’s existing medical schools Unfortunately, this approach is limited by the existing infrastructure for both preclinical and clinical education at the majority of U.S medical schools and the capacity of their physical plants As a result, a number of different approaches have been taken and many of them raise concerns about the quality of the. .. Shortfall of Academic Physicians Just as there is a physician shortage in communities across the United States, there is also a critical demand for physician–scientists, physician–educators, and clinician–investigators (the academic workforce) in virtually all of our AMCs Furthermore, it is just as important to retain young investigators as it is to retain established investigators A recent survey by the. .. group of students and trainees who can provide outstanding patient care regardless of the population that they serve Create a National Task Force on the Workforce Crisis Although individual AMCs can oversee the quality of education at their own institutions, financial limitations may preclude their ability to succeed across all areas of the educational program As importantly, the funding for new medical... operating room and look at open heart surgery to see not the perfect world of the textbook but the real world These statements contradict the fundamental principles of medical education that have existed since the time of Flexner: linking the laboratory and the clinical arena Another new medical school in the planning stages that raises concerns regarding its potential success is the Virginia Tech Carilion... Finally, the Georgia legislature approved the expansion of the Medical College of Georgia in Augusta and the addition of new campuses in Athens and Savannah; it appropriated $10 million 136    Pursuing Excellence in Healthcare a year for 12 years for operational support and $210 million for capital improvements at the different campuses [43] The expansion plans for these schools have raised several... interest in the debate Another group that has recognized the need for an authoritative body to address America’s healthcare workforce issues is the Association of Academic Health Centers A white paper coauthored by Daniel Rahn, president of the Medical College of Georgia, and Steven Wartman, president and CEO of the Association of Academic Health Centers [62], noted that a “crucial factor precipitating the. .. Pursuing Excellence in Healthcare This is not just a rural problem; over a dozen states have reported physician shortages or an expectation of physician shortages, a large number of specialties have pointed to shortages in their fields, and many practices in both rural and urban areas have reported an inability to fill vacant positions The workforce crisis has also had an enormous impact on the AMC,... students trained each year in the United States, the overall number of practicing physicians would not change substantially With an increase in the number of U.S graduates, programs that traditionally filled with international graduates would instead fill their programs with U.S graduates Thus, the total number of trainees would remain the same, but would be composed of a higher percentage of U.S graduates . in the pancreas that make insulin. Although he had a novel finding that had the potential to yield substantial gains in the understanding and treatment of dia- betes, his pathway to NIH funding. state allocation of $450 million [42]. Finally, the Georgia legislature approved the expansion of the Medical College of Georgia in Augusta and the addition of new campuses in Athens and Savannah;. Philadelphia College of Osteopathic Medicare campus in suburban Atlanta. It also did not take into account the fact that the new campus in Savannah was only a short distance from South Carolina’s