Author response to comment on "drug discovery: turning the titanic".

In the face of poorly understood disease complexity, a diversity of approaches is the best strategy.

[Transforming medicine through discovery. Major trends in biomedical research]. / Transformer la médecine et la santé par la découverte. Les grandes orientations en recherche biomédicale.

The NIH, which originated from the Marine Hospital Laboratory of Hygiene (1887), was established as the national agency for medical research by President F. D. Roosevelt in 1944. The NIH rests on its independent, world-class peer review process and its distinctive scientific and public advisory structure. The two-fold mission of NIH is to define research priorities based on public health needs and to allocate funding. Eighty-four percent of the budget supports 300,000 extramural scientists and research workers at more than 3,000 universities. Only 16% of the budget is spent within the NIH itself (on administration and the 27 institutes and centers, including some 10,000 intramural scientists, that make up NIH today). The ecosystem of science and biotechnology connects NIH, the public, Congress, universities, the FDA, industry, and investors. The budget, which in 2007 was $29 billion, is submitted to Congress by the Director. The impact of biomedical research over the last 30 years is demonstrated by an increase in life expectancy anda decrease in death and disability from many diseases. Five evolving challenges in public health include acute conditions becoming chronic, the aging of the population, health disparities, emerging or re-emerging infectious diseases, and emerging non-communicable diseases (obesity, mental illness). Medical strategies must clearly be transformed for the 21st century. Molecular diagnosis of preclinical disease is the paradigm of the future: intervening before symptoms appear because the preclinical molecular events are known and because we have the ability to detect at-risk patients constitutes the "future paradigm of the 4 P's." Currently, the fundamental scientific barrier is our limited understanding of the complexity of biologic networks. New theoretical concepts are needed in this "hardware-to-software phase." Any roadmap for the acceleration of medical discovery will have to integrate new pathways, future research teams, and the restructuring of clinical research.

Clinical research at a crossroads: the NIH roadmap.

As a result of the NIH investment in biomedical research, over the past 30 years we have seen many great advances impacting the health of our nation which have been fostered by the effective translation of scientific advances. However, rising costs for both research and health care mean that the NIH must make strategic decisions that maximize the return on its investment. Because treating end-stage disease is so costly, both personally and financially, learning how to pre-empt illness through molecular knowledge and behavioral interventions is the only viable strategy for maintaining the nation's health in the coming years. In order to speed scientific discovery and its efficient translation to patient care, the NIH developed the Roadmap for Biomedical Research. The Roadmap provides an incubator space for funding innovative programs to address a panoply of scientific challenges and has engendered a new culture of cooperation among researchers seeking new avenues for collaboration. An important feature of the Roadmap is the Clinical and Translational Science Awards (CTSA). The program's goals are to eliminate growing barriers between clinical and basic research, to address the increasing complexities involved in conducting clinical research, and to help institutions nationwide create an academic home for clinical and translational science. By adopting a strong strategic vision now, the NIH will be able to stand at the ready as future challenges and opportunities emerge. In keeping with our mission, the NIH's current and future actions will be defined by the requirements of the scientific community and the public health needs of the nation.

International medical graduates in the United States: a view from an ECFMG certificant.

The author was instilled with a passion for mathematics and physics by his father, who taught those subjects in a small Algerian town. Another indelible influence came during a high school mathematics class when his teacher gave the class a problem to solve. Little did the students know that it was Fermat's Last Theorem, which stumped them, and before that, every mathematician since 1630. This experience taught the author that failing to get the final answer was part of learning. He became enchanted with imaging techniques and after earning his medical degree in Algeria, came to study at Johns Hopkins. There he received the training he desired in diagnostic radiology. The author believes science has no borders and would like to see the opportunities that were extended to him in 1975 given to immigrants today. Although the United States produces many graduates in the sciences and mathematics, the nation still has a shortfall and must, he argues, work harder to educate and inspire this country's youth in addition to welcoming the brightest and most able scientists from around the world. He also discusses the crucial role of the National Institutes of Health in furthering global health by funding international biomedical research and by transforming medicine in the 21st century.

US biomedical research: basic, translational, and clinical sciences.

The National Institutes of Health (NIH) is the world's largest biomedical research agency, with a 75-year record of responding to the nation's key medical challenges. Today, medical science is entering a revolutionary period marked by a shift in focus from acute to chronic diseases, rapidly escalating health care costs, a torrent of biological data generated by the sequencing of the human genome, and the development of advanced high-throughput technologies that allow for the study of vast molecular networks in health and disease. This unique period offers the unprecedented opportunity to identify individuals at risk of disease based on precise molecular knowledge, and the chance to intervene to preempt disease before it strikes. Conceptually, this represents the core scientific challenge of the coming century. The NIH is committed to the discoveries that will change the practice of medicine as we know it in order to meet this challenge. The NIH Roadmap constitutes an important vehicle for generating change-a most critical element of this plan is the reengineering of the national clinical research enterprise. This reinvention will call for the transformation of translational clinical science and for novel interdisciplinary approaches that will advance science and enhance the health of the nation.