We have extensively discussed in the past the challenges to the efficient development and validation of useful therapeutics [5–8]. We will limit the discussion the most outstanding; the first it the financial support of translational sciences. It should be emphasized that the problem is different for academia and the commercial sector. The commercial sector is not lacking funds but the problem is the containment of the cost of performing broad based clinical trials that could lead to licensing. Thus, the challenge for the commercial sector is reduction in spending. The bureaucratization of clinical research is clearly jeopardizing these efforts unnecessarily and something needs to be done to reduce the burden of clinical experimentation . Better pre-clinical testing to guide the selection and predict accurately the effectiveness of therapeutics could also decrease costs. Furthermore, the identification of surrogate biomarkers that could predict the long term effectiveness of treatment (on survival) early on during a clinical trial could alleviate the costs but shortening the length of clinical investigations unlikely to be successful. These of course, are not new concepts but they remain a priority and something translational scientists should continue to focus as a priority. Yet, it is our contention that very little is done in clinical investigation to understand the mechanism of action of drugs in humans and identify causes of failure. We believe that clinical trials are still conducted sparingly with the minimal goal of testing clinical effectiveness as dictated by regulatory agencies to justify licensing but with little intent to identify causes of failure of a given treatment. In particular, little use is done of high throughput technologies that could provide mechanistic insights beyond those predicted by the trial conceptualization. We strongly believe that the bedside-to-bench direction of translational sciences remains under appreciated [8, 9].
For academia the challenges are different and revolve around lack of funding; the proportions between spending to test a new concept in experimental settings are logarithmically less than those spent to validate the same further in the clinics. Few hundred thousand dollars may help a basic scientist provide a proof of concept that a new strategy is worth being investigated in the clinics; this is little money compared to the billions of dollars spend by the commercial sector to license a product. Yet, such funding is not easy to obtain. We suggest that the solution is not to compete with other academic entities such as the basic sciences but rather to identify alternative sources through public education  and through partnership with the commercial sector . Indeed, academia can provide broader support to biotechnology development than the focused efforts of the biopharmaceutical industry and, as a consequence, play a complementary role. This applies particularly to the realm of entrepreneurship. A modern translational medicine center could provide expertise and facilities to help small biotechnology companies who cannot afford to cover all the aspects of biotechnology. Such partnership could enhance funding for academia through venture capital benefiting with its creativity the commercial sector. It should be emphasized that the proportions between spending for heath care (in the trillions) compared to the spending for research by governments (in the millions or few billions) is astounding. Yet, most of health care spending is devoted to chronic conditions for which the treatments are not effective. Wouldn't it be more logical to shift the balance toward finding new solutions rather than spending a large proportion of the gross domestic product for treatments we know do not work. As Einstein said, it is crazy to keep doing the same thing and expect different results. For health care, this is the sad reality.
Of course, there are many more challenges that translational scientists are facing, such as a fragmented infrastructure, lack of adequately trained investigators, bureaucratic and regulatory burdens, lack of support by the public which may question the value of biomedical research . Yet the challenge remains in our conduct first . It behooves to the translational scientists to challenge the status quo, and not to accept compromises by educating the public, patients' advocates, basic scientists, ethicists, regulatory agencies and politicians . Only by changing the way translational scientists will conduct their own efforts and providing examples and proofs of principle they will be able to affect the necessary changes.