Key issues in translational medicine: A perspective from scientific journals

1. Key issues in translational medicine: A perspective from scientific journals Juan Carlos López Chief Editor Nature Medicine

2. What is translational research? • NIH definition: “To improve human health, scientific discoveries must be translated into practical applications. Such discoveries typically begin at “the bench” with basic research [...] then progress to the clinical level, or the patient's “bedside.” • “Scientists are increasingly aware that this bench-to-bedside approach [...] is really a two-way street. Basic scientists provide clinicians with new tools for use in patients [...] and clinical researchers make novel observations about [...] disease that often stimulate basic investigations.” • But where are the new medicines?

3. Limited success in drug development Munos, B. Nat. Rev. Drug Disc.8, 959–968 (2009)

4. Where do we go from here? • Three projects to foster translational research • Herrenhausen Symposia • Eureka Certificate Program in Translational Medicine • Science Café

5. Herrenhausen Symposia • Goal: To identify the most important roadblocks to translational research in different fields of biomedicine and to propose potential solutions • Methodology • Outcomes

6. Herrenhausen Symposia

7. What have we learned? • The roadblocks are remarkably similar across disciplines: • We need to learn more about the biology of disease • We need to develop better animal models • We need to find better biomarkers • We need to design better preclinical and clinical trials • We need to invest in infrastructure and human resources • Ways to overcome the roadblocks have not emerged yet

8. Grand challenge:Developing human resources (I) • There is a profound disconnect between the goals of translational research and what is expected of scientists to advance in their careers • Scientists are evaluated in a time scale much shorter than that of any truly translational project • Funders and universities commonly value individual contributions over teamwork • Journals favor big conceptual advances over the kind of work that is ultimately translated into a therapeutic advance

9. Dronedarone—Atrial fibrillation Golimumab—Rheumatoid arthritis Sapropterin—Phenylketonuria Prasugrel—Atherothrombosis Ustekinumab—Psoriasis Tocilizumab—Rheumatoid arthritis Febuxostat—Gout Etravirine—HIV Lacosamide—Epilepsy Alvimopan—Postoperative ileus Icatibant—Angioedema Romiplostim—Immune thrombocytopenic purpura Dabigatran etexilate—Venous thromboembolism Plerixafor—Hematopoietic stem cell transplantation Tolvaptan—Hyponatremia Journal of Cardiovascular Pharmacology Annals of the Rheumatic Diseases Journal of Pediatrics British Journal of Pharmacology Journal of Immunology Journal of Experimental Medicine European Journal of Pharmacology Antimicrobial Agents and Chemotherapy Journal of Medicinal Chemistry Journal of Medicinal Chemistry British Journal of Pharmacology Cytokine Journal of Medicinal Chemistry Blood Journal of Pharmacology and Experimental Therapeutics High-profile journals’ criteriavs. translational research

10. Two ways to think aboutthe results

11. Grand challenge:Developing human resources (I) • Every field of biomedicine needs to attract, train and retain new talent • Every field equally needs to develop ways to recognize the contribution of individual scientists to translational projects, which take place over very long periods and involve very large teams

12. Grand challenge:Developing human resources (II) • Physician-scientists are often markedly unaware of all the pieces that must fall into place to develop a new therapy • Intellectual property protection • Interaction with regulators • Target validation and toxicology • Fundraising • The importance of teamwork, etc. • Enter the Eureka Certificate Program in Translational Medicine

14. The Eureka Program • Goal: To expose budding translational researchers to a lot of what they don’t know about the long road from bench to bedside • Mentoring • Case studies • Lectures • Workshops • An equally important goal is the formation of international networks that the trainees can harness to advance their research

15. The Eureka Program http://www.eurekainstitute.org

16. Grand challenge:Developing human resources (III) • Biotech is in dire straits, and the pharmaceutical industry needs a new source of innovation • Academia is the obvious place to go to, but the terms need to be right for the partnership to work • Scientists (and their employers) often have unrealistic expectations about the value of their research • Industry wants to discuss with academics the reality of the drug-discovery process

17. The Science Café • A Nature Medicine-Nature Biotechnology project • It puts young scientists with a track record on translational research in contact with investors • Goals: to foster both the development of scientist-investor networks and investment in science with translational/commercial potential • Three sites: Boston, San Francisco and London • Frequency: two or three times a year per city • Inspiration: SciBX

18. SciBX

19. The Science Café—Methodology • Review 40–50 biomedicine and biotechnology journals • Identify those articles from each of the three regions that, in our opinion have the highest translational potential • Invite the authors of 3–4 articles to give a 10-minute talk to 20–30 investors/VCs • Mentor the scientists to make their talk as suitable to this audience as possible • We very rarely find more than the 3–4 papers necessary for each SciCafé, and most scientists we invite need a lot of mentoring before they can give their presentation

20. The Science Café—Results • Top VC fund. 800 requests for money from researchers trying to commercialize their science. How many were funded? • ZERO • 12 scientists spoke at the SciCafé in the same city and year. How many struck deals with the VCs? • EIGHT • The model works, and we are developing it to suit the needs of other parties (e.g. companies, governments)

21. Conclusions • There are scientific and extra-scientific obstacles to translational research • Among the extra-scientific obstacles, career-development priorities and lack of formal training on translational research are critical, but they tend to receive limited attention. This is partly the motivation for some of our projects • The large investment in translational research being made globally may not bear fruit without a similar commitment to advanced training and career development