Key issues in translational medicine: A perspective from
scientific journals
Juan Carlos López
Chief Editor
Nature Medicine
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?
Limited success in drug development
Munos, B. Nat. Rev. Drug Disc. 8, 959–968 (2009)
Where do we go from here?
Three projects to foster translational research
Herrenhausen Symposia
Eureka Certificate Program in Translational Medicine
Science Café
Herrenhausen Symposia
Goal: To identify the most important roadblocks to translational research in different fields of biomedicine and to propose potential solutions
Methodology
Outcomes
Herrenhausen Symposia
What have we learned?
The roadblocks are remarkably similar across disciplines:
We need to learn more about the biology of diseaseWe need to develop better animal modelsWe need to find better biomarkersWe need to design better preclinical and clinical
trialsWe need to invest in infrastructure and human
resources
Ways to overcome the roadblocks have not emerged yet
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
High-profile journals’ criteriavs. translational research
Dronedarone—Atrial fibrillation Golimumab—Rheumatoid arthritis Sapropterin—PhenylketonuriaPrasugrel—AtherothrombosisUstekinumab—PsoriasisTocilizumab—Rheumatoid arthritisFebuxostat—GoutEtravirine—HIVLacosamide—EpilepsyAlvimopan—Postoperative ileusIcatibant—AngioedemaRomiplostim—Immune
thrombocytopenic purpura Dabigatran etexilate—Venous
thromboembolismPlerixafor—Hematopoietic stem cell
transplantationTolvaptan—Hyponatremia
Journal of Cardiovascular PharmacologyAnnals of the Rheumatic DiseasesJournal of PediatricsBritish Journal of PharmacologyJournal of ImmunologyJournal of Experimental MedicineEuropean Journal of PharmacologyAntimicrobial Agents and ChemotherapyJournal of Medicinal ChemistryJournal of Medicinal ChemistryBritish Journal of Pharmacology
Cytokine
Journal of Medicinal Chemistry
BloodJournal of Pharmacology and
Experimental Therapeutics
Two ways to think aboutthe results
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
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 protectionInteraction with regulatorsTarget validation and toxicologyFundraisingThe importance of teamwork, etc.
Enter the Eureka Certificate Program in Translational Medicine
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
MentoringCase studiesLecturesWorkshops
An equally important goal is the formation of international networks that the trainees can harness to advance their research
The Eureka Program
http://www.eurekainstitute.org
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
The Science Café
A Nature Medicine-Nature Biotechnology projectIt puts young scientists with a track record on
translational research in contact with investorsGoals: to foster both the development of
scientist-investor networks and investment in science with translational/commercial potential
Three sites: Boston, San Francisco and LondonFrequency: two or three times a year per cityInspiration: SciBX
SciBX
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/VCsMentor 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
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)
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