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