NATURE MEDICINE • VOLUME 9 • NUMBER 5 • MAY 2003 493

COMMENTARY

‘Days of Molecular Medicine’, the 2003symposium sponsored by the SalkInstitute, the University of California SanDiego (UCSD) Institute of MolecularMedicine and Nature Medicine, included a forum for discussingnew partnerships between academia and the private sector, witha particular emphasis on the construction of translational ‘high-ways’. The global importance of the topic was underscored by theinclusion of speakers from UCSD, the US National Institutes ofHealth (NIH), the UK’s Medical Research Council (MRC), France’sInstitut National de la Santé et de la Recherche Médicale (Inserm)and various industries. Forum participants included representa-tives from academia, foundations, medical research societies andthe pharmaceutical industry.

Pierre Mendès-France, former prime minister of France, said inhis 1953 nomination speech that “the Republic needs scientists:their discoveries, the prestige that is linked to them, and their applications all form part of the grandeur of the country.” Themain challenges to scientific research that governments face arehow to organize academic research to promote efficient technol-ogy transfer and collaborative research, how to build nationalstrategies that benefit the academic and private industrial sectors,and how to create value from the knowledge produced by re-search. The ultimate goal of medical research is to incorporate re-search-based evidence into clinical practice so as to respond toidentified public health concerns. Basic research must thereforelead to both improved health and improved wealth, and transla-tional programs can bridge these aims. One such example startedfrom an academic collaboration between basic scientists andphysicians and led to the establishment of a large-scale interna-tional clinical trial for heart failure, co-sponsored by a public in-stitution and a private company (Box 1). Charles Murry, aninternationally renowned scientist in the field of muscle cell dif-ferentiation at the University of Washington in Seattle, recentlycommented on the program: “As the first application of cell-based, regenerative medicine to human heart disease, this studysets a standard for how cell-based therapies can be moved safelyto the clinic.”1

Translational research embracing a continuum of investigativeapproaches will probably expand very rapidly as a result of theoverwhelming amount of information generated by the humangenome program. The main goal now is to accelerate the transla-tion of discoveries arising from structural genomics, post-genometechnologies, gene function, gene-environment interactions andmodel organisms into a mode of delivery that will benefit humanhealth. Generic needs for industry include a greater understand-ing of the underlying biology and mechanisms of action of thera-peutics (a need that is enhanced by the compressed time frame ofdrug development), access to human disease specimens and pa-tient cohorts, and access to well-developed disease models.Generic needs of academia include large-scale application of tech-nical expertise to biological questions of interest, access to large-

scale chemical libraries and robotics, andfunding of infrastructures. Commonground based on mutual trust and respectmust be found, as scientific questions, if

not the approaches, are shared.The 1980s and 1990s were the golden age of ‘Big Pharma’, but

the expiration of patents, decreases in sales growth (two block-buster drugs per year are needed to generate adequate revenues),decreases in drug approvals by the US Food and DrugAdministration, and government pricing pressures present majorchallenges to the industry. Moreover, the consolidation of majorpharmaceutical companies has not markedly increased the num-ber of new drug approvals. Over the last few years, small entrepre-neurial biotech companies have emerged as major suppliers ofinnovative products, and collaboration with academic groups isconsidered to be a cost-effective way of extending a large compa-ny’s research. This has led academic and governmental institu-tions to take steps toward accelerating the translation ofinnovation. As underlined by Claude Lenfant of the NIH, the existing translational infrastructure is the result of a combinationof steps, ranging from comprehensive legislation directed specifi-cally at promoting technology transfer from academia to indus-try, to specialized programs that indirectly enable it.

The Bayh-Dole Act of 1984 in the United States, and the 1982and the 1999 Allègre Innovation Laws in France, were majorsteps that gave institutions performing government-sponsoredresearch ownership rights to intellectual property arising fromthat research, ensuring that the investigators themselves wouldderive a financial benefit. A 14 December 2002 editorial in theEconomist referred to the Bayh-Dole Act as “possibly the mostinspired piece of legislation to be enacted in America over thepast half-century…Overnight, universities across America be-came hotbeds of innovation…” In France, the Inserm patentportfolio, actively managed by Inserm’s department of technol-ogy transfer, increased by 75% from 1976 to 2001.

Recently, under the impetus of George Radda, the MRCTechnology company was created with the vision of creating alever for strategic capabilities and building capacity for compre-hensive support of technology exploitation to maintain a long-term leadership position. Christian Bréchot, Director General ofInserm, strongly supports the development of Inserm Transfert,a subsidiary of Inserm launched in 2001, whose main missionsare to offer new entrepreneurial opportunities to researchersand to facilitate the development of Inserm’s innovative tech-nologies. The UCSD College of Integrated Life Sciences (COILS)Initiative, presented at the forum by Andrew Holmes, aims tocreate an environment in which the missions of education, re-search, patient care and public service will be optimally ful-filled. COILS is a new type of partnership linking the Institute ofMolecular Medicine, the Clinical Investigation Institute and theAcademy of Clinician Scholars. Another alternative is to pro-mote dedicated programs to increase translational research such

Building the translational highway: toward newpartnerships between academia and the private sector

KETTY SCHWARTZ & JEAN-THOMAS VILQUIN

At the crossroads of academia and industry, translational research provides the vehicle for the application ofmedical discoveries and developments. A productive and expanded relationship between these two sectors is

essential for the continued success in translating basic research findings to the clinic.

©20

03 N

atu

re P

ub

lish

ing

Gro

up

h

ttp

://w

ww

.nat

ure

.co

m/n

atu

rem

edic

ine

494 NATURE MEDICINE • VOLUME 9 • NUMBER 5 • MAY 2003

COMMENTARY

as the National Heart, Lung and Blood Institute’s Programs forGenomic Analysis and Programs of Excellence in Gene Therapy,and the MRC’s UK Biobank and the Stem Cells Cross ResearchCouncil Headline Program.

Even with the necessary government support, building national and international translational highways requiresmen and women to drive the racing cars, the family sedans,and the trucks. Physician-scientists who are trained in basic,disease- or patient-oriented research and can balance the risksand rewards of developing new therapies are needed.Addressing the national crisis caused by the shortage of such‘rare birds’ is now a top priority. New educational models andcareer paths must be envisaged in both the academic and private sectors, with the aim of providing cross-disciplinarytraining for MDs and PhDs2.

UCSD, by creating a new model for multidisciplinary educa-tion, has become one of the leading institutions for trainingphysician-scientists, pharmacist-scientists, PhD translationalscientists, and physician-pharmacists. New partnerships be-tween the public and private sectors, together with broad-based support from various sources (USCD faculty membersand department chairs, the Academic Senate Council, theConflict of Interest Committee and the NIH) are fostering top-level cross-disciplinary training across UCSD and the La Jollamesa. Inserm is launching new employment policies and career tracks. The Avenir program, which began last year on anexperimental basis and is now fully operative, is designed tostrengthen the autonomy of young French and foreign post-doctoral fellows involved in original projects. This programprovides three years’ of financial support for postdoctoral posi-tions along with laboratory space and privileged access to corefacilities. There is also support for clinicians participating inareas of patient-based research and attractive new scientific

careers for institutional researchers through the Interface re-search grants system, which consists of renewable five-yearcontracts. As emphasized by Jeff Leiden (Abbott Laboratories,Inc.), Andrew Chan (Genentech) and Silvano Fumero (SeronoGroup), academia is a fantastic place for a career, but over thelast 15 years, excellent opportunities have arisen to continuebasic research in industry, with the agreeable surprise of poten-tial bench-to-bedside round trips. Joint training programs be-tween academia and industry have been or are being launchedby the above companies on the common grounds of basic biol-ogy, human disease pathogenesis and development of drugsfor human diseases. The ultimate goal would be to enable eachindividual to obtain both academic (teaching, patient care, re-search and security in tenure) and industrial (successful team-work, drug approvals and security in profitability) satisfaction.

Box 1 Myoblast transplantation for heart failure: a Franco-American partnershipHeart failure is expected to represent the dominant cardiac disease of the third millennium in Western countries4. The limitations and

relatively poor success of current interventions fully justify the search for alternative therapeutic options that would, in the long term,modify the natural cause of the disease. In the mid 1990s, cell transplantation emerged as a new approach to repairing the damagedheart and various cell types were considered. Transplantation of fetal or neonatal cardiomyocytes was successful, but technical and im-munological issues limited their clinical use5–8. Recent reports suggest that adult cardiomyocytes can be obtained from stem cells presentin various tissues9–15 and may promote neoangiogenesis13–16. The clinical usefulness of these cell progenitors will depend on the capacityto characterize them and to obtain sufficient quantities for repairing large areas of necrotic tissue. Clinical trials are already ongoing17–20.

In France, a group of basic scientists, cardiac surgeons, cardiologists and hematologists used precursors of skeletal muscle fibers21, theso-called ‘satellite cells’ or myoblasts, because they can be easily obtained and expanded from autologous adult skeletal muscles. Their re-sults, together with those of other teams, demonstrated that transplantation of myoblasts in the infarcted area improves myocardial func-tion22–30, an effect that persists over time30,31. These results provided a strong rationale for a clinical investigation. A protocol to preparelarge amounts of clinical-grade human adult myoblasts within a short period of time was developed in agreement with the guidelines ofthe French Health Agency (Agence française de sécurité sanitaire des produits de santé). The cell culture process was subjected to patentapplication, and a start-up company was founded by some of the investigators (Myosix SA). From June 2000 to November 2001, ten pa-tients with post-ischemic heart failure were included in a phase 1 trial32,33. From an open skeletal muscle biopsy, autologous cells wereprepared within three weeks and injected into a non-viable and non-revascularizable infarcted area as an adjunct to coronary artery by-pass grafting. Functional and histological analysis documented the feasibility and safety of the approach and provided preliminary indi-cations of efficacy32–35.

The development of a phase 2 trial to the definitively determine efficacy and adverse effects became mandatory. A partnership be-tween a French institution (Assistance Publique–Hôpitaux de Paris) and Genzyme Biosurgery, an American company already involved inautologous cell therapy (cartilage and skin), which facilitated the sharing of expertise in clinical design and cell culture processes and lo-gistics, and the harmonizing of regulatory requirements, quality control and quality assurance between both countries. The MyoblastAutologous Grafting in Ischemic Cardiopathy (MAGIC) study, launched in 2002, is coordinated in Europe by Philippe Menasché and inNorth America by Patrick McCarthy. Three hundred patients, the first of whom was enrolled in November 2002, will be included in thisjoint multicentric, international, randomized and blinded trial. The cells will be provided jointly by two centers located in France andthe US.

DiscoveryIntellectual property Licenses

Start-upcompanies

Proprietaryproducts

Equities &revenues

Increasing Commercial Value

Time ( >10–14 years)

Fig. 1 Commercial value chain and revenue creation is a long-term in-vestment. The usual time between a fundamental discovery and its healthand economic returns is 10–14 years. (Courtesy of Norman Hardman andGeorge Radda.)

©20

03 N

atu

re P

ub

lish

ing

Gro

up

h

ttp

://w

ww

.nat

ure

.co

m/n

atu

rem

edic

ine

NATURE MEDICINE • VOLUME 9 • NUMBER 5 • MAY 2003 495

COMMENTARY

Besides wide highways and adequate and competent dri-vers, what else is needed? The fuel, of course. Andrew Senyei(Enterprise Partners) and Lenfant highlighted the necessity oflong-term investments from both governments and venturecapital (Fig. 1). Translation does not happen spontaneously,and in some ways the invention itself is the easy part.Innovation fails to create value when it cannot attract the re-sources required to develop it; a dollar’s worth of academicinvention or discovery requires upwards of $10,000 of privatecapital to bring it to the market. Globally, government is thebiggest venture capitalist of a country. The US government,for example, has invested huge sums of money in health-related research—between 1950 and 2002, NIH appropria-tions totaled over $250 billion. Because of the rapid and re-markable increases in the NIH budget over the past severalyears, and despite the 1999–2001 burst and decline in venturecapital, NIH support and venture capital funds were equiva-lent in 2002. Between 1992 and 2001, however, the collectiveresearch investment of the Pharmaceutical Research andManufacturers Association (PhRMA) exceeded the NIH in-vestment, and the gap between the support of the NIH andPhRMA widened during that time. Moreover, during the sameperiod, research investment by the Biotechnology IndustryOrganization increased by nearly the same amount as that ofthe NIH (Fig. 2). There is no doubt that increasing the fund-ing for research conducted at universities and academic med-ical centers is extremely important for creating the newproducts that we use for prevention, diagnosis and treatmentof diseases and to obtain a financial return for the country’seconomy. Improving the translational highway will enabledecision makers in industry and government to factor in theresearch advances of academic medicine in allocating theselarge investments.

Finally, at the forum, Lenfant warned of the hazards oftranslational highways. Despite the common scientific inter-ests between academia and industry, there are real difficultiesin terms of technology transfer, intellectual property, finan-cial conflicts of interest and patient rights. There are also dif-ficulties in making drugs licensed from academic institutionsavailable on reasonable terms: it is crucial that the results ofresearch be available for use in developing countries and thatour efforts to expedite translation extend to the developingworld3. Above all, the development of translational highwaysshould by no means interfere with the funding of academicresearch for the benefit of humankind.

1. Minami, E., Reinecke, H. & Murry, C.E. Skeletal muscle meets cardiac muscle.Friends or foes? J. Am. Coll. Cardiol. 41, 1084–1086 (2003).

2. Varki, A. & Rosenberg, L.E. Emerging opportunities and career paths for theyoung physician-scientist. Nat. Med. 8, 437–439 (2002)

3. Beachy, R.N. IP policies and serving the public. Science 299, 473 (2003).4. Berry, C., Murdoch, D.R. & McMurray, J.J. Economics of chronic heart failure. Eur.

J. Heart Fail. 3, 283–291 (2001).5. Soonpaa, M.H. et al. Formation of nascent intercalated disks between grafted

fetal cardiomyocytes and host myocardium. Science 264, 98–101 (1994).6. Reinecke, H. et al. Survival, integration, and differentiation of cardiomyocyte

grafts. A study in normal and injured rat hearts. Circulation 100, 193–202 (1999).7. Scorsin, M. et al. Does transplantation of cardiomyocytes improve function of in-

farcted myocardium? Circulation 96, 188–193 (1997).8. Scorsin, M. et al. Comparison of the effects of fetal cardiomyocytes and skeletal

myoblast transplantation on postinfarct left ventricular function. J. Thorac.Cardiovasc. Surg. 119, 1169–1175 (2000).

9. Deb, A. et al. Bone marrow-derived cardiomyocytes are present in adult humanheart. A study of gender-mismatched bone marrow transplantation patients.Circulation 107, 1247–1249 (2003).

10. Laflamme, M., Myerson, D., Saffitx, J. & Murry, C.E. Evidence for cardiomyocyterepopulation by extracardiac progenitors in transplanted human hearts. Circ. Res.90, 634–640 (2002).

11. Quaini, F. et al. Chimerism of the transplanted heart. N. Engl. J. Med. 346, 5–15(2002).

12. Toma, C. et al. Human mesenchymal stem cells differentiate to a cardiomyocytephenotype in the adult murine heart. Circulation 105, 93–98 (2002).

13. Jackson, K.A. et al. Regeneration of ischemic cardiac muscle and vascular en-dothelium by adult stem cells. J. Clin. Invest. 107, 1395–1402 (2001).

14. Orlic, D. et al. Bone marrow cells regenerate myocardium. Nature 410, 701–705(2001).

15. Orlic, D. et al. Mobilized bone marrow cells repair the infarcted heart, improvingfunction and survival. Proc. Natl. Acad. Sci. USA 98, 10344–10349 (2001).

16. Kocher, A.A. et al. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remod-eling and improves cardiac function. Nat. Med. 7, 430–436 (2001).

17. Assmus, B. et al. Transplantation of progenitor cells and regeneration enhance-ment in acute myocardial infarction (TOPCARE-AMI). Circulation 106,3009–3017 (2002).

18. Strauer, B.E. et al. Repair of infarcted myocardium by autologous intracoronarymononuclear bone marrow cell transplantation in humans. Circulation 106,1913–1918 (2002).

19. Stamm, C. et al. Autologous bone-marrow stem-cell transplantation for myocar-dial regeneration. Lancet 361, 45–46 (2003).

20. Tse, H.F. et al. Angiogenesis in ischaemic myocardium by intramyocardial autol-ogous bone marrow mononuclear cell transplantation. Lancet 361, 47–48(2003).

21. Mauro, A. Satellite cell of skeletal muscle fibers. J. Biophys. Biochem. Cytol. 9,493–495 (1961).

22. Marelli, D. et al. Cell transplantation for myocardial repair: an experimental ap-proach. Cell Transplant. 1, 383–390 (1992).

23. Murry, C.E. et al. Skeletal myoblast transplantation for repair of myocardialnecrosis. J. Clin. Invest. 98, 2512–2523 (1996).

24. Taylor, D.A. et al. Regenerating functional myocardium: improved performanceafter skeletal myoblast transplantation. Nat. Med. 4, 929–933 (1998).

25. Pouzet, B. et al. Intramyocardial transplantation of autologous myoblasts: can tis-sue processing be optimized? Circulation 102, III210–III215 (2000).

26. Pouzet, B. et al. Factors affecting functional outcome following autologous skele-tal myoblast transplantation. Ann. Thorac. Surg. 71, 844–850 (2001).

27. Pouzet, B. et al. Is skeletal myoblast transplantation clinically relevant in the era ofangiotensin-converting enzyme inhibitors? Circulation 104, I223–I288 (2001).

28. Reinecke, H., Poppa, V. & Murry, C.E. Skeletal muscle stem cells do not transdif-ferentiate into cardiomyocytes after cardiac grafting. J. Mol. Cell. Cardiol. 34,241–249 (2002).

29. Rajnoch, C. et al. Cellular therapy reverses myocardial dysfunction. J. Thorac.Cardiovasc. Surg. 121, 871–878 (2001).

30. Ghostine, S. et al. Long-term efficacy of myoblast transplantation on regionalstructure and function after myocardial infarction. Circulation 106, I131–I136(2002).

31. Al Attar, N. et al. Long-term (1 year) functional and histological results of autolo-gous skeletal muscle cells transplantation in rat. Cardiovasc. Res. 58, 142–148(2003).

32. Menasché, P. et al. First successful clinical myoblast transplantation for heart fail-ure. Lancet 357, 279–280 (2001).

33. Menasché, P. et al. Autologous skeletal myoblast transplantation for severepostinfarction left ventricular dysfunction. J. Am. Coll. Cardiol. 41, 1078–1083(2003).

34. Hagège, A. et al. Viability and differentiation of autologous skeletal myoblastgrafts in ischaemic cardiomyopathy. Lancet 361, 491–492 (2003).

35. Pagani, F.D. et al. Autologous skeletal myoblasts transplanted to ischemia-dam-aged myocardium in humans. J. Am. Coll. Cardiol. 41, 879–888 (2003).

Unité Inserm 582, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, FranceE-mail: k.schwartz@myologie.chups.jussieu.fr

0

5

10

15

20

25

30

35

1992 1993 1994 1995 1996 1997 1998 1999 2000 2001

Year

Do

llars

(in

Bill

ion

s)

PhRMAPhRMA

NIHNIH

BIOBIO

Fig. 2 US health research and development expenditure by source, inbillions of dollars. (Courtesy of Claude Lenfant, NIH.)

©20

03 N

atu

re P

ub

lish

ing

Gro

up

h

ttp

://w

ww

.nat

ure

.co

m/n

atu

rem

edic

ine