Benjamin Franklin divided mankind into poets and engineers. While poets analyse their motives, engineers make things. Orthopaedic surgery is predominantly a profession of applied medical technology, not of scientific analysis. So what is the relevance of orthopaedic research and why does it have to be supported?
In recent decades, orthopaedics has become a major medical specialty in Europe and elsewhere; it will become even more important in the future because of projected demographic developments and the social emphasis on the welfare of the elderly. This challenge calls for a critical appraisal of its scientific assets. Total hip replacement has become a symbol of public success, but many other surgical treatments are still archaic and not based onfirm scientific backing (Fig. 1). Present methods for patient evaluation largely lack the scientific rigor of prospective, double-blind studies, common to other specialties and very little is known in orthopaedics about the epidemiology, aetiology and prevention of musculoskeletal diseases and disabilities. These problems can only besolved by a commitment to scientific research in the orthopaedic community itself. This responsibility cannot be delegated. Most orthopaedic surgeons repair deficiencies in the musculoskeletal system by established, or at least sensible, surgical
methods. Relatively few, usually in academic hospitals, are also actively engaged in the development and testing of new technology and in scientific research. During the last 20 years, however, these activ- ities have proliferated, in parallel with the growth of the specialty itself. Societies hįvežbeen foned, conferences organised, and scientific joumals published, all exclusively devoted to orthopaedäc tesežrot . Trainees and residents participate actively in research and a number of orthopaedic research laboratories have emerged, employing scientists from basic biomedical or other disciplines. Orthopaedic research has grown into an identifiable entity. The questions which I address are that if such a research entity is a scientific field in its own right, how is it str ctured,how are its scientific goals characterised,how does it relate to progress in clinical orthopaedics, and can the supranational role of Europe in its development be enhanced?
The structure of orthopaedic research.
A field of scientific research has no formal intemational organisation, but becomes a virtual entity from different foci such as research groups and laboratories, academic departments, international societies, conferences, scientific joumals and funding programmes. The most prominent forum in this field is the Americįn Orthopaedic Research Society which was fom ed in the 1950s by a few orthopaedic surgeons.
It holds Annual Meetings, in conjunction with the American Academy of Orthopaedic Surgeons (AAOS); the 42nd was in Atlanta in February 1996. Since 1974 it has published formal yearly Proceedings. At the 24th Annual Meeting in 1978, 199 papers were presented, whereas at the 4lst in Orlando there were 804 papers and posters selected from 1527 total submissions. Of the attendance of over 2000, half were clinicians (surgeons and residents) and the other half basic scientists from biochemistry, bioengineering and other biomedical fields. The ORS started the Jurnal f Orthopaedic Research in 1983. It now has six issues per year, and its quality and success are illustrated by its impact factor (Table I), its 60% to 70% rejection rate and its publication delay of over one year for accepted manuscripts.
Other societies in the USA feature orthopaedic research at their conferences including the AAOS and AOA, the specialty societies and those dedicated to orthopaedic-related basic sciences such as biomechanics, biomaterials and bone biology.
The work presented at the meetings and published in the journals is funded from five different sources: (1) direct funds from universities to provide continuity to their research programmes; (2) direct funds from orthopaedic hospital departments from patient income to demonstrate their scientific accomplishments; (3) agencies for research sponsored by the govemment such as the National Institute of Health or the National Science Foundation; (4) non-profit foundations, such as the Orthopaedic Research and Education Foundation or other private institutions; and (5) the drug and medical device industries.
At the basis of American success lies the principle of peer review in a structure of competition, as in all sciences. This helps to ensure that the restricted funds available are allocated to the best research proposals,thatthe professorships go to the most able minds, and that the limited number of pages in scientific joumals are filled by the best articles. It is, like democracy, not an ideal system, but the best available. It can be hard on the individual scientist and it is not devoid of political ambiguity.By-and-large, however, it works to provide structure and.continuity to a scientific field, to establish a network of experts, and to develop the quality of work.
At an intemational level, SIROT is the only world-wide organisation devoted exclusively to orthopaedic research, but it does not draw as large an attendance as the ORS. At the initiative of the ORS, the first Combined Meeting of the American, Canadian and Japanese Orthopaedic Research Societies was held in Banff, Canada, in 1991. The second Combined Meeting, which included the European Orthopaedic Research Society, was held in San Diego, USA, in 1995. Both attracted some 500 participants and were quite successful. A third meeting will be held in Japan in 1998. Several countries in Europe have strong orthopaedic research traditions; notable national research organisations are the British Orthopaedic Research Society and the Swiss Arbeitsgemeinschaft fčr Orthopaedie. Only recently has an intemational European research structure begun to emerge. The European Societies of Biomechanics and Biomaterials (founded mostly by orthopaedic surgeons and scientists) started in the mid-1970s and the European Orthopaedic Research Society (EORS) in 1989. Like the ORS the EORS now meets annually, in one year at an EFORT Congress and in the altemate year with one of the national orthopaedic societies. In Munich in 1995, 98 papers were read and 71 posters displayed to some 250 attenders. The EORS gives a number of yearly Research Awards and Travel Grants, and plans to start its own research journal.
Several orthopaedic research laboratories are associated with clinical depart ments in European university hospitals,involving both clinicians and basic scien tists. Their funding comes predominantly from national sources, similar to those listed above for the USA. In addition, EUfunding is becoming more prominent, particularly in the BIOMED programme.
At least seven orthopaedic-related proposals were submitted to BIOMED II in 1995,of which at least two were funded.By tradition, European research papers in orthopaedics are published in non-peerreviewed books or local joumals, but submission to intemational peer-reviewed journals is bec§ming more popular. Table I gives a list of such joumals graded according to impact factor by the SCI organisation. The impact factor reflects the frequency by which articles from the journal concemed are cited in other SCI journals. The half-life gives the number of years after which 50% of the articles are still cited. The top 25% of this list contain three non-orthopaedic joumals, three American orthopaedic journals and ne European joumal. Notable is the high position of J Orthop Res. Most of the European joumals are at the bottom. In several, however, the impact factor is not very high. Pediatrics, Am J Pathol and Pharmacological Rev, for example, which are leading joumals in their fields, have impact factors of about 2.8, 5.5 and 22.5, respectively. J Biomechanics, which publishes many orthopaedic related research papers, but is not included in the orthopaedic category for reasons unknown, hadan impact factor in 1994 of about 1.7. Some joumals for bone physiology and biomaterials go even higher. In many universities and funding agencies these impact factors are now used t§ rate the scientific quality of the research groups.
The message is that American orthopaedic journals are cited much more often than European ones, which means also that American auth§rs are cited more often. By implication, it follows that European orthopaedic research has a lower (average) quality. This will have to be tumed around. The nature of orthopaedic research. Traditionally, much of the research in ortho paedics is technology-driven. The goals are to develop or test new methods for surgical intervention, based on experience and a scientific body of knowledge, as is typical for an applied science. Conversely, the general objectives of the basic sciences are to add information or methodology to the scientific body of knowledge, independent of its eventual applications.
Applied science is solution-driven, basic science is problem-driven. Orthopaedics therefore has a strong tradition in the development and assessment of technology as witnessed by the elaborate ties with industrial manufacturers, and by the emphasis on postoperative patient-evaluation studies in orthopaedic joumals. It does not have a strong tradition in basic research, but this has changed in recent years.
Of the papers presented at the 24th ORS in 1978 most were either clinical, bio engineering or biochemical in nature. There was very little research based on mixed approaches. Emphasis was on tissue biomechanics, biochemistry, physiology and pathology (bone, cartilage and ligaments), which made up about 60% of the orally presented papers, and several clinical subjects (joint replacement and ligament reconstructions, fractures, spine, allografts infections) which comprised 40%. In later years this has not changed very much, although the role of the basic scences (mostly biochemistry and biomechanics) is still increasing. The number of postoperative patient-evaluation studies has decreased. Recently, more papers have been presented based on combined clinical, biomechanical, biochemical and cell biological approaches to the solution of a scientific question. It is here that we see the emergence of a scientific body of knowledge which is ty orthopaedic. The number of papers presented at the Sth Annual Conference of the EORS in Munich in 1995 was similar to that for the 1978 24th ORS meeting, as were the subject categories. The orientation towards basic sciences however, was less emphasised.
The EORS has very few members from the non-clinical basic sciences, and appears to be less scientifically but more technologically orientated than the Amer- ican ORS. Or, as some would happily put it, the EORS emphasises clinical relevance more than the ORS. Whether that should please us, however, is not so certain. Clinical relevance and the basic sciences. Orthopaedic research cannot prosper without the basic sciences. The ultimate ly relevant project identifies a clinical problem and eventually solves it, to the extent that the solution can be clinically applied. Many surgeons have the feeling that orthopaedic research projects tend to start out with that perspective, but then the basic scientists get in the way. They are more interested § the scientific goal of adding information to a body of knowledge, acquiring fame and funding in the process, rather than solving the immediate technological problem. This is not altogether untrue. The problem is, however, that not many clinical questions can be solved by clinical research alone. If the question is, for example, whether prosthesis A or B provides the best results, it can best be answered in a prospective, multicentre trial, using clinical methods only. The question, however, as to why prosthesis A is better than B, and what this implies for prosthetic design, implantation techniques and indications in general, requires much more than just clinical research. New surgical methods can be developed on a trial-and-error process, but we have seen in the past, particularly in regard to non-cemented žoint replacement, how ineffective, and ven dangerous, such procedures can be.
To improve orthopaedic treatment effectively on a realistic time scale, more information about underlying biological processes is required. To accomplish that the input of basic science is clearly needed.
The applicability of basic research is often questioned by clinicians, and its complexity is not always appreciated.
Fig.2.The choice for an expe§men al model in an investigation mus be based on considera- tions of closeness to reality versus control over the experimental parameters. No type of model is nherently supe§or to another; which one to choose depends only on the kind of scientific question posed; they differ only in the balance of these two faculties.
Conversely, there are questions in the minds of the basic scientists about the scientific quality ofclinical research. The basis of this conflict is, I believe, to be found at the heart of scientific methodology, as illustrated in Figure 2. To answer a particular scientific problem several models may be used: these include clinical (a patient series, for example) animal, laboratory (in vitro, ex vivo or physical), and computer-simulation models. With any of these four, the prime issues to consider for the investigative protocol are closeness to reality and experimental control. A patient is very real, but in a clinical investigation it is impossible to keep control over all the experimental parameters. On the other side of the scale, a computer-simulation program is remote from reality, but provides virtually absolute control over the experimental parameters. The other two models are in between these extremes.
The point is not that one method is better than another. Their applicability depends on the objective of a study,whether it is meant to identify a problem,provide an explanation, find new quantitative data, develop hypotheses aboutcertain relationships, or confirm them. To solve a scientific problem and to reachclinical applicability, all these different methods may have to be applied in concert. The problem of basic and clinical scientists alike is often that they tend toconcentrate on the methods which they know well, rather than on the question to be answered. They tend to fit the question to the method, rather than vice versa. This makes life easier, but tends to produce solutions in search of a problem. Conflict between clinical and basic research is counterproductive.

In the recent past we have seen repeatedly that new sc entific methodology can enhance clinical research. Obvious examples are CT and MRI and, more particular for orthopaedics, roentgen stereophotogrammetric analysis and DEXA scanning. These methods provide precise information about processes which occur after surgical interventions. These processes can be reproduced in well-con trolled in vitro culture or animal models, so that they can be better understood and manipulated. We have seen that they can be mimicked in laboratory or computer-simulation models to provide potential explanations for the suspected relation ships. These explanations can then be validated again in well-contr§lled clinical studies, eventually to innovate accepted means of treatment. To the tra- ditional surgeon, educated in the trial-and-error innovation method, this may seem an elaborate route towards improvement. This route is justified, however, by consideration of what has really been achieved in the last 20 years by trial-and-error methods, using traditional clinical parameters and radiography as measures of success. The further development of professional research in orthopaedics needs the input of basic research. This raises several questions. Should this basic research be performed by orthopaedic surgeons orresidents? Should the fruits of basic research be taken from other fields or should orthopaedic research have its own dedicated basic scientists? The answers depend very much on the ambition of the orthopaedic community to maintain a scient fic field in its own right. This requires a steady flow of basic-research funding, which can be based only on the respect and understanding of the biomedical scientific community at large. It can only exist, however, when it has unique scientific objectives and its own body of knowledge and methodology.
The objectives of orthopaedic science. If orthopaedics has scientific goals of its own and a unique body of knowledge, how can they be characterised? I suggest that the core objective of orthopaedic surgery is to restore musculoskeletal function by ". . . creating the biological and mechanical environment in the musculoskeletal tissues which allows them to heal, adapt and maintain themselves". For example, consider the treatment of a knee ligament injury. Its objective is gradual healing to normality, defined as full adaptation to function and requiring just the right balance between tissue flex- ibility and strength. If the repair tissue is loaded excessively and stretched too much, it will not heal; if it is not loaded at all, it will resorb. Many fundamental questions can be derived from this clincal problem. What mechanical signal do the cells receive? What is the relationship between signal and metabolism? What is the role of vascularity, and how and when is it restored? How is extracellular matrix generation affected by load? How do the cells know in which direction the colla- gen is to be laid down? Can this be enhanced by morphogenetic proteins or other agents? What is the optimal loading profile for the tissue in the course of time? Which external loading regime on

Fig. 3 . A well-known paradigm for the mechano-biology of connective tissues from Pauwels. The morphogenesis of different tissues is supposedly dependent on the relative proportions of shear deformation and hydrostatic compression. Although the existence of such mechanisms is very likely, the cell-signalling processes through which they work and the quantitative relationships between mechan cal vanables and cell-matrix expressions still elude us. This infonnation is vital for the scientific basis of orthopaedics.
the knee produces that optimal profile to the ligament tissue? I could have selected other examples, related to fracture healing, arthritis, osteoporosis, scoliosis or oncology. Our aim should be to apply a particular orthopaedic technology today, in such a way that w ž can pred ct, precisely and reproducibly, what the tissues create tomorow.
Of course, this goal is at present unattainable in practice, not because of the failure of technology, but because not enough is known about the relevant biological processes. It is precisely the absence of such information that should define the specific objectives of ortho- paedic research (Fig. 3). This kind of info - nation cannot emerge without the involvement of biomedical disciplines such as anatomy, biochemistry physiology, cell biology molecular biology, biophysics, biomechanics and biomaterials. The objectives, however, are so particular for musculoskeletal tissues and orthopaedics that a unique collection of multidisciplinary information and methodology is required to fulfil its purpose.
It is for this reason that orthopaedic research can be seen as a scientific field in its own right. To focus thought on this, I have proposed to apply the term `musculoskeletal mechano-biology' to this particular quest for scientific information. The prime function of the musculoskeletal system is to provide motion and carry load: it seems highly likely that the tissues which fulfil this role are maintained by the load itself. I do not claim that biomechanics is the most important scientific discipline for orthopaedic research, but it is, however, the most specific for this field when compared with any other medical specialty. The term mechano-biology strikes a nice balance.
Wolff's law is at the core of the mechano-biological body of knowledge. This is our law; no other is so specific to orthopaedics. If it were a real law in the traditional sense, it would yield precisely the kind of scientific information about bone which we need to realise our goal of predicting how surgical interventions affect tissue fitness in the long term. But it is not; it is merely a series of observations sustaining the paradigm that bone mass depends on load. No quantitative information relating load to bone mass can be derived from it; there is no expla- nation of the cell-signalling processes and biochemical reactions involved. Yet this information is central to our scientific objectives. We need it, not just for bone, but also for other musculoskeletal tissues. Our `scientific' basis is defined by empty shells, and it should be our ambition to fill them with hard da Such ambition will help orthopaec research to develop the moment which it needs. The enhancement of European orthopaedic research. Progress in orthopae dics, necessary to fulfil future pubdemands, requires scientific resean Yet, despite successful initiatives in invidual countries, in Europe orthopaeresearch has achieved less internatię prominence than that in the USA. ambition to fill them with hard data. Such ambition will help orthopaedic. research to develop the momentum which it needs.
The enhancement of European orthopaedic research. Progress in orthopaedics, necessary to fulfil future public demands, requires scientific research. Yet, despite successful initiatives in individual countries, in Europe orthopaedic research has achieved less international prominence than that in the USA. To improve the balance we must strengthen our scientific basis, develop a European scientific network and enhance education in the relevant basic sciences.
It is not just a matter of principle that Europe, as a supranational entity, should play a major role in the development of orthopaedic research. The international orthopaedic community has that responsibility, as I have argued in my introduction, as dę individual academic departments in each country. Scientific research in orthopaedics is world-wide, and to participate successfully in a competitive global structure we need a home reference base of substance and consistency. The countries of Europe are too small to provide the substance, and the world is too large to provide the consistency. Europe, like the USA is the size to produce a network of experts with a wide enough multidiscipl nary consistency. Such a network could provide a forum in which European scientific quality can thrive. The fuel for this process is peer-reviewed competition. Competition can only enhance quality if the players keep to the rules. This is a major problem in Europe. Most of the funding for orthopaedic research and the establishment of academic chairs, are organised on national levels. International peer review is precluded by the lack of a supranational organisation and there fore, for our own good, we should voluntarily organise this ourselves. The founding of EFORT was an excellent initiative towards a European forum for orthopaedics. The enhancement and organisation of European orthopaedic research should now become one of its prime objectives. EFORT must fight the notion that orthopaedic research is a parttime interest of a few academic individ- uals, who wish to impress their colleagues.
Orthopaedic science must be promoted as a basis for professional careers. In this endeavour, EFORT will find that the EORS will be its main ally, to be used as a vehicle towards this goal. The EORS is still relatively small, but it has the dedication, the experts, the international organisation and the ambition to build a European structure for orthopaedic research.
Such a European structure can accommodate international collaboration and student exchanges, the scientific education of orthopaedic residents and provide a forum for peer-review of research proposals and publications. As argued above, this structure must be character- ised by strong interactions between clinical and basic research. Technological innovation and patient-evaluation studies will remain as important as ever, but must be based on scientific objectivity, and related to functional biomechanical relationships and the mechano-biology of the tissues. For this purpose, residents must be exposed to the relevant basic sciences in their training periods. In addi- tion, the structure must involve basic scientists from the relevant biomedical disciplines, who will become dedicated to musculoskeletal mechano-biology.
The development of a scientific field always suffers from the `chicken-and egg' problem. Without funding there can be no scientific activity to provide an adequate momentum to lead to funding for the research work. A European orthopaedic research structure will not emerge overnight, but there is already an enormous scientific potential in Europe for orthopaedic science, and much funding for research in general. All this needs from the orthopaedic community, and from EFORT, is a strong push in the right direction.

Created on 21-11-1996 at 19.00 by Nicola Vachaviolos