‘Mind the gap’

Abstract

If you travel on the London Underground rail network, your arrival at certain stations is greeted with a loud exhortation to ‘Mind the gap’. For good reasons, lost in antiquity, the train and the platform are less close to each other than they ought to be. A similar gap between the needs and aspirations of academia and industry holds back innovation, discovery and economic growth. Despite apparently enormous effort and investment, the ability of western democracies to harness their academic life-science research into effective clinical and industrial ‘translation’ is still far from optimal. Abolishing this gap needs to be addressed with new vigour as competition from emerging nations such as India and Singapore could easily whittle away the current competitive advantage of Europe and the USA.A great paradox confronts medical science and society. At no time in our history has our knowledge of biology been so advanced or promised so much in terms of improving human health and wealth. The papers in this special issue of Trends in Cell Biology testify to the excitement and relevance of current academic research, yet, at the same time, progress in the development of new medicines is slow and appears very inefficient. The number of new drugs approved by the Federal Drugs Administration is actually falling in the face of a massive increase in R&D spending by the major pharmaceutical companies. This is causing serious concern on the world's stock exchanges. High-profile drug failures, relentless competition from generic manufacturers and pricing issues are causing pressure to build on traditionally safe pharma stocks. Even the traditional solutions of mega-merger and ‘in licensing’ have not been greeted with much enthusiasm. This is a serious matter for society and government to address. Without market support, the industry will not be able to grow as the fund managers who invest our pension funds will meet their margins by investing in other safe stocks such as tobacco and arms manufacture.The question then emerges as to why this is so. One explanation is the ‘low-hanging fruit model’ supported by some thoughtful pessimists. This suggests that western medical science has been so successful that most treatable diseases have found appropriate intervention. The difficult remaining chronic age-related syndromes are left and the heroic days of medical intervention are past: the future lies with incremental advance and prevention. Such pessimists argue that society is increasingly paying high prices for heavily promoted medicines that don't really work. Recent reports that placebo knee surgery (a small surgical incision) was as effective as the $5000 arthroscopic lavage and debridement operation normally used in osteoarthritis of the knee and the controversy over hormone-replacement therapy support some of these concerns. A number of cogent arguments can be raised against this view. First, new life-threatening medical challenges emerge even in highly developed countries – with AIDS, MRSA and smoking being clear examples. Second, new ‘diseases’ of great social and economic importance, which might traditionally have been considered unimportant, have been defined by the enormous response to new interventions. This is exemplified by the unrecognized importance of erectile dysfunction revealed by the unprecedented sales of Viagra. Finally, aging, while inevitable, can be managed so as to deliver a very high quality of life and an acute ‘good’ death if the major debilitating chronic diseases of the elderly can be controlled. As the population of the West ages dramatically, this issue becomes increasingly important for economic and social viability. The impact of a successful treatment for senile dementias, for example, would be enormous. Clearly, what is required by society is the delivery of safe, profoundly effective medicines delivered at a cost and efficiency that makes them economic.The solution to these problems lies in the promotion of outstanding science and its prompt application to practical problems. What barriers lie in the way of these objectives? While there are many, I chose here to focus on two that struck me as being of particular importance. The first concerns the governance of basic science and its quality, and the second concerns the process of technology transfer from academic to commercial enterprises.Academic scientists now live in an intensely competitive world where their output is measured constantly. The measures of output are surrogate measures, usually based around peer-reviewed publications ranked by citation index. The assessment of worth is often made or guided by young administrators who have limited experience as professional scientists. This system, which has developed rapidly over the past two decades, selects strongly for the rapid, superficial and brass-necked author who will argue relentlessly for publication with editors and reviewers. It does not select for originality or utility, nor does it encourage a sense of faith and common purpose between the funding agency and the grantee. It is transparently open to fraud and abuse, which the recent tragic case at the Bell labs makes all too clear, and it discourages the acquisition of real, certain knowledge and its application. It also massively undervalues the development of novel technology. Thus, the movements in the evaluation of science and the direction of science funding are resulting in a science of less strength and utility and which is thus less suitable for commercial development. It was remarkable, for example, that, in the much-praised UK University Research Assessment Exercise (RAE), patents were not counted as publications. This is an issue of vital importance as effective new treatments can only be developed on the basis of rigorous science. Rigorous science flourishes in elite well-funded centres where assessment is judged on longterm performance and key scientists are given the freedom and support to tackle time-consuming projects. Even a superficial examination of the Laboratory of Molecular Biology in Cambridge compared with any other UK academic center reveals how cost effective such an approach can be. I haven't done the calculation, but the cost per Nobel Prize must be the best in the world.Despite these deep-routed problems, the basic research carried out in our universities and hospitals is of fundamental importance to the industry, and much is still of a suitable standard. However, in many cases, the interaction between the commercial sector and the academic centres is blocked to a substantive extent by the misguided actions of university and charity-supported technology transfer offices. When I once asked a noted UK venture capitalist what his solution would be to the dearth of successful spin-out companies in the UK, his simple reply was to summon all the technology transfer officers of the major UK universities to a conference and then ‘shoot them’! What causes such extreme reactions is of course a lack of mutual understanding. It is unthinkable that the hardworking and diligent officers of the technology transfer offices come to work each morning thinking how they can hold back the success of their institution and the economic growth of their nation. Yet their actions often achieve exactly that result. Typically, the officers will act to file patents on university research of dubious value and then attempt to sell or licence them to commercial concerns, often at ludicrous asking prices and without the support of the inventor. By contrast, what the institute needs is the active engagement of its scientists in interaction with industry and in the creation of new companies. What industry wants, be it a big established company or a start-up, and will pay for, preferably in arrears, is access to the scientist and technology in a rapid and open form. Universities and institutes worry about being ‘ripped off’, a mythic fear fed by stories of monoclonal antibodies and other old gems. Monoclonal antibody technology, given to all, has been of tremendous benefit for mankind and has provided great commercial success – it is thus a wonderful example of successful technology transfer. Universities and research councils are funded by the taxes paid to the state, and economic success ensures that a nation has sufficient revenues to fund its academic institutes and that its citizens support its charities. It is therefore reasonable that universities and other academic institutes should think first (or be encouraged to think first by suitable incentives) to contribute to the success of the economy and secondly to their own profit. Even start-up companies pay large amounts of tax as each employee will give half their annual earnings to the state. Many successful entrepreneurs will end up giving to their alma mater in the future. The current system encourages delay and inaction so that often ideas are lost and opportunities missed. The formation of interaction with industry and the founding of new companies have tremendous longterm benefits in terms of training, job creation and positive publicity.What solutions can be offered that will help the knowledge economy and prevent my venture capitalist friend going to jail for mass murder? How can we fill the gap? Some simple rules could be applied by the heads of academic research institutes and universities. Recognize and encourage only really outstanding science. Make those judgements within your own organization and praise and reward excellence. Encourage scientists to work with industry and to establish companies. Do something, never nothing. Take equity in return for services. Recognize the macro-economic benefits of technology transfer. Be patient and encouraging. If you can't deal with an idea or concept, give it away rather than cause the world to lose it. Do experiments; no one knows how to do this perfectly, so try different ideas. Be quick: other are chasing hard. Mind the gap!‘It is therefore reasonable that universities and other academic institutes should think firstto contribute to the success of the economy and secondly to their own profit.’ If you travel on the London Underground rail network, your arrival at certain stations is greeted with a loud exhortation to ‘Mind the gap’. For good reasons, lost in antiquity, the train and the platform are less close to each other than they ought to be. A similar gap between the needs and aspirations of academia and industry holds back innovation, discovery and economic growth. Despite apparently enormous effort and investment, the ability of western democracies to harness their academic life-science research into effective clinical and industrial ‘translation’ is still far from optimal. Abolishing this gap needs to be addressed with new vigour as competition from emerging nations such as India and Singapore could easily whittle away the current competitive advantage of Europe and the USA. A great paradox confronts medical science and society. At no time in our history has our knowledge of biology been so advanced or promised so much in terms of improving human health and wealth. The papers in this special issue of Trends in Cell Biology testify to the excitement and relevance of current academic research, yet, at the same time, progress in the development of new medicines is slow and appears very inefficient. The number of new drugs approved by the Federal Drugs Administration is actually falling in the face of a massive increase in R&D spending by the major pharmaceutical companies. This is causing serious concern on the world's stock exchanges. High-profile drug failures, relentless competition from generic manufacturers and pricing issues are causing pressure to build on traditionally safe pharma stocks. Even the traditional solutions of mega-merger and ‘in licensing’ have not been greeted with much enthusiasm. This is a serious matter for society and government to address. Without market support, the industry will not be able to grow as the fund managers who invest our pension funds will meet their margins by investing in other safe stocks such as tobacco and arms manufacture. The question then emerges as to why this is so. One explanation is the ‘low-hanging fruit model’ supported by some thoughtful pessimists. This suggests that western medical science has been so successful that most treatable diseases have found appropriate intervention. The difficult remaining chronic age-related syndromes are left and the heroic days of medical intervention are past: the future lies with incremental advance and prevention. Such pessimists argue that society is increasingly paying high prices for heavily promoted medicines that don't really work. Recent reports that placebo knee surgery (a small surgical incision) was as effective as the $5000 arthroscopic lavage and debridement operation normally used in osteoarthritis of the knee and the controversy over hormone-replacement therapy support some of these concerns. A number of cogent arguments can be raised against this view. First, new life-threatening medical challenges emerge even in highly developed countries – with AIDS, MRSA and smoking being clear examples. Second, new ‘diseases’ of great social and economic importance, which might traditionally have been considered unimportant, have been defined by the enormous response to new interventions. This is exemplified by the unrecognized importance of erectile dysfunction revealed by the unprecedented sales of Viagra. Finally, aging, while inevitable, can be managed so as to deliver a very high quality of life and an acute ‘good’ death if the major debilitating chronic diseases of the elderly can be controlled. As the population of the West ages dramatically, this issue becomes increasingly important for economic and social viability. The impact of a successful treatment for senile dementias, for example, would be enormous. Clearly, what is required by society is the delivery of safe, profoundly effective medicines delivered at a cost and efficiency that makes them economic. The solution to these problems lies in the promotion of outstanding science and its prompt application to practical problems. What barriers lie in the way of these objectives? While there are many, I chose here to focus on two that struck me as being of particular importance. The first concerns the governance of basic science and its quality, and the second concerns the process of technology transfer from academic to commercial enterprises. Academic scientists now live in an intensely competitive world where their output is measured constantly. The measures of output are surrogate measures, usually based around peer-reviewed publications ranked by citation index. The assessment of worth is often made or guided by young administrators who have limited experience as professional scientists. This system, which has developed rapidly over the past two decades, selects strongly for the rapid, superficial and brass-necked author who will argue relentlessly for publication with editors and reviewers. It does not select for originality or utility, nor does it encourage a sense of faith and common purpose between the funding agency and the grantee. It is transparently open to fraud and abuse, which the recent tragic case at the Bell labs makes all too clear, and it discourages the acquisition of real, certain knowledge and its application. It also massively undervalues the development of novel technology. Thus, the movements in the evaluation of science and the direction of science funding are resulting in a science of less strength and utility and which is thus less suitable for commercial development. It was remarkable, for example, that, in the much-praised UK University Research Assessment Exercise (RAE), patents were not counted as publications. This is an issue of vital importance as effective new treatments can only be developed on the basis of rigorous science. Rigorous science flourishes in elite well-funded centres where assessment is judged on longterm performance and key scientists are given the freedom and support to tackle time-consuming projects. Even a superficial examination of the Laboratory of Molecular Biology in Cambridge compared with any other UK academic center reveals how cost effective such an approach can be. I haven't done the calculation, but the cost per Nobel Prize must be the best in the world. Despite these deep-routed problems, the basic research carried out in our universities and hospitals is of fundamental importance to the industry, and much is still of a suitable standard. However, in many cases, the interaction between the commercial sector and the academic centres is blocked to a substantive extent by the misguided actions of university and charity-supported technology transfer offices. When I once asked a noted UK venture capitalist what his solution would be to the dearth of successful spin-out companies in the UK, his simple reply was to summon all the technology transfer officers of the major UK universities to a conference and then ‘shoot them’! What causes such extreme reactions is of course a lack of mutual understanding. It is unthinkable that the hardworking and diligent officers of the technology transfer offices come to work each morning thinking how they can hold back the success of their institution and the economic growth of their nation. Yet their actions often achieve exactly that result. Typically, the officers will act to file patents on university research of dubious value and then attempt to sell or licence them to commercial concerns, often at ludicrous asking prices and without the support of the inventor. By contrast, what the institute needs is the active engagement of its scientists in interaction with industry and in the creation of new companies. What industry wants, be it a big established company or a start-up, and will pay for, preferably in arrears, is access to the scientist and technology in a rapid and open form. Universities and institutes worry about being ‘ripped off’, a mythic fear fed by stories of monoclonal antibodies and other old gems. Monoclonal antibody technology, given to all, has been of tremendous benefit for mankind and has provided great commercial success – it is thus a wonderful example of successful technology transfer. Universities and research councils are funded by the taxes paid to the state, and economic success ensures that a nation has sufficient revenues to fund its academic institutes and that its citizens support its charities. It is therefore reasonable that universities and other academic institutes should think first (or be encouraged to think first by suitable incentives) to contribute to the success of the economy and secondly to their own profit. Even start-up companies pay large amounts of tax as each employee will give half their annual earnings to the state. Many successful entrepreneurs will end up giving to their alma mater in the future. The current system encourages delay and inaction so that often ideas are lost and opportunities missed. The formation of interaction with industry and the founding of new companies have tremendous longterm benefits in terms of training, job creation and positive publicity. What solutions can be offered that will help the knowledge economy and prevent my venture capitalist friend going to jail for mass murder? How can we fill the gap? Some simple rules could be applied by the heads of academic research institutes and universities. Recognize and encourage only really outstanding science. Make those judgements within your own organization and praise and reward excellence. Encourage scientists to work with industry and to establish companies. Do something, never nothing. Take equity in return for services. Recognize the macro-economic benefits of technology transfer. Be patient and encouraging. If you can't deal with an idea or concept, give it away rather than cause the world to lose it. Do experiments; no one knows how to do this perfectly, so try different ideas. Be quick: other are chasing hard. Mind the gap!‘It is therefore reasonable that universities and other academic institutes should think firstto contribute to the success of the economy and secondly to their own profit.’ David Lane is the founder and Chief Scientific Officer of Cylclacel Ltd, a Dundee-based Biotechnology company that is developing new treatments for cancer and other major medical needs. The views expressed in the above article are his own and not those of the organizations for which he works.