Translational science: drawing the line

Humankind has been researching and engineering for as long as we have existed. It was a matter of survival back then and it is still is nowadays. This long and involved process that spanned over several millennia has enabled civilisations to rise and fall. Thousands of years of science and scholarly traditions have led to the accumulation of an incommensurable amount of knowledge spread across various disciplines including mathematics, physics, chemistry and biology.

What is translational science?

The latin word “Scientia”  means knowledge, but it is only recently that the concept of “translational science” has emerged.  To understand the essence of this neologism the expression needs to be broken down into two definitions “translation” and “science”.

The mathematical definition of translation corresponds in geometry, to the process of moving something from one place to another. The second word science is defined as follows: the intellectual and practical activity encompassing the systematic study of the structure and behavior of the physical and natural world through observation and experiment.

The combination of these two definitions leads to the concept of translational science, which is the translation of fundamental science into practical applications. A famous illustration of this is the serendipitous discovery of penicillin in 1928 by Alexander Fleming which broke open a new field in modern medicine. In other words, fundamental science is the engine that powers translational research. If for any particular reason, the engine stop running, then there is nothing left to be translated.

In order for science to be developed in an unbiased way it needs to be performed free from any interest, otherwise conflict arise and findings tend to matches expectation and not observations. This point is crucial and clearly is a roadblock for translational science which, by definition is developed to be applied in order to generate a useful application and potential profit.

Science is unique in the sense that it is not made to deliver a product; it is designed purely to generate knowledge. Obviously there are major directions in science, but there is not a pre-determined end point. Instead, each discovery leads to the next one and adds to our understanding of the world in which we live. It is an endless process that is really often convoluted. Taking advantage of a particular discovery to make an invention that will be useful in a specific context is a different process that cannot be assigned to fundamental science. It corresponds to an engineer perspective where a technical issue is solved by a technological advance. Research directions in fundamental science have to remain limitless, otherwise, the scope of discoveries, and therefore the range of potential applications, would be limited to a predefined scientific horizon.

A recent example of this, is the discovery of molecular scissors known as “crisp/rcas9” which is currently revolutionising biological and medical research. It is now possible to edit the genome of a living organism without complex procedure, this has opened up new research avenues and therapeutic options. Such a discovery was originally made by scientists working on understanding the basic molecular mechanism driving of viral infection in bacteria.

For practical and ethical reasons it is not sustainable for academic science to get engaged in products development.  The lack of funding in academia for one part and the industry commitment and better ability to develop translational science leaves no doubt about role distribution.

Where things become blurry is that there is no clear demarcation defining where fundamental science does stop and where translational science is starting. There is not even a  clear definition of what translational science is, this notion can vary between research fields. It is just a vague concept that is being abused since in essence every fundamental discovery is potentially translational, but in reality only a really low percentage will become translated. This confusion is mostly due to the time scale difference. While academia establishes project planned over a decade translational research projects span over a shorter period of time (a few years).

Why has translational science been so successful over the past few decades?

Translational science draws on the large amount of knowledge that has accumulated over the past century. Sadly, this wealth of basic findings is not endless. The accumulation of knowledge generated by fundamental science has suddenly started to down-size due to a major shift into translational science activity that mostly feeds on previous ground-breaking discoveries, but that does not generate any novel fundamental findings itself. Translational science owes its success in part to a high level of attention from the media. This has contributed to draw support from the public arena but this push by the media in a desperate search for a scientific buzz also comes with a risk. In fact there is a real threat for scientists of potentially losing credit in the long term if the community fails to deliver.

How does the system remain sustainable in the long-term?

It is critical to maintain the right balance between fundamental science, which constitutes the foundation of any progress, and translational science, which converts a discovery into a useful application. This equilibrium is hard to maintain simply because the rate by which these two sciences evolve are dissimilar. In the case of basic science, significant advances are relatively slow mostly due to the fact that science relies on serendipity and scientific wandering. Some unexpected paths have to be explored over decades to enable a ground-breaking discovery. Failure is an essential part of the discovery process. Further, basic science is often limited by available technology. Ancient concepts are revisited regularly due to the development of new technology that enables us to probe fundamental mechanisms in more depth.

By essence, observation and experimentation are slow processes that rely more and more on complex research tools. Since science is becoming increasingly specialised and dependent on cutting-edge technologies, the discovery process is becoming increasingly more challenging. For instance, one of the bottlenecks of modern science is managing the huge datasets generated by genomic research. In that particular case, the physiological interpretation of the data is one of the limiting step. For this particular reason, it will take time to bridge the gap between genomics approaches and personalised medicine for instance.

By contrast, translational science is evolving at a rapid pace, since it is being determined by a specific endpoint, and its proof of principle, feasibility and viability have been already established by fundamental science.

Where to draw the line between fundamental science and translational science?

This discrepancy has been masked until now by the fact that a lot of knowledge has been accumulated in fundamental science and translational science could draw from this gigantic gold mine. However shortages in option start to arise in particular industries, since basic knowledge is running out. For instance in the case of drug discovery, conventional molecular targets have been over-exploited and pharmaceutical industries and academia have fallen short in discovering new molecular mechanisms that would lead to alternative therapeutic avenues.

National research agencies are pushing hard to encourage translational science, but the way it is being developed is not optimum. Funding bodies are trying to impose a shift of fundamental science into translational science, instead of promoting more bridging strategies that would enable academics and industries to work in a complementary fashion. At the international level with the merciless competition for commercialisation, this strategic choice could cost even more than not investing into fundamental science. At the end of the day, any novel drug of technology that reaches the market will be used on a global scale, and the price of buying its patent will cost a lot more than the initial amount of money that would have been necessary to discover its principle.  Governments and other funders must recognise the importance of having a thriving base of fundamental knowledge from which to translate, for both economic and health reasons.

Last but not least, an essential aspect of fundamental science is often forgotten, its main function, which is to generate knowledge. There is no direct dollar value for knowledge and expertise, however one of the industries directly benefiting from this output is the education sector. Translating knowledge into the education system is far more valuable in the long term than any drug that is being commercialised, and it is pretty daunting to envision a future where the engine of human progress would fall into decay.

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