NCATS Director of Clinical Innovation
Mike's Blog
You Say ‘Po-tay-toe’ and I Say ‘Po-tah-toe’
By Michael G. Kurilla M.D., Ph.D.
April 29, 2024
At the recent ACTS meeting in Las Vegas, there was quite a bit of conversation concerning ‘translation’ and specifically the distinction between translational research and translational science. Contemplation about this distinction has generated dialogue since the founding of NCATS and continues to spark debate. Some have expressed the notion that research activities (beyond basic science) must conform to an either/or scenario where the Venn diagram of translational research and translation science is two non-overlapping circles. This dichotomy then leads to attempts to define/classify/categorize activities into neat little checkbox lists (research OR science). We need to unpack this a bit.
Let’s first pause and remember that NCATS stands for the National Center for Advancing Translational Sciences and that the CTSA Program stands for Clinical and Translational Science Award. We’ve heard comments that with the new CTSA UM1 NOFO, there has been a dramatic pivot away from translational research towards translational science. A pivot seems unnecessary since from the program’s inception and NCATS’ creation, translational science has been front and center.
Regardless of the focus (research versus science) the core concept here is translation. From the current NCATS Strategic Plan, translation is defined as “the process of turning observations in the laboratory, clinic, and community into interventions that improve the health of individuals and the public — from diagnostics and therapeutics to medical procedures and behavioral changes.” (emphasis added). Interestingly, the criteria for a Nobel prize also includes the phrase, “conferred the greatest benefit to humankind.” Alfred Nobel was a chemist, but clearly understood translation, ‘translating’ nitroglycerin (a dangerous, unstable, and explosive liquid) into dynamite with multiple commercial applications (mining and construction, especially). Some of his impetus may have been due to his younger brother having been killed in a nitroglycerin explosion.
For basic research/science (odd how no one ever tries to make a distinction here), the intent is the furtherance of knowledge that may or may not have any practical value beyond the niche scientific community as consumers of the work. Scientific observations and experimental results become the starting point for further investigation, ‘wherever that may lead.’ And new knowledge is always welcome, even if it takes decades or longer for someone to do something useful with it. Knowledge for the sake of knowing more is the primary goal, and doing better is aspirational.
Translation on the other hand deliberately picks a specific destination. In the pharmaceutical sector, you plan backwards. You may have identified a new target gene that suggests the possibility of addressing an unmet medical need, but the first question is not about design of the high throughput screening assay, but rather, what will the label look like on the approved product. Once you know the label, you can design the type of Phase III trial to achieve that label and then continue backwards with Phase II, then Phase I, then all the necessary preclinical work, etc. Of course, no plan survives first contact with the enemy, but even though ‘plans’ may not always be helpful in the end, ‘planning’ is essential and always useful.
Translational science is defined (from the NCATS Strategic Plan) as “the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process.” And finally, translational research is any activity advancing an ‘observation’ through those steps in the translational process. As such, translational science versus research is not an either/or issue, but rather, all activities focused on translation are clearly translational research. Overlaid on top of those activities is the possibility of a translational science component if an aspect of the work includes a focus on a particular step in the translational process by either refining, enhancing, simplifying or even better, innovating a whole new approach to navigate the translational process, accelerate translational progress, or enhance the impact of translational research efforts. For example, the Apple Watch atrial fibrillation study, while specifically focused on the detection of a-fib using a common wearable device, also identified challenges in the conduct of that trial that are likely to be encountered in any large, decentralized trial. As a result, the approaches and solutions developed during the course of that trial will likely be generalizable for other, future decentralized trials. Those investigators were multi-tasking, conducting translational research as well as translational science at the same time (without a net, no less!)
Additional commentary overheard at the ACTS meeting concerns the perception that training young investigators in translational science is a ‘dead-end’ exercise as there is no follow-on funding (R01) through NCATS for translational science. And since other NIH ICs don’t fund translational science either, the need to ‘pivot’ back to translational research is trooped out again as a discussion point. While it’s true that other NIH ICs are not focused on translational science per se, as it's not in their mission, they do have an intense interest in translation itself. Being recognized as someone trained in translational science will be seen as a plus for any activity that includes a translational component. One could also assert that no other NIH IC is focused (in their mission statement) on the science of community engagement, trial design, biostatistics, or dissemination & implementation, but NIH ICs value those skills and fund plenty of research utilizing those skillsets (as well as some science in those areas as part of larger projects). And in the same way that someone trained in enzymology may apply those skills to a particular clinical field (since there are enzymes everywhere), they can still be a card-carrying enzymology scientist (largely funded through NIGMS) and also be recognized (and funded) for their enzymological research activities (in addition to their enzymological science) applied to a specific field of inquiry supported by other NIH ICs.
Lastly, some historical perspective: for much of the 2nd half of the 20th century, the formula for improving health was an NIH driven engine of basic scientific discovery with the pharmaceutical, biotech, and device industries taking responsibility for ‘translating’ those discoveries into implementable health solutions. Over time (and for many reasons), industry has shifted their focus away from the initial steps immediately after discovery, towards the later and more expensive stages (Phase III registrational trials, commercial scale production, fill/finish, regulatory actions, and global distribution). As such, the academic and non-profit sectors have recognized the opportunity to take on more and more translational activities to advance novel and innovative health solutions to a stage where hand-off to a commercialization partner can occur. What was once a proprietary and closely held corporate advantage (the secret recipe for ‘translation,’ team science, and project management) has migrated to a diverse academic community. In addition, novel and emerging science & technology demand novel and innovative approaches to ‘translating’ that science & technology into health solutions that everyone can actually use without going broke.
If we can envision a future where not every newly developed health solution must be a blockbuster drug, command premium pricing, or be something that can make a biotech CEO a billionaire, then CTSAs need to step up their translation game to participate in reimagining and articulating (with appropriate ‘translation’) what future health care and health care delivery can look like. The birthing of 21st century medicine is yours to deliver. It’s time to snatch the pebble, grasshoppers!
There’s a way to do it better – find it.
-Thomas Edison