The important versus the exciting: reining contradictions in contemporary biotechnology

The applicability agenda of modern Biotechnology needs no explanation or justification. As any technology, the ultimate value of Biotech is to deliver materials, molecules or processes of interest for the medical, agricultural and environmental market. However, if one takes a look at high-impact journals or reads grant proposals on topics presented as Biotechnological research, one legitimately wonders when and how the many exciting results and concepts that often make headlines will get close to actual, beneficial uses to society and economy. There is indeed a Valley of Death in terms of funding between original scientific discoveries and applications that is typically punctuated by the scores (1–9) of the so-called Technical Readiness Level (TLR). But – important as it is – in our opinion, the issue is not just about funding but also about overcoming the conundrum exciting vs. important. The first gets all the attention, receives all funding and it is frequently published in prestigious journals. No surprise that the most creative minds flock to identify and get engaged in exciting endeavours, not the least because of the career benefits involved. However, exciting seminal discoveries in Biotechnology are worth nothing if they are not followed up all the way to technological readiness. Fleming’s observations on penicillin had to wait two decades until Florey and Chain figured out ways to scale-up the production process. But who remembers the last two? In sum, it seems that finding or developing properties with a biotechnological potential is exciting. But scaling up and designing processes is perceived as boring, a sort of second-level endeavour to be addressed also by second-level professionals. In this Crystal Ball, we would like to take the opportunity to argue how wrong this is. Scale-up is in fact the most important bottleneck that contemporary Biotech has to address if it is to find its niche in a large-scale industrial landscape. This is different from the small-scale production of very high added value biomolecules, such as pharmaceuticals, and the GMO-based agriculture. Let us take an example close to the core Microbial Biotech agenda: whole-cell catalysis and biotransformations. The literature has plenty of metabolic engineering cases where microbial strain A (or even an artificial consortium) is heavily refactored genetically by scientist B to produce compound C (biopolymers, biofuels, fragrances, food additives, speciality chemicals etc.). Although the yields are typically not great, the high-prominence work on this project done by researcher B often stops there (the generation of a new property). What happens next (if it does) generally disappears from the high-visibility radar and B moves on to engineer another strain A that produces another interesting molecule C and so on. The scale-up and the downstream processing (the most limiting factors for raising industrial interest) are taken for granted, handed over to engineers and generally considered devoid of much interest. This state of affairs creates a scenario in which genetic and metabolic engineering of biological systems advance at the speed of light. But process engineering seems to be stuck in century-old principles. The iconic and still prevailing production setup for biomolecules synthesized by microorganisms is that of a fed-batch fermentor with sizes anywhere between millilitres to cubic metres, inoculated with a single strain and grown in a sterile culture medium. After fermentation, the biomass has to be separated, the product of interest extracted and the liquid medium disposed of as waste. While much of the progress in reactor design has focused on automation and control, in reality the principles behind such fed-batch fermentations are not that different from ancient Egyptians producing beer thousands of year ago! Can we do better? The answer is yes, provided that we reformulate what appears to some like mere technicalities into exciting research issues. Let Received 12 November, 2018; accepted 12 November, 2018. *For correspondence. E-mail vdlorenzo@cnb.csic.es, Tel. +34 915 854 536. Microbial Biotechnology (2019) 12(1), 32–34 doi:10.1111/1751-7915.13348