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Biotechnology is considered to be one of the key technologies of the 21st century. It is a motor for the international competitiveness of the German economy and makes an important contribution to the bioeconomy. Our author Katja Lüers visited the biotechnologist Prof. Wolfgang Wiechert at the research center and talked to him about current developments and perspectives in so-called white biotechnology. This is relevant for processes in industry.

Even the ancient Romans loved wine, bread and cheese - humans have been using microorganisms such as bacteria and yeasts to produce or refine food for thousands of years. What initially happened as a result of chance discoveries, today occupies an entire branch of science whose areas of application go far beyond food production: biotechnology. It can be found in antibiotics, animal feed, skin creams or detergents: For example, enzymes in detergents accelerate chemical reactions and can remove proteins and stubborn dirt at low temperatures. The winner: the environment, because the washing powder contains fewer environmentally harmful substances.

Reaching into nature's toolbox helps industry to work in a more resource-conserving and environmentally friendly way - a key on the way to a bio-based economy and thus to a bio-economy: renewable raw materials instead of crude oil. This industrial biotechnology is also called “white biotechnology” and is differentiated in terms of content from “red biotechnology” (medical-pharmaceutical biotechnology) and “green biotechnology” (agricultural-plant biotechnology).

High investments and long development times

The search for a suitable microorganism or a suitable enzyme for industrial production is reminiscent of the famous search for a needle in a haystack. Once the researchers have finally found what they are looking for, they first optimize the organism or the enzyme and the process in the test tube. This is followed by “upscaling”: The process must also work on an industrial scale, because the desired substance, for example an amino acid, should not only be produced by the gram, but in tons. Last but not least, the product has to be isolated from the nutrient broth and cleaned, experts speak of "downstream processing".

Prof. Wolfgang Wiechert
Copyright:Research Center Jülich / Ralf-Uwe Limbach

"Everything works much faster today than it did 20 years ago, but - especially in comparison to the chemical industry - it is still too slow," says Prof. Wolfgang Wiechert, who heads systems biotechnology at IBG-1. For example, if a biotechnologist has discovered a bacterium that produces an amino acid as a potential dietary supplement, he cannot say anything about whether a competitive production process will even emerge, nor how many years it will take for it. “These development times, which are difficult to calculate, and the associated economic uncertainties are the main reasons that investors still steer clear of biotechnology,” explains the professor for “Computational Systems Biotechnology” at RWTH Aachen University.

In order for biotechnology to remain on a growth path and to expand its leading position in the international market, it must increase its competitiveness. This is where Wiechert's position paper "New impetus for biotechnology" comes in, which he wrote with other scientists and presented at the 2018 annual conference of the DECHEMA Society for Chemical Technology and Biotechnology.

In essence, the authors are concerned with how research and development will succeed in accelerating the development of biotechnological production processes and products as a whole: “We are not talking about improving individual technologies, but about radical change in workflows, processes and business models will fundamentally change, ”said Wiechert. The end result could be a development laboratory that resembles an automated production line. This should shorten development times and, above all, make them more predictable - the key to opening up new markets and developing business models.

View into a biotechnological laboratory at the Institute for Bio- and Geosciences, Biotechnology (IBG-1).
Copyright:Research Center Jülich / Sascha Kreklau

The revolution begins in the laboratories

Whether in the USA or in Europe - a lot is already happening in those laboratories that are equipped for this. "We are observing a strong trend towards miniaturization and automation worldwide," says Wiechert. Laboratory robots have found their way, as have high-throughput technologies, i.e. processes with the help of which certain information can be recorded and analyzed more easily, quickly and to a greater extent: "These automation technologies are all already available and can be bought," explains Wiechert.

The real driving force behind a change in biotechnology is miniaturization. An example from Jülich: Wiechert and his team cultivate microorganisms on a laboratory scale in certain containers, so-called bioreactors. The aim is to optimize the single-cell organisms so that they can later be used in industry on a large scale. The decisive factor is that this cultivation must be carried out under conditions that are typical for the subsequent production bioreactor in industry, i.e. a good supply of oxygen and nutrients.

But that used to take up a lot of space: “Just eight such vessels fit on a table,” says Wiechert. There is now a space and time-saving alternative: the microtiter plates with their 50 bioreactors or more each fit on a DINA5 sheet. They are filled and sampled automatically. “Nobody has to pipette anymore,” says Wiechert.

In addition, the interdisciplinary team is developing so-called microfluidic single-cell bioreactors: the researchers can carry out several hundred growth experiments at the same time on a chip the size of a one-cent piece. "In contrast to the microtiter plate, the chip is not yet ready for series production," says the institute director.

Robotic system for automated pipetting
Copyright:Research Center Jülich / Ralf-Uwe Limbach

Evaluation as a bottleneck

But experimenting in the smallest of spaces does not trigger a revolution. The interplay of miniaturization, automation and digitization is decisive: “If we reduce experiments microscopically, it is impossible for people to set them up by hand because of the large number of experiments. That is why we control the processes electronically, automate and standardize them, ”explains Wiechert. The mass of high-quality data, in turn, has to be evaluated quickly, and digitization is almost imperative. “Automated data analysis is therefore the next necessary step - we have to catch up,” said Wiechert. The bottleneck is no longer the experiment, but the evaluation.

Changed job description

Microtiter plates are filled automatically
Copyright:Research Center Jülich / Ralf-Uwe Limbach

As a result, the work of the biotechnologist on the computer changes: The scientist becomes the final information reviewer and process decision-maker. In the future, he will design the experiment, write the “recipe” and feed the information to the computer that oversees the automation system in the laboratory. After the end of the experiment, the computer provides the researcher with the evaluated data. The only people who are still allowed to enter the laboratory are the technicians who wait for the robots.

What sounds like a laboratory of the future is already part of everyday life in some US biotechnology companies such as Amyris or Zymergen. German companies such as GeneArt or Boehringer Ingelheim are also increasingly focusing on the simplification of work processes in culture, expansion and cell monitoring.

The challenge for the industry: "It will hardly be possible to gradually replace the classic work processes and methods that still exist in the laboratories with automated processes," explains Wiechert. Instead, the automated procedure has to be established from the ground up - the pieces of the puzzle are already in place in individual working groups and institutes. "But a change is only possible when the technologies work together," says Wiechert with conviction.

Jülich strengthens the growth engine biotechnology

The biotechnologists at Forschungszentrum Jülich have set out to further strengthen the growth engine biotechnology: "We are pioneers across Germany in automation and digitization, and even at the forefront of automated process development internationally," says Wiechert. Two successful projects have been placed at the IBG-1: On the one hand there is the Microbial Bioprocess Lab, or MiBioLab for short - funded by the Helmholtz Association. “With this we make our methods palatable to the industry, taster courses, so to speak, without a company having to invest in an automated system immediately. We now have global players like Sandoz or Christian Hansen on board - we need multipliers like these to drive the automated development of economical production processes for the manufacture of chemicals, pharmaceuticals, feed or food additives, ”says the expert.

On the other hand, the DigInBio project - digitization in industrial biotechnology - funded by the BMBF has existed since the beginning of 2018. There, digitization methods are developed that combine individual work steps into a continuous digitized process, i.e. away from isolated solutions towards a single workflow.

Wiechert cannot fully predict how such a revolutionary change in biotechnology will affect the world of work in the long term. "But it is clear that if we do nothing and continue to invest in outdated techniques and methods, other countries will take over the top position!"

Katja Lüers

Last change: February 17, 2020