How is biotechnology different from genetic modification?

Bioethics

Dr. Bärbel Hüsing

To person

is head of the Biotechnology and Life Sciences division at the Fraunhofer Institute for Systems and Innovation Research ISI.

Dr. Sven Wydra

is head of the Bioeconomy and Life Sciences division at the Fraunhofer Institute for Systems and Innovation Research ISI.

Dr. Heike Aichinger

is a research associate and project manager at the Fraunhofer Institute for Systems and Innovation Research ISI.

White genetic engineering? This means the use of genetically modified microorganisms, cell cultures or enzymes for the industrial production of various products such as vitamins, food or biogas.



Use of pesticides: Here, too, chemically synthesized active ingredients are increasingly being supplemented and replaced by biotechnologically produced active ingredients. Photo: AP (& copy picture-alliance / AP)

definition

In industrial biotechnology, often referred to as "white biotechnology", biotechnological processes are used in industrial production processes.

The abilities of certain microorganisms, cell cultures or enzymes [1] - to produce, convert or break down substances - are used for technical applications. In this way, many different products can be produced, such as food and beverages, vitamins and flavorings, active pharmaceutical ingredients and pesticides, chemicals, materials and bioenergy carriers (such as bio-ethanol or biogas).

Biotechnological processes play an important role in many industries today because they complement and expand the spectrum of industrially usable production processes. These include the chemical and pharmaceutical industry, food and beverage production, the textile industry, pulp and paper production, leather production and energy supply.

Reasons for using biotechnological processes in industrial production

The use of biotechnological processes in industrial production is associated with the expectation of improving existing processes and products and developing new ones. These can be products
  • in which the original production method is replaced by biotechnological process steps in order to be able to produce more economically or in a more environmentally friendly way (e.g. the fermentative production of citric acid by the mold Aspergillus niger instead of extraction from citrus fruits or stone-washed jeans, whose washed-out appearance is now with the help of enzymes instead of what was previously achieved by washing with pumice stones);
  • replace or supplement conventionally manufactured products and, if necessary, still have special properties and quality advantages (e.g. biodegradable, washing-active substances, so-called bio-surfactants, bio-ethanol as an alternative fuel);
  • that are unique and could not or could not be produced economically in any other way than biotechnological means (e.g. yoghurt, cheese, complex molecular structures, proteins as drugs, detergent enzymes;
  • use biomass as a starting material instead of fossil raw materials (e.g. "bioplastics", biofuels).

Significance of genetic engineering for industrial biotechnology

Biotechnological processes are not to be equated with genetic engineering: Classic biotechnological processes, in which naturally occurring microorganisms or enzymes are used, have been established for centuries, especially in food and beverage technology (for example the use of yeast in bread, beer and wine production).

Due to the rapid technological progress, the immense increase in available genetic information and the drastically reduced costs for genetic engineering processes (e.g. sequence determination), genetic processes are already routinely used today for the identification and characterization of new production organisms or enzymes. A growing understanding of the mechanisms underlying certain (desired and undesired) properties of production organisms makes it possible in many cases to identify new production organisms on the basis of their genetic characteristics. The organisms selected in this way are not genetically modified.

As a rule, however, naturally occurring organisms are only suitable to a limited extent for industrial production processes. That is why almost all production organisms used are those that have been optimized for industrial production processes and with which high production yields can be achieved. Many companies often use "own" strains of microorganisms for which they have the sole rights of use. These are genetically modified accordingly for new applications (for example the production of a new enzyme). By changing the genome, the metabolism of microorganisms can be optimized for the respective production processes (so-called metabolic engineering) or new genes can be transferred to an established production organism so that, for example, an industrial enzyme can be produced in it on a large scale. Various genetic engineering methods are available for this. A fundamental distinction must be made as to whether foreign DNA sequences are introduced into the genome of an organism so that the resulting organism can be described as transgenic, or whether exclusively random methods such as UV mutagenesis were used, in which the resulting organism changes in the Has genetic material, but these cannot be distinguished from natural mutations. For a few years now, methods have also been available that enable the precise modification of the genetic make-up (also known as "genome editing"). While so far only those organisms in which foreign DNA sequences have been introduced into the genome are considered genetically modified under German and European law, a discussion has now broken out about when an organism is to be considered genetically modified and what criteria are used to determine this evaluate is. Among other things, the European Court of Justice is currently dealing with this question.

Most products that are manufactured with the help of biotechnological processes or with genetically modified microorganisms are intermediate products that are processed in other industrial processes (sometimes also in other sectors) into end products with which the consumer ultimately comes into contact. As a rule, these intermediate and end products no longer contain any viable production organisms, but they may contain enzymes that were used as processing aids or genetically modified DNA.

The food market is a specialty within industrial biotechnology. Threshold values ​​are specified for genetically modified agricultural raw materials and for foods made from them, and special labeling is required if these are exceeded. Because of the negative attitude of retailers and consumers towards genetically modified food raw materials, genetically modified starter cultures and enzymes as well as additives that have been produced with the help of genetically modified organisms (also known colloquially as "gene products"), many products are available in different versions (conventional or gen (technology) free). The exact differentiation from such products can be difficult in individual cases, however, since genetic engineering methods may have been used in the course of the manufacturing process, but this can no longer be detected in the end products. This can be, for example, genetically engineered feed additives such as vitamins or amino acids (see www.transgen.de). As a rule, it cannot be assumed that there are health risks for end consumers when consuming products that have been manufactured using genetic engineering methods. Regardless of whether the production organisms are genetically modified or not, the use of microorganisms and enzymes in industrial production processes can pose a risk to human health. Primarily employees in biotechnological production plants are affected.

Since the mid-1970s, safety measures have been developed, made legally binding and introduced into industrial practice, with the aim of preventing hazards and protecting employees from infections, allergies or toxic effects. Most microorganisms that have been optimized for industrial purposes are likely to be significantly inferior to natural organisms in terms of their ability to survive in the free environment. An environmental risk can be seen in the spread of antibiotic resistance in particular. Many bacteria are capable of so-called gene transfer, i.e. the transfer of genes to another organism. Since many production organisms carry resistance genes for selection purposes, there is a risk that, in the event of a release, these resistance genes will be transferred to naturally occurring bacteria. The most important measures when working with genetically modified microorganisms are therefore to use harmless production organisms and to produce them in closed systems from which they are not released into the environment. (Federal Institute for Occupational Safety and Health (BAuA)). The use of genetic engineering can also make a contribution to safer production processes and products, since toxic properties of microorganisms can be specifically switched off or a non-critical production organism can be developed instead of a naturally occurring but toxic organism.

Novel biotechnological processes

In order to be able to use the immense advantages of industrial biotechnology efficiently in the future, on the one hand the already existing biotechnological processes must be continuously improved, on the other hand novel processes are required which are suitable for industrial use. Important trends are the closer integration of chemical and biotechnological process steps and the transfer of engineering approaches to biotechnological processes. In Germany, a large number of research institutions and smaller biotechnology companies are involved in the development of new technologies. A high hurdle, however, is the transfer of new concepts into economic applicability. Various examples already exist of how complete, non-natural synthesis pathways were constructed in a production organism; however, so-called synthetic biology is not yet being used on a large scale. "Genome editing" now also opens up extensive potential for industrial biotechnology. Among other things, it is expected that the targeted manipulation of the genomes of production organisms will overcome existing limitations and thereby open up a wide range of new areas of application for biotechnology, for example for the production of biofuels by microorganisms, in waste and wastewater treatment or for manufacturing of bio-based chemicals.

Economical meaning

There are only approximate data on the commercial exploitation and economic importance of industrial biotechnology. The "Key Enabling Technology Observatory" of the European Commission estimates employment in Germany, which depends on production using industrial biotechnology, at just over 50,000 people in 2013 (KET Observatory 2015).

Small and medium-sized enterprises (SMEs) play a much smaller role in commercial exploitation than medical (red) biotechnology. Most of the companies in Germany that specialize exclusively in biotechnology are primarily active in red biotechnology. 63 dedicated biotechnology companies, almost exclusively SMEs, clearly focus on industrial biotechnology in Germany (BIOCOM 2017). This number has remained fairly constant over the past few years. Small and medium-sized companies in this area have problems developing profitable business models. Especially in the case of mass products (e.g. basic biotechnological chemicals or bioplastics), they usually only play the role of research and development service provider or supplier due to the high capital and resource requirements. Only a few companies have their own development and production activities to a significant extent (see Aichinger et al. 2017).

The figures given for industrial biotechnology do not include any biotechnology research institutions or companies that only process biotechnological products or use established processes. It also excludes large companies for whom biotechnology is only part of the basis of their business.

But especially among the large companies in the chemical industry, a considerable number of strategic priorities have been set in industrial biotechnology and are expanding their activities in this area (e.g. BASF, Evonik, Wacker), even though their core business is still classical chemistry.

What's the future like? Is there a transition to the bioeconomy?

The turnover and share of biotechnological products and processes in all goods produced is still low. After all, there are also some obstacles to the spread of industrial biotechnology: In addition to the already mentioned critical attitude of consumers towards biotechnological and genetic engineering production processes, e.g. for food and feed, the often higher costs and prices compared to conventional products should be mentioned here. Processing companies and consumers are often unwilling to pay more for these products. According to expert estimates, however, there will be a significant increase in the coming years (BIO TIC 2015). There is great potential for industrial biotechnology through its possible contribution to the transition to a bioeconomy based on renewable raw materials instead of fossil raw materials.

Such a transition to the bioeconomy is seen as one of the central challenges of the coming decades. In Germany and many other countries, strategic research programs and political strategies have been adopted in recent years, which are intended to create the basis for a sustainable, bio-based economy (e.g. "National Research Strategy 2030" and "Political Strategy" of the Federal Government). In spring 2017, the German federal government also announced an agenda for the "biologization of production" (bioeoekonomie.de 2017). Often, the focus is no longer solely on replacing fossil raw materials with vegetable raw materials. Contributions to the achievement of climate and environmental protection goals and the "Sustainable Development Goals" of the UN are also gaining in importance and legitimacy for the promotion of the bioeconomy (Hüsing et al. 2017).

In the bioeconomy, biotechnological processes can contribute to a large number of product segments (bulk chemicals, fine / specialty chemicals, biofuels) to an economical and sustainable production method. In contrast to many conventional chemical processes, for which the majority of fossil raw materials are used, biotechnological production processes are generally based on vegetable and thus renewable raw materials. In addition, the use of biotechnological processes promises to make a significant contribution to climate protection: The energy requirement for biotechnological processes is often lower than for chemical syntheses and lower CO2 emissions are incurred. This means that stricter environmental requirements in production can partly be complied with through biotechnologically manufactured products.

However, there is always concern that in the future food and feed production, energetic and industrial use will increasingly compete for agricultural raw materials and that the agricultural areas will be cultivated too intensively and not in a sustainable manner. The challenges for the next few years will therefore be to expand biomass production for energetic and industrial purposes without endangering food and feed production, polluting the environment, destroying natural areas or contributing to an increase in food prices.

Here, too, great potential is ascribed to industrial biotechnology, since, for example, with the help of biotechnological processes, non-edible plant parts can be made usable or plants can be used that grow on inferior cultivation areas that are not suitable for food production anyway. In order to be able to use the available renewable raw materials as fully as possible, there will probably be so-called biorefineries in the future - these are large factories that process plant biomass into a variety of chemicals and intermediate products, into energy sources, feed and fertilizers and then further processing companies with these products (Federal Government, 2012; BMBF 2016). When processing the biomass, biotechnological processes will also be used: for example, microorganisms or enzymes can be used to break down the biomass.However, the currently existing processes are still too expensive and inefficient, so that the development and improvement of the processes will be central challenges in the years to come. It will also be the task of industrial genetic engineering to provide large quantities of highly efficient enzymes and microorganisms at a low price.

credentials

Aichinger, H., Hüsing, B., Wydra. S. (2016): Industrial Biotechnology: Processes, Applications, Economic Perspectives. TAB work report, Berlin: Office for Technology Assessment at the German Bundestag.

Bioökonomie.de (2017): Biologisierung on Political Agenda, message from July 31, 2017, http://biooekonomie.de/nachrichten/biologisierung-auf-politikagenda.

BIOCOM (2017): The German Biotechnology Sector 2017.

Bio-TIC (2015): Overcoming hurdles for innovation in industrial biotechnology in Europe - BIO-TIC Market Roadmap

BMBF (2016): White biotechnology - opportunities for a bio-based economy.

Federal Government (2012) Roadmap for biorefineries as part of the Federal Government's action plans for the material and energetic use of renewable raw materials. BMELV, BMBF, BMU, BMWi (ed.). Berlin.

Hüsing, B .; Kulicke, M .; Wydra, S .; Stahlecker, T .; Aichinger, H .; Meyer, N. (2017): Evaluation of the "National Research Strategy BioEconomy 2030". Effectiveness of the initiatives of the BMBF - Success of the funded projects - Recommendations for further strategic development

KET Observatory (2015): KETs Observatory Newsletter, Issue 4.