Supertrends: Welcome to Supertrends Interviews. Today, our guest is Stefano Bertacchi. Stefano has expertise in industrial biotechnology and bioeconomy. He holds a PhD and is an assistant professor in fermentation chemistry and biotechnology at the University of Milano Bicocca. He was also recognized as an EU Bioeconomy Youth Ambassador. Hello, Stefano.

Stefano Bertacchi: Hi.

Supertrends: Maybe we can start with something basic. The term "biotechnology"  is used almost everywhere these days, but I sometimes wonder how many people really understand what biotechnology is. Could you explain it in simple terms?

S.B.: Biotechnology can have several definitions, but the simplest one is the use of living cells or parts thereof—like enzymes, which are often proteins—to obtain products and services that are useful for people, industry, or other applications. This is a broad definition and includes classic biotechnology processes such as bread-making, brewing, yogurt-making, or cheese-making, which use microbes to transform raw materials derived from plants or animals into useful products.

The term biotechnology also includes other types of processes using different types of organisms. These can be whole animals or plants, single cells, groups of cells, or enzymes. Examples include the use of enzymes in detergents to remove stains from our clothes or genetically modified cancer cells to produce pharmaceutical compounds. Another example is recombinant vaccines or the new mRNA vaccine technology.

Biotechnology covers a broad spectrum of technologies, which makes it challenging to explain and regulate. We have various sectors within biotechnology, from health and green biotechnology to industrial and environmental ones. Health biotechnology is particularly significant due to its market size and its implications from political and societal perspectives, though other areas are also important.

Supertrends: So, we could say that biotechnology is not a new thing at all. It's been with us for a long time. We're just much more advanced now in how we use it.

S.B.: Definitely. We might say that it was born alongside society and then developed really fast. We have to remember that we didn’t know the structure of DNA until not so many years ago. Since then, a lot of things have happened very quickly. It’s also hard to keep up with the speed of all these new technologies. Every year brings amazing advancements, but it often feels like you’re running behind. In the last 10 years alone, so much has changed, and from my experience in research, I’ve seen how rapidly things evolve.

Supertrends: Regarding emerging biotechnologies, do you think some are more important than others? Do you have any favorites that you think will be the most impactful?

S.B.: I might be biased due to my research field, but technologies related to developing bioreactors are important. Also, collecting more data from biological processes and understanding what happens inside the cells with advances in metabolomics, proteomics, genomics, and epigenomics is crucial. We also need to be able to process these large amounts of data rapidly.

Genetic modification and synthetic biology, including technologies like CRISPR, are also significant. While CRISPR-Cas9, a system that can precisely cut DNA, is well-known, there are now many variations and always new developments in this area. Genetic editing can have a profound impact on both industry and agriculture by enabling the development of various types of microbes and plants.

Then we have the healthcare sector. Gene therapy and vaccine development are definitely game-changers and are important to people. When you touch on health topics, they sometimes become more important than, for instance, energy-related topics. Both are among the most important sectors, but from a societal perspective, health is definitely more relevant. Additionally, there is more money behind health because politics can push in that direction. That's why, in the bioeconomy, we do not consider the health sector because it already receives substantial funding. Instead, we are focusing on other areas. We will probably discuss this later.

Supertrends: Coming back to health, gene editing is no longer science fiction. It's happening now. This raises various ethical questions. Could you elaborate on the potential ethical issues and how we might address them?

S.B.: Ethical issues are indeed significant and must be addressed from the beginning to show society and policymakers that we are not just mad scientist and are aware of the implications. I'm speaking generally for scientists, though I do not work in the health sector, as mentioned.

The boundaries of biotechnologies can be difficult to define, as they depend on cultural, ethical, and religious perspectives. For example, the cloning debate in the 90s, with Dolly the sheep, raised many ethical concerns, though it didn't have as profound an impact as initially feared.

Regarding gene editing, for example, Jennifer Doudna and Emmanuelle Charpentier, inventors of the gene-editing system CRISPR-Cas9, organized a big conference with many scientists and said, "OK, we set this as a boundary, do not touch human embryos at this or that stage." But then again, that's just that bunch of scientists deciding. But who can actually control and regulate national governments? In the European Union or the US, there can be specific laws to set boundaries. But enforcing these boundaries can be complex, given the global nature of scientific research.

Additionally, showing the public that scientists are concerned about these issues is crucial. As a science communicator, I see some people saying that these technologies are cool, but some people are scared. For example, think about the gene drive for local mosquito extinction. Of course, that's not a small thing; it significantly impacts an ecosystem. You have to talk with the local community, but they might not even know what a genome is. So, the ability of scientists to talk about their research—its possible impacts, the potential benefits, and also the possible downsides—is really important.

I don't have a main solution because it depends on specific situations. If you want to do biofuels, there are other ethical concerns about the use of biomass and land, et cetera. Biotechnology has so many shades that it's difficult to have one silver-bullet solution for everything, also from an ethical point of view.

Supertrends: So, communication is key to making sure people are aware of all possibilities and can understand the pros and cons.

S.B.: Exactly. Effective communication is essential for engaging with peers in science, the public, and policymakers. Ultimately, it is policymakers who make decisions about what can and cannot be done. For example, regulations exist for GMOs. In the European Union and the US, regulatory bodies are involved in these decisions, and while compromises are often necessary, involving scientists in these discussions helps ensure that decisions are informed and balanced.

Supertrends: Changing topic, you’ve already mentioned that you’re working with microorganisms to produce various products. What exactly are you working on? What can microorganisms produce in principle?

S.B.: I am working on the development of biorefineries and focusing on microbial factories. Essentially, I provide microbes with biomass, often from residual sources. For example, I use lignocellulosic biomass from waste or side-streams from other industries, such as the food one. We primarily work with yeasts and sometimes with bacteria to obtain products of industrial interest.

In my scientific career, I’ve worked on the production of carotenoids using yeasts that naturally produce these compounds, instead of extracting them from plants. I’ve also been involved in producing bioplastics with engineered yeasts, as well as vitamins, fuels, and components of feed for aquaculture. The portfolio is broad because nature offers such a diverse range of possibilities.

I’m currently at the University of Milano-Bicocca and also collaborating with the National Biodiversity Future Center, a significant EU-funded project in Italy. We use gene modification and synthetic biology with microbes, particularly Saccharomyces cerevisiae, one of the most common model microorganisms. Our goal is to transform molecules into compounds that don’t naturally exist, creating novel chemical compounds.

Currently, I’m focusing on aromatic compounds released from various types of residual biomass. For instance, I’m working with spent coffee grounds from vending machines, which are of course popular in Italy, and with residual material from the pruning of urban parks in the metropolitan area of Milan. Essentially, I apply enzymatic hydrolysis to these biomass sources to release sugars, which are then provided to microbes to produce the desired products.

In summary, we can exploit microbes for their natural abilities and "mine" biodiversity to find them. But, as already mentioned, we can also enhance their capabilities through genetic modification, using DNA from various organisms—ranging from sharks to bacteria—and inserting it into microbes to enable them to produce something they wouldn’t naturally be able to.

Supertrends: So, basically, there are numerous options for what you can produce using microbes.

S.B.: Yes, on paper. But in practice, it's always challenging. We have to remember that a cell is like a reactor where millions, probably billions, of reactions happen simultaneously and are highly regulated through natural or induced evolution. Sometimes it's hard to understand why or how something happens. Knowing what's happening inside the cell would be really important, as I already said.

Supertrends: Could microbial production help solve upcoming food security problems? With our changing climate and growing population, could using microbes in this way be beneficial?

S.B.: Yes, it could be for different reasons. Firstly, a lot of microbes are sources of nutrients like vitamins, or they can be engineered to produce specific compounds that we currently obtain from plants or animals. This could be very interesting and useful. There are examples like Spirulina bacteria, which is not something new. It has nutritional value and to make it grow, you don’t need a field or a farm—just a building. They grow with CO2. However, you need to convince people to eat bacteria. In this case, they are advertised as microalgae, but from a microbiological point of view, they are bacteria. It’s a matter of communication and regulation as well. Where do you put the boundaries of microalgae or bacteria? That is a matter of taxonomy, which is another story.

Another example is using precision fermentation to produce different types of molecules that are normally present in our food—especially those from animal origins, which have a big environmental impact.

Plant protection is another area where we could exploit microorganisms. We must remember that plants do not live alone. They have microbes, especially around their roots. The microbial communities, or microbiomes, living in the roots often work for the plant, enhancing its abilities and acting as a kind of pesticide. This helps the plant cope with different types of diseases.

Microbes can have a significant impact on food security, addressing the challenges we face. As EU Bioeconomy Youth Ambassadors, we've also emphasized biotechnology as a whole, considering microbes as an alternative protein or nutrient source beyond both animal and plant products. This is crucial because we can’t keep deforesting, which is unsustainable.

Supertrends: So, one potential problem is acceptance by people. What about the cost of nutrients or other products produced by microbes in bioreactors? Is it efficient and profitable at the moment, or would it become more so if it were more common?

S.B.: Let's say that we are probably in the middle of an exponential phase of growth and market impact. More and more of these technologies are becoming available and less expensive. Of course, it depends on the final cost of the product. While we talk a lot about sustainability, economic sustainability also needs to be considered.

On one side, these enterprises are generally very expensive, so we are asking for more financial help from institutions for these kinds of industries—especially those with the potential for significant impact but which currently need more support. Compared to the past, cost efficiency has improved, allowing for faster progress. However, it remains one of the main hurdles. A broader acceptance from the public could significantly increase the market for these products, helping to develop them further and potentially decrease costs.

When dealing with topics like biofuels or bioplastics, there's competition against fossil fuel sources. It's challenging because crude oil is highly profitable. From a barrel of oil, you can derive plenty of cheap materials, energy, and so on. The difficulty lies in competing, especially at the beginning, with industries that have been developed around such raw materials. However, as technology advances and market acceptance grows, we can expect improvements in both efficiency and cost-effectiveness.

Supertrends: This leads us smoothly to the bioeconomy. Considering we’ve discussed biotechnology, what is the relationship between the bioeconomy and biotechnology? Additionally, how does the bioeconomy differ from the traditional economies we have?

S.B.: The bioeconomy can be defined in really different ways, but the most common one is that it is a part of the economy that deals with biomass valorization or exploitation, depending on if you want to give it a positive or negative spin.

What exactly is biomass? Basically, it’s all organic material that is animal, vegetable, or microbial. We, as humans, are made of biomass. Plants and microbes are biomass, whereas rocks are not. This means the food sector is part of the bioeconomy. The paper and pulp sector is also part of the bioeconomy. Even the wood furniture industry falls under the bioeconomy. These three sectors are probably the most impactful in this space. I like to say that the value of the bioeconomy is high because it includes food. For example, Italy is strong in the bioeconomy, partly because of its food sector, as well as forestry.

Biotechnology is a small part of the overall bioeconomy, but it depends on how you define biotechnology. It can be considered part of the food sector since it involves transforming raw materials. You could also think about it as biomanufacturing. In the European Union, it constitutes about 5% of the total if we consider it so.

In the bioeconomy, you do not focus on health—at least in the European Union and probably in the US too, as I have already mentioned. However, you need to be careful when considering subsectors and where to invest sustainably. For example, the tobacco industry could be part of the bioeconomy since tobacco is a plant.

As already mentioned, I was appointed in 2022 as an EU Bioeconomy Youth Ambassador, giving me the opportunity to work closely with the bioeconomy team of the DG for Research and Innovation of the European Commission. This group developed the European Union's bioeconomy strategy, which is set to be updated in 2025 as part of the biotechnology and biomanufacturing initiative. We, a group of young people from all over Europe—with me being the oldest—wrote a document (Bioeconomy Youth Vision) aimed at reshaping how the bioeconomy is approached.

The bioeconomy could be unsustainable if not managed properly. It’s important to integrate sustainability into its definition and measure it effectively. Simply exploiting natural resources, like burning trees for bioenergy, isn't a sustainable solution. Among many others, one of the goals was adding biotechnology and synthetic biology, including genetic modification, to the bioeconomy strategy. This approach, while controversial among many stakeholders, e.g., politicians, environmentalists, is crucial for a sustainable future. Balancing science, economics, politics, and public activism is essential in this context.

Supertrends: I see. It sounds like the bioeconomy is quite complex. It doesn't seem to be a completely new concept when you mentioned all those examples. However, people are now talking about moving towards a bioeconomy, implying it's something new. But as you said, it is probably more about how we use the bioeconomy to be more sustainable.

S.B.: Definitely. Moving towards the exploitation of biomasses often means phasing out fossil resources. But this shift also introduces competition for biomass, which is not infinite. While biomass might seem easily accessible, it isn't as simple as just going out and cutting a tree. You must consider the collection of biomass and its environmental impact.

That's why we're working on the development of biorefineries based on residual biomasses, which are generally considered waste. The definition of what constitutes a residue or trash is important from a legislative point of view. If something is classified as trash, it can be considered dangerous, and you can't use it until it's properly managed. So, policy-making is crucial in this area.

Supertrends: It seems like there are many challenges and aspects that still need regulation to ensure clarity and alignment for everyone involved.

S.B.: Yes, it is very complex.

Supertrends: To conclude, could you name some bioeconomy initiatives from recent years that you find particularly interesting? Perhaps some projects or products made from biomass that have particularly caught your attention?

S.B.: One significant area of development is in the energy sector, where side-streams are being exploited without direct combustion—for instance, converting waste cooking oil into biodiesel is notable, though not entirely new.

In green chemistry, there are initiatives to produce compounds identical or very similar to those derived from fossil resources. For example, nylon can now be made from biomass using genetically modified microbes, although production is currently low.

Another interesting development is the creation of enzymes capable of degrading plastics. This innovation isn't just for environmental cleanup in oceans, which isn't practical or advisable due to the release of harmful compounds. Instead, it has immense potential for the biochemical recycling of plastics. Additionally, bioremediation using enzymes or microbes to manage toxic compounds in soil and water is promising.

The breadth of ongoing projects and the potential they hold are remarkable. The European Union has various initiatives, sometimes conflicting, which adds complexity but also demonstrates the extensive effort being put into this field. As a scientist and academic, I'm grateful for the opportunity to be involved in these initiatives, despite the added complexity it brings to my work. It's crucial for me to understand and communicate these developments effectively to ensure a broader understanding and acceptance.

The text is a transcript of an interview conducted on 16 July 2024. The interview was conducted as part of Supertrends'  "Interviews with Experts"  series. Please note that the transcript may have been lightly edited for editorial reasons.