Will biotechnology save the world?

Jens Nielsen is a professor of systems biology at Chalmers University of Technology in Gothenburg, Sweden, where he heads research on yeast metabolism. He is one of the leaders in the field of metabolic engineering and developing the concept of cell factories – using yeast to produce different chemicals, fuels or medicines. He also deals with human metabolism including the influence of intestine flora on our health.

He was invited a number of times to the Renewable Resources and Biorefineries conference and finally he came – to the University of Environmental and Life Sciences in Wrocław. During the 13^th edition of the conference, which UPWr co-organized, we talked about whether world without oil is possible, how intestine bacteria influence our health and if bacteria will cure us one day.

* * *

Can you imagine a world in which the whole industry is based on biomass and cell factories?

It depends how we define industry. Calculations show that we are not able to produce enough biomass to replace all fuels used today. However, I can easily imagine a world where all chemicals – those used today and those which we will need in the future – will be produced from biomass. Just like some important fuels such as, e.g., aviation fuels. However, we will also have to rely on other means of transport, such as electric cars.

How do cell factories actually work? I’ve heard that you can compare them– simplifying things of course – to beer production in tanks.

Absolutely! Beer and wine production are classic processes in which yeast transforms sugar into ethanol. We use exactly the same mechanism in cell factories – but instead of ethanol we obtain a product we are after.

In side reactions, when yeast decompose amino acids and other compounds from initial components we obtain specific taste markers which determine the taste of beer or wine and cause them to taste different. In chemical production we are interested in we program the process in such a way as to limit side reactions to the minimum – we are only interested in the main, target product.

If scientists know how to utilize yeast for biofuel, biochemicals or bioplastic production, why isn’t this knowledge widely used? Is it about money or lack of infrastructure?

The biggest problem is high development cost. We are able to design cell factories in which production would be cost-competitive. Developing the production process, however, requires a lot of time and is hugely expensive. I think that there will come a time when we’ll have to find the money but we’re probably not ready just yet.

Let’s say we want to produce biofuel – it has to be very cheap to compete with oil. The profit margin is thus extremely low, and if we already have a huge debt, because we have been investing in R&D for years, then it’s a big problem. That’s why industry resists and is not willing to make such investments. And this won’t change as long as the price of oil fluctuates. If businesspeople were sure that oil now costs, for example, 50 dollars a barrel and it will always cost like that – they would be able to take it into account in their investment plans and would know when the investment would pay off. With constantly changing oil prices, it’s a multi-million-dollar risk which nobody wants to take.

Changing the subject a little – what is the influence of gut flora on our health?

We still don’t know it. Though it’s almost certain that there is an influence and not an insignificant one either. We know for instance, that intestinal flora of diabetics is very different from that of healthy people and that many different illnesses – including autism, depression and other mental disorders – are connected with intestines. People suffering from these illnesses have different flora too.

The question remains however, which is the cause and which the effect. Does illness cause the change, is it some bacteria that influence our bodily chemistry or even neurochemistry and how do they contribute to illnesses?

Recent research, which we participate in, identify specific substances produced by gut bacteria influencing insulin receptors in liver cells. When scientists gave these substances to mice, they indeed observed this interaction. This is probably the first research proving that gut bacteria can produce substances that have a direct impact on our physiology.

So the theory saying that intestines are like our second brain and are also responsible for our mental health may be true?

Yes, there must be something in it when we use the phrase “gut feeling”. I’m sure it’s true but we still have little scientific evidence for that. On the other hand, there is already too much evidence to regard it as pure coincidence.

What does the state of out intestines depend on then? Genes, diet?

Again – nobody has thoroughly researched it yet, but it seems to be determined by both genes and our lifestyle. So we are in a complicated position where our genes determine colonies in our intestines and what colonizes them influences body reactions, lifestyle, nutrients we ingest and further development of gut bacteria. This interaction is difficult to explain.

We have recently been taking part in vast research in which we have access to dietary data and gut microbiota of over 2 thousand people. The problem is that people eat very differently and when it comes to talking about what they have eaten… they usually aren’t very honest. So we will sequence the genome as well as gut microbiota. I hope that after this research we will finally determine the interdependence of genetic predispositions, lifestyle, diseases and state of intestines.

Do you think that if we understand this relationship better, we will be able to cure some illnesses by administering specific bacteria? Apparently, such cancer treatments already exist.

This particular therapy was tested on mice with cancer – some of them did not respond to immunotherapy but got better after being given some lacking bacteria. These results are very promising and indeed allow us to suppose that soon we’ll be utilizing bacteria for treatment.

We already take probiotics, that is pills with bacteria and some time ago a lot was being said about fecal microbiota transplant…

Transplant of feces along with gut flora from a healthy donor are used to treat e.g. very serious colon infections caused by Clostridium difficile. this is practically the only available treatment and it works – people get over extremely serious conditions.

Now we can only imagine possibilities we’ll have when we achieve a little more precision and learn to program pills with the specific aim to “push out” some infections from the body. But it will finally happen.

And if somebody wants to lose weight? Should they rather go to a dietician or to a scientist – biotechnologist?

(Laughter) A few years ago we published research results on cell metabolism in which we made mathematical models of gut flora composition. The models allowed us to suppose that different people react differently to different diets, depending on their gut flora. Everyone asked me then how to lose weight. The best answer is always – eat less, it always works (laughter). But people would of course want to get an easier solution than to change their habits.

In Scandinavia nobody trusts science – literally nobody. Maybe except car designing. It’s the French who believe science more than other nation so our French partners say that if people were given a computer-designed diet, everyone would follow it.

Making a good diet with traditional methods is also extremely complicated so maybe in the future dieticians will use computer models to achieve greater precision. I don’t know. Time will tell.

So what will be the biggest challenge of biotechnology in the next years or decades? What will biotechnologists work on the hardest?

Considering all we have talked about, I think that we will soon see a breakthrough when it comes to the amount of bioproducts – because despite the problems I’ve mentioned, there is a growing need for balance and so-called sustainable growth. There is growing consumer demand for biochemistry, bio-packaging for products which we buy every day in our supermarkets. The chemical industry will have to meet this demand. It’s the same case with bio jet fuel. I guess that political factors linked with consumers’ expectations will initiate or rather accelerate, as it’s already happening, the process of production and implementation of bioproducts.

And when it comes to medical field – within the next 10 years we should have first medicines based on microorganisms. Though, this is, of course, easier said than done.

mj