“The use of technology in biology is certainly not new,” says Nadine Bongaerts, synthetic biologist and Chief Innovation Officer of the French start-up Gourmey. It is the first French cultured meat company to work on an ethical foie gras made from stem cells.

“We have been using yeast and bacteria for making wine, beer, and bread for thousands of years. But today, we are able to domesticate other cell types for the production of more products. For example, thanks to advances in cell biology we know to grow animal cells in large quantities. This is very useful for making cultured meat.”

Also read the article we published last week about the cultured meat from Mosa Meat.

“Biology has increasingly fused with other technologies such as computer science, robotics, physics, and chemistry,” Bongaerts says. This fusion is also called synthetic biology. “It is actually biotechnology, but much more advanced. For me, it’s about the ability to modify biological systems in such a way that they can do something that humans see the benefit of.”

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Small factories

According to Bongaerts, nature is made up of little factories. “If you zoom in on flowers, for example, you can see a tiny factory that makes scents. Even at the level of proteins, you can see that some structures look like cogs and tiny wheels. It looks as if a person made that design, but it has really come through evolution. That in itself is fascinating. Synthetic biology makes it possible to combine all those different natural parts of engineering.”

Bongaerts cites the company Genentech as an example, which in the 1980s put a piece of a human insulin gene into a bacterium. “That bacterium then started producing human insulin. This is still helping millions of diabetics today around the world.” Before then, insulin came from the pancreas of pigs. “You then need kilos of pig organ for just a few grams of insulin. And then it is still pig insulin.”

“By modifying DNA, you can turn a cell – such as a bacterium – into a mini-factory which enables it to reproduce rapidly. So you can make natural products on a large scale that way. Otherwise, you’d have to get those products from the original source, and that’s often very intensive, costly and maybe cruel to animals as well.”

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Nadine Bongaerts © Patrick Gaillardin

Smarter medicine

Also, using a biological process often does not end up creating toxic byproducts, Bongaerts points out. “It is a much cleaner process. The amount of waste products is lower and the process requires less energy. Cells can often grow at temperatures between 30 – 37 C degrees, or even lower. It doesn’t take several hundred degrees Celsius to cause a particular reaction. I think it would be great if we could replace chemistry with a biological system like this.”

Bongaerts goes on to say that we can also make smarter medicines using the same kind of technologies. “We now primarily use medicines where you take, or are administered, a certain molecule in the form of a pill or an injection. The problem is that, for example in the case of cancer, current drugs not only target the cancer, but also hit the healthy cells.”

The synthetic biologist cites CAR-T cells, a form of cancer immunotherapy, as an example. “These cells can detect cancer cells. As a result, a very targeted cancer therapy is created. The patient’s own body cells basically get an extra feature, they actually attack those cancer cells.”

DNA scissors

In 2019, Emmanuelle Charpentier and Jennifer Doudna received the Nobel Prize in Chemistry for their “DNA scissors,” i.e.: CRISPR Cas 9. This technique allows you to cut into an organism – a genome – at a very precise spot and add new DNA. “If you want to modify a piece of DNA, you first have to make sure that you also are working in the right place. Those DNA scissors can be programmed, so to speak, to delete a segment at precisely the right spot and then add a new piece of DNA. Because the cell repairs itself – it cannot continue to live with broken DNA – that new piece of DNA is then incorporated into it.”

Among other things, this technology makes it possible to make crops climate-proof. “I don’t see any other solution turning up any time soon. We can’t wait for evolution to produce climate-resistant plants. We don’t have time for that. Anyway, to tackle climate change, we will have to bet on more horses.”

Another interesting development is the ability to read DNA, also referred to as DNA sequencing. “What I find really amazing is that with this technology, scientists were able to read out the entire COVID-19 genome in just two weeks. In 2002, that took six months with the SARS virus. So, you can see how fast the technology has progressed.”

Storing data

Besides being able to read DNA, it is also possible to print DNA, this is known as DNA synthesis. DNA printing is so efficient that consideration is being given to storing all kinds of data inside DNA, Bongaerts notes. “For example, Microsoft and Twist Bioscience – a DNA synthesis company – are working together to look at the storage of information in DNA. Already, there are all kinds of movies stored in it, sections of books translated into DNA code, and they have printed that DNA code out completely as well. You no longer need a large hard drive then, just a few milligrams of DNA.”

However, using this on a mainstream basis is still a long way off, Bongaerts states. “It’s still too expensive to store something in DNA, plus you want to be able to read it out quickly. It hasn’t gotten that far yet.”

Of course, Bongaerts also sees the drawbacks that come with synthetic biology. “As the technology gets better and easier, it also becomes more and more accessible. That is something I do worry about. Due to rapid digitalization, we have to deal with cybercrime too. We also really need to start thinking about how we can secure ourselves against biocrime (the misuse of viruses, bacteria, fungi or parasites, to intentionally make people sick, ed.).

Not without risks

Carina Nieuwenweg is working on providing that security against biocrime. She is a synthetic biologist, doing her PhD research on CRISPR Cas at the Wageningen University & Research in The Netherlands, but she also has a background in military strategy studies. In addition to her PhD research, she is working on that “bit of security.”

As to whether biocrime really exists? “Yes and no,” says Nieuwenweg. “We are aware of the potential dangers of misuse, but there has not been a situation yet where it was a close call.” It’s hard to pinpoint examples of potential dangers because most of that is confidential, the synthetic biologist says. However, she can mention one example. “Scientist Fouchier, even before Covid, did research on ‘gain of function’ of certain viruses and which mutations the virus could use to jump over to mammals. It is useful information for understanding and preventing a potential pandemic. At the time, the criticism directed at the publication was that people could also be harmed by this.”

To prevent biocrime, agreements have been reached both internationally and nationally. E.g., internationally, the Geneva Convention has agreed that countries should not produce chemical or bioweapons. There are rules and methods in place to monitor those agreements. Parties like NATO have experts do what are called horizon scans. “They do scans of things that might cause us to fear certain technologies such as synthetic biology. If there is a risk of misuse, how great is the threat exactly?”

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Carina Nieuwenweg © Koen Manusama

Controversy

In the Netherlands, the Hague Centre of Strategic Studies recently published a report on the potential hazards. A research organization like TNO also has experts who carry out horizon scans into the hazards and what can be done about them. Every year, the Dutch National Institute for Public Health and the Environmen (RIVM) organizes a national conference on the latest insights and what policymakers need to be aware of, Nieuwenweg adds. “Technology is advancing at an ever-increasing pace. It’s quite difficult to keep adapting your policies to that.”

As well as horizon scans, there is also such a thing as “safe by design,” where from the outset, you think about the security of a potential product or application that you are developing. Nieuwenweg continues: “We don’t just come up with a product. We are thinking about security from day one. This is a really important subject within synthetic biology. As soon as you start modifying organisms, strict security regulations apply.”

It’s admittedly somewhat of a controversy, Nieuwenweg observes. “In the past, we actually didn’t know exactly what we were doing as far as DNA was concerned. We have been modifying plant and animal DNA for centuries by selecting them for certain characteristics. In the case of plants, at some point we started throwing chemicals at them. That was actually pretty random. Now there is a technology, CRISPR Cas, that is much more targeted and accurate, but the regulations are much more strict.”

In the supermarket

Of course, Nieuwenweg recognizes the hazards that this all poses. That is one of the reasons why she chose Military Strategic Studies as her master’s degree. “But it is also in part down to how the media portrays it. Look at a movie like Rampage in which the ‘bad guy’ uses CRISPR Cas to make giant, evil rats. Yet most people who choose to work with biotech do so to make the world a little better.”

According to Bongaerts, the supermarket is the place that can contribute to changing people’s perceptions. “If you can buy milk that doesn’t come from a cow, but from bacteria that produce milk protein, or meat and fish made with stem cells, then people will start to understand more clearly what this might mean for their daily lives. Synthetic biology is often still abstract. You can see it in the case of medical innovations, as patients are more inclined to use them if they help them get better. These kinds of innovation can instantly alleviate their problems.”

Also read: Dutch TU Delft biotechnologists turn yeast into mini-factories for making medicine

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About the author

Author profile picture Corine Spaans is a writer. She is particularly interested in the stories of the people behind the innovations and has a passion for sport (innovation).