On March 31 2021, PLOS Computational Biology introduced a new journal requirement: mandated code sharing. If the research process included the creation…
Founded in 2004, Evolva is one of the first synthetic biology companies ever created, and it is a beautiful example of a successful business in our field. Evolva employs more than 175 people around the globe and since 2009 it has been listed on the Swiss Stock Exchange (SIX: EVE). Evolva’s CEO Neil Goldsmith kindly agreed to walk us through the company’s history, goals, and philosophy in a very inspiring interview.
A bit of history
At the time in which Evolva was founded people were not speaking much about synthetic biology, at least using this terminology. As Goldsmith points out: ‘We actually did not know that we were setting up a synthetic biology company because the term was not really in use. At the time we called what we did ‘genetic chemistry’.’ The concept was similar, but the Evolva team was putting it in a different way. ‘When everybody started to use the term synthetic biology we did, too.’ Evolva was created around the idea of doing combinatorial genetics to make new biosynthetic pathways for the pharmaceutical industry. The company originated by the collaboration between three people: Neil Goldsmith, and co-founders Alexandra SantAna Sorensen, Søren V.S. Nielsen, as a spin-off of the US company Phytera. In Phytera plants cell cultures were manipulated to make new chemistries by, for example, giving them essentially a fungal infection. Even though the scientists in the company managed to build a large library of plants cell cultures, they soon discovered that they could not preserve them well. This is when Phytera started looking for a new host that could be handled more easily, such as yeast: ‘I was working on YACs (yeast artificial chromosomes for sequencing applications) at the time trying to understand what happens when you get multiple YACs in one cell, and we came to discover that we could use YACs as a combinatorial system to make new pathways,’ says Goldsmith.
This is how Evolva was born. ‘It took five years to work out the sweet spot for what we were doing: not new chemistry for pharma, but existing ingredients found in nature for which the supply chain had either become hugely problematic or was in fact wholly unethical, relying upon rare, rapidly vanishing plants and animals. We were one of the few that did not come at [synthetic biology] from the biofuel side.’
Technology and products
Evolva uses baker’s yeast for brewing their products. ‘Occasionally we do some work in other organisms, but we use mainly yeast,’ specifies Goldsmith. ‘For different molecules and markets, you might choose E.coli or algae for other uses. But in our case we tend to focus on things that happen in plants and animals; therefore, it is easier to express eukaryotic systems in yeast.’ Evolva has a great portfolio of products to show ranging from chemicals for nutrition, agriculture, personal care to fragrances and flavours and legacy products. I was intrigued to know if Goldsmith had a product he was proudest of: ‘Proudest might be the wrong word. We have three ingredients that we see as most important to us, at least in the near to mid-term: Stevia [the zero-calorie sweetener], Nootkatone [a cross-over ingredient used in flavours & fragrances, and soon perhaps as a repellent against a range of insect pests including the mosquitoes that transmit Zika virus], and Resveratrol [a naturally occurring molecule found in wine that is also a cross-over ingredient, which is currently being used in nutritional supplements, and is being examined for use in healthy aging applications]. We think that [these molecules] are important in that they each bring a significant benefit to the end user that was not there before. It is necessary but not sufficient to just make something cheaper. This may suit much bigger companies, but for us it is different. With Stevia, for example, we are making a blend of sweeteners (Reb D and Reb M) that overcome the bitterness of the current Stevia products which allows to making zero calories colas (or other drinks). This translates to a really important benefit for the consumer and we think this is where we need to focus.’
Goldsmith confirmed that Evolva is becoming more product focused. For instance, three of their products now have a dedicated website: Resveratrol, Nootkatone and Valencene. Resveratrol is a fine example of the company focus. While it is a molecule that shows great potential in clinical studies (such as its potential to slow the rate of aging of neuromuscular junctions or lungs), it has not been adopted as widely as it could have been because of the difficulty encountered in its production: it is not feasible to extract it from wine or grapes. Evolva offers an alternative for its production hoping that this will ultimately translate into potentially valuable uses of Resveratrol.
Focus on sustainability, and the 1% give back program
As a company, Evolva tends to focus on the production of ingredients that are inherently scarce in the natural environment. Any program to obtain this kind of products directly from the natural source has a relatively high impact for the amount of material you get. Evolva offers valuable production alternatives, by brewing the products in yeast. ‘[Sustainability] is sort of inherent in the ingredients we focus on,’ says Goldsmith.
While researching the company, I came across Evolva’s 1% policy, which strikes me as a fantastic initiative that every company should follow. As the company takes inspiration from Nature for their products and uses tools from sciences, they feel compelled to do something to ‘give back’. Hence, they donate the 1% of their product-derived revenues to support the conservation of biodiversity and basic science in developing countries.
This is also in line with the principles of the CBD (The Convention for Biological Diversity, read more about this here). ‘We see the CBD as a superb idea in its spirit, but something that has unfortunately been implemented in a way that hasn’t really taken into account how science is done and, in fact, not even how nature is constructed. This idea that there is this treasure in nature and that emerging countries are sitting on pots of gold is sort of a politician’s fantasy. The 1% policy is us trying to make sure that we stay and support the spirit of the CBD. We want to support nature and genetic resources that ultimately we are using. We think more companies should sign up for such things especially since synthetic biology is very controversial [for its very nature]. Hence we should try and show that we are working in a responsible manner.’
Goldsmith’s view on the synthetic biology revolution and the democratisation of biology
The people at Evolva think that it is great that there is such an explosion of interest and funding in the synthetic biology world [namely, the creation of a multitude of start-ups in recent years]. ‘This is gonna move everyone forward much faster. The array of technologies is becoming bewildering. It is fascinating from this point of view.’ However, Goldsmith also makes two interesting points:
- ‘We aren’t going to all do well if all we do is ‘taking each other’s washes’. We see a lot of companies selling tools to other synthetic biology companies. This is fine, but ultimately you have to come up with products that are going to sell and be used by people outside our community. People need to spend more time thinking bigger picture, learning more about what other people need — and how we can help to address them.’
- ‘Related to that I was saying (and since I have been doing this for more than 12 years) to bring a product through requires joining up so many things. It’s not only all the different technologies. An example: a lot of people focus on the fermentation and the genetics but actually the purification process is one of the most important bits, and it tends to be left aside. In a way, the whole field is held back by the rate limiting steps such as large-scale fermentation and purification technology: the rate of change of purification technologies is glacial compared to molecular biology tools. Innovation needs to come also for what is seen as more prosaic bits.‘
What Goldsmith is saying is that it is important not to let this fascination for tech and labels make us forget the larger picture. There are so many things that matter more than the clever branding of your biotechnology platform. What matters, in the end, is whether you can produce a product with genuine consumer benefits— ethically, responsibly, sustainably, and of course cost-effectively so that it has the opportunity to reach the mass market.
And for what concerns democratisation of biology Goldsmith has a very particular opinion, with which I tend to agree. ‘[Biology] is intrinsically harder than IT: the entry barrier for an average person to start doing synthetic biology is just that much higher. In part because of the specialist facilities you need.’ This translates in the concept that it is much harder to ‘do garage stuff’ in synthetic biology than it is in the IT environment. ‘The democratisation of biology is probably going to come one day, but more slowly than we think, mainly because the tools are not [yet] robust enough. The underlining architecture needs to be much more robust than it is today.’