Synthetic biology: the next stage in genetic engineering

Inside every single organism on this planet is a set of genetic code that dictates its characteristics and capabilities.

Over the past forty years, scientists have used genetic engineering to manipulate the genes of plants and animals to create genetically modified organisms and food that can live in harsher conditions or resist diseases.

But we’re now starting to have the ability to manipulate these genes to far greater levels.

Synthetic biology, a loose term given to the creation and control of genes (with a focus on the engineering side), has been described by many in the field as its next great step.

Speaking at the Royal Society in 2012, chancellor George Osborne predicted that the industry would be worth £11 billion a year by 2016.

Proponents have declared the possibilities virtually endless, from revolutionising food, fuel and vaccines, to creating the potential for life extension.

Critics, meanwhile, claim it could be used to make super-diseases, and that synthetically modified plants could destroy our planet’s ecosystem.

Vaccines and Diseases

Dr Jay Keasling, professor at the University of Berkeley, senior faculty scientist at the Lawrence Berkeley National Laboratory and Discover magazine’s Scientist of the Year, is a leading authority in the field of synthetic biology.

He and his team engineered E.coli and baker’s yeast to help produce artemisinin, a malaria vaccine, for a significantly lower cost than normal methods.

“We shipped the first 1.7 million treatments to Africa in August, and will have the capacity to produce between 100-150 million treatments annually. So yeah, I think lives are being saved right now,” he says.

Keasling believes that synthetic biology “could solve some real problems” and could be used to create vaccines for other diseases as well.

For example, the J. Craig Venter Institute (a non-profit genomics research institute) and Novartis (the biggest drug company in the world) have created synthetic vaccines for the seasonal flu that cut the creation time down from 4-6 months to just four days.

Keasling, however, cautions that there are dangers to the relative ease of synthetic biology, where genes can be typed into a computer almost like code, ordered over the internet, synthesised at DNA synthesis companies which create them artificially using sugar, and then delivered to your door, freeze dried to use however you wish.

There are even databases of genetic code that you can use for your own sequences. “So someone could build a virus like the poliovirus, right? The sequence is out there. It’s publicly available. It doesn’t take too many people skilled in the art… it could be done by someone not that skilled in the art,” says Keasling.

“So, yeah, we do have some concerns about synthetic biology. I think it’s at a stage where it could do damage, but it can also do some incredibly good things as well.”

Kevin Costa, managing director for the Synthetic Biology Engineering Research Center (Synberc), appreciates the risks but says: “It still takes a lot of time and expertise to rebuild a known pandemic virus.”

“So someone could build a virus like the poliovirus, right? The sequence is out there.” 

Synberc, a multi-university research centre established to help lay the foundation for synthetic biology, tries to teach scientists how to reduce risk.

We can build “engineering bugs that are dependent on specific nutrients so that they can’t escape” from the lab or factory. Or you can “build terminator switches into bugs, so that once they’ve done their job, they terminate themselves, a programmed death.”

This way, bugs that have a job of creating a product like fuel in an enclosed environment have less risk of escaping into the wild.

Researchers at Synberc also worked with the DNA synthesis companies to “make sure they weren’t inadvertently sending harmful DNA sequences out.

“That has been a successful ground-up effort to try and avoid somebody in a garage either intentionally or inadvertently creating a partial sequence to the Spanish Flu, or something like that.”

Fuel and decreasing petroleum dependency

Dr Keasling is also involved in developing better fuels, as well as trying to reduce the amount of petroleum we use in our products.

His organisation, the Joint BioEnergy Institute (JBEI), has developed technologies to engineer crops so that they take up less space to produce sugar for the biofuels he’s also developed.

These jet fuels and diesels are already being used in buses and planes. “We’ve now got technologies to replace other chemicals that would otherwise come from petroleum, so I think it’s progressing nicely.”

“There’s a huge number of chemicals that come from petroleum, I’d like to replace that with renewables,” he adds. “It’s all about using synthetic biology to help sustainability. It would be nice if we could have enough food and also have enough biomass so that we could produce the things that we now get from petroleum, particularly when we’re burning that petroleum and putting that carbon in the atmosphere.”

However, not everyone agrees with his work: “There’s even some people that disagree that we should engineer microbes to produce an anti-malarial drug. I think with every technology there are going to be people who aren’t happy with it, but that’s okay.”

There are also risks with certain biologically-engineered plants, as Kevin Costa explains: “Think of creating energy from algae and you’d have algae ponds out in the desert, and they soak up the energy from the sun and produce fuel. But the ponds will be open to the environment, bugs are going to get out. So there are certain things we need to do before those applications go live to ensure that we’re managing the ecological risk appropriately.”

Food

Biotech company Evolva made headlines earlier this year because it had biologically engineered baker’s yeast to produce Vanillin, a vanilla flavouring that is already used in 99 per cent of vanilla-flavoured products. Its Vanillin is now commercially available.

“The problem I have with the way the narrative has been going in the media about the food angle is that it’s so alarmist, and actually so wrong in some cases, that the general public feels misinformed about food production and cynical about science” says Stephan Herrera, vice president of strategy and public affairs at Evolva.

“Consider the way nature works, nature mutates, cells self-replicate, they multiply, they divide, they grow, they interact with other creatures, with other organisms. That’s the way nature works.”

I wish I could spend less time splitting hairs about biotech and more of my time talking about real problems

The fear is, however, that an engineered organism could escape and multiply across the world, possibly changing from its original form.

“We’re using baker’s yeast,” says Herrera. “The idea that baker’s yeast is somehow this organism that’s going to get out into nature and somehow become this organism that’s scary, is really just wrong. The fact is that there’s no environmental release of the organisms.”

His view is that simply changing yeast genes to produce Vanillin is “very different than working with the genetics of an organism and then releasing that into the wild in the form of a plant, a fish, or something.”

Evolva also aims to create products like saffron (currently very expensive) or agarwood essence (which requires felling an endangered tree).

“You’re talking about a tiny food ingredient, a low-volume food ingredient – we’re not talking about staples, we’re not going to start producing soya or maize, or any type of ingredient that is going to cure hunger.”

“But, it may be able to fortify food, it’s already making vitamins, it’s going to make other key ingredients in the future that are going to be a part of foods.”

He believes that new products may not necessarily be created, but the ability to have products like saffron at a significantly cheaper price will open it up to new markets.

Evolva has, however, received criticism from some, including Friends of The Earth, over the fact that their Vanillin is a genetically engineered food and that due to it being identical to normal Vanillin, it doesn’t have to be labelled any differently on food packages.

“The World Health Organisation, the Food and Agriculture Organisation, the American Medical Association, and the list goes on, have looked at GMO ingredients and found them to be perfectly safe. Members of a truly civil society can debate and even disagree about whether these groups speak sooth or truth. But, personally, I wish I could spend less time splitting hairs about biotech and more of my time talking about real problems that exist here and now in the world,” says Herrera.

In his opinion, if people “forget how it was processed, once people know, and they feel you’re being transparent and you’ve said ‘yeah we’re using biotechnology, but here’s the thing – the yeast comes out during production and the end ingredient is exactly what you’ve been eating for generations’. Once they hear that, there’s only two questions: how much does it cost? And does it taste good?”

Dr Steve Suppan, senior policy analyst at the Institute for Agriculture and Trade Policy (IATP), disagrees. “There’s the displacement of developing country farmers from being able to make a living off of crops that aren’t easy to grow to look at, as synthetic biology is attempting to reproduce it in a fermentation tank – the Evolva flavouring products are probably the most prominent example.

“I think there’s a dubious, very questionable, social benefit to having a fermentation tank-based process relative to the social destruction that’s going to be caused if those farmers are displaced in mass. I mean there just won’t be crops that are comparatively profitable. I think that’s a legitimate concern.”

The Next Big Thing

As scientists are only just getting to grips with the possibilities of synthetic biology, it’s hard to say what the future holds.

According to Kevin Costa: “There’s also the issue of public engagement. Is the public ready for certain technologies to come online? We have them here in the labs, and it’s just a question of ‘is there the political will to fund these things, to do things?'”

Costa says Synberc is developing ‘programmable organoids’ to simulate human organs, allowing you to “rationally test drug candidates to see if the drug candidate is working, or having toxic effects,” replacing the need for animal testing.

“That’s an example of something that’s just waiting to get the funding to take off and go, and could have tremendous impact on the way we do business,” Costa says.

Another possibility is that of reviving dead species: “De-extincting the passenger pigeon, that’s a technology we have now, that we can do today, and the question is – should we do it? Humans extincted that species. Should we bring it back?”

Further along into the progress of synthetic biology, these questions become all the more important. “Of course, in the future, there will be some far out applications, and those are the sort of sensational things I think make people worry.

“Theoretically, we can go in and make changes to human DNA. Again the question is: should we?”

“Theoretically, we can go in and make changes to human DNA. Again the question is: should we? And how do we do that the best way? In some ways, the technology is marking time while our social and regulatory systems catch up and think about what’s the best way to advance the science.”

Costa also believes “there are certainly going to be ethical ceilings that we hit. I certainly think of trans-human issues, if you could create inequalities between people, biological haves and have nots.”

In theory, humans could – or at least those with money could – upgrade their, or their children’s, intellect, lifespan or physical capabilities.

“That’s a bright red line in my mind, and it’s not clear how that will play out… There are clear bright lines that we’ll approach, but we’re not going to cross, at least not until folks are ready,” Costa says.

Regulation

With this in mind, and the possible dangers synthetic biology might bring, many are calling for either greater regulation or funding.

Todd Kuiken, Senior Research Associate at the Woodrow Wilson Center, Science and Technology Innovation Program, is head of their synthetic biology project. He says: “There’s currently little to no funding looking at the ecological implications of synthetic biology.

“There’s been a lot of money put into the engineering component, the understanding of how to build genetic circuits, but looking at the ecological implications side of that? That’s been lacking.”

“In order to reduce the risks of synthetic biology, our understanding of ecology, biology in general and how us manipulating biology, has implications, needs to improve. It’s critical for us to understand it.”

As for regulation, Kuiken says: “A lot of the regulatory structures can probably handle synthetic biology if you make some adjustments, but currently we’re operating under that original genetic engineering regulatory structure and are trying to fit synthetic biology into that.

“I was at the UN Convention on Biological Diversity, where they’re beginning to try to lay out what that international framework would look like. But there’s certainly no agreement on what that should be, and what came out of that meeting was that they’re basically going to form an expert working group to start diving into those questions.”

With synthetic biology still in its early stages, the one sentiment shared among everyone in the field we spoke to is that there’s a lot of work to be done, a lot to be discovered and a lot to truly fathom. Scientists and regulators alike have yet to be able to gain a full understanding of its potential and limitations.

Using synthetic biology in our global ecosystem has its risks, but in the view of Dr Keasling, that’s just the price of progress.

“Every technology has that potential. People see this all the time, with their credit cards being ripped off. We accepted computers in our lives, we accepted that technology, and one of the risks can be huge financial ones. But we accept that, and for the most part, buy into that.

“I’m not trying to dismiss the risks of synthetic biology, I’m just trying to say that every technology developed has positives and negatives and we have to weigh those.”

Illustration by Alltoomuch