IS THIS THE TECHNOLOGY TO WIN Kiwis over to GE?
You’ve heard of fermenting yeast to make beer, but what about brewing GM microbes to make bioplastic? Using designer microbes to make stuff in fermentation vats has been described as the next manufacturing revolution. But is GE-free New Zealand ready for it?
Veronica Stevenson bet her house deposit on a bee. Before using GM microbes to make stuff was all the talk (Impossible Burger, mRNA vaccines), Stevenson set out to find the genetic recipe for the plastic-like film that lines the nest of a solitary Aussie bee.
All she had to do was work out which bit of the bee’s DNA linked to the nest material and put that code into a micro-organism, which then makes it in a fermentation vat, or bioreactor.
Finding the bees was a nightmare. Sequencing the genome was tricky. Gathering funding was challenging (hence investing her house deposit).
Still, she overcame every obstacle. ‘‘We’ve sequenced the genome. We’ve expressed the genome in two microbial systems. So we’ve proven that we can make it. Which is a massive thing.’’
But when it came to the trial and error stage of perfecting the process, Stevenson ran into the legacy of New Zealand’s famously strict genetic engineering rules, which the Productivity Commission this month concluded failed to take into account technological advances, and should be reviewed.
‘‘Because the regulatory environment is what it is, there’s just no infrastructure,’’ Stevenson says. ‘‘Just the ability to move through the product from concept to commercial viability.’’
In December, Stevenson’s company Humble Bee announced a six-month partnership with United States biotech company Gingko Bioworks.
Their automated system can test 3000-5000 gene variants, different microbial hosts and processes to devise the perfect formulation.
It’s the genetic equivalent of a sophisticated recipe tester, trying out thousands of tweaks to ingredients, quantities, or temperatures.
While New Zealand may never be able to justify a research facility on Gingko’s scale, Stevenson is frustrated the country is not doing more to embrace the multibillion-dollar potential of synthetic biology.
‘‘In Australia, three or four years ago, they realised this was huge . . . and they threw hundreds of millions of dollars at it. They have a centre for research excellence on it. They have a venture capital fund specifically for this space.
‘‘And New Zealand is like, it’s just not on the radar. Which is a real shame. I just feel like we’re missing out.’’
How does the technology work?
While most Kiwis probably eat GM wheat, corn and soy in imported foods, the idea of releasing genetically engineered organisms is likely to remain a hard sell in New Zealand. Stevenson and many scientists argue we should at least have the conversation.
But the beauty of the technology behind Humble Bee is that the end product is not genetically modified.
Known as precision fermentation, the process is a hot topic because it can be used to make anything from fossil-free biofuels to the animal-free milk products that some predict will bring down the dairy industry.
Basically, you isolate the DNA sequence that encodes for something you want to make, insert it into a microbial host, which then produces it in a fermentation vat.
The product is then extracted and purified from the fermentation soup, or from the microbe itself.
‘‘The stuff we’re doing is not scary,’’ says Stevenson. ‘‘What we’re going to produce is not going to be released into the wild. It’s not going to have an impact, interacting or sharing genes with other things.
‘‘It’s not going to crosspollinate with something. It’s an inert substance.
‘‘It’s a big vat. You pull out what’s expressed from the microbes and you give it to your biofabricators and they can make it into a film or turn it into a yarn. And then that gets incorporated into clothes. It’s like synthetic spider silk.’’
It’s not a new process – it’s been used for 40 years to make insulin, as an alternative to extracting it from pig pancreases.
But the field is burgeoning now, because the comparative ease of genome sequencing and DNA synthesis means it’s suddenly accessible. Pfizer used it to make its Covid vaccines, and Impossible Foods ferments genetically engineered yeast to make the heme that gives its plant-based burger its meaty taste.
As Scion’s biotechnology research group leader Gareth Lloyd-Jones explains, 20-30 years ago you might get a PhD for cloning one gene.
‘‘Whereas now, you could probably in a month design an experiment to clone any gene, and order it, get somebody to synthesise the DNA for you, and deliver that in a form which you can put into the host, and the DNA vector you want to use to produce it.
‘‘All the technology around how you make it is cheaper. The amount of options as to what you can produce it in is broader. So everything has become so much bigger in terms of what you could think of doing.’’
So how is New Zealand placed to get its slice of the pie?
The pioneers we’ve lost
Remember LanzaTech, New Zealand’s biotech poster child, which in 2014 moved to the United States?
Founder Sean Simpson started out using a microbe that naturally converts carbon dioxide into ethanol in a process called gas fermentation. The idea was to capture carbon from industrial waste and transform it into a fossil fuel replacement – a climate change double whammy.
But that was just the beginning. The real prize was to genetically engineer that microbe to make other things – acetone or the starting materials for rubber or plastics.
But Simpson knew New Zealand’s regulations would prevent him doing that at scale. It wasn’t all that pushed him offshore, but it was a factor.
‘‘If we’re going to use agricultural waste, societal waste, industrial waste to deliver sustainable fuels and chemicals, and replace oil, then biology has a significant part to play . . . And New Zealand is basically saying, we don’t want any part of that. Which is fascinating to me.’’
Contrary to popular belief, there is no ban on genetic modification here. You can apply under the Hazardous Substances and New Organisms Act (HSNO) to do genetic engineering, but it has to be done in ‘‘containment’’. That means inside an approved and regularly audited facility.
That was never going to work for LanzaTech’s industrial-scale bioreactors, and scientists say the approval process for GM development outside containment is so difficult it creates an effective moratorium. That closes off opportunities to turn great ideas into businesses, Simpson says.
‘‘It’s not like we cannot undertake genetic manipulation in New Zealand. We can, and we do. We don’t want to do it at a certain scale.
‘‘And I can’t understand the justification for that. It’s technical masochism. We’re going to build a little bit of it, but when it gets really exciting, we’re going to stop. If this could turn into something, we’re not going to do it.
‘‘What Veronica has done is remarkable. But imagine the number of people who never even bothered to try and get that far, because of the hurdle that they knew was ahead of them.’’
In Matt Gibson’s profile pic, he’s proudly sporting a vintage All Blacks jersey. But the New Culture founder is beaming in from San Francisco, where he’s developing animalfree dairy mozzarella.
Dairy cheese has a terrible environmental footprint, making it a prime target for sustainability advocates, Gibson says. But the plant-based alternatives are ‘‘pretty awful’’.
But what if you could cut out the middle gal – the cow – and make dairy cheese without the climate guilt?
Milk protein casein gives cheese its character – the melt, the stretch, the flavour.
So that’s what Gibson makes, using precision fermentation. He genetically engineers microbes to produce casein in fermentation tanks.
The extracted and purified casein is the same as casein from milk, and it’s not GM. The genetic
manipulation occurs only in the process, not the product. It’s then combined with plant-based fats and transformed into mozzarella through traditional cheesemaking.
He’s hoping to start selling commercially next year.
‘‘We are making animal-free dairy cheese today. We’re making a lot of it. It melts, it stretches, it browns. It does everything you’d expect dairy mozzarella to do.’’
But it won’t be doing any of those things in New Zealand.
Gibson started New Culture in Auckland in 2018. He needed a lab for initial experimentation, but universities weren’t interested (he didn’t want to sponsor a PhD student and lose control of the intellectual property).
Commercial labs were keen to help, but their GM approvals were too narrow.
‘‘I just realised there was no way I could do any work, without having to get my own certification and set up my own lab, and that would cost a lot of money, compared to the United States, where nothing like that is required.
‘‘After six months of trying, I realised it was a fruitless endeavour.’’
So he moved to San Francisco, where he joined the IndieBio accelerator programme.
And now he’s making cheese – and New York Times headlines – far from home. ‘‘Ultimately, if New Zealand doesn’t embrace this, they are going to be left behind, and the future of dairy is going to be elsewhere, and it will be a shame.’’
Just how big a deal is this?
Reports of the dairy industry’s imminent death have been greatly exaggerated.
Non-dairy products make up 15 per cent of the US dairy market, and a think tank report suggested animal-free dairy could kill off the cow milk industry by 2035.
That, says Gibson, is fantasy. His back-of-an-envelope calculation estimates just replacing New Zealand’s dairy output would require pretty much every existing fermentation tank in the world.
‘‘It’s not going to happen in 10 years.’’
But it’s still a major risk for a country that relies so heavily on white gold, he says.
‘‘The risk is that the economy’s biggest or second-biggest industry is going to become obsolete. There’s still going to be some demand for animal-derived dairy, but ultimately it’s going to become a niche product, and you’re going to put a lot of people out of work.’’
Auckland University’s 2020 Future of Food report notes international calls to swap from ruminant-based foods to plantbased ones ‘‘could significantly affect the acceptability of New Zealand’s pastoral products in some markets’’.
The Ministry for Primary Industries, however, does not see novel methods for producing protein as a replacement for traditional forms. Any food produced with genetic modification also needs special Food Standards approval in New Zealand.
But the opportunities are much broader than just food. Australia’s Synthetic Biology Road Map estimates the technology – of which precision fermentation is one part – could be worth $27 billion a year and 44,000 jobs in Australia by 2040.
But are GE-free flag-waving Kiwi consumers ready to embrace genetic modification as a process rather than a product?
Humble Bee’s bioplastic is just one example of the technology’s potential environmental wins – providing more sustainable alternatives to fossil fuel-based products.
That means it has potential to win over the greenies who have traditionally opposed genetic modification.
There’s also a new generation of Kiwis who did not grow up in the shadow of GE-free placards. In 2019, 150 scientists aged under 30 signed an open letter to the Green Party asking it to reconsider its anti-GE stance.
Greenpeace does not oppose ‘‘laboratory fermentation that does not result in environmental release of viable GM organisms’’. But it does not want to wait for lab-based food to reduce climate emissions.
Strong anti-GM voice
The Sustainability Council would not say whether it opposes precision fermentation in principle, or its use to make casein, saying it has to assess every case separately.
Executive director Simon Terry says using genetically modified organisms to aid fermentation is less risky for the environment than GM crops.
However, it should not be exempt from regulation, and the benefits should still have to outweigh the risks.
The hopeful stayers
One of the first questions potential investors ask about caseinculturing Kiwi startup Daisy Lab is ‘‘Why would you be doing this in New Zealand?’’ says co-founder Irina Miller.
‘‘Our response has always been well, yes, it is challenging. But it’s not impossible.’’
Both Miller and co-founder Nikki Freed are foreigners. They know it would be cheaper and easier to build their company just about anywhere else. But they want to do it here.
‘‘I’m very interested in sustainability,’’ says Freed, who is also the lead technologist at Auckland University’s genomics facility. ‘‘We want to see New Zealand succeed and become a great, green place for our kids to live.’’
Miller toyed with the idea of making animal-free dairy in 2016-17, while working for Fonterra. She figured someone else would do it. But when no-one did, she started Daisy Lab, in 2020.
The environmental gains from switching from cow udders to fermentation tanks could be huge, with one estimate finding it reduces greenhouse gas emissions by 91 to 97 per cent. There are no accurate estimates for New Zealand’s pasture-based farming.
Microbes still need to eat. Still researching at tiny scale, Daisy Lab is feeding its microbes pretty much pure sugar. But ultimately they hope to use food waste. If precision fermentation took off, farmers could grow sugar beets to feed the country’s army of microorganisms.
Daisy Lab’s long-term vision is to tap into the dairy industry’s supply chain for powdered milk, which is 80 per cent casein and makes up 95 per cent of all our milk exports. Farmers could be like micro-brewers, growing fermentation feed and making milk protein without the cow.
Freed and Miller have been surprised at the lack of backlash to their plans. That’s partly because people understand they won’t actually be eating GMOs. But Freed thinks it’s also about their motivations.
‘‘At the heart of what we’re trying to do is make a better planet. We’re trying to improve sustainability.
‘‘We’re trying to improve animal welfare . . .Traditionally, other GMO have got a bad rap, because it’s more about making those seeds farmers have to buy each year. It’s profit-driven.’’
Down country in Waikato, Andy West is brewing enzymes. His company Synthase Biotech works out of a containment lab leased from AgResearch at Ruakura.
Genetically engineered microorganisms produce the enzyme in a fermentation broth, it’s purified and they’re currently trialling it to improve animal fertility.
They’re only making litres of the stuff at present, but it’s so potent they can manufacture enough in their existing facilities.
‘‘Can we produce it here? Yes. Is it really so difficult that it’s not worth doing? No.’’
That said, West, who used to head AgResearch, reckons New Zealand is languishing, a legacy of a shortage of research funding and investment in startups.
Enzymes are high value and used for everything from cleaning products to probiotics, and New Zealand should have more companies making them, West says. Denmark, for example, has a thriving multinational enzyme company.
Instead, there are very few, and a bid to set up a centre of excellence in enzyme research was repeatedly rebuffed.
Precision fermentation could be ‘‘radical’’, especially in terms of lab-grown meat and dairy, West says. ‘‘This is an area where I personally feel that New Zealand does need to be building capacity. And I think it’s got to be done in a deliberate strategic manner.’’
What would it take for NZ to go big on precision fermentation?
Gibson counts off four barriers to getting the technology off the ground in New Zealand – outdated GM regulations, scarce investment dollars, a smaller talent pool and shortage of infrastructure (shared lab space and fermentation capacity).
Miller is confident Daisy Lab can test its method and even supply vegan dairy to New Zealand and a niche Australian market, within the current regulations.
‘‘We would have to buy, build or repurpose a facility – be it something built from scratch or an old brewery. But it would have to be all assessed and approved by MPI.’’
While regulations are important, fermenting GM microbes that make dairy protein is relatively low-risk, yet the containment requirements are similar to those for Covid, Miller says.
‘‘In terms of the technology at large, and what potential it has, then the legislation would definitely become a road block.’’
Gibson says New Zealand also needs more, larger precision fermentation tanks. Companies need everything from pilot scale (100-1000L) to demonstration scale (10,000-50,000L), to commercial scale (100,000+L), though commercial production could be contracted overseas.
‘‘For any company to be economically viable, you have to scale up your process. And it’s easier to do that locally, than half a world away.’’
There’s no national stocktake of precision fermentation tanks, but biotech consultant Andy Herbert says one thing is clear – there aren’t enough.
‘‘The soil is not very fertile for new things to emerge.’’
While research institutes such as Scion and Callaghan Innovation have some capacity, what’s really needed is two or three research institutes or universities with lots of small fermenters, plus a pilot plant, Herbert says.
Scion’s Lloyd-Jones says getting HSNO approval has got easier, but then you need a containment lab, which also has to be approved and audited.
‘‘The facility itself would be a barrier, so a startup couldn’t just start doing it. You could theoretically buy an old redundant microbrewery and do it, but you wouldn’t have all the conditions satisfied to allow you to do it.’’
Scion can run fermentations at 10L and 100L.
Lloyd-Jones says the technology has the potential to be ‘‘very disruptive’’. But things like enzymes and fragrances make a more economic starting point than milk protein.
‘‘I think it does need a few companies to give it a go. I think they have to give it a go in a high value space, to justify the investment. ‘‘
Callaghan Innovation has a suite of fermentation bioreactors at its Lower Hutt site, which can process up to 1000L per batch. They’re used to make anything from alcohol to components for vaccines, to probiotic mixtures.
Callaghan says barriers to precision fermentation include the complexity of determining who owns the genetically modified organism that produces the target product; the significant investment needed to manipulate microorganisms; New Zealand’s limited talent pool; and the lack of immediate access to specialised manufacturing infrastructure for new companies.
Back at Humble Bee, Stevenson is philosophical about the company’s future. She has some advanced manufacturing funding from Australia to make proof-ofconcept products and is working with Deakin University’s Institute for Frontier Materials.
‘‘I’m not going to get myself into a state where I’m mourning the opportunities that my country didn’t take.
‘‘I can do what I can do. I can stimulate the sector. I can have these kinds of conversations. I’m not going to lose sleep over it.’’