Twenty years after the Corngate scandal turned genetic modification into a political hot potato, leading science figures hope a new review will bring changes. Jamie Morton reports.
It's called ciltacabtagene autoleucel.
Its trading name, Carvykti, doesn't roll off the tongue any easier.
But it marks a major milestone in one of our most complex, contentious and enduring debates: genetic modification.
In Carvykti's case, scientists may argue this tech isn't GM at all, but something subtler.
And its target isn't corn crops or possums, but multiple myeloma, an incurable blood cancer estimated to kill nearly 200 Kiwis each year.
Here's how it works.
A patient's immune cells are taken and genetically modified to create cancer-killing Car-T cells, before being reinserted to become living drugs, much like a vaccine.
In August, it became the second-ever genetically-modified organism to be approved for uncontrolled release here.
Our chief scientist calls that a "significant step forward" for access to modern medicines.
Yet, she argues, the regime our researchers work under remains more of a regulatory rigmarole than it needs to be.
Consider this case: a US company's "one-and-done" therapy, where a person's genes are permanently edited to lower their risk of heart attack.
After being cleared by MedSafe and a special Health Research Council committee, it's now being trialled in a New Zealander – yet developing the tech itself here would've proven extremely difficult.
"It is frustrating for researchers when experiments in containment in the laboratory have tougher regulatory hurdles than doing the experiment in humans," says Professor Dame Juliet Gerrard, a respected biochemist serving as the Prime Minister's Chief Science Advisor.
In a 2019 briefing to Jacinda Ardern, she offered the colourful hypothetical scenario of a grandmother cured of cancer, only to find she couldn't leave the lab because she'd become a GMO.
Three years later, she's hopeful a new Government review will iron out some of the issues she and others have been increasingly calling for action on.
This review doesn't mean GM maize crops will soon begin sprouting up across our countryside.
Rather, its scope appears limited to the biomedical world, in lab-contained, health-focused science like Carvykti.
Officials are also looking at whether our regime should be focused more on risk than the tech involved.
"There are many developments in biomedical research, from cancer therapies to vaccines, and we'd like our regulations to keep pace with these developments," Environment Minister David Parker tells the Herald.
"Moving to a risk-based approach ensures that our regulations don't become out-of-date with each new technological advance."
Corngate to Crispr
You might argue that manipulating the genes of plants or animals isn't new: humans have been doing it since the dawn of civilisation through selective breeding.
But genetic modification as we know it today spans back only to the 1970s, when a pair of US biotechnologists showed they could cut a gene from one organism and paste it into another.
Possible applications, from new medications to cleaning up oil spills, seemed endless.
But its implications for human health and ecosystems swiftly drew concern from scientists and governments.
The advent of US crops genetically modified to resist herbicides and pests alike – notably Monsanto's Roundup-ready soybean – inevitably worried environmental groups.
Food crops created from mixed genetic sources sparked consumer fears of Frankenfoods.
In 2000, unease at home eventually prompted the Government to turn to a Royal Commission panel that ultimately found our regulations appropriate - and charted the "proceed-with-caution" course our country has taken ever since.
Even then, some scientists were pushing back against suggestions that the science should be completely outlawed here.
In a Herald article that dubbed GM the "debate of our time", the late biotech scientist Dr Jim Watson spoke of a "totally unprecedented" era of discovery that would play out regardless of whether New Zealand ignored it.
Two years later, when investigative journalist Nicky Hager dropped a bombshell into 2002's general election, ignoring GM simply wasn't possible.
An odd new word exploded into the public consciousness: Corngate.
Hager's book, Seeds of Distrust, detailed an accidental release of GMO-contaminated sweetcorn seeds and alleged cover-up – all of which happened under a voluntary moratorium on GM releases, and while the commission was being held.
A blind-sided Labour Government scrambled to deny any GM corn had leaked into the food chain.
Prime Minister Helen Clark famously labelled broadcaster John Campbell a "little creep" after an unanticipated grilling on prime-time TV.
And an exhaustive parliamentary inquiry later concluded the corn's contamination could be "neither proven nor disproved".
Looking back on the episode today, Hager recalls feeling how the political storm that enveloped his book overshadowed the important lessons within it.
"Then gradually, over the years afterwards, I became aware the authorities had become much more careful about imports of genetically-modified seeds and substances," he says.
"So, while at the time the things that the book was about got lost, my strong impression is that it ultimately served a useful purpose."
All the same, Watson's prediction of astounding scientific leaps continued playing out overseas.
The biggest was genome editing – something scientists often describe as separate from GM – which ushered in a new generation of clever tools like the Nobel Prize-winning CRISPR-Cas9.
These offer the potential to tweak single genes known to control the development of diseases – such as the BRCA1 gene known to raise the risk of cancer – or change those already causing them.
Scientists have shown how Crispr can edit gene variants in human embryos linked with heart failure, improve Covid-19 testing, or pack more vitamin D into tomato plants.
Although it can leave a modified organism virtually indistinguishable from an unmodified one, many scientists here argue that our over-arching Hazardous Substances and New Organisms (HSNO) Act allows for no such subtlety.
An organism is either modified - or it's not.
Burdens and burgers
Our peak science body, two chief scientists and the Productivity Commission have all concluded our laws need to catch up with technology.
Back in 2018, the Ministry for the Environment even advised our regulations were growing tough to enforce, particularly after a 2014 court decision effectively ensured gene editing stayed just as controlled as earlier techniques.
Because successive governments haven't prioritised updating the HSNO Act, Gerrard says our legislation has aged around a "time-stamped list" of genetic tools, increasingly leaving legal and scientific definitions misaligned.
"The original debate was characterised as a binary choice, GM-free or not: it was always much more nuanced than this."
Mutagenesis by radiation or chemicals, for instance – a process that causes multiple uncontrolled changes to DNA - is much less regulated than a single, controlled change at a specific point: something Crispr has made possible.
"It's a bit like having an act which imposes a greater penalty on electric cars than petrol cars, because electric cars were not invented in 1998."
Regulations under the Australia New Zealand Food Standards Code, which any food derived or developed from a gene-edited organism must meet, are also being tested by new science.
Food Standards Australia New Zealand, which is carrying out its own review, has already approved a range of GM crop varieties for use in foods, including types of soybeans, rice, corn, potatoes and canola.
While many of the base crops are grown in Aotearoa, the GM varieties aren't.
Our supermarkets might be stocked with imported processed foods that contain GM ingredients and must be labelled accordingly, but they're bare of actual GM fruit, veges and meat.
One controversial exception is Impossible Foods' plant-based patty, containing a GM soy protein and another ingredient made from GM yeast designed to give it a trick-meat taste.
When these "fake" burgers hit Countdown's shelves in March, a press release from GE Free NZ promptly followed: and the state of our regulations came under the spotlight once more.
Milk and methane
It's now been more than a decade since our Environmental Protection Authority (EPA) last received an application for GMO field tests.
But that's not to say GM hasn't retained a space - albeit a tightly-leashed one - in Kiwi science.
Plant and Food Research has long used genetic tech in natural crop breeding programmes to pinpoint certain functions that give parent plants desired characteristics, but to date hasn't developed GM foods for commercial use.
In a 2020 op-ed, its chief executive David Hughes called for a "new conversation" on gene editing – pointing out that 100,000 Kiwis born at the time of the Royal Commission were now of voting age.
"Our Institute sees great promise for gene editing in helping Kiwis continue to sustain our prosperity, communities and environment in this changing world," he said.
"We accept that others may not feel the same. New Zealand needs to weigh its options."
At AgResearch, scientists have been exploring how GM high metabolisable energy ryegrass can help slash methane emissions and nitrogen losses, but have looked overseas to carry out field trials.
Within the lab, they've been looking at whether gene-editing might unlock a pathway in white clover leading to specific compounds that might also help cut methane and nitrogen pollution.
There's the prospect of "climate-smart" cattle – gene-edited to tolerate warmer temperatures and perhaps produce fewer emissions – as well as transgenic goats that might aid new cancer therapies.
One recent AgResearch-led study suggested these goats might be useful platforms for producing monoclonal antibodies – breakthrough breast cancer drug Herceptin being one example – in their milk.
Other studies have investigated developing genetically-altered, hypo-allergenic, high-protein milk in cows – and growing organs within gene-edited pigs for human transplantation.
Researchers at forestry-focused Scion, meanwhile, happened to be the first in the world to use Crispr gene editing in conifer species, when they showed Douglas fir trees could be grown without reproducing – or sprouting up where they weren't wanted.
Like AgResearch, the Rotorua-based Crown research institute, which has a decades-long history of GM research in trees, has had to look to the US to progress this science in outdoor trials.
Otago University geneticist Professor Peter Dearden says that, because of the slowness and struggle in approving new organisms for genetic work, Kiwi students here often never get the chance to use gene tech here – even within containment.
Getting funding, too, is another big challenge: especially as agencies often require a business case before committing cash.
"The common thought, and the reality, is that pathway to market is really hard for a genetically modified thing," Dearden says.
"The settings not only stop us doing things, but stop us getting funding to do the work to even test these technologies to see if they are fit for purpose."
Even after four decades, he says low-risk work is hampered by an apparent assumption that any GM work is dangerous.
"Put this alongside the damage that neonicotinoids (insecticides chemically similar to nicotine) have been doing to insect populations, and you have to ask why one of these things is so strongly regulated, and the other available at your local supermarket."
Dearden, who heads Otago-based Genomics Aotearoa, offers another example: experiments to speed up development of new apple varieties.
One way to do this is using GM trees that produce apples fast, allowing scientists to short-cut the process, then cross out the GM material so the apples can grow without it.
"In New Zealand, these non-GM plants, have to be treated as if they are GM," he says.
"Surely what is needed is for us to regulate those plants on the basis of their risk - something we should be able to measure."
He feels much of the issue today is still wrapped up in the global industrialisation of agriculture decades ago.
"Twenty years ago, the GM things being proposed were all about big seed companies wanting to be allowed to bring them to New Zealand," he says.
"I think that's a bad idea, but not because of the GM, because of the loss of autonomy of our agricultural systems.
"We are in a better position now to be looking at solutions to New Zealand problems, rather than accepting industrial solutions from overseas."
Pests and plants
In 2019, Dearden was part of a Royal Society Te Apārangi-appointed panel that canvassed some of these.
One was controlling pests with tech that squashes populations by boosting chances of certain genes being passed down.
A team of Otago scientists are now researching a similar concept in a study targeted at possums, while another lab-based project is focusing on rats.
Other oft-discussed genetic tools include producing a "Trojan female" - whereby all male offspring are infertile - and species-specific toxins, such as norbormide, which could be highly effective and target only rats.
Amid fears of unintended consequences, the idea of unleashing gene tech on pests ravaging our native wildlife has unsurprisingly found little Government appetite.
Some heavyweight conservationists, including the late Sir Rob Fenwick, have urged Kiwis to at least talk about it.
Several recent studies suggest New Zealand's bold dream of being predator-free by 2050 won't be realised without some kind of breakthrough wonder-tech, although this didn't need to be GM.
While Crown-owned Predator Free 2050 has funded research involving gene tech, it stresses that no decision has been made on it being actually used.
"There are currently a lot of knowledge gaps surrounding such approaches, most notably on what they could actually do, what the risks of deploying them in the environment are, and what the social licence for such tool use in New Zealand is," its science director, Professor Dan Tompkins, says.
To date, the bulk of such research here has focused on that social license aspect.
"In applying gene editing to pest control, my sense is the public place greater emphasis on saving our taonga species, and so support tools that may achieve this, especially where they may reduce use of other methods such as toxins like 1080," University of Auckland conservation biologist Professor James Russell adds.
"But I think, and wisely so, New Zealanders will reserve their judgement until they see how gene edited pest control actually works in practice, following controlled trials either here or overseas, should the technology ever reach that stage."
Dearden nonetheless views pest eradication as one of biotech's main potential applications here.
Another is how we confront our fast-worsening climate crisis.
"I think we need to move beyond growing animal proteins, and build a sustainable industry producing high quality protein from plants, algae and bacteria... and to do this well, we will need GM," he says.
"The benefits in climate change, environmental footprint of food growth and exports will be huge."
Sector lobby Biotech NZ points out how, amid a global market forecast to be worth more than a trillion dollars by 2025, New Zealand is ranked fourth for innovation potential in biotech.
At the same time, its chief executive Zahra Champion tells the Herald, our regulations have kept us out of step with our trading partners, and held us back from building science capacity.
If there was reform, she worries it may take companies years to either upskill staff or recruit from overseas – and some star players like Mint Innovation and Lanzatech have simply opted to move operations offshore.
But proponents of reform say we also shouldn't look past potential gains for agriculture.
"With the pace of climate change accelerating, the need for crops that are resilient to heat, floods and drought will continue to grow," Gerrard says.
"Our competitors may get ahead of our exporters in breeding for these traits if they use new genetic tools and we do not."
Federated Farmers national president Andrew Hoggard says producers and consumers should be "empowered to make an informed choice about the regulated use of the technology".
Hoggard singles out the overseas ryegrass trials as one result of our "prohibitive genetics policy".
On this point, Parker contends there's nothing stopping AgResearch applying to the EPA to do the research here.
"There's no moratorium on them doing that work, but as yet they have not made that application."
Principles and politics
Gerrard's predecessor, Professor Sir Peter Gluckman was given the go-ahead by then-prime minister John Key to host discussions between key ministries and players, but found dairy giant Fonterra "wasn't keen to move".
But Gluckman, who's sounded blunt warnings of New Zealand becoming a "biotech backwater", sees the bigger issue as a political one.
"Right from the early days of the debate 20 years ago, there was a lot of disinformation and misinformation about," he says.
"The fact that it became a partisan issue gave at least one party a significant political position to take - and the opportunity for strategic discussions were lost."
Ever since, he says New Zealand has failed to follow the precautionary principle it originally agreed on.
"The whole point of precautionary approaches is to modify them as more knowledge becomes available."
Any serious attempts at reform, Gluckman says, will need to be "apolitical" - or at least occur at the right stage of the electoral cycle.
Asked if he thought the issue was simply too vexed to burn political capital on, Parker acknowledged there were "strong views" on the topic – and any major review would require a "wide public conversation".
Because of the amount of work required, the Government hasn't committed to one.
Its current stance is generally in line with that of the Greens, a party that remains opposed to GMOs being released into the food chain or environment.
"We support the limited use of genetic modification for ethical purposes, such as diagnostics and in the development of medicines and treatments," spokesperson Eugenie Sage says.
At the opposite end of the political spectrum, Act wants a "wholesale review" of legislation, with leader David Seymour branding our approach "superstitious and medieval".
"We can do amazing stuff in reducing methane from cows, but we have to go to California to do this outside [containment]... that's just a shameful situation for New Zealand."
National, too, seems eager for progress.
"We think our existing legislation is outdated, and prevents innovative technology that may be able to provide some of the solutions to the biogenic methane issue we have," the party's environment spokesperson Scott Simpson said.
"We've taken the view for some time that it's time New Zealand had a sensible, informed debate."
But is there a mandate?
Surveys to date suggest Kiwis remain divided on GM, if not mostly against it.
Around a third of 9000 people polled in a 2019 Stuff survey thought GM food shouldn't be sold here at all – and a similar proportion thought it safe to eat.
More recently, Christchurch company Research First similarly showed only a third of the people it polled had initial support for gene editing in food production.
Nearly half agreed they'd have concerns about buying GM fruit and veges, or even buying products from animals that'd eaten gene-edited food.
When a separate research team investigated specific views toward using gene drives in pest control, they found support among only about 32 per cent of some 8200 respondents, who appeared much more comfortable with pest-specific toxins (52 per cent).
Another group focused particularly on how gene editing aligned with Māori values, which they found could be either enhanced or diminished, depending on how the tech is applied.
More Māori supported its use against diseases rather than "cosmetic" health applications, or for conservation over agriculture, Waikato University's Associate Professor Maui Hudson says.
"Māori are cautious, but willing to engage if issues around benefits and control are addressed."
Over time, Māori opinions had generally been presented as fundamentally against it.
"As our knowledge of GM and gene editing has evolved, our discussions have matured and there is a more considered reflection of the relative benefits and risks of its use."
Use is what Gerrard sees as the heart of the issue.
While most Kiwis might accept gene editing to cure cancer, they'd likely reject it being used to modify children – a scenario that played out in 2019, when a rogue Chinese researcher horrified the science community with an illegal experiment to produce HIV-immune babies.
"It is not the tool itself, rather what the tool is used for that is the important difference between these two examples," Gerrard says.
"There will be a range of views on the many possible applications of genetic editing in between these two scenarios.
"But at the moment we lack a clear regulatory and legal framework to enable New Zealanders to make these important choices."
Risks and rebuttals
When Research First asked respondents against gene editing to give their reasons, they ranged from the tech being not natural or necessary, to uncertainty about lasting effects on people and our planet.
Some also cited an enduring argument against radical reform: the harm it might cause to the clean, green image New Zealand shops to the world.
While Fonterra is investing in gene-editing biotech overseas, the dairy giant also tells consumers that nothing its farmers grow contains GMOs, saying: "It's not in our nature".
Dozens of its products, from milk powder and cheese to protein ingredients, have been verified by the global Non-GMO Project: the fastest-growing label in a market worth nearly $20b in annual sales.
In a Stuff op-ed last year, Lewis Road Creamery and Southern Pastures' Prem Maan talked of an alliance developing "almost by stealth" to foist GMOs on New Zealand, which he warned could hand our premium export markets over to GM-free Ireland.
In recommending a regulatory review, the Productivity Commission also acknowledged the need to assess consumer attitudes here and abroad, along with potential impacts on our trading brand and firms keen to stay GM-free.
"New Zealand is a small country that depends on around 85 per cent of its produce being exported," GE Free NZ president Claire Bleakley says.
Staying that way, Bleakley argues, will keep enabling us to sell into every market – while allowing GMOs into our environment might leave us having to compete with countries closer to our major markets on cost and travel.
John Caradus is sceptical about such claims.
A scientist who heads AgResearch-owned Grasslanz Technology, Caradus points to studies that indicate no long-term damage to using GM in our food production, including a paper he published himself this year.
It noted how our top trading partner, China - which annually imports some $17b of our goods like dairy, meat, wood, flour and starch – is also a big importer of food products from Australia, despite our neighbour's looser GM laws.
While China might prohibit domestic cultivation of commercial GM crops, that's soon likely to change.
In the meantime, the nation of 1.4 billion remains the world's biggest buyer of soybeans, mainly for animal feed, and much of which comes from GM-variety crops in the US and South America.
Parker says countries like Australia haven't seen damage to their brand by releasing GMOs and the international context might change if more nations ease on GM crops, as the UK also appears to be doing.
Another big question, he says, is whether New Zealand doesn't have one global brand at stake, but several.
Might gene-editing sterile pine trees hurt our food exports?
Will our apple exports suffer if we start selling beef from cows that've eaten GM ryegrass?
To Parker, neither side of the debate has convincingly answered these questions for him.
Bleakley has plenty more arguments for New Zealand sticking with its regulatory regime.
Despite its name, her group isn't opposed to regulated, contained and ethical research being carried out within labs – but still views the HSNO Act as fit-for-purpose, in that it details the process for GM plants and animal safety trials.
Gene editing, she says, should stay just as controlled as older tech.
As no one has researched the long-term effects on the environment or human health of organisms engineered with these technologies, she argues, "we need regulation to ensure their safety".
Not all scientists agree with the main arguments for reform, either.
Canterbury University's Professor Jack Heinemann, who's sometimes been at odds with fellow geneticists over the issue, doesn't see why liberalising some aspects of lab research should mean deregulating gene tech elsewhere.
Like Bleakley, he's also unconvinced by the argument that the HSNO Act couldn't anticipate new tech like Crispr.
As he sees them, they're not new technologies, but new "re-agents" for techniques similar to those being used back in the 1970s.
And rather than Gerrard's petrol and electric car, Heinemann argues the "real analogy" is one between a single-head and electric, multiple-attachment screwdriver.
"The range of outcomes and possibilities is the same but how fast you can turn the screw, and the variety of screw heads that you can interface with, have increased," he says.
"What the new reagents do is make it easier to manipulate genes in more species, more individuals of a species per unit time, more often in the same organism and by more people.
"These are all transgressions of scale. The potential for harm increases with scale. Safety doesn't."
Heinemann ultimately thinks we have two options for managing this risk: we either control use of the tech, or control access to it.
More generally, he's sceptical about hyping the benefits of gene tech long before there's proof of it, noting that four decades of research is yet to deliver us drought-resistant GM crops.
"What has changed in the last 40 years is that we know much more about plants and it may be possible through any number of techniques whether they be gene technology or not, to deliver on these promises," he said.
"Even though I am a geneticist, I remain nonplussed that we depend on gene technology to do so."
All the same, Gerrard and many others in the sector keenly await movement on this decades-long debate.
"If we can think about regulation based on the risks and benefits of individual applications of GM, we will be in a better space, and this will allow us to have more, rather than less, control of our environment," Dearden concludes.
"I think the way ahead is to stop worrying about how something was made, but worry about what it does."