Scientists who gathered recently to discuss gene editing shared their frustration at the slow development of the technology in New Zealand. Tom Ward reports.

Recently the NZ Institute of Agricultural and Horticultural Science (NZIAHS) held a one-day forum at Lincoln University on the subject of gene editing (GE).

The 12 scientists who spoke were all in favour of the need to develop this science in NZ, and without exception showed their frustration at the difficulty and expense of advancing the technology in this country. NZIAHS, a group supporting primary industry science, organised the forum to assist the Royal Society (RS) in promoting a national, science-based, discussion about GE.

The RS is a NZ body promoting knowledge of all sorts. The topic is vast and complicated, with the GE acronym itself being confusing – GE has in the past denoted the term genetic engineering, now we are using it to mean gene editing, and both terms are a part of the wider field of molecular biology. Since the Royal Commission’s report into genetic modification in 2000, there has been no informed public debate and the legislative and regulatory controls, at both local and national government levels, have become, if anything, stricter. However, there have been major developments in the science over the past 20 years. As far as I can deduce, gene editing has taken over the other genetic modification technologies.

A panel, put together by the society, recently completed a three-year review of the science in NZ. The review found that after 20 years very strong views were still held, particularly on transgenesis (between-species gene transfer). It found that young people were more inclined to consider the intricacies of GE technology, and that politicians were aware of GE but uncertain how to respond. It found the legislation is not fit for purpose; for example, some gene technologies are virtually undetectable, and there is no legislation to deal with the international trade in GE.

Maori investment in primary production is growing and they do not have a co-ordinated view on GE. For example some will want GE out in the environment so they can accelerate manuka improvement for honey production. Others do not want that, but there is a high awareness among Maori of the potential for GE to deal to some of the congenital diseases Polynesian peoples are more susceptible to.

Overall, the generally low level of knowledge about GE in the NZ population needed to be addressed.

Plant biologist Dr Paula Jamieson built some perspective around GE by taking us through a history of plant breeding. Firstly, she defined GE as “taking a gene from one species, and putting it into another with which it could never naturally breed”.

Jamieson pointed to the numerous arguments against GE, i.e. tinkering with nature, Frankenfoods, escape into the wild, farmers cannot save seed, big companies control the food chain, unexpected consequences, and contaminating organic produce.

Breeder techniques

In classical plant breeding, within the same species, male and female chromosomes match, and reproduction relies on successful pollination and fertilisation.

With hybridisation the breeder either (1) crosses inbred lines or cultivars of the same species, or (2) does wide crosses between different species (or genera) and the offspring are usually infertile. With the former (1) you get hybrid maize, hybrid broccoli, hybrid pansies and while this generates hybrid vigour, seed cannot be saved because the next generation will be too diverse. With the latter (2), you get for example, a mule as a result of putting a horse over a donkey and the mule will be infertile because the chromosomes cannot match. However, in plant breeding, since the 1930s a chemical called colchicine, which doubles the chromosomes, has been used and we now get a fertile plant.

Embryo rescue is a technique where, in wide crossing, the endosperm which sustains and feeds the growing embryo is insufficient (unbalanced), and the embryo can be ‘rescued’ by culturing it

in coconut milk or banana, or a synthetic endosperm. This has allowed plant breeders to do between-species crosses for decades, e.g. orchid breeders. Breeders have also done crop crosses, e.g. triticale, from wheat (a tetraploid) and rye (a diploid) with colchicine and embryo rescue. Triticale, which is fertile, is a new artificial genera grown all around the world. There is no legislation covering this technology.

‘While there are risks, we at least need to debunk naysayers with informed debate.’

Trans-genetics in NZ

Mutation breeding, either chemical or radiation, is another technique used by breeders. There are thousands of mutant varieties registered in 170 plant species, 25% of which are ornamental. Of the crops (75%), rice, wheat, barley, peas, and grapefruit are examples where mutation breeding has brought increased yield, quality, disease resistance, herbicide resistance, and alkaline and acid tolerance. The technique has been used for 80 years and there is little regulatory control over the magnitude or type of genetic change; it is random, multiple and unspecific. Another example is the organic beer brewing industry, which used Golden Promise barley, a gamma ray mutation, for 20 years.

Genetic engineering is inter-kingdom transfer (i.e. animal to plant, and vice versa) which cannot be done with any other plant breeding technique. An example is firefly in tobacco. Foreign DNA is inserted into a plant, usually using a specific bacteria, and is random. Traces of the insertion remain. These plants are grown widely around the world, the most common being herbicide tolerant (Roundup ready maize, canola), insect tolerant (bt maize, eggplant), and virus tolerant (pawpaw in Hawaii). No GE plants are grown in NZ.

However, in laboratories in NZ, trans-genetic organisms are being developed, i.e. medicines, such as insulin, and vaccines. Foods are imported that are genetically modified, e.g. canola and soybean. In NZ there are no field trials, which may be permitted when controlled. There has been only one release, an equine flu vaccine, the use of which is very tightly controlled.

The scientists at the forum were very critical of the costs and difficulties, particularly the public submissions, of the application process for permission to conduct trials. This pushes ownership and development of the technology offshore. Furthermore, because the legislation is such a handbrake on research, no one can see how the technology can be marketed, further reducing capital available for development.

The USA is unregulated, Australia is unregulated if gene inserts are minor, Chile and China proceed on a case-by-case basis, the EU is fully regulated, and Argentina is unregulated if no new genetic material is used.

New gene editing system

The most recent (exciting) development in the molecular biology field is an editing system, CRISPR. This is derived from a naturally occurring bacterium defence mechanism which ‘snips’ small sequences of DNA from interlopers (attacking organisms) and copies them into its own genome for future identification should the bacterium attack again. The clever part is that scientists have adapted this discovery so that any specific DNA sequence in a collective DNA ‘book’ can be identified, selected, removed and replaced. The introduced sequence can even be removed and the original sequence reinserted.

In plants, with CRISPR, we can already reduce seed shedding in ryegrass, increase seed size and number in crops, reduce abiotic stress, enhance disease resistance, improve digestibility and herbicide tolerance, edit neurotoxin genes in endophytes, and speed breeding in tree crops.

Dr Suzanne Rowe from Agresearch described how, over eight years, the company has bred a functional sheep with a 24% reduction in methane emissions. This is not genetic engineering/gene editing, just conventional selection technique and has cost $10 million. GE has been attempted and 600,000 DNA markers have been identified but not successfully sequenced yet. The researchers still cannot find a gene of larger effect for gene editing. In any case most emissions are from cattle.

Trying to modify microbes

Dr Travis Glare of the Bio-Protection Research Centre spoke interestingly on modifying microbes to increase their efficiency in primary industry. His focus is on killing insects. Due to chemicals meeting resistance, or being seen as potentially carcinogenic, there are demands for more biological, environmentally friendly methods to control weeds, pests and diseases. These are called biopesticides, and may be a virus, bacterium or a natural product derived from a plant. The genomes in these organisms are easily modified and scientists working in this area do not really need genetic modification or CRISPR. We already use biopesticides in human and veterinary medicine, e.g. insulin from a pig’s pancreas. These microbes have different methods of operation, i.e. direct infection, toxicity, induced resistance, resistance priming, hyper parasitism, competition and antibiosis. Examples are Beavaria and metarhizium, both of which have a scorpion toxin inserted. Beavarium kills insects 15 times faster than in its natural state, with a 40% lower kill time. Metarhizium kills mosquitoes nine times faster and caterpillars 22 times faster. Despite these successes, this technology is only 5% of the pesticide market.

Dr William Rolleston, a former Federated Farmers president and co-owner of South Pacific Sera, a South Canterbury-based blood product business, spoke about the history of molecular biology in New Zealand. The Royal Commission in 2000 disagreed with activists who argued risks of misadventure from genetic modification were so great that all GM should be stopped, and recommended the country should proceed with caution. According to Dr Rolleston, the past 20 years has seen claim and counterclaim, with more caution than process. The CRISPR-Cas9 discovery has, however, been a significant development because it is very precise.

Animal organisms difficult

Tobacco plant with firefly gene.

Prof Peter Dearden, an insect geneticist who is very interested in keeping insects alive, suggested that while CRISPR-Cas9 has made genetic modification on animals possible, gene editing animal organisms is in fact very difficult. Very few animal organisms have actually been gene sequenced (flies, mice very badly) so nearly all the gene editing possibilities for animals have been done on models. For example, honey bees can be gene edited to resist insecticide sprays, but this has raised concerns about ‘Frankenbees’. Wasps, a major predator of bees in NZ have been gene sequenced but we do not yet know how to edit that sequence, how effective the editing would be, or whether the wasp would become predatory on other organisms (wasps are not a pest in Europe).

While gene editing is said to be very accurate, there is a very great difference between editing (removing) one sequence in a species, and introducing DNA into a sequence. The latter is definitely genetic engineering. Deardon’s opinion is that there cannot be a sensible conversation with the NZ public until the risks are known.

Plant biologist Prof Andy Allen says the world’s most important crises are climate and population, and by 2050 there will be another one billion people on earth, requiring a 52% increase in food production since 2010. That means another 600 million hectares for food production (an area twice the size of India) which will increase CO2 equivalent emissions by 15 gigatons.

Allan explained how a 60-year conventional breeding process to obtain a red-fleshed apple can be reduced to seven years by introducing DNA to make the plant constantly flowering, then removing that DNA when the red-fleshed state is reached.

Another example is the kumato, a wide cross between a tomato and a wild relish which sells for $11/kg compared with $6/ kg for a tomato. Conventional breeding techniques require 300 million molecular changes; using gene editing only four base pairs need to be changed. This is not allowed under current legislation.

I do not pretend to be an expert in molecular biology, I thought I would give it a crack. The technology has clear benefits, both for human health treatments and nutrition outcomes. The rest of the world, the European Union aside, is moving forward on this. There is expected to be increased pressure on feeding a warming world and a growing world population, such that improved food and science efficiency will be required. While there are risks, we at least need to debunk naysayers with informed debate.

  • Tom Ward is a South Canterbury-based farm consultant 027 855 7799,