'Biopharming' with plants

In 1997 Scottish biotechnology company PPL Therapeutics NZ was granted approval from the Environmental Risk Management Authority (now the Environmental Protection Authority) to experiment with genetically modified transgenic sheep in the Waikato to create medical therapies for cystic fibrosis sufferers.

The process involved in the trial is known as biopharming, in which animal or plant host organisms are genetically engineered to contain human genes so they can effectively operate as cellular factories, producing pharmaceutical substances such as antibodies, proteins and vaccines, for human medical use within their tissues.

PPL’s trial was the first livestock field trial approved in the country. Transgenic rams containing human genes were imported, bred with ewes, and their progeny were to express a protein in their milk that would be extracted and used as an experimental drug.

Time to grasp the agri-food nettle (genetically modified or not)
Clinical trials using this protein were already underway in Europe and the United States, and while early results showed some promise, during phase two testing, several participants started having respiratory issues and dropped out. Delays in further development of the medication and disappointing results led to the end of the experiment, and ultimately PPL was liquidated following a withdrawal of support from investors, Bayer (formally known as Monsanto).

The experiment in Waikato lasted seven years and around 3000 sheep were bred for it. With birth defects, mass euthanasia, deformities, poor health and spontaneous death from causes such as organ ruptures, it would be hard to argue that these animals had a happy existence. After the liquidation of PPL, all genetic material was destroyed – a euphemistic way of saying the animals were slaughtered, incinerated, and their ashes buried in a concrete container in the ground.

There has never been much of an appetite for biopharming in Aotearoa which is not surprising. It has faced myriad challenges, with concerns around animal welfare, gene containment, impact on the whakapapa through the mixing of human and animal genes, and the high rates of commercial failure and restrictive regulations in the use of food species.

As a result there have been fewer than 20 applications approved by the EPA since the 1990s. Most recently the Bioeconomy Science Institute, formerly AgResearch, declared it has no plans to experiment with genetically modified animals in New Zealand after closing its containment facility last year, but are exploring options with overseas research partners.

However, plant biopharming has much potential to be a widely accepted method of developing genetically engineered medications. This technology offers not only extraordinary opportunities for developing human pharmaceuticals, but also for creating more sustainable materials, industrial chemicals, and fortified foods. It can also support conservation efforts. For instance, plants can be bred to produce a signal that indicates contamination from heavy metals, industrial pollutants, or to show they are under stress from drought, cold, UV radiation, viral or fungal infections, or nutrient deficiencies.

The technology is scalable, stable, cost effective, has a lower risk of transferrable diseases. Plants have short growth cycles, which could mean more rapid responses to things like vaccine development in an emergency. And of course there are fewer ethical concerns around the suffering of sentient beings.

Importantly, this technology is not new, it has been in development since the 1980s (the first protein expressed through a plant was a human growth hormone) meaning there is a well-established international field of research to draw and build on.

There are still plenty of technical challenges so investment in this area would require significant public and private funding on top of regulatory overhaul, but medical research is typically the most accepted, well funded, and profitable of genetic engineering ventures.

While this is likely to be more acceptable than animal biopharming, there are still ethical considerations. Tobacco plants are commonly used as host organisms because of their physical characteristics (large leaves, fast growth, and weak immune system responses which allows for more effective and predictable genetic manipulation) their low risk of entering the food chain, and their well understood genetics due to a long history of use in plant biology experimentation – tobacco was the first plant ever genetically engineered in 1983.

The problem is that investigations into the use of tobacco in biopharming is often invested in by large tobacco companies attempting to diversify their portfolios. In 2022, Health Canada approved a biopharmed, tobacco-based Covid-19 vaccine Covifenz; the World Health Organization refused to evaluate or endorse the product because the company that created it, Medicago, was heavily invested in by Philip Morris International.

Biopharming in Aotearoa has to date been marked by controversy, failure, and ethical concerns, but a movement towards plant biopharming presents a new opportunity for scalable, cost-effective, proven, and innovative technologies – particularly medical ones. Plant molecular biopharming is still a complicated case study because of its interactions with the environment and clinical research, two realms that are ordinarily more clearly separated.

The delicate balancing act of preserving hard-earned safeguards with innovative technological opportunities is currently playing out with the debates over the Gene Technology Bill, and biopharming is just one case study of how this is deeply rooted, literally and figuratively, in Aotearoa’s soil, identity, and legislation.

As these technologies advance globally, Aotearoa must modernise its regulatory framework to include cultural values, public investment, and meaningful engagement with te ao Māori, to ensure that novel technologies are neither rejected reflexively nor adopted uncritically.