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Fifty years after Asilomar, where scientists themselves drew up safety rules for recombinant DNA, the Netherlands is once again grappling with the boundaries of biotechnological progress.
During the anniversary symposium Biotechnology in Motion of the Netherlands Commission on Genetic Modification (Cogem), held on 30 October, participants looked back on half a century of genetic modification – and, above all, forward to the future of a technology that has by now permeated virtually every domain of biology: from sustainable industrial production and plant breeding to gene therapy and even the construction of synthetic cells. What will the next phase of genetic modification look like? Bionieuws gauges the expectations and concerns of four experts in the field.

Marianne de Visser, emeritus professor of neuromuscular diseases at the University of Amsterdam and board member of Cogem
‘I think there are an incredible number of reasons for enthusiasm. My background is in neurology. The idea that we can now treat a muscle disorder such as spinal muscular atrophy – a condition that used to kill children at around seven months of age – so effectively with gene therapy that these children learn to walk and do not need to be put on a ventilator is fantastic. These are tremendous steps forward. But challenges remain. In June last year, Cogem published a report on gene therapy and its costs and accessibility. Last week, the Healthcare Institute also released an interesting report on market-acceptable prices. The development costs of gene therapies are very high. Price negotiations for gene therapy for haemophilia B have now stalled, which means it will not be included in the basic benefits package. Difficult choices will have to be made, particularly now that more budget must be freed up for defence. I would like to make a case for citizen consultation. A well-informed group of representative citizens is certainly capable of making nuanced decisions on these matters.’
‘I would advocate for more Dutch research into this kind of treatment for rare diseases, and for more public–private partnerships. In this way we can reduce market exclusivity and prevent the United States and the pharmaceutical industry from running off with the benefits.’

‘Half a century after the first recombinant DNA experiments in E. coli, products of genetically modified micro-organisms (GMOs) are part of our daily lives. Diabetes patients use human insulin produced with GMOs, we wash at low temperatures thanks to enzymes from modified fungi, and E10 petrol contains ethanol produced by modified yeasts. As far as I am aware, more than forty years of intensive industrial production has not led to any harm to people or the environment from the GMOs used. Regulations for research with GMOs such as E. coli and baker’s yeast have been relaxed; the administrative burden is time-consuming but manageable. Greater problems lie with industrial application in Europe, for example in the case of food ingredients. It is not the criteria but the agonising slowness of procedures that constitutes the bottleneck.’
‘When an authorisation procedure in Europe can take as long as five or six years, whilst in the United States it can be completed in one, companies are left with little option but to locate production outside Europe. This leads to a loss of knowledge, jobs and revenue. Renewable carbohydrates are currently the principal feedstock. The use of alternative feedstocks, produced via (electro-)chemical CO2 reduction, offers opportunities for substantial emissions reductions and independence from imported raw materials. GMOs play a key role in this. Capitalising on these opportunities requires both investment in research and infrastructure and the streamlining of regulations. I hope that a new government will actively pursue this.’

‘I think gene editing will become a new tool for plant breeders. With CRISPR-Cas we are already able to introduce mutations at targeted locations. Switching off a single gene is currently the easiest approach. In the future we could use this as a means to make potato or banana varieties disease-resistant more quickly, for example. The link with sustainability is always strongly emphasised, but heat and drought resistance are harder to achieve because multiple genes are involved. I think that improving sustainability has more to do with how you use a plant within the cropping system.’
‘CRISPR-Cas was invented in 2012. The first plant products developed using it are only now available in small quantities – for example, seeds from the GABA-enriched tomato in Japan. I expect more crops to reach the market in the coming years, but this depends heavily on EU regulations and consumer attitudes. We should do a better job of informing people about what is currently being done in plant breeding, so that they can make an informed choice.’
‘In 2018 the EU ruled that the new gene-editing techniques fall under the old GMO legislation. A proposal for revised legislation has been on the table for two years now, but it remains stuck, partly on debates about patents on these kinds of techniques – whilst the problem is broader than that.’

‘The Netherlands has a strong future in genetic modification. We have a number of exceptionally good universities focused on this field. That gives us the opportunity to tackle major climate and health challenges.’
‘My group is working on building a synthetic genome. At the moment we cannot yet construct a bacterium independently. This also opens the way for mix-and-matching: the cell division of a yeast combined with the DNA replication of a bacterium. The ultimate goal is to be able to build a perfect organism for specific purposes, such as capturing CO2 from the atmosphere and breaking down plastic.’
‘In the past we always used the same organisms for the same applications. These are not perfect: a bacterium or yeast always has its own role and function, and you cannot guarantee that it will not interact with other organisms. A synthetic cell is a blank slate, and our dream scenario is that we can programme it however we wish.’
‘Politics remains a concern. There is currently very little investment in education and research. Money often does go towards innovation and applied research, but there needs to be a balance with funding for fundamental science. The public is quite willing to accept genetic modification, provided communication is transparent and clear policy is in place.’
