The FDA’s decision on approval of AquAdvantage GM salmon came as a surprise even to Ron Stotish, the founder and CEO of AquaBounty, the company behind the new product. There had previously been no signs that the application for approval (which was submitted in 1995) would now suddenly come to a conclusion. The agonizingly long approval process had time and again demanded new requirements, inspections and documentation, and when it seemingly come to an end after nearly 20 years a load probably fell from Stotish’ shoulders. It is almost a miracle that the small technology company AquaBounty from Maynard (Massachusetts) managed to survive this long stretch at all. One would have to be absolutely convinced of the idea and the product to withstand the crossfire of international public criticism that showered down on Stotish and his company. According to Stotish the development of the genetically modified salmon and the disputes over its approval cost the company nearly 85 million US dollars. Perhaps that is one reason why Intrexon Corp. (Blacksburg, Virginia) took over 48% of AquaBounty in 2010 and in the meantime even holds 62% of the shares. But it seems that this investment could finally be paying off: only one day after the FDA decision AquaBounty’s share price rose on the London Stock Exchange by 122% to GBP 27.75 (EUR 39.70).
So what kind of salmon is this that can raise such tremendous hopes among some people while others who have been trying to stop the fish’s production for years cannot cease from uttering incessant warnings. Really, the idea of transgenic salmon is irresistibly easy. Traditional animal breeding, as pursued by all pigeon or rabbit breeders, is also geared to clearly defined breeding goals. In the case of farm animals this usually concerns features such as better feed conversion, resistance to disease, and faster growth. With conventional farming methods it normally takes numerous generations to achieve the aspired objectives. And even then, it is not always possible to fulfil all the breeder’s dreams. Traditional breeding methods will always fail, for example, if certain prerequisites – the necessary genes for a desired feature in the genetic material of the particular species – are missing. But that is where modern genetic engineering can help. For with this method it is in the meantime possible to cut the required gene sequences from the genetic material of one species and transfer them to another target species, in this case, a salmon. This saves time, is relatively accurate, and often even bestows onto genetically modified products additional features which they would never have developed naturally in the course of evolution.
And that is exactly what AquaBounty did. In 1989 researchers in the company’s laboratory in Fortune (Prince Edward Island, Canada) put together a molecular structure consisting of the growth hormone gene of Pacific chinook salmon (Oncorhynchus tshawytscha) and a promoter, also called a primer, from the American ocean pout (Zoarces americanus). In technical jargon geneticists refer to this gene construct for short as “opAFP-GHc2”. The genes that produce the growth hormone are very similar in both chinook and Atlantic salmon. A comparison of their basic building blocks, the nucleotide sequences, showed 90% conformity. And the produced hormones are also almost identical: 95% conformity in the case of the protein sequences and 98% of the amino acids. This explains why the growth hormone of chinook was just as effective in Atlantic salmon when the researchers injected their opAFP-GHc2 construct into the eggs of Salmo salar. Without any complications the construct was integrated into the genetic material of Atlantic salmon which consists of nearly 40,000 genes. The “foreign gene” was immediately active and remained stable over several generations as could be demonstrated in backcross experiments. AquaBounty had created a new salmon line with unusual growth characteristics and they protected it under the brand name AquAdvantage salmon.
“Time is money” holds true in salmon farming, too
What makes the AquAdvantage salmon special is its growth rate, which is two to four times higher than that of the conventional farmed salmon Salmo salar which are indeed already trimmed to growth through targeted breeding. But note: AquAdvantage salmon are not larger than normal salmon, but they grow much faster and therefore reach their marketing weight of 4 to 5 kg already 16 to 18 months after hatching instead of the usual three years. The explanation for the speed lies in the combination of the growth hormone gene with the primer, which starts or stops the reading of the gene. Normally, the primer switches off the gene in the autumn when the days get shorter and the temperature drops. The fishes then take a break in growth until spring, when the growth hormone gene is activated as the temperature rises. In the case of AquAdvantage salmon the researchers insert a primer which renders the gene "activated" throughout the year, especially in cold weather. The American eelpout or ocean pout lives in the icy waters of the Subarctic. From their genetic material the AquaBounty researchers isolated a primer which actually controls a gene that produces special proteins to protect the blood and body fluids of the fish from the cold. For understandable reasons it is mainly during the winter that the so-called “antifreeze proteins” are needed, which is why the primer activates the gene particularly at this time. The clever researchers incorporated the "winter active" primer into "opAFP GHc2" with the result that the AquAdvantage salmon grow in cold water, too.
AquaBounty celebrates the development of their fast-growing salmon as a revolutionary breakthrough in aquaculture. Halving farming time naturally reduces the use of resources, means less feed, work, water pollution and lower costs. Because the GM salmon would be farmed in land-based recirculating systems, production could be carried out close to the markets, too. This shortens transport paths and reduces the carbon footprint of farming. Apart from that, diseases and parasites that are often a plague to salmon farms in the open sea are easier to control in the indoor facilities which would render the use of drugs unnecessary.
Opponents of the use of genetic engineering in food production, however, fear the incalculable risks of such methods for humans, animals and the environment. Nobody could at present seriously estimate what long-term consequences eating genetically modified foods might have for consumers. Allergies, diseases and other health hazards could not be ruled out for certain. If GM salmon escape from a farming facility and by mating with wild salmon spread their growth genes among these populations this could even lead to the extinction of that species. In this context reference is usually made to the theory of "Trojan genes" and their catastrophic consequences. The theory is based on an insight gained in experiments that large males are much more attractive to females than their smaller rivals. Thus, they can spread their growth genes more rapidly, which can weaken and eventually extinguish fish populations. In contrast to Darwinian Theory it is then not the fittest, but the least fit individual that mates most frequently. Computer models show that in a group of 60,000 wild fishes already 60 transgenic fish suffice to bring the population to extinction in only 40 generations.
GM salmon allegedly no different from normal salmon
Studies of GM salmon had so far revealed no evidence of a significantly increased allergen potential compared to normal salmon, says the FDA. Biologically, however, there are several differences between AquAdvantage salmon and their wild counterparts. GM salmon eat proportionately more, for example, which is probably connected to their rapid growth. In an overall comparison over their entire lifespan they need less food than normal salmon but their individual appetite is greater. In contrast to a salmon’s normal behaviour they are also often found individually at the water surface. GM salmon are allegedly not such good swimmers as wild salmon. Their muscle fibres are thinner than usual and the fishes therefore need more energy to achieve a poorer performance. Some immune functions of the GM salmon are also said to be reduced. And whether transgenic salmon would be viable at all in the wild is uncertain. Due to their rapid growth they would smoltify earlier, however, migrate to the sea and then also return a lot sooner to spawn in the rivers. The spawners’ performance is also a controversial topic. Allegedly the males develop weak hooked chins and are of a pale colour. Their nest building is said to be unsatisfactory. Semen analyses show that the GM salmon produce relatively few sperm and these are also atypically slow and sluggish.
AquaBounty believe they have eradicated the possible risks caused by escapes. AquAdvantage salmon are all female and they are “triploidised, i.e. rendered unfertile, at the start of their development. The success rate of this sterilisation is 98.9%, and batches with a share of over 5% diploid fishes are destroyed. Apart from that, GM salmon are to be farmed in land-based facilities. There were thus already several physical barriers that make the fishes’ escape practically impossible – with the exception of malicious activities. FDA has already announced that the farms will be monitored regularly and particularly thoroughly. But opponents of genetic engineering have ethical concerns, too, and think that with the genetic modification of animals human beings are crossing a moral border, playing God, intervening in evolution, and creating new creatures based purely on utilitarian criteria and thus completely alien to nature. Already now up to 80% of all processed foods in the USA contain genetically engineered components but these were mainly cereals, maize, soy or potatoes. Approving the production of GM salmon was thus a precedent that could open up Pandora’s Box. To help “waken up” the public, opponents of genetic engineering like to use terms such as turbo or rocket salmon, monster salmon and “Frankensalmon”. An unfortunate choice, for Frankenstein’s creature was initially rather more naïve than evil. It did not become a monster until its well-meant attempts to make contact with human beings were rejected with outright hostility.
Throughout the world, laboratories and genetic engineers seem to be waiting for a start signal like the approval of GM salmon. In China researchers have created a GM goat with more muscle and longer hair, and Intrexon, to whose company network AquaBounty belongs, has a whole arsenal of surprises waiting which ranges from cloned bulls to genetically modified anti-dengue fever mosquitoes. From a purely technical point of view the possibilities in this area have exploded since the development of the sensational CRISPR technology with which DNA can be accurately cut and modified (genome editing). That is why the people at Intrexon no longer speak of genetic engineering but of synthetic biology. Up to now, however, the problem has been the political environment and the lack of an official production licence which would enable these skills to be put to practical use.
Approval of GM salmon breaks a taboo worldwide
It was in the tense atmosphere of all these factual and emotional arguments that the FDA had to come to a decision on AquaBounty’s application. The US Food and Drug Administration was, of course, aware of the magnanimity of the decision: it would be of far-reaching, indeed global significance, would kick up a dust in the economic and political landscape and possibly open the gate to a new era. The desire to do everything right and allow no mistakes does not, however, explain why this process took an agonizingly long 20 years and why it is still not at its end. The FDA explains the long processing time with the new kind of concerns which the application entailed and for which there were so far no routine procedures. After all, it was the first of its kind. Not until the new version of the Federal Food, Drug and Cosmetic Act had there been a legal basis for the approval process. On this basis the FDA examines the genetically engineered changes in the animals concerned according to the same rules as an animal drug, something which critics immediately criticized. They accuse the authorities of squeezing a new, cutting-edge technology into an old, outdated legal framework. The White House is now examining whether the current legal framework still “fits” genetically modified products or has to be revised.
In 2010 an advisory committee of the FDA announced that it was highly unlikely that genetically modified salmon would have adverse effects on human beings and the environment and that it was just as safe as conventional salmon. Critics accuse the authorities of basing this appraisal mainly on data and information provided by AquaBounty themselves. Apart from that, the bar had been set much too low. AquaBounty disagreed, saying that AquAdvantage salmon was probably the best studied fish in history and that the technology was safe and sustainable. Objections were again filed, examined, and deadlines extended. In 2013 the environmental agency in Canada allowed the commercial production of genetically modified salmon eggs at the AquaBounty Hatchery on Prince Edward Island. On 19 November 2015 the US Food and Drug Authority FDA approved the production of AquAdvantage salmon and released it for sale and consumption for US consumers. This led to protests, not only in the USA but – as was to be expected – worldwide.
Virtually all the big salmon producers renewed their promises not to produce genetically modified salmon. More than 200 wholesalers, restaurants and seafood chains in the USA want to do without GM salmon, nearly half a million US citizens demand in a petition to the state authorities that production be prohibited. They are supported by 300 environmental, consumer and health organisations that also oppose GM salmon. Several US supermarket chains said they would not sell genetically modified salmon, among them Whole Foods Market, Target, Trader Joes, Aldi and Costco. And the first US states have opposed AquAdvantage salmon, especially Alaska that is worried about the impact on the image of its wild salmon and on the markets they serve.
A lot of people find it particularly outrageous that GM salmon does not have to be marked in any particular way. After all, in the USA, too, there are strict rules for the declaration of ingredients in foods. Consumers can then recognize whether a food is an organic product, a free-range chicken or hormone-free beef, and how much fat and calories it contains. But a clear indication that a product is a genetically modified product is not required. The FDA gives the reason for this idiosyncratic practice with the finding that there are no appreciable differences between the biology and the nutritional profile of genetically modified and normal salmon. Under the Federal Food, Drug and Cosmetic Act the FDA can only demand additional labelling on foods if there are considerable differences between the products. AquaBounty welcomes the decision: both products were identical, consumers would not notice any differences. A GMO label could irritate customers because it suggests that AquAdvantage and normal salmon have different qualities. Consumer protection organisations claim that the customer has a right to know exactly what he is buying and what he is eating.
In Europe, the approval of genetically modified salmon by FDA strengthens resistance against the EU-USA trade agreement TTIP. Opponents of the agreement fear that Intrexon will submit an application for the salmon’s admission to the EU market. Since the fish does not have to be marked genetically modified in the USA the producer could complain at the ominous arbitration courts if the EU were to insist on its labelling obligation. Already today the meat from offspring of cloned animals can be marketed in the EU without special labelling. Evidently the storm of protests and concerns has had effect: At the beginning of February 2016 the FDA imposed a provisional import and trade ban on genetically modified salmon until the authority has formulated and adopted exact guidelines for the correct labelling of salmon. Experts believe that this could again take several years. AquaBounty took note of the decision, saying they could not have delivered the salmon at this point in time anyway for the transgenic salmon farm in Panama first had to start up their production. The first GM salmon would be ready to enter the market at the earliest in two years’ time. So the issue is only postponed and not cancelled. Both sides, the supporters and opponents of genetic modification, have just gained a bit more time to gather additional arguments and reposition their troops.