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The first GMO salmon was engineered in Norway

Professor Peter Alestrøm, NBMU: - In my mind, it is completely idiotic to ban research on genetically modified fish. In stead, we could have patented the fish here in Norway and via this patent controlled how it was used. Photo: Gorm K. Gaare.

Professor Peter Alestrøm, NBMU: - In my mind, it is completely idiotic to ban research on genetically modified fish. In stead, we could have patented the fish here in Norway and via this patent controlled how it was used. Photo: Gorm K. Gaare.

Years before AquaBounty started working on their now approved GE-salmon, Norwegian genetic engineers created a GMO salmon by implanting growth hormone genes into salmon eggs. The Norwegian research projects were stopped by priests and politicians, and the salmon destroyed.  The story of the Norwegian GMO salmon is widely unknown, but the scientists involved remember it well enough.

  

  



Attempts to create a fast-growing GMO salmon were made in Norway in the 1980s in several different projects. Effectively closed after a heated debate, the research contributed to the later development of the AquAdvantage salmon.

The development of the fast-growing GMO salmon AquAdvantage recently approved for sale in food stores in the USA, can be traced back to the end of the 1980s. Years before that American scientists had developed a super-mouse, followed by Norwegian attempts to fuel the growth of farmed salmon by implanting the gene for the human growth hormone intosalmon eggs at the University of Oslo in 1984. 

In 1985, a similar growth-project was established in Bergen on the west coast of Norway, this time with the obvious intention to commercialize the result.

The story of this revolutionary research activity is not only one about scientists trying to achieve things no one had done before. It also illustrates how sensitive and heated the debate about manipulating the code of life could become.

Come the 1990s, the projects were effectively killed by a combination of investors fleeing and governmental research funds refusing to support genetic research on fish.

Password: "bfmvideo" Norway also made a GMO salmon from Oslo Business Memo on Vimeo.

 

In the following, Blue Frontier Magazine presents interviews with some of the researchers active in this revolutionary research as well as scientists following and commenting on the development of genetic research over the last 30 year.

 

Breeding breakthrough

Norway, with a population of only five million inhabitants, is the world’s 8th largest fish farming nation. The size and importance of the salmon farming industry to the country’s relatively small economy can perhaps best be illustrated by the fact that it is fish farming many point to when the question is asked what this raw material producing country shall live off after oil is replaced by renewable energy sources in a future climate-friendly world.

Some give one man the sole honour of the Norwegian salmon industry’s breakthrough. The man was Professor Harald Skjervold. In the words of another professor from the same field, Peter Aleström, Skjervold was the man who taught the industry that the fish was a domesticated animal that should be bred professionally and efficiently. As a young scientist, Aleström moved to Oslo some 35 years ago to take part in an inventive project to increase the growth in fish.

 

The Oslo connection

- It was Harald Skjervold who took the initiative to the work I took part in. In my opinion, he is responsible for salmon farming being so important to Norway as it is and he did it by explaining how salmon could be selectively bred.

In Oslo Aleström came to work under Professor Kaare M. Gautvik at the department for Medical Biochemistry at the University of Oslo.

There he also met the Ph.D. student Erik Rokkones, with whom Aleström was going to collaborate in injecting human growth hormone genes into fertilized salmon eggs.

 - Initially, we studied the human growth hormone with a human medical angle. The fish dimension was completely new for us.

 Skjervold’s goal was to copy what scientists in Seattle, led by Richard Palmiter at the University of Washington in Seattle had achieved by enhancing the growth of mice by using human growth hormone. 

 - This research surprised us all like Dolly later did. The transgene mice in the Seattle laboratory grew to double their normal size. It was spot on. Skjervold was extremely well informed about how it was done. Now he wanted us to do the same with salmon.

They soon developed a method. But working with salmon eggs was not easy.

- Because of all the stored nutrients, you don’t see much inside those big eggs. The size of the egg itself does not help much. After all, the cells inside the egg are as small as other cells.

The injection period was limited to the fish’ spawning periods and could only take place a couple of weeks every year. During the preparations, the team visited several companies and scientists in the US. In the spirit of sharing research results, Professor Palmiter at the in Seattle gladly gave them samples of the gene construct that he used on the fast growing mice.

- We brought it with us home. It was a normal form of exchange between scientists. It would have taken us about a year if we had made the construct ourselves.

Back in Oslo, the gene construct was injected into the salmon eggs.

- For us, this was completely normal research activity. We did not see it as a problem that the gene had human origin. The connection man-fish was not in our heads. And it would not have made any difference if we had used a gene from another animal than man. We chose this human gene because it was what we had access to. Today you can buy it of the Internet.

Then the hullabaloo started. (Aleström uses the Swedish word kalabalik.)

 

Peter Alestrøm. Foto: Gorm K. Gaare.

Peter Alestrøm. Foto: Gorm K. Gaare.

Failed mammal cover-up

Skjervold called for a press conference at the laboratory where the gene injection took place. Asked by on journalist about the origin of the gene that was injected, he simply answered “from a mammal”, without specifying which.

- He tried to avoid saying that the gene material was human. I guess he knew by then that the question indicated a theme that could become delicate. 

 The debate that followed included several news stories on national television, bishops warning against the mixing of species through hight-tech research, heated rounds on biotechnology in the Parliament and in the end, ten years later, biotech regulations that permanently killed the idea of a genetically modified Norwegian salmon.

 In hindsight, from his cramped office at the Norwegian Veterinary Institute in Oslo, Aleström admits that it probably was not so smart to try to fool professional journalists in this way.

- We should have been more open about which gene we were using. The result is that a storm blew up.

 Scientifically the researchers were only about half-way there.

 - We had shown that the gene was integrated into a one-year-old fish. However, our fish did not grow like the mice in Seattle. The gene was there, but it probably did not work.      

- Why did it not work?

- There can be many reasons for that. If we had been allowed to continue, I think we would have achieved increased growth.

In the end, the founding stopped their work. Aleström did not approve of how Norwegian research authorities stopped the research work. He interprets it as a fear of what an application of the achieved knowledge could lead to.

- It is very important that we as a society can stop unwanted usage of knowledge. It is a completely another thing however to stop the knowledge production itself, as long as it is not directly unethical. In my mind, it is completely idiotic to ban research on genetically modified fish. In stead, we could have patented the fish here in Norway and via this patent controlled how it was used.

Aleström sees this as a sign that Norway does not prioritize free science the way it is done in other countries we should compare ourselves to.

In fairness, he adds to the story the fact that Harald Skjervold himself had close ties to the fish farming industry. As we shall see, Skjervold founded a similar research project in Bergen that was conducted by private companies, established for the purpose of developing a farmable genetically modified salmon.

- This contributed to the activity not being regarded as basic science in the debate that followed but as product development.

Even if experiments with genetic modification of salmon was stopped in Norway, it might be said to have contributed to the Canadian AquAdvantage salmon that was recently approved for sale at the American food market by the US Food and Drug Administration (the FDA).

Three fronts 

Altogether, injection of growth hormone genes into fish was conducted in three projects in Oslo, Bergen and Trondheim during the second part of the 198os.

The mentioned project in Oslo started up in 1984. A year after, similar research was conducted by the private company Norbio in Bergen, later resulting in the establishment of Marine Genetics. The third project, that came about in 1987, was a cooperation between researchers at the University of Oslo, Norges Tekniske Høgskole (NTH) and the aquaculture group at SINTEF, the two latter situated in Trondheim.

Erik Slinde took part in the work in Norbio in Bergen. Norbio was partly founded by the businessman Erik Sande of Selmer Sande AS.Among the differences between the Oslo and Bergen project was that in Bergen, the industry was directly involved from day one.

An additional and important difference was that in Bergen genetic material from fish was used in stead of the human growth hormone gene that was used in the Oslo Research.

Our aim was to grow a transgene salmon by using the salmon’s own growth hormone, says Slinde, adding that they were a smaller group of five people involved in the project.

The results were published in the research article “Biotechnology in Aquaculture with special reference to Transgenic Salmon”.

- We injected many thousand eggs and were later able to register that the gene was incorporated in the salmon that grew up.

Also this project was in the end stopped. It did not help much that the Bergen project had used fish genes and not human ones.

- The investors left. We then applied to the The Research Council of Norway in order to be able to keep the fish alive, but did not get founding. My interpretation of the atmosphere was that the Council’s decision was based on general reluctance to genetic technology as well as religious motives, says Slinde.

He ads the fact that private companies were involved also may have influenced the decision to turn off research founding.

-  This fact implied that some actors could have made money from the technology, which was not anything the authorities wanted. 

Slinde calls it a “catastrophe for Norwegian research” that the fish was not kept alive.

- I a global context there are clear signs that countries outside Europe are much more willing to develop this technology and then turn it into business.

Slinde did not take part in the actual slaughter of the transgenetic salmon.

- But I did of course suggest let it lose into the ocean outside Bergen.

Slinde denies that setting free the GMO salmon would have harmed the environment in any way.

He adds that in his view, all salmon farmed in Norway is principally already GMO. 

- Over the next two years 20.000 tonnes of triploid salmon is going to be sold from Norway. Since the virus vaccine against pancreatic necrosis is made using gene technology, principally our salmon is already genetically modified.

This is however strongly denied by Odd Magne Rødseth, head of the breeding company AquaGen. He confirms that the vaccine is developed by genetic techniques, but says that, in order NOT to end up with the salmon being GMO, the salmon injected with the vaccine against infectious pancreatic necrosis does not get the dna material used to make the vaccine injected with the vaccine.injection.genetic process is performed outside the fish, and that the genetic component is removed before injection of the vaccine.

- The IPN vaccine is indeed developed using DNA, but the DNA-relevant part of the vaccine development is performed outside of the fish. The DNA material is removed before the vaccine is injected. This way the IPN vaccine does not make it into the fish GMO, says Rødseth.

Approved, then denied

Another scientist active in the experimental work with the growth hormone gene in Bergen, Audun Helge Nerland, was the one responsible for trying to continue the work, especially to test if extra copies of the gene was incorporated in the fish. 

His applications for financial support coincided with the Government’s work on the new regulations for gene technology. His first application was approved, only to be denied later the same year.

- I interpreted the refusal as a political desicion. 

Regardless of the lack of funding the, researchers went on screening the fish.

- I have to underline that all this time the fish was held in secure containers on land. 

Nerland tells the story of two journalists visiting from France, asking questions about gene modification. He told them openly about the company he had worked with that had tried to find techniques for developing a fast-growing fish. The journalist told that they already had visited the Norwegian Research Council, where they had been informed that such activity never had and never would be conducted in Norway. 

- Today many see the work we did as unsuccessful, since nothing really came out of what we did. However, one can only speculate what would have come out of it if we were allowed to continue. Perhaps we today would have been able to make a completely sterile fish, that only became fertile if it was fed a specially designed feed. This could have been a fish that could not mate with wild salmon. Maybe we would have had a fish resistent to PD, ILA or sea louse, asks Nerland.

Constructing and dismantling

In 2007 a young researcher, Terje Finstad at NTNU – Norwegian University of Science and Technology - rote his master thesis on what he called “the construction of a genetically modified fish in Norway in the 1980s”.

Terje Finstad.

Terje Finstad.

In a note from the Norwegian Council for Scientific and Industrial Research he finds the following laconic passage about the work with transgenetic fish: ”The project is cancelled. The results will probably not be followed up due to strict restrictions on the usage of transgenetic fish.”

Finstad shows how the debate included both environmental, political and religious issues. He writes about the debates in Stortinget, the Norwegian Parliament, ands show how the ambiguity of the fish itself created a problem when it met the political debate. For the researcher, the ambiguity had opened for cooperation across barrieres and contributed to financing of the projects. “Facing politics it looks like the fish’ ambiguity created confusion”.

Two central regulations were adopted in the early 1990s. In one of them, Genteknologiloven (the law of gene technology) a paragraph states that genetically modified organisms must not be let out into nature. Together with the experiences of how farmed fish can escape, an idea of developing a genetically modified fish for farming purposes became what Finstad calles “inappropriate”.

 

Failed rhetoric

In 2000, professor Bjørn Myskja at the institute of philosophy at NTNU in Trondheim took part in the planning of a research programme for biotechnology and ethics.

He explains how the plan committee then interpreted popular opinion as strongly opposed to genetically modified food to an extent that the interest in such research in Norway was “relatively low”.

 - Today, much of this has changed.

 - How?

-   The facts on the ground has changed, to quote military jargon. Other countries that we have continous exchange and contact with have genetically modified animals, not least as a result of the globalisation of trade and commerce. I think that popular opnion has changed somewhat. More people know more and have therefore a more nuanced view of technology. At the same time there are still few that are positive to the though about eating genetically modified food.

 - Why has not genetically modified food enjoyed a greater success than it has?

 - One explanation might be that so many of the attempts to success has not fulfilled the expectations. Additionally we prefer what we percieve as natural food and as a result many rule out the thought of buying and eating GMO products.

 - What if a salmon appeared that had half the CO2 footprint, double the amount of Omega 3 and half the price of its non-GMO competitor. Would it be a hit at the local supermarket?

- I doubt it would even be included in the sortiment of the supermarket in the first place. Probably it would have been stopped even before it reach the supermarket chain. The fish farming industry would not risk to have its image destroyed by the consumer opposition a GMO salmon could have created.

- Would the genetical modification of salmon, as it was conducted here in Norway in the 1980s, have been met with the same political debate if it was conducted today?

- It would have raised a debate, but maybe of another sort. Today, in a time when we for instance have GMO plants, pure research projects would not have been met with the same degree of criticism.

- Do you think the the AquAdvantage Salmon will be a success?

- First, we should not overestimate the effect GMO has on growth. The GMO salmon grows somewhat faster, but some breeding experts say that effective breeding gives us an equally strong growth. Whether this new salmon will be a hit in the stores remains to be seen. In the USA there is no demand for the branding of genetically modified products as GMO as we have here in Europe. But also in the USA they have consumers that are very sceptical of GMO food. This skepticism can hurt the store of a chain of stores if it was taken in for sale.

 - How do you evaluate the effect we have had from gene technology so far?        

- It has not have as far-reaching results on all areas as was forecasted earlier. But we should keep our eyes open. There are new techniques on the way in, like the CRISPR-Cas9, or genetic editing, which is said to come with great results.

- Why did GMO not yet solve the sea louse problem?

- Maybe because the scientists do not se a convincing hypothesis that can serve as starting point for a fruitful research project.

- You say that the researchers themselves must take part of the responsibility for popular oposition against gene technology. How?

- Researches have a clear responsibility for using they knowledge in a good way. They must remember that the oposition against their methods does not come out of stupidity. One reason for the strong objections is that the researchers have not done a good enough job in my view. For instance, it does no good to claim that all technology is good and that there are no differences between GMO and traditional breeding. In stead they should try to show how the technology can be used in a good way. In stead of using time and energy to argument for approval for products that gain very few people, for instance like plants tolerant to Roundup, they should concentrate on solving real problems like production of sufficient amount of nutritious and safe food to common people.

In april 2013, two and a half years before the AquAdvantage salmon was approved by the FDA, opening the way for the first GMO animal to enter the food supply chain anywhere in the world, The Norwegian Biotechnology Advisory Board commented on the new salmon in a letter to the FDA. Bjørn Myskja, interviewed above, was a member of the advisory board.

The letter states that even if the fish there is a remote chance that the sterile fish could reproduce in the wild, since five percent, according to data from AquaBounty Technologies will not be sterile.

The advisory board conclude that ”Considering the criticisms that have been raised against the health and environmental risk assessments, in our opinion approval for the AquAdvantage salmon should not be granted”. 

Asked to comment on the opinion of the Norwegian Biotechnology Advisory Board, Dave Conley, director of corporate communications at AquaBounty Technologies, Inc., responds in these words.

AquAdvantage Salmon are all-female and sterile (triploid), meaning they cannot mate with themselves or with other Atlantic salmon.
AquAdvantage Salmon triploidy has been routinely confirmed to 99.8% efficacy.

There is ongoing research in several independent labs, including in Norway, to develop methods of ensuring 100% sterility in farmed salmon. The goal of AquaBounty is to achieve 100% sterility of AquAdvantage Salmon to eliminate environmental risks.

The scientific literature shows that transgenic salmon are poor competitors and would probably not survive if released into the wild. The transgene would likely disappear from the population in a single generation.

AquAdvantage Salmon are required, under the conditions of use for its FDA approval, to be farmed only in land-based, contained aquaculture systems.
Our approved grow-out facility is located in the highlands of Panama, where the risk of escape is zero due to the multiple, redundant physical barriers employed to ensure containment of the fish. Panamanian and FDA regulatory inspectors visit this site frequently to assess the integrity of the facility and our standard operating procedures.
In over 25 years of research and culturing of AquAdvantage Salmon, there has never been an escape from our facilities in Canada or Panama.

As stated in the FDA review documents and the FDA approval announcement, AquAdvantage Salmon represents a very small risk to the environment of the United States when farmed in land-based systems.

In 2013, Environment Canada approved our hatchery for commercial egg production after a risk assessment concluded there AquAdvantage Salmon eggs were a very low risk to the environment.

Any producer wanting to buy AquAdvantage Salmon eggs must be approved by the national regulatory authority in their country to grow AquAdvantage Salmon, and have a land-based facility inspected and approved by the national regulatory authority in their country.

The Food and Drug Administration (FDA) approved AquaBounty Technologies' application to sell the AquAdvantage salmon to U.S. consumers on November 19, 2015.

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