GE salmon... Is the FDA’s review process for genetically engineered animals fit for purpose?

To explore whether the regulatory process in question is fit for purpose, the Food & Drug Law Institute’s Food and Drug Policy Forum​ has published papers by those for and against GE animals, using AquaBounty Technologies' experiences as a case study.

(AquaBounty - which has become the whipping boy of the anti-GMO movement - is seeking to gain approval for its genetically engineered AquAdvantage Atlantic salmon, which includes a gene from the faster-growing Pacific Chinook salmon enabling it to reach maturity twice as quickly as standard Atlantic salmon.)

In the red corner​ is Tim Schwab, senior researcher at anti-GM lobby group Food & Water Watch, who has penned the article: ‘Is FDA Ready to Regulate the World’s First Biotech Food Animal​?’ (spoiler alert - he thinks ‘NO’).

In the blue corner​ are Dr Alison L. Van Eenennaam, Dr William M. Muir, and Dr Eric M. Hallerman*, who have penned the response: ‘Is Unaccountable Regulatory Delay and Political Interference Undermining the FDA and Hurting American Competitiveness​?’ (spoiler alert - they think ‘YES’).

Food & Water Watch: FDA risk assessment process is ‘woefully inadequate’​

Schwab, who describes the FDA’s assessment of AquAdvantage as a 'new animal drug' as “woefully inadequate”, ​says the process is flawed because it relies on the applicant conducting its own studies.

The FDA, he argues, should “do its own scientific analysis of biotech food animals, instead of depending entirely on data provided by drug sponsors whose financial interest in the results create inherent conflicts of interests...​

“Approving GE salmon under the current process would establish a dangerously lax legal and regulatory precedent for a whole new era of biotech animals, whose potential risks to consumer health, animal health, the environment and the economy will not be meaningfully examined by FDA prior to commercialization.”​

He adds: “Independent scientific experts from VMAC ​[the FDA’s Veterinary Medicine Advisory Committee], academia and within the US Fish and Wildlife Service criticized FDA’s risk assessment, calling for new scientific studies, which the Agency has not conducted. Requests under the Freedom of Information Act (FOIA) to the USFWS revealed widespread opposition among scientists to GE salmon approval.”​

AquaBounty’s sterilization process is imperfect ​

He goes on to claim that studies show that the AquAdvantage GE salmon “exhibited allergenic potency rates that were 19.5 to 52.5% greater than non-GE salmon” ​and had “a 39.8% greater level of IGF-1, a hormone linked to cancer in humans”.​

While the AquAdvantage salmon are all-female, sterile and designed to be grown only in FDA-approved contained facilities, he adds, “AquaBounty’s sterilization process is imperfect, and FDA noted that up to 5% of GE salmon could be fertile, which could amount to many thousands or even millions of fertile fish​ [potentially escaping and breeding with wild fish] once commercial production begins.”​

Meanwhile, containment measures at AquaBounty’s facility in Panama “appear insufficient to withstand the region’s frequent extreme weather and severe flooding”, ​he says.

Finally, he argues that the technology doesn’t even confer any meaningful benefit: ”FDA’s analysis of the GE salmon’s growth rates fails to meaningfully demonstrate whether this fish can actually grow faster than existing salmon in commercial production”.​

Few if any technologies could survive flawed process that looks only at risks, not benefits​

However, in their riposte to Schwab’s paper, Dr Van Eenennaam, Dr Hallerman and Dr Muir argue that by focusing exclusively on risks, without also considering benefits - or the risks associated with not​ approving biotech animals and sticking with existing food production systems – the FDA review process is unfair and unscientific.

Crucially, they argue, it doesn’t make sense that the trigger for regulatory review is currently the process​ used to produce an animal, rather than the unique characteristics and attributes​ of the animal in question.

The review process also fails to take into consideration risks associated with conventionally​ bred farmed fish, which undergo no regulatory scrutiny, they point out.

“No technology could survive a risk-only analysis, as all technologies are associated with both risks and benefits. The bio-safety considerations associated with GE animals have to be compared to the full range of risks associated with existing alternative approaches and the risks of inaction. ​

“For example, Atlantic salmon are commonly produced in floating net-pens. Hazards presented by conventional production include: (1) local eutrophication due to nutrient enrichment from decomposition of uneaten feed and animal wastes, (2) transmission of parasites and pathogens among cultured and wild fish populations, and (3) interbreeding of cultured and wild populations, leading to outbreeding depression and demographic decline of wild populations. A shift to greater fish production in on-shore facilities presents the option of reducing these environmental impacts.”​

FDA should respond within 180 days of submission of regulatory compliance data​

Indeed, wild-caught fish deplete oceanic stocks and do not present a long-term, ecologically sustainable solution to rising global fish demand, argue the scientists, who say the FDA should have to act on GE animal applications within 180 days following the submission of all pre-defined regulatory compliance data.

“A recent study​ found that transgenic AquAdvantage salmon had better feed conversion ratios, higher nitrogen retention efficiency, and achieved target weight gain in a considerably shorter period (40%) than conventional Atlantic salmon fed the same experimental grower diet in freshwater until they tripled their weight. ​

“Total feed required to produce the same fish biomass was reduced by 25% in the transgenic fish; representative of a significant and economically-relevant reduction in overall feed intake which is by far the most significant cost associated with salmon aquaculture.”​

No Atlantic salmon has ever successfully mated with any of the Pacific salmon species ​

Should the GE salmon escape from enclosed FDA-regulated facilities, data shows that selection over time would likely purge the transgene from established salmon populations, they predict. 

"Based on the data, the long-term risk of GE salmon​ [multiplying in the wild] is close to zero as no fitness advantages in any component were demonstrated, resulting in a purge scenario for the transgene."​

And they add: “No​ Atlantic salmon ​has ever successfully mated with any of the Pacific salmon species and so fears that sterile, female Atlantic salmon housed in a contained facility in the highlands of Panama will escape, migrate to the ocean, and then traverse thousands of miles across tropical seas and interbreed with wild Alaskan Pacific salmon are scientifically unfounded.”​

There would be an outcry from taxpayers if FDA is required to conduct all the safety tests​

Meanwhile, Schwab’s argument that the FDA should conduct its own safety tests is completely impractical, they add.

“This would require the FDA to house and conduct experiments on many species, including all domesticated fish, shellfish, dogs, cats, cattle, swine, sheep, goats, and poultry. Clearly, the FDA is not equipped to undertake such experiments.​

“There also would be an outcry from taxpayers that they are helping companies commercialize products through FDA testing. It also is unclear how the FDA could impartially evaluate the data it produced.”​

Uncertainty undermines credibility of FDA’s science-based regulatory system ​

Most depressingly, AquaBounty’s experience is likely to put off all but the most patient – or fabulously wealthy – investors in GE animals in future, they predict, noting that AquaBounty first submitted its investigational new animal drug application in 1995 and is still​ waiting for a ‘yes’ or a ‘no’ from the FDA - which gave it the provisional thumbs up in 2010.

“This protracted regulatory review is undermining the credibility of the FDA’s science-based regulatory system. ​[The] uncertainty has had a pervasive chilling effect upon the development and commercial adoption of GE animals more generally.”​

Is opposition politically or commercially motivated?​

Equally frustrating is the fact that opposition to the technology is often politically or commercially motivated, they claim.

“Regulatory decisions and timelines should not be swayed by a tally of public comments on issues unrelated to the science-based evaluation received during a comment period, or the ability of special interest groups to effect congressional interference in regulatory decision making.”​

Experiments should be designed to assess defined reasonable risks​

But what about the tests conducted by AquaBounty?

One question that those calling for more rigorous tests should answer is: “What is the appropriate tissue, test methodology, and sample size to assay for an ‘unintended’ effect?” ​they ask.

“[Demanding] ever-larger samples sizes in… studies to prove the absence of an undefined risk suggests a lack of understanding that it is logically impossible to prove a negative.​

“Experiments to be conducted for regulatory compliance should be designed to assess defined reasonable risks, including: identified hazards; potential harms; biologically meaningful differences in the metrics required.”​

Both papers are available for download here.