Risks not properly addressed

The US Food and Drug Administration (FDA) has approved a transgenic GM pig for use in food as well as human therapeutics.

The so-called GalSafe pigs were developed by a medical biotech company, Revivicor, Inc., which was acquired in 2011 by United Therapeutics Corp.

GalSafe pigs are the first GM animal to be approved for both human food consumption and potential therapeutic uses. The pigs are engineered with the aim of eliminating alpha-gal sugar on the surface of the pigs’ cells. People with alpha-gal syndrome (AGS) may have mild to severe allergic reactions to alpha-gal sugar found in red meat (e.g., beef, pork, and lamb).

Tick bite connection

In the US, the condition most often begins when a Lone Star tick bites someone and transmits alpha-gal sugar into the person's body. In some people, this triggers an immune system reaction that later produces mild to severe allergic reactions to alpha-gal sugar found in red meat.

The syndrome appears to have arisen, or become widespread, relatively recently. The allergy was first formally identified as originating from tick bites in the United States in 2002 and independently in Australia in 2007.

Risks and limitations of the GM pigs

The risks and limitations of the GM pigs are not properly addressed in the FDA evaluation. They are listed below.

Antibiotic resistance: The GM pig contains the nptII gene, which encodes for the NPTII protein, which in turn confers resistance to the antibiotic neomycin. The risk is that this gene could escape to pathogenic bacteria, making them antibiotic resistant. The FDA dismisses this possibility, saying that the presence of the protein "is not expected to result in an increase in antimicrobial resistance in the affected environment". But it adds the qualification, "However, even if this increase occurs, it is only expected to occur in the local environment (i.e., the soil environment where manure, carcasses, or other animal remnants from GalSafe® pigs are applied)".

The FDA says the pigs will be kept confined and exposure to their wastes will be "limited" due to the fact that they will be produced only at two sites, named in the approval. The application says, "No more than 1,000 GalSafe® pigs per year will be produced at a single facility in northern Iowa and slaughtered at a single abattoir (slaughterhouse) in southern South Dakota that is inspected by the United States Department of Agriculture."

However, critics may conclude that even a "limited" release of antibiotic resistance bacteria does not stay "limited" and thus may pose a wider risk.

Food safety: The food safety risks of GM food animals are different from those of GM plants. Even non-GM plants are highly prone to making their own toxins in order to repel pests and diseases. Thus with a GM plant, careful testing and evaluation are needed to ensure that the plant does not unexpectedly contain new toxins, or higher levels of existing toxins, compared to the non-GM parent.

In contrast, it is highly unlikely that a GM animal would be toxic, as it would end up poisoning itself.

But allergies are another matter – and the concerns on this topic remain. The developers manipulated the pigs' genes to remove one allergenic substance – the alpha-gal sugar. This was done by destroying the function of a gene called GGTA1, which encodes for an enzyme called glycoprotein galactosyltransferase alpha-1,3, which is responsible for producing the alpha-gal sugars. This was achieved by targeting the insertion of the nptII transgene into the GGTA1 gene, thus effectively destroying its normal function.

The developers checked to ensure that the transgene only inserted in the desired GGTA1 gene location in the genome. But they appear not to have investigated the possibility that the genetic manipulation process may have caused different kinds of disruption to the genome. These could result in the production of new mRNAs (messenger RNAs), which in turn could result in the production of  different allergens – for example, in the form of mutant proteins.

Animal feeding studies do not reliably reveal allergens, and in any case these types of tests haven't been carried out with the meat from these pigs. So the only way to see if the pork from GM GalSafe pigs is allergenic is to feed it to human volunteers, both those with no history of allergy to red meat and those who have alpha-gal syndrome. The developer company has confirmed that tests have not been done on people with the allergy.

Transplants: While the developer company hopes that the GM pigs will produce tissues and organs that are safe for human transplants, this is uncertain because many other factors, beyond alpha-gal sugar, trigger human rejection of pig-derived transplants. Thus previous attempts to reduce transplant organ rejection in baboons by using organs from GM pigs in which the alpha-gal gene has been knocked-out have not been successful over the long term. And worries about transmitting pig viruses to humans via transplanted organs remain.

The aspiration to produce organs and tissues for human transplantation has been around for decades but thus far has failed.

Animal welfare worries: The developer company's application contains no information about how many of these GM pigs have to be bred to end up with the required number of viable pigs. The history of GM animal production is characterised by large numbers of deformed and born-dead animals.

Market considerations: Given that the target market for food production – AGS-affected people – is extremely limited in size and profitability, the main target market for these GM pigs will be the human transplant market. 

Lawsuit against FDA mulled

In conclusion, the risks to the general public from the GM GalSafe pigs are focused on the antibiotic resistance gene and potential allergens. And hopes for safe and effective therapeutic applications are premature.

Jaydee Hanson, policy director at the Center for Food Safety, told the Guardian that they are considering whether to sue the FDA over the GM pig approval. Hanson said, “My greatest concern is that we don’t know if this is safe to eat, or as an organ transplant source, and no scientists, nor the public, have seen the data. Nor was there any FDA public consultation process, as there normally would be.”