Oct 08 2015

CRISPR and a Hypoallergenic Peanut

Anyone with a child in school is probably aware of the need for peanut free zones. You get a notice when your child returns from school on the first day stating that at least one child in their class has a peanut allergy, which means nothing with peanuts gets sent to school for your child’s lunch. If you are a parent of a child with a peanut allergy you understand how important and serious this is – your child is literally one errant Snickers bar away from death.

The general consensus is that food allergies have been on the rise in developed countries, although studies show a wide range of estimates based upon study techniques. A US review found the prevalence of self-reported peanut allergies ranged from 0-2%. A European review found the average estimate to be 2.2% – around 2% is usually the figure quoted. In a direct challenge study, at age 4, 1.1% of the 1218 children were sensitized to peanuts, and 0.5% had had an allergic reaction to peanuts. That means there are millions of people with peanut allergies.

So far there is no cure for the allergies themselves. Acute attacks can be treated with epinephrine, but there are cases of children dying (through anaphylaxis) even after multiple shots. The only real treatment is to obsessively avoid contact with the food in question. Peanuts, tree nuts, and shellfish are the foods most likely to cause anaphylaxis.

There is, however, a potential solution. Researchers have been working for years on developing a cultivar of peanut that does not cause allergies. Attempts to achieve this through conventional breeding and hybridization have failed and does not seem likely to succeed. The only real hope of a hypoallergenic peanut is through genetic modification. We are, in fact, on the brink of achieving this goal, but anti-GMO fears are getting in the way.

There are 7 proteins that have been identified in peanuts that cause an allergic reaction. The allergic reaction from peanuts is entirely an IgE mediated Type I hypersensitivity response. The proteins crosslink with the IgE antibodies, which then bind to mast cells and basophils (cells in the immune system) causing a significant inflammatory response that clinically causes the allergic reaction. One peanut contains about 200mg of protein, and as little as 2mg is enough to cause objective symptoms of an allergic reaction.

What makes a food protein an allergen is interesting. About 700 amino acid sequences have been identified that help confer allergenicity to protein. These protein segments allow the protein to survive processing and digestion, and allow the protein to bind to IgE antibodies.

In 2005 a study was published showing that it is possible to silence the gene for the Ara H2 protein, the primary allergenic protein in peanuts. A 2008 follow up by the same team showed decreased allergenicity of the altered peanut. So where are our hypoallergenic peanuts? This is a complicated question, and I don’t think I can give a full answer.

The delay in marketing a hypoallergenic peanut seems to be due partly to technical issues – it turns out to be a lot more difficult to make the necessary changes than at first thought. However, it also seems to be due to the anti-GMO campaign, which has been scaring away investors and making politicians gun-shy.

Meanwhile, scientists have developed a new technique that promises to revolutionize genetic engineering, called CRISPR – Clustered regularly interspaced short palindromic repeats. This is a system found in procaryotes as part of an adaptive immune system against viruses. The system can be used for relatively cheap and easy gene editing.

Chloe Gui, a scientist with Aranex Biotech, is working with CRISPR technology to identify and then edit out the genes for the major allergenic proteins in peanuts. CRISPR is more precise than older techniques and has the potential to succeed in the goal of an allergy-free peanut. Gui, however, complains that the investors the startup needs to complete their research is difficult to come by because “GMO” has become a bad word. Further, GMO regulations have not yet accounted for CRISPR technology, creating uncertainty in the market.

Conclusion

Peanut allergies are a real and serious health concern. We have in our grasp the technology to essentially eliminate the problem from the world, as thoroughly as smallpox has been eliminated. We can simply edit allergenic proteins out of cultivated peanuts. Conventional breeding has failed to accomplish this, and it doesn’t seem likely that it will be able to.

This is simply an extension of the past several thousand years of altering the plants and animals in our environment to make them more suitable for human consumption. Just about everything you eat has been massively altered through human intervention. Now we have the technology to make precise specific changes.

Irrational fears of this new technology, fueled by pseudoscientific propaganda, have created a significant negative attitude toward GMOs in the public. This is a great example of how misplaced fear can lead to negative outcomes. People will literally die from peanut allergies because the solution is delayed or rejected due to unwarranted fears.

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