Gluten-free GM wheat can help celiac patients

posted in: Science | 25
Artist rendition of MyPlate food guidelines
Artist rendition of MyPlate food guidelines

Have you ever seen the popular MyPlate? It is a simple graphic to indicate the type and amount of food needed for a balanced diet in humans. If you have seen it, you will notice that a large section of the plate includes foods derived from cereals and grains, which are a great source of carbohydrates, an important biomolecule that our body uses as a primary energy source for all cells. Wheat is one of the most important grains worldwide, and you probably eat it daily in foods such as bread, cookies, waffles, sweets, pastries in general, pasta and many other dishes.

Now, can you imagine a disease that does not allow you to eat any food that is prepared with wheat? It would be very difficult for me, because in my country, Chile, we generally eat bread at breakfast, lunch and dinner, in fact, we are the world’s second largest consumer of bread after Germany. However, although it could be difficult to imagine, the inability to eat wheat exists and is called celiac disease. It is an autoimmune disease characterized by intolerance to gluten, a set of proteins called gliadins found in wheat as well as in rye, barley and oats. In celiac patients these proteins cause an inflammatory reaction in the mucosa of the small intestine, causing symptoms that include pain and discomfort in the digestive tract, constipation and chronic diarrhea, stunted growth (in children), anemia and fatigue. It can often lead to vitamin and nutrient deficiencies due to the decreased ability of the small intestine to properly absorb nutrients from food.

Worldwide, celiac disease affects an average of 1 in 100 people to 1 in every 170 people. The only solution for people with the disease is to follow a strict gluten-free diet for life, which involves abstaining from food made with wheat (and the other grains with gluten) and replacing these usually with food made with rice or corn flour. This strict diet significantly increases spending on food because of the higher price of gluten-free products.

A Biotechnological Solution

An alternative is to produce a variety of gluten-free wheat. However, we must consider that the variety of wheat that is used in bread (Triticum aestivum L.) may contain 50 to 70 different  functional genes for gliadins which are inherited in blocks, and they are located on the short arm of chromosome 1 and 6. Bread wheat is allohexaploid, which means that it is made up of the genomes of three different grasses, so the gliadin genes are actually on a total of 6 different chromosomes. Because of this, it is very difficult to produce a wheat variety without all the gliadin genes by conventional breeding techniques such as selection and hybridization.

cariograma
Karyotype of bread wheat (Triticum aestivum L.). The large and complex bread wheat genome is composed of 21 pairs of chromosomes. It is alohexaploid as it has three diploid genomes from three different ancestors. Image: http://goo.gl/02sL2J

To avoid this obstacle, a team of Spanish scientists led by Dr. Francisco Barro of the Institute of Sustainable Agriculture of Cordoba belonging to the Spanish National Research Council (CSIC) -a state agency of Spain- decided to develop a free-gluten wheat variety using the technology of RNA interference (RNAi) to silence or delete the genes that produce the problematic gliadins.

The team’s research was published in 2011 in the Proceedings of the National Academy of Sciences (PNAS) and revealed that 4 of the 17 lines of GM wheat with low amounts of gliadins (near gliadin-free) produced a reaction up to ~95% less toxic when compared to conventional wheat. This was confirmed by analyzing the serum with T lymphocytes (the cells that recognize gliadins and trigger the toxic reaction) from celiac patients with the flour from modified wheat lines.

Another advantage is that these modified varieties offset the gliadin content deficit by increasing up to 67% other proteins rich in lysine – an essential amino acid of very low abundance in conventional wheat. Furthermore, the results showed “normal values of texture, flavor and appearance, comparable with those of common wheat flour“.

Flour and gliadins graphic expression from wheat samples (wild type and the genetically modified line E82). | Source: http://goo.gl/ZBRBhO

In 2014, the same research team published an article in PLoS One where it reported that breads made with flour from low-gliadin wheat varieties showed breadmaking quality characteristics similar to those of normal wheat flour. In the sensory analysis, the tasters showed preference for low-gliadin bread versus rice bread; and showed statistically comparable levels with the traditional wheat flour in texture, flavor and appearance. The bottom line is that even without the normal levels of gliaden, you can still make good quality bread that people will enjoy.

Loaves and slices of wild-type wheat (line BW208); reduced-gliadin wheat (line D793); and rice.| Source: Barro, 2014 – DOI: 10.1371/journal.pone.0090898

The two modified wheat lines that showed greatest gliadin reductions were the E82 (~96% reduction) and D793 (~ 97% reduction) lines; which means that these lines allow a maximum daily consumption of bread up to 43.6 gr and 66.9 gr from both lines respectively. This would allow typical celiac patients to eat 3-4 slices of bread daily without any problems.

The next step will be a clinical trial for human consumption with a group of 40 – 90 celiac patients at the “Virgen de las Nieves Hospital” and “Reina Sofia de Cordoba Hospital”, both in Spain, which will start next month in September.

A difficult stage: Commercialization

Despite the great progress achieved so far and the great opportunity presented by this GM crop to improve the quality of life of celiac patients, the problems arise at the stage of approval and commercialization.

This is due to the contradictory legislation of the European Union (EU) on GM crops. The EU has just two crops commercially approved, the GM corn MON810 and the Amflora potato, but only the GM corn is grown. It is almost exclusively cultivated in Spain (over 130 thousand hectares per year) and smaller amounts in Portugal, Czech Republic, Slovakia and Romania – many other European countries have banned on GM crops without any scientific evidence to justify it. On the other hand, the EU has authorized the importation of 77 GMOs – including corn, cotton, soybeans, rapeseed and sugar beet. In other words, they directly hinder and/or prohibit the use of the technology, but at the same time they import huge quantities of the technology’s final product – curiously almost all the soy imported by Europe comes from South and North American countries, where GM technology adoption is over 90%. It is a paradox that unfortunately is undermining the competitiveness and productivity of European farmers.

This adversely affects the possibility of commercializing the “gluten-free” GM wheat, and in fact, no Spanish company has expressed interest in obtaining the patent of the crop to bring it to market. I sent an email to Dr. Barro to check this situation and he mentioned that the CSIC (which holds the patent on the GM wheat) hired Plant Biosciences Limited (a British company) to contact companies that may be interested in commercializing this crop. Many companies (mostly multinationals and none from Spain) have contacted them, and the one that has showed a lot of interest is the US company Dow Agrosciences.

Dr. Francisco Barro in a field trial of the “gluten-free”GM wheat – and using a shirt with the logo “GMO: Don’t judge before you know”. | Source: http://goo.gl/joUvwu

At this point I cannot fail to quote from blog post of Jose Miguel Mulet, a Spanish plant scientist from CSIC and a leader in the hispanic science/biotechnology communication community (the hispanic equivalent of Kevin Folta):

How can it be that a technology created with Spanish public funds end up in the hands of a private American company? Because of the aberrant anti-GMO European law. No European or Spanish company is interested in commercially developing this wheat due to obstacles in the authorization process, which virtually preclude its market release, although clinical trials are also being done in Spain. The result: licensing rights have been acquired by the American company Dow Agrosciences, given that the authorization process in the United States is much easier. So while here we are collecting signatures to subsidize gluten-free food, in the United States they have acquired the rights of an effective technology to reduce the cost.”

That is the sad part: an effective solution to a serious health problem has been developed, thanks to the work of a public institution, but it cannot be commercially available in the country that developed the technology. It is highly likely that Spain will import the flour and the products derived from the GM wheat from the United States in the future, while they could produce it at a lower cost in their own country if the law allowed it.

If you have a relative, friend or acquaintance who suffers from celiac disease, tell them that genetic engineering has already created a safe, gluten-free wheat, and also tell how opposition to this technology and the anti-GMO movement are possibly preventing its market release.

  • VeganGMO

    The high lysine side effect is a nice benefit for vegans who need to pay special attention to that essential amino acids!

  • http://www.uncafelitoalasonce.com/ Aitor Calero García

    Great Post! It’s a real shame that due to absurd EU regulations this type of wheat could not be produced in Spain :(

  • Diggsc

    It’s Frankenfood! It’s unnatural! It’s going to infect all the normal wheat around the world! We don’t know what it will do to humans in the future! We don’t like change! It’s Monsanto so it must be bad because, well, uh, because, FRANKENFOOD!!!!
    -signed,
    Every moronic white privileged well-fed Leftist you’ve ever seen wearing dreadlocks and a hemp shirt.

    • Stig Petersson

      But, it was not Monsanto :)

      • First Officer

        They’ll say it was. Or say some former employee, relative of an employee, neighbor thereof, former newspaper boy of a former employee worked on it, or supported the scientists, or got sandwiches for the team.

        • Warren Lauzon

          And one of the employees won a $5 lottery ticket, so will claim that the state is sponsoring them because bought and paid for politicians and stuff.

      • Warren Lauzon

        That is irrelevant. We all know that all bad genes come from Monsanto. I know it’s true because Food Babe told me.

      • Stig Petersson

        U’re just a bunch of one-eyed chewing gum texas lunitics who does not know a shit about GMO-production. Trying to joke this away does not impress me a BIT.

  • Jeremy

    Quick note, oats do not contain gluten. The issue is harvest and processing contamination. This affects a group of celiac sufferers who have a remarkably high sensitivity to ppm of gluten. It is less so now due to gluten free trend and awareness. Still it’s advisable to purchase “clean oats” just to make sure

  • Colleen Winters

    Uncontaminated oats do not contain gluten.

  • David Gehl

    Celiacs may be able to tolerate the GMO wheat but how will it be produced? As head of Agriculture and Agri-Food Canada’s Seed Increase Unit for twenty-five years I am aware of the practicalities of producing pure seed. I was involved in discussion with the Canadian Celiac Association regarding the production of gluten-free oats for consumption by celiacs. The oats have to be virtually free of contamination by wheat, barley, rye and triticale. It is possible to manually rogue oat fields of the gluten containing cereals because they are visually distinct. Similarly colour sorting technology can be used to remove non-oat cereals after harvest. How would it be possible to remove regular wheat from the gluten-free GMO wheat? So, while gluten-free GMO wheat looks like a good idea on paper the practicality of producing it to the requisite level of purity is very unlikely.

    • Stig Petersson

      I think I have an idea on how to sort that will work :)

    • http://www.biofortified.org Karl Haro von Mogel

      Good point, David, and glad to hear from you on the practical nature of production from your experience with oats. Although I am not familiar with the genetics of the oat trait, I suspect that it would be a recessive trait, where each contaminating cross-pollination would result in a grain that produces gluten, rather than being gluten-free.
      In the case of this gliadin-free wheat, is was developed using RNAi. The normal gliadin-producing genes are there, but deactivated by the microRNAs produced by the RNAi construct. These miRNAs are dominant traits, so the presence of one copy of the construct (hemizygous) should deactivate the functional genes from most varieties.
      What this means is that you could have the gliadin-free wheat possess two copies of the RNAi construct, so any cross-pollination would result in hemizygous grains. So cross-pollinations should still be gliadin-free. Nevertheless, eventually enough cross-pollination could result in a few grains without any copies of the RNAi construct. I should think that a unique selective trait such as an herbicide, for instance, could weed out any that do not have copies of the RNAi construct.

      This is an important question, and one that needs further exploration!

      • David Gehl

        Out-crossing is only one source of contamination in pure-seed production. Mechanical admixtures during seed transportation, conditioning, storage, planting, harvest, etc. are a significant source of contamination as is contamination by “volunteer” carryover of seed from previous crops. This is why regulations for pedigreed seed production have built in tolerances for the presence of other crop kinds and other varieties. The presence of off-types, other varieties and other crop seed is ubiquitous in pedigreed seed albeit at low levels. Obviously the level of contaminates in commercial grain is normally much greater than in pedigreed seed. The tolerance for the presence of gluten containing cereals in “gluten-free” oats to meet celiac requirements is equivalent to that of Foundation pedigreed seed. In the Canadian seed system this is two generations above the level of Certified seed sold to commercial producers for planting “grain” crops. Therefore production of gluten free oats (or wheat) requires a quality management system with multiple checks to ensure the end product is not contaminated above the specified level.

        • http://www.biofortified.org Karl Haro von Mogel

          Yes, you are right, there are other sources of contamination to consider. Thanks for adding that to the discussion! The developers should think about this issue as they work toward getting the product to market.

  • Liat

    Oats DO contain some kind of gluten relative protein. Most Celiacs ARE intolerant to oats and sometimes even more than regular gluten.

    • hyperzombie

      Oats now with “Super Gluten”
      Piss off your hypochondriac hippie neighbors, with the new “Super Gluten”.

    • Michael McCarthy

      “Most Celiacs ARE intolerant to oats and sometimes even more than regular gluten.”
      Really? The Celiac people seem to disagree with you.
      http://www.cureceliacdisease.org/archives/faq/do-oats-contain-gluten
      http://www.celiac.com/categories/Celiac–Disease–and–Oats..–Are–They–Gluten-Free…-c-3385
      http://allergicliving.com/2010/07/02/ask-the-celiac-expert-are-oats-ok/

      • Liat

        AGAIN, HUGE MISTAKE you’re all just repeating as if it’ll make it true… –
        I’ve been studing this issue long enough to understand usually
        people don’t know those facts they just link gluten to wheat and
        that’s a mistake – so let’s make that clear:
        (it’s not the
        contamination issue which is something by itself) – OATS NATURALLY DO
        CONTAIN THE PROLAMIN PROTEIN (“avenin”), GENERALLY KNOWN AS GLUTEN –
        it’s has a small difference from the wheat gluten but acts the same when
        you bake with it or in the body and celiacs react to it sooner or later
        as they do to wheat gluten and in many cases EVEN WORSE as the levels
        of it in the oats is pretty high. And as a celiac myself I know from
        first hand.


        READ MORE:
        kiallafoods.com.au/gluten-free-oats/
        http://www.gluten-free-around-the-world.com/are-oats-gluten-free.html
        http://www.gluten-free-around-the-world.com/what-is-gluten.html

        • Michael McCarthy

          I’m sorry, I think the University of Chicago Celiac Disease Center is rather more reliable than some blog.

    • http://ultimateglutenfree.com/ Peter Olins

      The main storage protein in oats (avenin) is related to the gluten family of proteins found in wheat—agreed.

      Can you share your evidence that most celiacs are intolerant of oats, and that the reaction can be greater than with gluten? Perhaps I missed some new evidence that contradicts the prevailing scientific literature.

      • Liat

        Peter, yes ofcourse – consuming oats when anti-gliadin antibodies are present cause an increase of anti-avenin antibodies so most celiacs after consuming oats for a while will sooner or later (depends on how they’re being careful enough with their diet) develop some kind of intolerance for oats. The intolerance is bigger i think mostly due to the amount of avenin in oats (which nowadays is bigger than ever with the genetically engineered food ) and the tendency of people to eat huge amount of oats and that’s how most allergies are triggered. Vice versa – Originally, oats were believed to cause celiac disease. In my case btw it was oats that triggered celiac, it causes my harsh symptoms far worse than wheat gluten.

        Read on avenin believed to trigger celiac on wiki:
        https://en.wikipedia.org/wiki/Oat_sensitivity

        • qetzal

          Liat,

          Have you actually read that link? Because it doesn’t support your claim that most celiacs will also react to avenin:

          “A recent review of controlled oat tolerance studies indicated only one documented avenin-sensitive enteropathy (ASE) in 165, placing the risk of ASE at 0.6% of coeliac disease population. However, during the controlled studies, 17 candidates dropped out due to symptoms after ingestion of GF oats and were not tested at the completion of their respective studies. As a result, the actual risk of ASE in the coelic disease population may be slightly higher.”

          A search of PubMed for scientific papers with avenin in the title turned up several the found the same thing – that a small fraction of celiacs may also react to avenin, but the large majority don’t. I didn’t see any papers to support your position.

  • First Officer

    Obviously such flour will be labeled as gluten free. Would activists attack celiac sufferers who dare to buy it in the EU?

  • Connor Elson

    Celiac disease is a very difficult thing to live with and
    affects people in a very life altering way. It gets a bit funny to see all of
    the false information and self-diagnosing gluten-free advocates that have
    surfaced over the past few years. I guess having a sense of humor is a great
    way to deal with it as this video captures quite well. Hopefully this puts a
    smile on your face and makes you laugh a little. https://www.facebook.com/manchildempire/videos/vb.1589858387893958/1658430701036726/?type=2&theater