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.

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Daniel Norero is a student of biochemistry and works in the Laboratory of Molecular Plant Pathology at the Catholic University of Chile. Is the founder of the hispanic biotechnology advocacy movement "Sí Quiero Transgénicos" and also writes for the Chilean Skeptical Association and LatinAmericanScience.

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