When a transGMO weirdstuffthatisnotrice A to rice B is created say it has a protein from another nonrelated species, what kind of toxicology studies are made? For cis GMOs rice A to rice B for example, its usually something already consummed so not as much as a problem right?How do we know that the new proteins are safe to eat? how do we know a protein already tested will be express at a concentration level safe to eat?

Expert response from Joseph Jez

Professor of Biology and a Howard Hughes Medical Institute Professor at Washington University in St. Louis

Friday, 18/12/2015 13:15

To answer these questions, let’s start with some background on what is a protein, how a protein is made, and what happens when we eat.

The first rule is to remember the “Central Dogma” - the sequence of a gene (DNA) encodes the sequence of a protein. Next, proteins are made of combinations of 20 amino acids. Each amino acid shares a common chemical structure (NH2-CHR-CO2H) but with a different R-group. The amine (NH2) of one amino acid can link to the carboxylic acid (CO2H) of another to form a peptide bond. The sequence of a gene dictates the order of amino acids and how many are linked to form a particular protein. This means that proteins are diverse in both sequence and size.

Where do the different amino acid building blocks required for a protein come from? Depending on what organism you are – bacteria, plant, or human – the answer varies. Amino acid building blocks are either made de novo from other materials by an organism’s metabolism or are obtained from diet by digesting consumed proteins into amino acids. For example, plants contain all the metabolic pathways necessary to make the 20 amino acids. In contrast, humans only produce ten of the amino acids and need to obtain the other ten ‘essential’ amino acids from our diet because we lack the pathways for their production. Eating proteins made by other animals and plants leads to recycling of those amino acids for our metabolic purposes.

Consider a stir-fry plate with chicken, rice, and broccoli. That’s nearly 100,000 different proteins sitting on the plate! The chicken has approximately 25,000 genes and rice and broccoli each have approximately 35,000 genes encoding a variety of proteins. Imagine how many proteins a human consumes in a given day – and the more varied the diet, the more diverse the set of proteins.

So, when a transgene (i.e., DNA) is introduced into a plant, that plant produces the encoded protein from endogenous amino acid building blocks. This means that the building blocks of a protein encoded by a transgene expressed in genetically-engineered rice are no different than in any of the other approximately 35,000 proteins in rice.

With that in mind, the protein encoded by the transgene can undergo extensive toxicological and allergen testing, but the depth of the testing depends on the situation. A typical analysis involves bioinformatics analysis to determine how similar the protein is in sequence to known toxins and allergens; studies on the impact of digestion and heat on protein structure and function as it relates to dietary exposure; and on documenting a history of safe use.

Let’s take the case of using rice protein A as a transgene in rice B. If the protein is unrelated to toxins and allergens, is readily digested or denatured by heat, and is already eaten because we eat rice A (i.e., has a history of safe use), then there is no scientific basis to justify extensive testing. Now, if the transgene was from an organism not eaten by humans, was stable in digestibility/heat stability tests, or shared homology with known toxins and/or allergens, then these conditions may trigger a more thorough analysis. If there is a scientific reason to justify toxicological and/or allergen testing, the protein can be produced and used for food safety experiments.  These are typically 90-day feeding studies, in which the protein encoded by the transgene is feed to animals. It should be noted that in such studies, the proteins can be tested at levels equal to a 75 kg man eating 50 tons of corn in one meal! Once again, these studies are typically performed at levels that exceed expression levels of the transgene encoded proteins in the genetically-engineered plant. A detailed list of the testing of proteins for toxicity and allergenicity is too expansive to be covered here, but the extent of testing should be commensurate to the magnitude of risk associated with the new food.

For more information related to these questions, I suggest reading an article published in 2013 by Laura DeFrancesco, a senior editor at Nature Biotechnology, entitled “How safe does transgenic food need to be?”  (Nature Biotechnology nol. 31, issue 9, pages 794-802).  This excellent article was an independent and balanced analysis of exactly the types of questions asked here and goes into more depth on this topic.

Expert response from Joseph Jez

Professor of Biology and a Howard Hughes Medical Institute Professor at Washington University in St. Louis

Friday, 18/12/2015 13:15

To answer these questions, let’s start with some background on what is a protein, how a protein is made, and what happens when we eat.

The first rule is to remember the “Central Dogma” - the sequence of a gene (DNA) encodes the sequence of a protein. Next, proteins are made of combinations of 20 amino acids. Each amino acid shares a common chemical structure (NH2-CHR-CO2H) but with a different R-group. The amine (NH2) of one amino acid can link to the carboxylic acid (CO2H) of another to form a peptide bond. The sequence of a gene dictates the order of amino acids and how many are linked to form a particular protein. This means that proteins are diverse in both sequence and size.

Where do the different amino acid building blocks required for a protein come from? Depending on what organism you are – bacteria, plant, or human – the answer varies. Amino acid building blocks are either made de novo from other materials by an organism’s metabolism or are obtained from diet by digesting consumed proteins into amino acids. For example, plants contain all the metabolic pathways necessary to make the 20 amino acids. In contrast, humans only produce ten of the amino acids and need to obtain the other ten ‘essential’ amino acids from our diet because we lack the pathways for their production. Eating proteins made by other animals and plants leads to recycling of those amino acids for our metabolic purposes.

Consider a stir-fry plate with chicken, rice, and broccoli. That’s nearly 100,000 different proteins sitting on the plate! The chicken has approximately 25,000 genes and rice and broccoli each have approximately 35,000 genes encoding a variety of proteins. Imagine how many proteins a human consumes in a given day – and the more varied the diet, the more diverse the set of proteins.

So, when a transgene (i.e., DNA) is introduced into a plant, that plant produces the encoded protein from endogenous amino acid building blocks. This means that the building blocks of a protein encoded by a transgene expressed in genetically-engineered rice are no different than in any of the other approximately 35,000 proteins in rice.

With that in mind, the protein encoded by the transgene can undergo extensive toxicological and allergen testing, but the depth of the testing depends on the situation. A typical analysis involves bioinformatics analysis to determine how similar the protein is in sequence to known toxins and allergens; studies on the impact of digestion and heat on protein structure and function as it relates to dietary exposure; and on documenting a history of safe use.

Let’s take the case of using rice protein A as a transgene in rice B. If the protein is unrelated to toxins and allergens, is readily digested or denatured by heat, and is already eaten because we eat rice A (i.e., has a history of safe use), then there is no scientific basis to justify extensive testing. Now, if the transgene was from an organism not eaten by humans, was stable in digestibility/heat stability tests, or shared homology with known toxins and/or allergens, then these conditions may trigger a more thorough analysis. If there is a scientific reason to justify toxicological and/or allergen testing, the protein can be produced and used for food safety experiments.  These are typically 90-day feeding studies, in which the protein encoded by the transgene is feed to animals. It should be noted that in such studies, the proteins can be tested at levels equal to a 75 kg man eating 50 tons of corn in one meal! Once again, these studies are typically performed at levels that exceed expression levels of the transgene encoded proteins in the genetically-engineered plant. A detailed list of the testing of proteins for toxicity and allergenicity is too expansive to be covered here, but the extent of testing should be commensurate to the magnitude of risk associated with the new food.

For more information related to these questions, I suggest reading an article published in 2013 by Laura DeFrancesco, a senior editor at Nature Biotechnology, entitled “How safe does transgenic food need to be?”  (Nature Biotechnology nol. 31, issue 9, pages 794-802).  This excellent article was an independent and balanced analysis of exactly the types of questions asked here and goes into more depth on this topic.