The fear of GMO

Something that seems to be worrying to a lot of people – maybe even more within the vegan community – are genetically modified organisms (GMO). My feeling is that this is mainly due to a lack of understanding of the technology rather than a sound skepticism.

People seem to have the notion that GMO is detrimental to health, farmers and the environment. But I’ll have a go trying to explain what all this fuzz is all about regarding genes, breeding, DNA, RNA and GMO.

Background

What is DNA?

Now here is a little bit of biochemistry and molecular biology but bear with me. DNA or, deoxyribonucleic acid is a long molecule that consists of a phosphate and sugar, which constitutes the “backbone” of the famous double helix. Attached to each unit of phosphate and sugar is a nitrogen base, adenine (A), thymine (T), cysteine (C) or guanine (G). Together, a phosphate, sugar (monosaccharide) and the nitrogen base form a nucleotide.

A DNA molecule is a long sequence of nucleotides, even millions of nucleotides in a long string. Two strings of DNA molecules form hydrogen bonds between the nucleotides forming the double helix. But every nucleotide has a nucleotide buddy. ‘A’ always pairs together with ‘T’ and ‘C’ always pairs together with ‘G’. The important thing is that if you know the sequence of nucleotides of one of the strands, you know the other strand as well (if there is a T in one, the same position has an A on the opposite strand).

Each of these molecules of such a double helix is further supercoiled onto proteins called histones. These are like little beads where DNA is organized, basically to stuff away DNA that is not needed. These big DNA molecules, wound up on histones are called chromosomes.

Humans have 23 chromosomes that are unique, and then we have a set of backup copy of everything totalling to 46. For each chromosome we have one copy from our mothers, and one from our fathers.

All these chromosomes contain all the genes that make up humans, and every single cell (well almost) contain all this information. Information, by the way, that is around 3gigabytes of text from each parent, stored in every single cell. But this is also the case for your tomato plant. It also has chromosomes with many genes in the plant cells that make up the plant.

So, genes?

Usually when we say ‘gene’, we mean a stretch of DNA that encodes a protein. On the 23 chromosomes, the ~20 000 genes are encoded by the sequence of the nucleotides in the DNA. That means that the DNA encodes every single protein present in the human body. One could think of the gene as a blueprint for one or more proteins.

Proteins are what really make our bodies work. They make up the small structures that connect cells to one and other, they make up the small filaments that act as a skeleton within the cell, keeping an internal cell structure. They also catalyze almost every chemical reaction going on in our body (detoxification of alcohol, converting the food we eat into molecules that could be used for energy in the cell and so on), act as hormones etc. I could go on forever, but they do basically everything.

When a protein is to be produced let’s say ADH1B (that is just a name of the gene), a gene that happens to produce a protein that is involved in the detoxification of alcohol. This gene is located on chromosome number 4 between the nucleotides 99 304 964 and 99 321 401. The gene is transcribed by a number of proteins into RNA, which is a single strand of a molecule very much like DNA. This RNA molecule contains the sequence of the gene (with the small difference that thymine is now replaced by a very similar nitrogen base called uracil) and is further processed until it can be translated into a protein (I will not cover this in depth here).

The gene starts with the triplet ‘ATG’ that defines the start of the transcription into RNA, and the signal to stop, or where the gene ends is defined by one of the stop codons found in the genetic code.

The RNA is exported out from the nucleus of the cell and hooked up on to a ribosome (that is actually constructed by proteins and RNA molecules). The ribosome will slide across the RNA molecule, reading the sequence in triplicates and constructing a chain of amino acids according to genetic code.

The genetic code translates groups of three nucleotides into specific amino acids; for example, AAG would result in a lysine. The chain of amino acids that is produced is called a protein.

Since I told you that all information is held within all cells in our bodies, all of the genes cannot be active producing proteins in chaos. Brain cells produce a set of proteins that might differ from a cell in your liver. So, genes in the cells are highly regulated by different molecules that turn on and off expression (that is transcribing from DNA to RNA, to protein) but also by the organization of the histones that could physically make the DNA unavailable for reading.

Genetic variations and mutations

The specific sequence of amino acids that make up the protein is very important for the protein function. It determines the three dimensional structure of the protein, but also it can affect the site of the protein that is actually doing the catalysis of a given reaction.

When cells in our body divide, the cell has to copy the entire genome (that is, all DNA existing in a cell, or rather the sequence of every chromosome) since the daughter cell also needs the genes to function. The proteins that copy the DNA is incredibly good, but since there are 6 billion nucleotides to copy, sometimes errors occur, and the daughter cell might differ slightly in DNA sequence. This is called a de novo mutation in genetics, because it’s a new mutation, and not a variation that you inherited from your parents. But unless we talk about diseases such as cancer, this is not typically the genetic basis for the differences we see between human individuals. Instead in the population, individuals vary slightly in the sequence of DNA (originally de novo mutations). Typically it’s single nucleotides that differ between individuals, and since they might affect the functions of proteins, our traits vary as well. De novo mutations have to occur in the germ cells to be able to be inherited to the children. The germ line mutations that are inherited, that is passed from parent to child, is the genetic basis for the variation of traits that we can observe.

But how?

A very clear example how these genetic variations can influence our traits is something that occurs when one triplet of DNA is changed from an amino acid coding triplet, into a stop codon. That would prematurely stop the translation from RNA to protein, resulting in a truncated protein that might not work at all.

But luckily we have backups of each chromosome, which means all the genes as well? That is true, but maybe both your parents carried a gene that had this stop codon variant in a gene. Then you will be homozygous for that specific gene. Different variations of the same gene are called alleles, and if you have different alleles for a gene, you would be heterozygous for that gene. If you are homozygous for a non-functional allele (maybe it has variation that has a premature stop codon) your cells are not able to produce that specific protein. That might or might not influence your traits.

If you are heterozygous for a specific gene and one allele is not producing any functional protein, which would result in some disease if you didn’t have any backup, that allele is recessive. That is, if your other allele is able to produce a functional protein. In many cases, recessive alleles are variants of genes that do not produce any functional protein, but the copy from the other parent is sufficient to supply the cells with that protein.

Breeding

I hope you are with me now, why genetic variation can result in differences of the traits of an organism. And breeding is a way of producing individuals that have specific traits that you want. A very illustrative example of the power of breeding is the Brassica oleracea which been bred into a variety of different types of cabbage, such as broccoli, cauliflower and Brussels sprouts to name a few (Dixon, 2007).

When breeding, you select based on traits. If you grow enough plants, due to genetic variation, their traits will vary across a spectrum. If you select individuals having traits that are closer to what you want, and use them as parents for the next generation, the new offspring might vary in the trait you are interested but shifted closer towards your desired trait.

When you successively breed, selecting a few individuals each round, the population will be inbred and the amount of genes that are homozygous will increase – since the variation will be reduced. This allows recessive alleles to penetrate and result in larger variety of traits. However, since inbreeding results in high amount of homozygosity a lot of traits that are deleterious for the individual will pop through. But since you just select whatever you want, it’s not necessarily an issue, since you just care about your trait (Allard, 1999).

You make sure that your trait is heritable, and that there is some variation in the trait, and then you only care if you get your trait or not. Using this type of classical artificial selection, you don’t really know which genes that have the variations, only that they result in the trait you want.

A different way is to cross different species of plants to mix the genes to increase the genetic variation in a new hybrid. This is not possible in many animal species, but in plants one has successfully created many different hybrids. Such as peppermint, which is a hybrid of two different mint species. Another example of a hybrid is the banana that we eat.

Yet a different strategy to perform more efficient breeding is to subject the plants to some mutagen, such as gamma radiation or mutagenic chemicals such as EMS (Gottschalk & Wolff, 2012). This will induce mutations randomly in the genome to increase the genetic variation that the breeder starts with. This can of course also result in many non-viable plants, but again, you will just select the ones that show the traits you want.

Earlier I told you that humans have 23 unique chromosomes, but twice – totalling to 46. This is called diploid, to have two of all chromosomes. In other organisms and our sperm cells and egg cells the cells can just have one copy of each chromosome that is called a haploid. Higher ploidies – polyploidy means that you have three (triploid), four (tetraploid) or more copies of each chromosome. This is something that we find in many of the plants that we eat. Mainly to cope with the fact that many hybrids become sterile, but can be overcome by inducing polyploidy by exposing the plants to for example the highly toxic chemical colchicine.

That would be the basics of breeding, but modern breeding includes a variety of methods to further increase efficiency of breeding. Additionally, relevant genetic concepts to understand breeding better is heterosis, pleiotropy and heritability, but that exceeds the ambitions of this post.

GMO

In modern breeding, one sometimes knows which kinds of genes that are involved in the trait you are interested in. But to not be classified as GMO, you need to use techniques that are not classified as GMO if your end-product is not to be considered GMO. If you know your desired genetic end result, you have to use classical breeding techniques to reach that goal. So, which techniques are not considered ‘classical’ and which are defined as GMO.

Definitions

The US department of agriculture (USDA) writes in their glossary:

“Genetically modified organism (GMO): An organism produced through genetic modification.” (USDA, 2013)

Ok, but what does genetic modification mean according to USDA? Well:

“Genetic modification: The production of heritable improvements in plants or animals for specific uses, via either genetic engineering or other more traditional methods. Some countries other than the United States use this term to refer specifically to genetic engineering.” (USDA, 2013)

So other countries might use the term of genetic engineering:

“Genetic engineering: Manipulation of an organism’s genes by introducing, eliminating or rearranging specific genes using the methods of modern molecular biology, particularly those techniques referred to as recombinant DNA techniques.” (USDA, 2013)

What does the food and drug administration of the US say?

“The 1992 policy applied to all foods derived from all new plant varieties, including varieties that are developed using recombinant deoxyribonucleic acid (rDNA) technology. This site refers to foods derived from plant varieties that are developed using rDNA technology as “bioengineered foods.”” (FDA, 2015)

What does the European Union say about the matter?

“These desirable characteristics appeared through naturally occurring variations in the genetic make-up of those plants and animals. In recent times, it has become possible to modify the genetic make-up of living cells and organisms using techniques of modern biotechnology called gene technology. The genetic material is modified artificially to give it a new property (e.g. a plant’s resistance to a disease, insect or drought, a plant’s tolerance to a herbicide, improving a food’s quality or nutritional value, increased yield).

Such organisms are called “genetically modified organisms” (GMOs). Food and feed which contain or consist of such GMOs, or are produced from GMOs, are called “genetically modified (GM) food or feed”.” (Comission, 2015)

One could probably say that it seems like we can define GMOs as something that is produced by using modern molecular biology in practical terms. That is, that we use molecular biology to alter the organism rather than just to study the result of breeding or its “natural state”.

They specifically mention recombinant DNA technology, and that means in layman’s terms that we cut and paste in DNA molecules usually produced by PCR – which is used to amplify/copy high amounts of DNA molecules – using different enzymes from bacteria.

So what can we do?

It’s hard to say exactly where the limits are since new technologies are constantly being developed in biology that is made available to the biotech industry. But it’s certainly possible today to turn off or remove genes, increase the expression of genes, move genes from one species to the other. And I don’t think that we have explored even a small fraction of the possibilities yet. But some GM-crops that are well known are golden rice (A-vitamin producing rice), pesticide resistant crops, and insect resistant crops.

Within science, GM technology has been used for almost 40 years, and is now days vital for production of medications. One example is the production of insulin that diabetics of type I is very dependent on. In the past, insulin was produced by extracting insulin from the pancreas of slaughtered cattle and pigs. Today we have simply put the gene into E.coli bacteria to express the human insulin directly, no animals harmed (Crea, Kraszewski, Hirose, & Itakura, 1978).

I think this example is particularly interesting from a vegan perspective since it involves harm reduction from killing animals for medical production using GMO.

Healthy?

There is a possibility for specific GMOs to pose a threat to the environment and human health. However, that would be with emphasis on ‘specific’. It is possible to imagine GMOs that is actually dangerous; one could for example express a gene in a plant that is producing a toxic protein. On the other hand, it’s possible by using genetic engineering to produce a crop that only differs in a single nucleotide, a result that could be reached using classical breeding as well.

The Swedish board of Agriculture recently ruled that some crops produced with the genetic engineering technique CRISPR-Cas9 cannot be considered GMO under the European legislation because it’s potentially impossible to discriminate GMO from non-GMO since one could arrive at the exact same end result (UPSC, 2015).

If you have a two potatoes that is genetically identical, but one is produced by genetic engineering and one is produced by breeding, it’s really hard to think of a reason for the GMO potato to be dangerous simply by the technique it has been produced with.

The idea that GMOs generally would be a health issue, is as strange to me as general fear of electronics. The invention and use of electricity allowed production of products that are fantastic, some that are great, some that are good and some that have been proved to be dangerous or not very nice in any way. But would that be an argument to ban electronics? That it’s possible to create dangerous products? But people in general are not scared of electrical products since the principles of how it works have reached the public consciousness.

The only reasonable option is to assess safety of GMO products on a case-by-case basis. As is done for GMOs, but there is really no reason why products produced by conventional breeding shouldn’t be assessed in a likewise manner.

A study that is constantly being linked from GMO-fearing people is the study “Long term toxicity of a Roundup herbicide and a Roundup-tolerant genetically modified maize” by Séralini et al. It’s very thankful for the people that want to portray GMOs as dangerous because the article featured images of rats with huge tumors. However, the study has received tremendous critique, to the point that the study was retracted from the journal it was originally published in. The number of animals used in the study was too low; the animals used were inappropriate (they show relatively high frequency of the tumors in question) which makes the whole study quite unreliable (Wallace Hayes, 2014). To use a single retracted study as basis for claiming that GMOs are dangerous in general, is absurd to say the least. Also, Wikipedia has a quite nice summary of the whole affair here: https://en.wikipedia.org/wiki/S%C3%A9ralini_affair (accessed: 03/01/2016).

The AAAS has also made a statement that GMOs are generally safe (Aaas, 2012).

But, the environment?

Some GMOs could probably pose a serious threat to the environment, but here I would use the same reasoning as for the food safety, that it has to be assessed case-by-case. Yes it’s true that some GMO crops has increased the use of pesticides in some areas, but that is an argument against that specific product and not GMOs in general. On a global scale GMOs seem to have reduced the pesticide use with other potential environmental benefits (Phipps & Park, 2002).

Conclusions 

Genetic modification of crops is already widely in use. In many countries GMOs has to be clearly labeled, for example Sweden (SLV, 2015). There are potential issues with the products that can be produced using GMOs, but the problems are not necessarily isolated to GMOs, but also conventional products. There is no reasonable reason to think that GMOs in general pose a threat to human health or the environment.

References

Aaas. (2012). Statement by the AAAS Board of Directors On Labeling of Genetically Modified Foods. Assessment, (October), 2012.

Allard, R. W. (1999). Principles of Plant Breeding. John Wiley & Sons. Retrieved from https://books.google.com/books?hl=en&lr=&id=74hdQoEc8XsC&pgis=1

Comission, E. (2015). Genetically Modified Organisms. Retrieved January 3, 2016, from http://ec.europa.eu/food/plant/gmo/index_en.htm

Crea, R., Kraszewski, A., Hirose, T., & Itakura, K. (1978). Chemical synthesis of genes for human insulin. Proceedings of the National Academy of Sciences of the United States of America, 75(12), 5765–5769. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC393054/

Dixon, G. R. (2007). Vegetable Brassicas and Related Crucifers. CABI. Retrieved from https://books.google.com/books?hl=en&lr=&id=eR5-NpnIZWsC&pgis=1

FDA. (2015). Food from Genetically Engineered Plants. Retrieved January 3, 2016, from http://www.fda.gov/Food/FoodScienceResearch/GEPlants/default.htm

Gottschalk, W., & Wolff, G. (2012). Induced Mutations in Plant Breeding. Springer Science & Business Media. Retrieved from https://books.google.com/books?hl=en&lr=&id=ofLvCAAAQBAJ&pgis=1

Phipps, R. H., & Park, J. R. (2002). Environmental benefits of genetically modified crops: Global and European perspectives on their ability to reduce pesticide use. Journal Of Animal And Feed Sciences, 11, 1–18. Retrieved from <Go to ISI>://000174458700001

SLV. (2015). Genmodifierad mat, GMO. Retrieved January 3, 2016, from http://www.livsmedelsverket.se/livsmedel-och-innehall/genmodifierad-mat-gmo/#Märkning

UPSC. (2015). “Green light in the tunnel”! Swedish Board of Agriculture: a CRISPR-Cas9-mutant but not a GMO. Retrieved January 3, 2016, from http://www.upsc.se/about-upsc/news/4815-green-light-in-the-tunnel-swedish-board-of-agriculture-a-crispr-cas9-mutant-but-not-a-gmo.html

USDA. (2013). Glossary of Agricultural Biotechnology Terms. Retrieved January 3, 2016, from http://www.usda.gov/wps/portal/usda/usdahome?navid=BIOTECH_GLOSS&navtype=RT&parentnav=BIOTECH

Wallace Hayes, A. (2014). Editor in Chief of Food and Chemical Toxicology answers questions on retraction. Food and Chemical Toxicology : An International Journal Published for the British Industrial Biological Research Association, 65, 394–5. doi:10.1016/j.fct.2014.01.006

 

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