What is Genetic Engineering?

Are genetically engineered organisms really harmful?

A lot of discussion is going on right know whether or not it is healthy and acceptable to cultivate and eat genetically engineered organisms (GMOs)- in particular plants. The amount of information available is immense and mostly gives an impression of an uncontrolled development of plants with unpredictable properties. In this article I want to shed light on what genetic engineering is and what a genetically engineered plant is able to do. My research consists of engineering enzymes for a better performance towards a specific reaction and genetic engineering is the main method by which new enzyme variants are created. In the relation to that the ethical issue of genetic alteration is later discussed exploring the most common examples and related topics of genetically engineered crops, for example the case of the Lenape potato, Bt-corn, the ice-minus bacterium, golden rice and virus-resistant papaya.

Definition: Genetic Engineering

All definitions in literature describe that genetic engineering comprises of altering an organism on the genetic level- meaning they differ in their DNA from the naturally occurring organism- the so-called wild-type. An important distinction has to be made between transgenic and cisgenic modified organisms. If a genetically modified organism is transgenic, the gene from another organism was introduced into the organism- mostly into the inherent genome. The genome describes the sum of all DNA found in an organism. Cisgenic means that the gene came from an organism within the same or closely related species that can also be interbred with traditional methods. A genetically engineered or modified organism expresses a gene that has been introduced by genetic engineering methods. Gene expression means that the organism takes the “blue-print” -the DNA- and produces the corresponding protein. The expression genetically engineered organisms can interchangeably be used with genetically modified organisms- “GMO” in short.

What does a genetically engineered organism do?

All genes are coded in the DNA (DeoxyriboNucleic Acid). DNA is a long linear macromolecule that is made up off 4 different bases (specific chemical molecules) in a specific order. This set-up is universal in all organisms. Therefore, when talking about a introducing a new gene into an organism, a chemical molecule is introduced into the organism that is made up of the same chemical structures as the inherent genome of the organism. The universal genetic code makes it possible that the new gene can be read by the inherent translation machinery that converts the gene-“blueprint” into a protein. All proteins are made up of the same 20 amino acids in different sequence and length. Specific proteins are also called enzymes. An enzyme catalyses a chemical reaction. A catalyst- here the enzyme- is necessary to make chemical reaction occur that does not occur spontaneously. To illustrate an example for a spontaneous reaction- if you add baking soda to a coke bottle you will create a rigorous fountain of coke because of the now gaseous carbon dioxide. The most well-known and ubiquitous example for a catalyzed reaction is the use of a catalyst for the exhaust fumes of cars- where toxic carbon monoxide is turned in to carbon dioxide. An enzyme does the same-it turns one molecule into another molecule. The sum of all these reactions is called the metabolism of an organism. When another gene is introduced, a new enzyme or a better variant of an enzyme is expressed or produced. This new enzyme catalyses a reaction the organism could not do before or a natural reaction is performed faster. This leads-for example- to enhanced growth.

Are GMOs harmful?

Searching the web for information on GMOs reveals a plethora of information available, a fearful portion of it I would categorize as “pseudoscience”. Populist articles often miss scientific citations for the appropriate sources or outdated and falsified information. Therefore I would like to discuss the ever-present examples and general procedures.

Genetic engineering versus traditional breeding methods

The public is usually weary about eating genetically modified food. What are the most common fears that are connected to GMOs? Let´s discuss of the arguments provided by for example www.rawfoodlife.com [1]. One of the arguments is that genes are mobile (parts of genes relocate throughout the genome) and can create new variations of a plant. These new variations can lead to the production of new proteins and molecules in the plant that we eventually eat. However, not only genetic engineering can lead to this mix-up, but also methods considered as conventional breeding methods. I would like to introduce the case of the Lenape-potato [2] to illustrate this more clearly. It is a conventionally bred potato that had outstanding qualities regarding pathogen resistance and produced excellent potato chips. But it also contained high levels of the toxin solanine. To explain how that came about, one should know that every potato contains solanine to some extent. Only in the Lenape-potato-case the mutation of the genome caused that the production of solanine was increased. That also accounted for the good pathogen resistance. The point in comparing the Lenape-potato-case to GMOs is that there is actually not that much of a difference as far as risk is concerned. In both cases the genetic material is altered, for conventional breeding it can lead to cases like the Lenape-potato because the genome is randomly altered. The difference for explicitly modified organisms is that in that case we know which alteration we introduce into the organism. From my standpoint it can be compared to randomly pushing buttons on an unknown machine (Lenape-potato-case) versus pushing buttons after consulting a logbook of former observations what these buttons did (genetic engineering).

The creation of a “superorganism”

I also want to go into another aspect of the putative threat of unwanted new molecule production. It is important to know that enzymes can catalyze not only one but multiple reactions. Of course there are examples that there are incredibly fine-tuned enzymes by evolution to one specific reaction because survival depends on it. But for less crucial enzymes that is not the case. The scientific term for this is “catalytic promiscuity”. This principle is currently exploited by many scientists and is part of my research towards a greener chemistry. The catalytic promiscuity of an enzyme causes the enzyme not to have one product as an outcome but an array of products. It can be compared to a spray can to some extent. It always gives the object in front of it a specific colour. The shape or make of the object does not matter. With this background one can assume that the wild-type plant in its respective environment has already performed all possible reactions “by accident” with all possible molecules that are available. Therefore all possible reactions have already been “tested” by the wild-type organism. From that I would conclude that it is highly unlikely that a new “superorganism” is created that can do a complete new array of chemical synthesis. There is however the concentration issue, some substances are beneficial in small amounts but harmful in large amounts. Apart from that, every newly developed “food” has to be tested for its potential harmfulness which for example revealed the toxicity of the aforementioned Lenape-potato. All genetically engineered plants have to go through a rigorous approval process by for example the FDA.

Frankenstein and Frankenfood

A popular term popping up to negatively describe GMOs is “Frankenfood” [3]. Frankenfood is a negatively value-laden word for edible GMOs. It draws the analogy to the classic novel “Frankenstein” by Mary Shelley (1818), where Dr. Frankenstein creates a monster from “lifeless matter”. If one would strictly stick to this analogy, it will become obvious that it is erroneously drawn. The monster in the book is created from “non-living” matter. That is not the case for GMOs. To date it is not possible to create a living organism from scratch- just starting from DNA, which I would consider the “non-living” matter. GMOs are organisms that are to a large extent identical to its wild-type counterparts- meaning the organism present in nature. From my point of view it can be seen as adding a trailer to a car. You enhance the utility of the car by enlarging transportation volume but you don´t change the inherent purpose of the vehicle. If you transfer this example to GMOs, the new or altered gene makes up a very small portion of the entire genome of the plant. It is quite popular to refer to GMOs in negatively associated terms, for example in German it is widely referred to as “genmanipulierte Organismen” which translates to “Genetically Manipulated Organisms”. The correct translation is “GVO- GenVeränderter Organismus” instead of “GMO” which incidentally could also be seen as abbreviation of “GenManipulierter Organismus”. But of course “manipulated” fits more into the concept for fear-mongering.

Bt-corn and the insecticide-issue

A controversial example is Bt-corn- a classic transgenic plant [4,5]. Bt stands for Bacillus thuringensis. This useful bacterium produces a protein that acts as an insecticide. There are currently two ways in which this protein is used. The bacterium is applied in organic agriculture and sprayed on crop as an intact bacterium. The other method is Bt-corn, where the gene for the “insecticide”-protein is incorporated in the genome of the corn. The insecticide-protein is then produced by the corn plant itself. Bt-corn has met major opposition by environmental activists because of several concerns. One of them being the following scenario: the insecticide protein of Bacillus thuringensis is non-specific, that means it acts on all insects, not only the ones considered to be harmful but also endangered species. However studies show that this seems to be not the case [6]. From my point of view I see a bit of a dilemma here because what is missing is the clear statement that there is chemically no difference to organic, Bt-sprayed corn. It is very hard to make the distinction between endangered species and pest from a chemical or insecticide point of view because both belong to the same species. To put it quite brutally, it is intended by the farmer that the plant is not snacked on by insects. Those insects which do so die, no matter how pretty and endangered or not. The argument against both methods being equally dangerous would again be the concentration issue. The Bt-corn always produces the insecticide-protein, therefore it might also be there when it is not strictly necessary. Organic farmers claim Bacillus thuringensis is only sprayed locally and when it is necessary, thereby according to them the overall amount of the insecticide enzyme is lower. But however you look at the issue, the outcome should remain the same, you ingest Bt-toxin or the insecticide-protein, whether the field is labelled “organic” or not.

Spreading of genetic material

Another concern is that the genetic material might spread into nature via pollen and cross-bread into weeds. First of all, not every plant can be cross-bred in nature as much as we can´t mate with a chimpanzee. The chance however remains. If the gene for the insecticide-protein should make it into other plants, and Bt-corn would be abundantly cultivated there might be a chance that insects would get resistant to it. But thinking further into the future, the goal of Bt-corn opponents is to produce as much food organically as possible. To achieve an economic yield, one would have to continue spraying with Bacillus thuringensis bacteria. That means, the gene of the insecticide is equally spread into nature. Bacillus thuringensis bacteria will also not stay on the sprayed area because that was their intended use by the farmer, but they will simply spread and grow where they will find enough nutrients. That might also be outside the area of the organic field. Although gene transfer between bacteria and plants is rare, it is possible. From where I am standing the risk remains the same, just in one case it is labelled organic and in the other case GMO.

Ice-minus bacterium

There is another bacterium currently in application –the ice-minus bacterium [7]- that is engineered to prevent frost damage on fruit. It is an example for a cisgenic GMO. It is based on the principle that ice needs a nucleation source to actually start the freezing process. At a certain degree of latitude and climate this frost-protection can make the difference between a good harvest and a loss year. Many environmental activists raise concern about this bacterium spreading into the wild and prevent the natural process of freezing. Of course it can alter this process, but just by a little bit. The bacterium is attuned to its fruit environment and does not promote ice nucleation on surfaces like its counterpart- the ice-plus bacterium- during night frost. Should it be cold for a longer amount of time no bacterium can circumvent the laws of physics. Water is going to freeze, it just requires a longer period of time to do so.

Virus-resistant papaya

Next I want to introduce a successful “niche”-product- a papaya resistant to the papaya ringspot virus [8]. The GM-fruit was developed in Hawaii to counter reoccurring virus infection of papaya trees which significantly decrease harvest. The genes of a virus structure protein were transferred into the plant. This protein triggers a sort of defense or “immune response”. It is the same kind of principle applied for vaccines, except the plants produce the vaccine themselves. In comparison to the MMR-vaccine (Mumps-Measles-Rubella vaccine) where a weakened virus it introduces even less non-papaya enzyme because only parts of the virus are employed. The prevention of papaya virus infection was very successful to the point where 75% of the papaya plants are now the genetically modified version. The fruits are sold in the US and Canada. Research is underway to apply the same method to papaya plants cultivated in Asia since local virus strains there differ from the virus found on Hawaii. This is for me the most impressive example how biotechnology can actually help farmers to minimize harvest loss and provide financial security in a sense. Unfortunately papaya is not a mass product like corn or wheat. The reason why there hasn´t been a similar success with inherently “resistant” corn and wheat might be that there is not one but many species that can possible harm the plant like insects and fungi. The defense mechanism against those species is completely different than towards a virus. Furthermore a different method is required for every pest to be targeted specifically. That would mean incorporating multiple transgenes in the organism, which takes a lot of work since all have them have to be tested separately and then checked for cross-reactions. Since a lot of pests have influence on harvest loss for these products, one resistance might not impact as much and won´t qualify as selling argument. There is however research going on for blight-resistant potato. To me that sounds promising since the great famines have been caused by this pest in the 1840's and it still threatens potato harvest yield to this day.

Golden Rice

The most promising GMO plant to date is “Golden Rice” deriving its name from its yellow color. This rice is enriched in Vitamin A and is seen as a mean to prevent deficiency in this vitamin in developing countries. Vitamin A deficiency can lead to blindness and weakens the immune system. Therefore it is approximated to cause 1-2 million death a year. Field trials of Golden rice are still ongoing despite being developed in the 2000's. Right now a new variant is tested that is acclimatized to the respective surroundings. Furthermore more enrichment mechanisms have sought to be added for vitamin E, zinc and iron.
In disagreement with UNICEFs and WHOs opinion, I strongly support the research being done on and trials performed on “Golden Rice”. UNICEF and WHO had good results with vitamin A supplementation programmes, meaning just giving out pills to the affected population. But to my mind this tactic does not support encouraging self-sufficiency in the people. The ultimate goal would be that these people can take care of themselves. That would mean growing their own vitamin A treatment in form of golden rice. The pills would not have to be provided by outsiders and the whole logistics and transport behind it could be omitted. That would make our world a little bit more sustainable as well. To me it would be a great example of advanced technology of the industrialized nations helping people to help themselves. In some cases people are just oblivious to the situation in developing countries and may be fooled by the overabundance of fruit and vegetables in industrialized nations. Usually we get our vitamin a from fruits and vegetables, for example carrots, mangoes or sweet potato. Especially fruit are not available all year around, the ample supply is shipped to us from all over the world, take for example kiwis that are harvested in New Zealand. To me it almost feels like the retorting comment attributed to Marie Antoinette during the French revolution on the demand of the people for bread: “why don´t they eat cake?”. Those means are simply not available to poor people in developing countries. To my mind having a storable and already traditionally in the diet incorporated food readily available and cultivatable which provides enough vitamin A to avoid deficiency is a simple and elegant solution to this form of malnutrition problem.

Science and business practise

A lot of the critique is also related to the business practices of big companies like Monsanto. Their strategy comprises of the fact that farmers have to buy seeds from them every season instead of being able to save up their own seed for next year´s harvest. The reasoning behind it is to be able to cover their research cost with the help of patent protection. The costs for developing a new biotechnological product are enormous, starting from 1 billion US dollars per product for a pharmaceutical. If Bt-corn is so advanced however, everybody should want those seeds and enough profit should be made by selling only an initial batch. But since genetically engineered seeds are a relatively new technology, that means there not so much competition on the market and they can do pricing and marketing at will. But to me the marketing strategies are an issue apart from genetic engineering itself. In case of the golden rice everything is available freely even so the rice is patented and the permission of over 70 patent holders had to be secured. However like in all economic processes customer preference also drives this development, as in the case of the FlavrSavr tomato [9]. The purpose of the genetic engineering was to lengthen the time the tomato could stay on the plant without becoming gooey (overripe) to accumulate taste. It also has a longer shelf life to stay appealing for the customer over a longer time span. If we could accept that fresh tomatoes are not naturally available in winter and that the slightly ugly and gooey ones taste fine nonetheless, that would abandon the need for such genetic engineering. Instead one could focus on actually making beneficial plants with heightened vitamin levels, pest-resistance and higher yield.

Conclusion

The debate about about GMOs is at times very emotional. Some surveys also reveal lack of information on the topic. I don´t want to play the risk down that we alter something that is the result of billions of years of evolution. But to my mind the opposition is often founded in the underlying fear is that it is now possible to alter genes and genomes, the blueprint of every living being on earth. I can understand that for a lot of people it appears threatening to the very essence of their being. Genomes can simply be altered in a laboratory, which frankly looks quite like a hostile and foreign place to most people. People are afraid of this abstract concept of gene modification. But we have been doing it for thousands of years in the form of traditional cross breeding of plants, which is the trial and error equivalent to what genetic engineering actually is. As a scientist it is mind-boggling to see how much potential for improving crop is thrown away by categorically labelling genetic engineering as evil. Especially in the case of golden rice that is not marketed by a large company and contains verifiably heightened vitamin levels I do not understand why this potential is wasted. Of course one should act according to the precautionary principle and think and test thoroughly before applying a new technology. Although in this case it raises the question whether the moral principles of a western-industrialized society should be valued over possible loss of lives in a developing country. Even if we look at application in industrialized countries genetic engineering might actually help agriculture to be more environmentally friendly. For example in the case of the ice-minus-bacteria it might be possible to grow more fruit in Sweden and there would not be that much need for import. Considering the future, genetic engineering has definitely a place there, but the current start is far from optimal considering how the introduction into the market was handled. It was designed for maximizing instant profit, not a well-planned start for a long-term change in methodology how agriculture yield can be improved.

References

1. www.rawfoodlife.com
2. www.boingboing.net/2013/03/25/the-case-of-the-poison-potato.html
3. www.medicinenet.com/script/main/art.asp?articlekey=24845
4. http://www.planetnatural.com/bacillus-thuringiensis/
5. www2.ca.uky.edu/entomology/entfacts/ef130.asp
6. Sears, M. K., Hellmich, R. L., Stanley-Horn, D. E., Oberhauser, K. S., Pleasants, J.M., Mattila, H. R.,Dively, G. P. (2001). Impact of Bt corn pollen on monarch butterfly populations: a risk assessment. Proceedings of the National Academy of Sciences of the United States of America, 98(21), 11937–42.
7. http://www.brighthub.com/science/genetics/articles/43252.aspx
8.www.gmo-compass.org/eng/grocery_shopping/fruit_vegetables/ 14.genetically_modified_papayas_virus_resistance.html
9. www.californiaagriculture.ucanr.org/landingpage.cfm?article=ca.v054n04p6

Image Sources

1. www.robertariail.com
2. http://genius.com/Biology-genius-the-central-dogma-annotated
3. https://www.pinterest.com/pin/104005072616331403/
4. www.davegranlund.com
5. http://www.edna.bg/zdravoslovno/bio/genetichno-modificiranite-hrani-4627941
6. http://californiaagriculture.ucanr.org/
7. https://en.wikipedia.org/wiki/Ice-minus_bacteria
8. http://www.apsnet.org/publications/apsnetfeatures/Pages/PapayaHawaiianRainbow.aspx
9. http://www.allowgoldenricenow.org/8-media/16-german-case-for-golden-rice
10. http://www.allowgoldenricenow.org/the-crime-against-humanity

About Lisa Marx

Lisa is a PhD Student at KTH University in Sweden with exciting research in the field of Biotechnology. During her free time, she likes to go sailing.
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