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1/15/2019 How to Make a GMO - Science in the News

AUGUST 9, 2015 BLOG, SPECIAL EDITION ON GMOS HOW TO MAKE A GMO

by Chelsea Powell gures by Anna Maurer

Summary: Genetically modied organisms (GMOs) are organisms that have been altered using methods. Although genetic engineering is a common and essential practice in , its specic use in crops is controversial. The key steps involved in genetic engineering are identifying a trait of interest, isolating that trait, inserting that trait into a desired organism, and then propagating that organism. Methods for genetic manipulation have rapidly improved over the last century from simple selective breeding, to inserting genes from one organism into another, to more recent methods of directly editing the genome.

What qualies as a GMO?

A common misconception is that any animal or plant considered to be outside the realm of our reference for “natural” is a GMO. Images of abnormally large cows and tomatoes come to mind. However, the scientic community and the U.S. Food and Drug Administration (FDA) use a stricter denition for a GMO: an animal or plant that has been created through genetic engineering [1]. Genetic engineering is a term used to describe biotechnological methods used by scientists to directly manipulate an organism’s genome. Under this denition GMOs do not include plants or animals made by selective breeding, or animals modied by being given

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hormone supplements or antibiotics. In fact, we do not currently eat any meat products considered to be GMOs, although farm animals may be fed a genetically modied crop [2].

The main goal of the majority of genetic engineering performed on food is to increase crop yield and/or to improve the nutrient value in animal feed. No genetically engineered crops on the market in the United States have been modied to be unusually large (Table 1). Pictures of extremely large vegetables used to support the “Franken-food” image of GMOs are probably not GMOs at all; an unusually large vegetable would more likely be created through less controversial methods of selective breeding or nutrient supplements, not genetic engineering.

The process of genetic engineering

Genetic engineering is widely used in biological research. Mouse models are engineered for biomedical studies, bacteria are engineered to produce medications such as insulin, and crops are engineered for agriculture. All of these products of genetic engineering were created using the same basic steps: identifying a trait of interest, isolating that genetic trait, inserting that trait into the genome of a desired organism, and then growing the engineered organism (Figure 1). These steps are explained in detail below, using examples from as the details of their technologies are publicly available. Other major companies such as , BASF, Dow, , and Du Pont use similar methods, as outlined in brief on their respective websites [3, 4, 5, 6, 7].

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Step 1: Identify a trait of interest In order to identify a desirable new trait scientists most often look to nature. Successful discovery of a new genetic trait of interest is often a combination of critical thinking and luck. For example, if researchers are searching for a trait that would allow a crop to survive in a specic environment, they would look for organisms that naturally are able to survive in that specic environment. Or if researchers are aiming to improve the nutritional content of a crop, they would screen a list of plants that they hypothesize produce a nutrient of interest.

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An example of a trait currently in GMOs that was identied through this combination of luck and critical thinking is tolerance to the herbicide Roundup (see this article). Monsanto created “” plants after nding bacteria growing near a Roundup factory that contained a gene that allowed them to survive in the presence of the herbicide [8]. Although it is not on the market in the United States, Syngenta has designed with an increased amount of pro-vitamin A, which the human body may turn into the vitamin A (see this article). Researchers at Syngenta identied the gene sequence that produces pro-vitamin A and compiled a list of plants to screen with that sequence [9]. With a little luck, there was a plant in nature, maize, that contained a gene that would make Golden Rice produce pro-vitamin A at a level that could meet the nutritional needs of vitamin A decient communities.

Step 2: Isolate the genetic trait of interest Comparative analysis is used to decode what part of an organism’s genetic makeup contains the trait of interest. The genomes of plants with the trait are compared to genomes in the same species without the trait, with the goal of identifying genes present only in the former [8]. The genomes of different species with the same trait may also be compared in order to identify a gene, as was the case while developing Golden Rice [9]. If there is no database of genetic information for comparison, scientists will purposefully delete, or “knock out,” parts of the genome of interest until the desired trait is lost, thereby identifying the genes that lead to the trait.

In order to expedite this process, Monsanto has developed and patented a method known as seed chipping [8]. Through this method Monsanto shaves off parts of seeds for high-throughput genetic sequencing while leaving the rest of the seeds viable for planting. This creates a genetic database for plants before they are even grown, where a barcode system is used to match plants to their genotypes. Researchers may then use this database to identify new traits of interest as well as to optimize the desirable traits in a crop by selecting for the best genotypes based on plant phenotypes.

Step 3: Insert the desired genetic trait into a new genome Altering the genome of plant seeds is difcult due to their rigid structure. Many biotech companies use “gene guns” that shoot metal particles coated with DNA into plant tissue with a .22-caliber charge [8]. Monsanto no longer uses gene guns, but instead takes advantage of bacteria, called tumefaciens, that naturally invade seeds and alter plants by inserting pieces of their own DNA into a plant’s genome.

In biotechnology research it is common to genetically engineer bacteria to produce a desired . This is done by using enzymes to cut and paste a DNA strand of interest into a plasmid, which is a small, circular molecule of DNA [10]. Bacteria are then shocked using heat or http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 4/22 1/15/2019 How to Make a GMO - Science in the News

electricity so that the cells accept the engineered plasmid. By modifying A. tumefaciens, which is easier to modify than plant seeds themselves, researchers may use the bacteria’s naturally invasive behavior as a Trojan horse for inserting desirable traits into a crop’s genome.

Step 4: Growing the GMO After a genetic trait has been successfully inserted into an organism’s genome, the modied organism must then be able to grow and replicate with its newly engineered genome. First, the genotype of the organisms must be checked so that researchers are only propagating organisms in which the genome was modied correctly.

Biotech companies invest large sums into keeping these plants alive and reproducing once they have been successfully created. The companies use special climate-controlled growth chambers, and biologists often check on the plants by hand to make sure that they are growing as expected [8].

During this process biotech companies will use automated machines, such as Monsanto’s GenV planter, in order to track plants and calculate optimal seeding and growth conditions to create the best possible yields. GMO seeds often come with instructions on spacing and nutrition that result from these studies.

Future directions for the creation of GMOs

Humans’ ability to modify crops for improved yields and nutrients in a given environment is a keystone of agriculture. The technological advancement from selective breeding to genetic engineering has opened up a large realm of possibilities for the future of our food. As techniques for genetic engineering, such as new RNAi- and nuclease-based technologies that allow for direct modication of the genome (see this article and this article), steadily improve, our ability to create new GMOs will also grow [11]. As our scientic capabilities expand it is essential that we discuss the ethics and ideals surrounding GMOs so that we may effectively and safely use this technology in a way that is acceptable to the public.

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Table 1. Summary of the FDA’s Inventory of Completed Biotechnology Consultations on Genetically Engineered Foods as of June 30th, 2015. Crops listed in order of relative abundance of genetically engineered crop consultations (corn having the most consultations). This information is available to the public: http://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=Biocon

Chelsea Powell is a PhD student in the Chemical Program at Harvard University.

This article is part of the August 2015 Special Edition, Genetically Modied Organisms and Our Food.

References

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 6/22 1/15/2019 How to Make a GMO - Science in the News

1. “Questions & Answers on Food from Genetically Engineered Plants.” U.S. Food and Drug Administration. U.S. Food and Drug Administration, 22 June 2015. http://www.fda.gov/Food/FoodScienceResearch/Biotechnology/ucm346030.htm 2. Cossins, Daniel. “Will We Ever Eat Genetically Modied Meat?” BBC. BBC, 9 Mar. 2015. http://www.bbc.com/future/story/20150309-will-we-ever-eat-gm-meat 3. http://www.syngenta.com/global/corporate/en/products-and-innovation/research- development/rdapproach/Pages/research-areas.aspx 4. https://www.basf.com/en/company/research/our-focus/plant-biotechnology.html 5. http://www.dowagro.com/innovation/ 6. http://www.cropscience.bayer.com/en/Products-and-Innovation/Research-and- Innovation.aspx 7. http://www.dupont.com/industries/agriculture.html 8. Boyle, Rebecca. “How To Genetically Modify a Seed, Step By Step.” Popular Science. Popular Science, 24 Jan. 2011. http://www.popsci.com/science/article/2011-01/life-cycle-genetically- modied-seed 9. Paine, Jacqueline A., Catherine A. Shipton, Sunandha Chaggar, Rhian M. Howells, Mike J. Kennedy, Gareth Vernon, Susan Y. Wright, Edward Hinchliffe, Jessica L. Adams, Aron L. Silverstone, and Rachel Drake. “Improving the Nutritional Value of Golden Rice through Increased Pro-vitamin A Content.” Nature Biotechnology 23.4 (2005): 482-87. http://www.ncbi.nlm.nih.gov/pubmed/15793573 10. “Genetic Engineering.” BBC. BBC, 2015. Web. http://www.bbc.co.uk/education/guides/zg2bkqt/revision/2 11. Hsu, Patrick D., Eric S. Lander, and Feng Zhang. “Development and Applications of CRISPR- Cas9 for Genome Engineering.” Cell 157.6 (2014): 1262-278. http://www.sciencedirect.com/science/article/pii/S0092867414006047 12. “Biotechnology Consultations on Food from GE Plant Varieties.” Biotechnology Consultations on Food from GE Plant Varieties. FDA, 30 June 2015. http://www.accessdata.fda.gov/scripts/fdcc/index.cfm?set=Biocon

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53 thoughts on “How to Make a GMO”

MD.AL-AMIN MOJUMDER

MARCH 14, 2016 AT 8:59 AM http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 7/22 1/15/2019 How to Make a GMO - Science in the News

thanks for all info.they are very useful.

REPLY

akmal

JANUARY 24, 2017 AT 1:24 AM

good articel i using it right now for my experiment thanks

REPLY

Joe mom

OCTOBER 26, 2017 AT 11:25 AM

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REPLY

Human5484

MARCH 21, 2018 AT 5:32 AM

what do you mean by this Joe mom

REPLY

Makenzi

AUGUST 28, 2018 AT 2:01 PM

yeah girl you right http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 8/22 1/15/2019 How to Make a GMO - Science in the News

REPLY

Jules

DECEMBER 9, 2018 AT 10:32 PM

If an idiot and an imbecile had a baby it would be you.

REPLY

dave?

JANUARY 7, 2019 AT 11:12 PM

why do you say this

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Sammo

OCTOBER 17, 2016 AT 6:12 PM

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REPLY

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Cori

OCTOBER 29, 2016 AT 2:06 PM

This is such a great article! Thank you so much for helping my understanding of this subject!!

REPLY

Daniel

NOVEMBER 30, 2016 AT 1:59 PM

Im doing a project on this and this website is so helpful

REPLY

dave?

JANUARY 7, 2019 AT 11:13 PM

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REPLY

akhtar abbas

DECEMBER 13, 2016 AT 6:02 AM

nice article brother

REPLY

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 10/22 1/15/2019 How to Make a GMO - Science in the News

Godwin

DECEMBER 14, 2016 AT 4:45 AM

it’s really interesting but could you please in box me always

REPLY

Bob

FEBRUARY 1, 2017 AT 7:36 PM

(^-^) lol Nice website good job.

REPLY

Ashton Fraser

FEBRUARY 7, 2017 AT 9:21 PM

Gene gun? My science teacher says it’s fake and there’s no such thing and this is a Harvard site, is it true? Thanks

REPLY

SITNFlash

FEBRUARY 9, 2017 AT 8:19 AM

Gene guns are not fake–Wikipedia has a pretty good description of what a gene gun is. https://en.wikipedia.org/wiki/Gene_gun

Scientists call genetic engineering using a gene biolistic delivery.

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 11/22 1/15/2019 How to Make a GMO - Science in the News

REPLY

a person

OCTOBER 2, 2017 AT 12:20 PM

wikipedia is a site where people can put and change anything i wouldnt trust it

REPLY

Lowe Lundblad

MARCH 22, 2018 AT 11:54 AM

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106930

Study only conducted on a certain topic but I have seen similar research on other elds of study concluding similar things…

Mostly Wikipedia is very accurate, especially so when viewing the English version.

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No one

SEPTEMBER 26, 2018 AT 2:12 PM

Wikipedia is never accurate before.

Teah

FEBRUARY 22, 2017 AT 9:45 AM

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 12/22 1/15/2019 How to Make a GMO - Science in the News

It probably is I am a science teacher at highland and I am preatty sure it’s true ive seen one before

REPLY

a person

OCTOBER 2, 2017 AT 12:19 PM

what do u teach ?

REPLY

Smiy Boi

JUNE 10, 2018 AT 10:39 PM

Are you still alive after the shooting

REPLY

No one

SEPTEMBER 26, 2018 AT 2:10 PM

yes man smiffy boi

REPLY

dominick young

FEBRUARY 15, 2017 AT 9:08 AM

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 13/22 1/15/2019 How to Make a GMO - Science in the News

this was very helpful to my group

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a person

OCTOBER 2, 2017 AT 12:18 PM

ew gmos i prefer GEs

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Kenarter

FEBRUARY 15, 2017 AT 10:53 AM

Very good website me and my group were very impressed by it

REPLY

LOTRlover

FEBRUARY 18, 2017 AT 11:14 AM

This is really amazing! My Biology teacher made us read this article, and it was much more interesting than I thought it would be.

REPLY

Teah

FEBRUARY 22, 2017 AT 9:44 AM http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 14/22 1/15/2019 How to Make a GMO - Science in the News

@SITNFlash this website is more reliable than Wikipedia.

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SITNFlash

FEBRUARY 22, 2017 AT 10:39 AM

haha good point! The gene gun description on wikipedia is pretty good, though.

REPLY

monkeygod24

DECEMBER 11, 2017 AT 10:22 AM

no dip /////////////

REPLY

Barbara Larson

FEBRUARY 28, 2017 AT 2:23 AM

Great job. Very thorough.

REPLY

Isabelle

MARCH 2, 2017 AT 4:27 PM

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 15/22 1/15/2019 How to Make a GMO - Science in the News

Great website! It has lots of great info!

REPLY

Nomad

APRIL 8, 2017 AT 5:48 AM

Great website thank you.

Shame this is the end of “human”.

REPLY

Faladefemi

APRIL 8, 2017 AT 8:40 AM

Nice one here. Helpful for my seminar presentation.

REPLY

Cody

APRIL 19, 2017 AT 1:20 PM

This is a long good website.

REPLY

oguz

JUNE 15, 2017 AT 4:59 AM http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 16/22 1/15/2019 How to Make a GMO - Science in the News

Good job, thanks!

REPLY

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BigMummmmma

SEPTEMBER 3, 2017 AT 10:36 PM

Lol xd not as good as USCs article

REPLY

Newton -

SEPTEMBER 3, 2017 AT 10:37 PM

hahahah so true aye

REPLY

a person

OCTOBER 2, 2017 AT 12:22 PM

i like g newtons but sadly there named after a town in massachusetts and not after the scientist ;(

REPLY

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 17/22 1/15/2019 How to Make a GMO - Science in the News

Laura

DECEMBER 28, 2017 AT 7:53 AM

Would be interesting to share what you think in term of impacts on health when eating those GMOs ?

REPLY

SITNFlash

JANUARY 4, 2018 AT 10:10 AM

We have articles on that as well– see here: http://sitn.hms.harvard.edu/signal-to-noise- special-edition-gmos-and-our-food/

Thanks for reading!

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Colin

JANUARY 22, 2018 AT 10:34 AM

This is very helpful for project I’m using on GMOs but can you tell me a list of tech they use in making Genetically Modied organisms I’m looking for that specic thing. Other that website is extremely Helpfull to me keep up the good work

REPLY

J

FEBRUARY 27, 2018 AT 1:21 PM

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 18/22 1/15/2019 How to Make a GMO - Science in the News

You have a typo in step 3 of the diagram, it should be insert not inset. Thanks for the simple explanation though.

REPLY

CreativeName

APRIL 18, 2018 AT 4:37 PM

I expect these comments to be a little more scholarly, as of now I am unimpressed. You all fail in life and on here.

REPLY

EZEKIEL OSINACHI PASCAL

MAY 4, 2018 AT 9:48 PM

THIS WORK IS SO NICE AND HAS HELPED ME AND OTHER RESEARCHERS IN THEIR WORK.

REPLY

BruddaFromMansion

MAY 7, 2018 AT 10:41 AM

Thank you for posting this Article, this has very much helped me with my project in my science class. You’ve provided many information that I was able to Ace this !

REPLY

Gina

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 19/22 1/15/2019 How to Make a GMO - Science in the News

MAY 8, 2018 AT 3:13 AM

Thanks for your article. It was very helpful for me in breaking down the steps for GMO for a project in my Biology Class. I know there are a lot more technical details involved with scientic names I can’t pronounce, but when I’m only looking for the basic steps in layman terms, your article is quite helpful.

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ryan grith

MAY 17, 2018 AT 10:31 AM

you guys copied Wikipedia here is the link https://en.wikipedia.org/wiki/Genetically_modied_organism the edit history 2001 none of the edits show that they edited the denition of genetically modied organisms. therefore we can conclude that Harvard has copied Wikipedia you have modied the denition without giving credit to Wikipedia. get exposed.

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no one important

SEPTEMBER 26, 2018 AT 4:30 PM

calm down everyoneeeee

REPLY

Ehsan Ullah

DECEMBER 16, 2018 AT 6:29 AM

http://sitn.hms.harvard.edu/flash/2015/how-to-make-a-gmo/ 20/22 1/15/2019 How to Make a GMO - Science in the News

Its very good article really appreciated!

REPLY

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