Innovation – The Heartbeat of Research and Development

Last week, I had the wonderful opportunity of visiting Bayer Crop’s Innovation Center in Morrisville. This has been the most fascinating part of my internship to date. Thank you to all of the scientists who eagerly shared their knowledge with me. I will pay it forward by being a good steward of the information and nurturing scientific curiosity in my students.

Safety training: Upon arriving at the Innovation Center, I met with Deb, the regional biosafety manager. She explained to me the different regulating agencies involved with safety protocol (USDA/APHIS/PPQ). For my visit, I used well-known safety practices, such as personal protection equipment and hand washing. It was amazing to me how many of the safety guidelines are a part of middle school science classes, such as hand washing. Although simple, they are essential in the real-world to prevent environmental contamination. The innovation center is in the very beginning of the research process and the products have not yet been through the years of rigorous testing as the GM products of the market, so safety is essential.

What I learned about GM innovation: After safety training, I met with Brian who provided a flow map of the GM research and development process and Jon who gave me a tour of the lab. The innovation center begins the process with:

Step 1) Gene sourcing: Agrobacterium is a type of bacteria that naturally add DNA to a plant. Scientists at Bayer use this process to develop stronger plants, almost like a more efficient version of natural selection. Genetic modification is the process of using our knowledge of genetics to solve a problem. Isn’t this what all technology is? GM technology is no different. To start this process, scientists collect bacteria from soil samples and then grow it in the lab to create a bacterial library.

Sample of agrobacterium
Sample of agrobacterium

Step 2) Trait discovery: Gene mining or trait discovery asks the question: Can this bacteria protect plant A against problem B (example: protecting soy against soybean cyst nematodes). According to the USDA, nematodes cost about $80 billion in total crop loss annually. Bayer uses farmer feedback and other data to gauge which pests are causing the largest problems in the field. Bacteria have endless potential benefits, so scientists often find they are using the right bacteria, but asking the wrong question. Bacteria X may not protect soybeans from nematodes, but may be helpful in developing drought resistant corn. Therefore, even if the bacterium is not useful for the original purpose, it is stored for a different question at a different time. In the case of pest control, pests of interest are fed the bacteria to see how they respond. Then, IF it is effective (remember in R&D, failure is expected), then scientists must identify which ONE gene out of the approximate 5,000 genes in the bacteria is responsible for the pest control trait.

Step 3) Vectoring: The gene of interest is inserted into E Coli, because E Coli is the workhorse of the bacteria kingdom. Bacteria has a plasmid shaped DNA (meaning it is like an oval, rather than linear as human DNA). The bacteria’s DNA is cut using restriction enzymes. The DNA has “sticky ends” so the newly inserted DNA can connect easily. The gene of interest is paired with a selectable marker to help identify which plants received the gene in a vector. The selectable marker, in most cases, helps the plant survive an herbicide. This is useful, because the plants will later be placed into a solution containing an herbicide. If the plant survives, then it received both the selectable marker and the gene of interest. Therefore, it’s a keeper.

Step 4) Plant Transformation: Two methods for plant transformation are the gene gun (see video) and agrobacterium. Gene guns are a slightly older technology, which shoots gold flakes containing the gene of interest into the plant. Chris and I performed an embryonic isolation for corn and soy to prepare the plants for genetic modification. It was neat to see how the corn and soy looked different at first glance, but upon closer inspection they were functionally similar and actually have a lot of similarities to a chicken egg (see diagrams).

soy bean embryocorn embryo

Although from the animal kingdom, a chicken egg has similar structures and functions as plant seeds.

After extracting the embryos, the embryos are infected with agrobacterium through the process of co-cultivation. Corn is a lot easier to transform, because the embryo either receives the genetically modified trait or it doesn’t. Soy is more challenging, because sometimes the modified gene does not penetrate to the deeper levels of the meristem. It was neat to see soy plants that had both the original cells and the GM cells. These plants were half green and half white, because part of the plant could not carry on photosynthesis, because it did not have the selectable marker. Soy transformation takes place in the light, while the first few steps of corn take place in the dark, just like germination in the field.

After the agrobacterium has modified the DNA of the embryo, an antibiotic is added to stop the agrobacterium and callus induction occurs. Basically, this is rapid growth of the GM cells to identify where they are. The GM embryos are then selected and moved to progressively larger containers based on the plant’s stage of development. These plants will undergo efficacy testing. Then scientists select the healthiest and most efficient plants to send to the greenhouse at the RTP campus (More about this in a future blog, because I will be spending a week there!)

soy plant transformation process
soy plant transformation process
Life cycle of a stinkbug
Life cycle of a stinkbug

My hands-on lab experiences: In the afternoon, I visited the various insect nurseries. These insects were collected from the field and then bred at Bayer. It was neat to see the various life stages of each insect. I will never look at a stinkbug the same way again! We also set up leaf disk tests in which insects are placed in the same container as a small piece of leaf. Each cell represents a different type of leaf (some genetically modified and some not). Then, we observed previously set up assays to observe which leaves experienced the least amount of damage. We recorded the data, which will be used in efficacy analysis. Some leaves were almost completely eaten, and therefore, are not useful in pest protection. We also looked at in vitro assays to see which had the insects with the highest mortality rate in response to the proteins in the diet. Each sample was compared to a control. It surprised me how many of the samples looked like the controls. Hence, the innovation motto: “It’s ok to fail, but fail quickly.”

Creating classroom lessons: At the end of my visit, I met with Kate and Marie to develop the concepts of GM technology into activities for students. First, we made a model of DNA. I have seen variations of this model online, but this is the best I have seen, because it accurately shows:

Double helix model
Double helix model

*the double helix shape

*the difference in sugars between DNA and RNA

*the process of transcription

*the types of bonds between the bases

*antiparallel structure of DNA (gummy bears facing opposite directions)

*2 or 3 hydrogen bonds (distance of gummy bears to one another)

 

Yellow twizzler = DNA sugar, purple twizzler = RNA sugar blue twizzler = phosphate gummy bears = base
yellow Twizzlers = DNA sugar; purple Twizzlers = RNA sugar; blue Twizzler = phosphate; gummy bears = base
strawberry dna extraction test tub
The cloudy white material in the clear layer of alcohol is the DNA as it precipitates.

Next, we did a DNA extraction of strawberries and bananas. I have done this experiment with my students before, but doing this experiment with a scientist helped me gain a deeper understanding of what was happening on a molecular level. For example, Marie explained to me that many fruits (bananas, strawberries, and kiwi for example) are polyploids meaning they have multiple chromosomes in each set, while humans have diploids (two chomosomes in each set). Because these fruits are polyploids, it is easier to release the DNA from the cells. Also, she reminded me what each step in the DNA extraction does:

*original mashing – breaks down cell walls

*soapy water extraction buffer – breaks lipid-based cell membranes. This made sense to me, because dish soap also breaks down fatty grease from pots and pans.

*salt – interacts with the negative charge in the DNA

*alcohol – precipitates the DNA

Next, we talked about restriction enzymes! Oh my! This was well beyond my level of expertise, but with Marie and Kate’s help, I was able to understand what restriction enzymes do and how restriction enzymes are useful. Restriction enzymes break apart DNA. Different enzymes break apart the DNA at different places by recognizing a specific base pair sequence. When broken, the DNA can have sticky ends or blunt ends. With sticky ends, the restriction enzymes are palindromes (the same forwards on the top as it is backwards on the bottom), so that it can match up with the DNA sequence. Using vectoring, genes can be inserted here for such GM technologies as crop protection and insulin. Restriction enzymes can also be used in forensics, because they cut DNA into several pieces and then the DNA can be arranged by number and length of the pieces. DNA samples from the same organism will be cut in exactly the same way. Marie and I were brainstorming ways to create a mock crime scene in the classroom and use DNA fingerprinting to solve the crime. For example, “Who Stole the cookie from the cookie jar?” Some DNA from the perpetrator was left in the cookie jar and we know it was someone in the classroom. Each student donates a “DNA sample” (modeled by DNA sequence written on paper). The class uses restriction enzymes to differentiate between classmates and finds the matching DNA sequence from the cookie jar sample. This lesson needs a great deal of development, but it would definitely be engaging for the students. More to come on this later!

Restriction enzymes can cause stinky ends.
Restriction enzymes can cause stinky ends.

How my experienced impacted my view of science education:

*You never know where the kids will end up, so PREPARE THEM FOR ANYTHING! Some of my students may very well become research scientists, and that is fabulous. However, most will not. My future “civilian scientists” still need basic scientific knowledge, science-based skills (such as analysis), and scientific literacy in order to make personal and consumer choices.

*Take time to nurture natural curiosities. One scientist at the innovation center told me how taking nature walks with her class as a child inspired her to study Botany. Sometimes I get so busy with the “have tos” of curriculum, that I forget the power of slowing down and going for a walk.

*Expose all students to a variety of things: plants, insects, technology, whatever you have, so each student can find his or her niche. When I toured the insect nursery, I met people who love bugs. When I toured the greenhouse, I met people who love plants. In the communications department, I met people who love coding and creating websites. It is incredible how differently we are each wired and how essential each individual’s gifts and abilities are in the marketplace.

*Advocate for STEM Education! Another scientist shared with me how in previous years, America has experienced a deficiency in research scientists and has scouted from other countries, such as China and India. However, the industry is beginning to follow the work force. If America continues on the projected path, America may not be able to maintain its status as a world-wide leader in technology.

*Learn more about the Next General Science Standards. I recently read over these standards for my graduate class and was amazed at how well it connected with real-world science at Bayer. I will reflect more on this in future blogs.

*Create a unique classroom culture. I loved the culture at the BCS innovation center. It proved you can both be relaxed and professional. I hope my classroom has a similar environment. Yes, this is a place you can feel comfortable, but we will be productive. Comradery and a good sense of humor are actually production agents, not enemies of efficiency.

*An unexpected connection to social studies: Social Studies is the red-headed step-child in fifth grade. With reading, math, and science being tested subjects, Social Studies is often pushed to the back burner both in instruction time and budget allocations. However, the fifth grade curriculum is so important! Economy, US colonization and revolution, and the US Civil War are foundational topics for students. (This is why I LOVE fifth grade curriculum!) I walked through the labs and saw our economy vocabulary at work (see bold words). When scientists mentioned how farmers drive innovation by telling Bayer what pests are inhibiting plant yield, I thought of supply and demand. In our mixed economy, Bayer responds to consumer demand, while also abiding by government regulations. Also, Bayer Crop competes with other companies for consumer loyalty which drives their desire for high quality products. Specialization was also evident as Bayer focuses on a few crops (particularly corn and soy) and division of labor among employees. Some employees work with insects, while Marie’s staff works in the vectoring group. Specialization and division of labor build interdependence among employees and other businesses.

 

Personal Take-aways: One of benefits of visiting the innovation center was to see exactly how GM occurs and even participate some. There is so much media hype about this topic that leads the everyday grocery shopper to fear GM foods. Honestly, I understand their plight, because each of us wants to do everything we can to keep our families healthy. The consumer without a science background has to make a decision with limited and skewed information. Seeing the GM process and the extensive testing firsthand makes me feel better about choosing healthy and safe foods. I also learned that insulin uses the same technology as GM foods. The insulin-producing gene is inserted into bacteria and then into the bloodstream of a diabetic patient. GM foods are the most researched and tested agricultural product in history.

Conclusion: I was a little nervous being around so many well-educated and experienced research scientists. I do not want to appear uninformed. However, as a fifth grade teacher, I tend to be a jack of all trades, and certainly don’t know the finer point of cell biology and biotechnology. Developing stronger content knowledge was my main motivator for participating in the Kenan Fellows Program. Thank you to all the scientists who shared their expertise with me, so I can pass it along to my future scientists!

Links for more information:

http://www.ncbi.nlm.nih.gov/

https://www.neb.com/tools-and-resources/interactive-tools

http://nebcloner.neb.com/#!/

http://www.apsnet.org/edcenter/K-12/TeachersGuide/Pages/default.aspx

http://www.apsnet.org/edcenter/intropp/lessons/Nematodes/Pages/RootknotNematode.aspx

http://nrcsoya.nic.in/plant%20growth/soyseed.gif

UNC Gene therapy research for patients with cystic fibrosis using the same biotechnology as Bayer, but with a different purpose. Click the link to learn more: http://www.med.unc.edu/genetherapy/research-laboratories

http://www.slideshare.net/sweetfluer2005/angiosperm-seed-formation-and-development

Photo credit links:

https://www.sophia.org/playlists/lab-safety-and-equipment

http://www.plantphysiol.org/content/133/2/736/F4.expansion

http://www.geochembio.com/biology/organisms/maize/

http://discoveryexpress.weebly.com/homeblog/category/biology

http://www.sites.ext.vt.edu/virtualfarm/poultry/poultry_eggparts.html

http://www.intechopen.com/books/a-comprehensive-survey-of-international-soybean-research-genetics-physiology-agronomy-and-nitrogen-relationships/an-overview-of-genetic-transformation-of-soybean

https://www.pioneer.com/home/site/mobile/grow/insects/brown-marmorated-stink-bug/http://bvetmed1.blogspot.com/2013/01/restriction-fragments-mutations.html

http://www.instructables.com/id/Extracting-DNA-from-Strawberries/