First Semester Finished!

Woo-hoo! Party time at the Farthest North Frat House! "I Tappa Kegga" rulez! All finished with my first semester of grad school. 6 credits earned, 30 more to go. 4.0 average so far! I am seriously considering changing my specialty from Biotech Regulations to Bioinformatics as I really enjoyed learning about bioinformatics and all of the tools used in biotechnology. I hear that next semester will include more on-line panty raids and even an e-goat in the dean's office. Can't wait!



Anyhoo...here is the last paper I had to write for Ethics in Biotechnology class. The class was actually kind of lame. We had to read and discuss lots of outdated material, the text itself was written in 2002!  The writing projects were fun and I learned much researching for them. This last paper was a group project, but my original group of four quickly turned into a group of two as classmates dropped right and left. I left the name of my group partner off, but I think you will quickly see who wrote the paper. She did a good job of editing and formatting, though.

Here are the instructions for this paper:

You will put together a document as if you were a group of scientists/managers at a biotech firm trying to decide on policies for testing and marketing a new GM crop. You want to determine the best policy for a product in terms of research, testing, risk and benefit analyses, and marketing at home and abroad. You will produce a collaborative 3000-5000 (maximum) Word document, excluding bibliography and URLs. It may not include any work that any member of the group has submitted previously for another class at any time.

Consider the risks of your technology (e.g., human health, spread of genes to wild populations, creation of new viruses, toxicity to beneficial insects, economic impacts on subsistence farmers); benefits (e.g., feeding a hungry world, minimizing the use of harmful pesticides, lower costs to farmers); cultural perceptions (foods unacceptable in appearance or nature (nonorganic, "messed with," nontraditional)), and regulations surrounding the testing and release of such technologies (e.g., the length and extent of field testing, the inclusion of non-GM acreage).

You can use a technology that already exists as a model (e.g., FlavrSavr tomato or virus-resistant squash) and look at how it's been tested and marketed and what the problems have been, if any, as a starting point, but you will lose points if you copy it too closely. Go from there to discuss laboratory and field trials, nontarget risks, human health risks, acceptance by the public, labeling, education, use of the media, and regulatory problems. You might also compare the benefits and risks of your crop compared to the non-GM version. Give a short description of your genetically modified crop and how it was developed; then discuss testing, risk assessment, marketing, and regulatory issues. How will you make use of the media and market research? The science doesn't have to be exactly right. The idea here is to put together some of what you've learned and apply it to an example (real or imagined).

We wrote our paper as if it were a memo for the various departments at a biotech company. All of the science is accurate and it should give you a good idea of how GMO plants and products are developed. The thing about GMO plants that scares me the most are the marker genes that actually breed antibiotic resistant genes into nearly all GMO foods. I can't imagine that this antibiotic resistance is not transferred to our gut bacteria. Maybe I will be able to explore this further later.
  

 

Memorandum for Research, Development, Marketing, and Legal Departments

FROM:  Tim Steele, Managing Director, Vegetable Pharm, Ltd

SUBJECT: New Product Development, High Resistant Starch Potatoes

Department Heads: Our Company has expressed a desire to create a genetically modified (GM) potato cultivar. This potato, when fully developed, will contain a unique form of starch, known as Resistant Starch (RS). This product will be marketed under the brand name “TatertotRS^tm.” TatertotRS^tm is being developed in response to our competitor’s product, Hi-Maize^tm (Witwer, 2012), a conventionally bred corn that provides 50% RS when cooked, and BarleyMax^tm, a conventionally bred barley that contains 40% RS when cooked (Bird, 2012). This product will be unique in that it will be the first ever potato that can be eaten by diabetics and contribute to enhancing the health of the world.

Notes for the Research Department

We would like you to begin immediately seeking suitable cultivars of potatoes that can be used for genetic modification for RS production. These potatoes must be commonly used agricultural potatoes grown in North America for the supermarket trade and be low in overall toxins. TatertotRS^tm will be used in home and restaurant cooking and shall require no special preparation other than cleaning. The variety should have a peel that is thick and edible, such as Russett, NorCross, or California White. We would also like to explore the possibilities of using red and purple potatoes if this project is successful, so please include these other varieties in your research for suitable potatoes.

Background Information

A bit of background may help you to research suitable potatoes. Potatoes are native to the Andes Mountains where they were first discovered approximately 16,000 years ago by the hunter-gatherers who first settled the region. The potatoes eaten by our early ancestor were small, bitter and contained many toxins. Through cooking, drying, and freezing, the toxins were removed and the tubers made edible. These early potato eaters often observed the local animals eating a certain type of clay to avoid being poisoned and adopted this practice as well. Whether by accident or through prior knowledge, these stone-age people became farmers and plant breeders developing potato cultivars that were edible and withstood many different climates. When the Spanish visited the area in the 1400’s, they were impressed enough with the taste and nutritional qualities of the Andean potato to bring samples back to Europe where it was grown as food for humans and animals (Hawkes, 1993).

Over time, potatoes became one of the most important food crops in the world. Numerous types of potatoes were developed through cross-breeding and selective pressure. We now have a potato for every conceivable palate and for numerous industrial uses. The only thing that potato breeders have not been able to achieve is a potato with little glycemic impact. The glycemic index of an average potato is 75, much too high for most diabetics and also for the newly “carb conscious” public (Fernandes, 2005).

Starch Types

Potatoes contain two types of starch: amylose and amylopectin. The ratio of these starches in potatoes is always very close to 20% amylose and 80% amylopectin. Both starches, when heated, quickly convert to a rapidly digestible starch (RDS) that humans can break down in their small intestines with the help of amylase enzymes. When cooled, the amylose and amylopectin crystalize and become resistant to enzymatic digestion, and thus termed “resistant starch. (Zobel, 1988)”

Resistant Starch (RS) has been researched for the past 30 years and shown to act as a prebiotic, selectively feeding and influencing populations of beneficial human gut microbes (“commensals”). As a prebiotic, RS has been shown to have many health benefits similar to soluble fibers (Behall, 2006)…the marketing team will have the most up-to-date information on this if you are interested.

Crucial to this project will be increasing the amylose starch content of a new potato line. Amylopectin starch, which comprises 80% of wild-type potatoes, is not considered RS. The amylose portion of wild-type potatoes is much too low (20%) for wild-type potatoes to be considered “high in RS.”  There is a successful line of GM potatoes that are bred to contain nearly 100% amylopectin starch (Williams, 2010). We need to see the opposite…near zero amylopectin.

Also keep in mind that several cultivars of potato have been selectively bred for a high total starch content of nearly 23%, but these potatoes may not be as useful in cooking as their lower-starch counterparts. A starch content of 20% is seen in commercially available “baking” potatoes and is our target for starch content (Shumin, 1993).

Past and Present GM Potatoes

Many potato breeds now in use have already been genetically modified. There are some older GM breeds designed to resist several potato viruses and potato beetles. These breeds were approved in the U.S. and Canada in 1999, but completely discontinued after economic studies showed they had no economic advantage because most commercial growers rejected these simply for the GM label. The German biotech giant BASF developed a high amylopectin potato in 2010 (Williams, 2010), but in 2012, it was banned by the EU and the line discontinued (Tosun, 2014). The problems in the EU need to be thoroughly examined so that we do not encounter a similar problem. According to the German on-line agriculture journal DW:

The Commission gave its approval after the European Food Safety Authority (EFSA) said in a consolidated opinion in 2009 that it believed Amflora posed no threat to human health or the environment. However, the Commission failed to submit the EFSA report, which included dissenting opinions, to two advisory committees made up of representatives of EU member states (DW, 2013).

Our key business rival, J. R. Simplot Company just received U. S. Department of Agriculture  (USDA) approval on 7 November 2014 to begin selling their “no-bruise” potatoes. These GM potatoes are built so they produce less acrylamide, a compound in potatoes said to cause cancer when heated to frying temperature. This new GM potato will be a big hit with potato chip and French-fry manufacturers. McDonald’s is Simplot’s biggest customer and is sure to accept these new potatoes (Pollack, 2014).

Please keep abreast of current research in producing GM potatoes that are resistant to Phytophthora infestans, or potato blight. We’ve been hearing rumors that several biotech firms are getting close to releasing these new breeds (Park, 2009).

When the project is ready for the Development Team, the Research Team will be reassigned to begin registration activities with the USDA.

Notes for the Development Team

We believe that you will find it relatively easy to genetically modify any potato to convey a high amylose content. The biggest challenges will be producing a potato with the eating qualities of conventionally cooked (baked, mashed, sautéed) potatoes and also have the flexibility to be used in deep-frying applications (French fries, potato chips), or industrial uses (starch extraction, biofuel, animal feed). Many attempts will be required, therefore you should experiment with a wide range of potatoes and also consider using genetic material from cereal grains (corn, oats) or other tubers high in amylose content (yucca, yam).

Transgenic Procedures

We would prefer to produce the desired high amylose content through the use of Agrobacterium tumefaciens technology as we feel this will be the easiest and cheapest method of transferring the genetic code for amylose starch production. A. tumefaciens  is a soil based organism (SBO) that is naturally able to transfer its genetic material to plant cells. Please note that A. tumefaciens  is now often referred to by an updated scientific name, “Rhizobium radiobacter. (De Groot, 1998)”

A. tumefaciens  has been used to successfully create numerous GM plants such as FlavRsavr tomatoes, low-nicotine tobacco, and Golden rice. This bacteria is especially effective on dicotelydenous plants such as potatoes, tomatoes, and tobacco (Kramer, 1994). Even though several species of A. tumefaciens  are known human pathogens, their use as a vector for cloning new potato species should not pose a risk, but care should be taken in the labs that the genetically altered microbes are not breathed in or released to the atmosphere. A. tumefaciens  has been implicated in nosocomial infections such as bacteremia, peritonitis, and urinary tract infections as well as being commonly found in the respiratory tracts of cystic fibrosis patients (Aujoulat, 2011). 

A. tumefaciens is a natural plant parasite. It has evolved a mechanism to insert its genes into the cells of other plants. We will use this natural ability to transfer genes which convey high RS production into potato plants, then clone the plants until we have a breedstock of self-replicating high-RS potatoes. Recall that A. tumefaciens causes “crown gall disease,” a type of plant cancer, when it transfers its T-DNA, or “transfer DNA,” into a plant host. We will be taking advantage of this unique ability of the ubiquitous SBO to affect our desired genetic changes (Patel, 2011). Specifically, the procedures we’d like you to follow are outlined below:

Cointegrate Vectors

First, we’d like you to attempt to transform adult potato plants using “cointegrate vectors.” You will construct these vectors by recombining a vector gene for RS starch production between the right and left T-DNA borders of the T-DNA region within a Tumor Inducing plasmid lacking tumor-causing gene in A. tumefaciens as outlined by Patel in his manual (Patel, 2011). This may prove difficult as they are tricky to construct and dependent on a specific site in the recombination of plasmids, however, this will be the most “patentable” method and most difficult for our competitors to reproduce. The cointegrate vector technique has been used successfully to produce many GM plants with desired traits of drought and freeze resistance, and pest control (Zimmer, 2005).

Binary Vectors

If the cointegrate vector technique fails, you may consider using the simpler binary vector method. This method uses two plasmids, a “vir” gene (responsible for tumor formation) and a helper plasmid which is a vir gene lacking its T-DNA. This method has been found easier as these plasmids are easier to handle and not site-specific. There are numerous ways of doing this, but all rely on getting the amino acid sequence (“motif”) to covalently attach to the 5 prime end of the vir gene. This is accomplished by coating the T-DNA complex with vir proteins naturally secreted by A. tumefaciens. At this point, you will be less biotechnologists and more a witness to the miracle of life as the vir genes are attracted to importin proteins (alpha and beta) that carry the new genetic material through the nuclear pore complex, and with a bit of luck, the T-DNA will end up in the nucleus of the potato plant cell where chromatin will transcribe the T-DNA into the genome of the potato (De Groot, 1998).

Marker Genes

Additionally, we will be using a marker gene to ensure we have successfully transferred the amylose genes. For our purposes, we will use the naturally occurring “nptII” gene (DeVries, 1998). You may have some concerns as this is the gene that causes antibiotic resistance to neomycin and kanamycin (Matton, 2006). The nptII gene is widely used as a marker gene in most GM food crops and even in genetically modified microbes. Kanamycin and neomycin are rarely used anymore because they are no longer effective antibiotics as most bacteria they are designed to kill have become resistant to them (Paparini, 2004).

Plant Transformation 

Once you have perfected the method to transfer the amylose genes, you should plan on transforming the parent plant either through a leaf-disc array (cloning) or the floral dip (seed) method (Weinthal, 2013). In the case of the potato plant, a whole-plant cloning is desirable since seed propagation is a less reliable method to breed potatoes. Our new patented Tatertot^tm potatoes will be sold only as seed potato and not seeds in order to be more acceptable by the farming community. We also desire the new potato to be hybridized to prevent spreading to non-high-RS potatoes as we intend to carefully guard the product from trademark infringement.

Field Trials

When we have developed the breed, we will have to conduct extensive field trials to ensure the GM traits of the potatoes are stable through multi-year growing seasons and that they will grow under a wide range of climate and growing conditions, i.e., drought, frost , pests, soil types.

We anticipate that this project will take approximately 5 years based on current trends in regulatory science and registration activities through the USDA (Falck, 2013).

Notes for the Marketing Team

We want you to begin a marketing blitz for Vegetable Pharm, Ltd. discussing our intentions of developing a new potato that will benefit the health of the entire world. Begin spreading information about resistant starch (RS) and all its health benefits (outlined below). Downplay the GM aspect of the new breed of potato unless specifically asked, and then, do not mention the marker genes that are actually antibiotic resistant “superbugs” that may end up in hospitals and cause MRSA. Remember our strict “Don’t Tell” policy. If the conversation turns to GM, please use Martina McGloughlin’s “Ten Reasons why Biotechnology will be Important in the Developing World” essay (McGloughlin, 1999). These points have stood the test of time and are still presented in Biotechnology text books as facts. Also, please take note of the advertising done recently by Simplot on their new line of GM non-bruising potatoes which were just approved for sale and use this month as well as Okanagan Specialty Fruit’s new non-browning GM apple which is awaiting regulatory approval.

Electronic Marketing

It may behoove the Advertising Department to begin creating and commenting on blogs, forums, and other health websites to overstate the importance of RS. Keep this conversation going, gut health is the “topic du jour” in the blogosphere and potato starch has risen to the top of preferred ways to achieve great gut health. Ingredion, Inc. had cornered the market for years, but their line of Hi-Maize corn starches never became popular outside of scientific and food industry circles. The unveiling of TatertotRS^tm will be a watershed event in the world of healthy dieting if we can market it effectively!

Benefits of RS for Marketing Purposes

Remember, RS is a scientifically proven prebiotic. RS has been shown to have positive effects on (Anderson, 2009):

·         Cardiovascular Disease

·         Type 2 Diabetes and Glycemic Control

·         Laxation and Regularity

·         Satiety and Appetite Control

·         Body Weight

·         Reduced Risk of Cancer

·         Gut Barrier Function

·         Immunity

·         Reduction of Pathogens and Infection Prevention

·         Enhanced Short Chain Fatty Acid Production

·         Increased Beneficial Gut Flora (Bifidobacteria, Lactobacilli, others) 

Please use these and any other benefits from peer-reviewed, scholarly articles on the benefits of RS.

Description of resistant starches

RS is available in four types (Jenkins, 2000):

RS1 is the physically inaccessible starch that is locked within cell walls such as nuts shells, seed coatings and hulls, and other food matrixes

RS2 is in raw starch granules, sometimes called “native starch.”  These starch granules are protected from digestion by the structure and composition of the starch granule itself. The structure of the starch granules have an impact on the resistance of the starch—such as the shape of the granule, size of pores or susceptibility of the starch to germinate (Bird, 2010).

RS3 is retrograded or crystallized starch formed after cooking.  This is the starch found in cooked and cooled potatoes, bread crusts, cornflakes, and cold sushi rice.  RS3 is non-granular starch that resists digestion.  RS3 is interesting because it can withstand heat once it has formed (Bird, 2010).

RS4 is a man-made, chemically modified or re-polymerized starch.  It is not found in nature, but rather manufactured and used widely in the food industry to alter the characteristics of starch to decrease its digestibility.  RS4 can be produced by chemical modifications, such as conversion, substitution, or cross-linking, which can prevent its digestion by blocking enzyme access and forming atypical linkages (Robertson, 2012).

RS Marketing Strategies

It will benefit our bottom-line if we can discourage people from consuming RS types other than RS2 and RS3.  Our new Tatertot^tm potatoes will be the highest RS3 whole food in existence when cooked. For instance, a normal potato can be made to have about 5g of RS3 by cooking, cooling, and reheating.  Tatertot^tm potatoes will have approximately 50g of RS3 per potato!  This is nearly twice the recommended daily intake of RS and 10 times the average daily intake (Bird, 2010).

Worldwide Marketing Considerations

We must also prepare to launch this product across the globe.  While GM crops are generally taboo in the European Union (EU), Tatertot^tm potatoes, or products made from them, may be eagerly purchased when we extol the health virtues of RS.

RS solves many health problems plaguing first-world countries, particularly colon cancer. Australia has created a GM product known as BarleyMax, a high RS barley cultivar. Australia is the world capital for colon cancer, and their national health agency, CSSIRO, has placed the blame on lack of fiber, specifically, RS. Many studies show that RS is capable of stemming the tide of bowel cancers by producing a short-chain fatty acid, butyrate, that fuels the cells lining the colon and induces apoptosis of cancerous cells (Anderson, 2009).

Colon cancer is not a problem in third world countries where ample fiber and RS is already consumed, but we can possibly gain inroads to Africa and South America if we do a bit of creative marketing. For instance, RS is known to boost the immune system, and the ebola virus is said to target those with weakened immune systems, so we can market Tatertot^tm potatoes in Africa as “protection against ebola.” In South America, people in large cities are seeing diseases common in the western world, so restrict marketing to the residents of large cities such as Bolivia, Bogota, and others. Check medical annals for instances of diabetes and cancer in these areas and ensure that Tatertot^tm potatoes will be viewed as a favorable brand name.

Notes for the Legal Team

Advertisement

Please review the precedence for our options to legally patent this new GM potato. Also review our legal position to advertise this product as a health-food and find out exactly what terms we can legally use when advertising.

The FDA has strict rules on the use of advertising foods and supplements for health (Bird, 1998). Claims that can be made are often limited to generic terms such as, “supports a healthy immune system,” or “when included as part of a healthy diet may...” We need to ensure that we use all of the latest “buzz words” such as “low carb,” “prevents cancer,” and “benefits intestinal microflora.”

We would like for the legal team to develop a strategy to downplay the GM aspect of our new product as well. At present, a GM label is the kiss-of-death for consumer food products. While we can’t specifically lie about it, we should be held to no higher standards than any produce grower or supplier using GM products. Our product needs to blend in with all of the other non-GM products on the market, but also fetch a higher price due to its designer application.

Conflicts of Interest

Please look into the legalities behind publishing scholarly articles on the efficacy of high RS potatoes. We would like to provide scholarships to schools researching the properties of RS and to provide funding for the writing of these journal articles. How can we best do this without having a conflict of interest?

We have also hired a science writer who will be a “cheerleader” for our new products. Please ensure that all of his articles are reviewed for legal compliance and  keep an eye on his blog and websites which will be operated outside the scope of Vegetable Pharms, Ltd. We anticipate that over 50% of our marketing and promotions will be done on blogs and other non-regulated online media.

USDA Requirements

The legal team will actively engage with the USDA to ensure we meet all requirements to fast-track this project through their application and discovery procedures. As of 2011, the USDA has become extremely helpful to biotech companies in getting new GM crops on the market in record time. A bonus will be paid to the team for getting this product on the market ahead of schedule. The USDA has streamlined their process, but a thorough review is still conducted to ensure the proposed GM does not pose any risks to health or agriculture.

As soon as the USDA signs off saying there is no risk, our new product will fall under “non-regulated” status and we can begin marketing. The USDA promises us that the approval process should take no more than 2 years. Their new improvements are outlined thus (Jaffe, 2014):

·         A streamlined internal process, eliminating unnecessary steps and setting timeframes for completion of steps

·         New tools to help managers assign staff and effectively track progress on GM petitions

·         Faster internal review and clearance of documents

·         Enhanced system of public input on petitions

Risk/Benefits Analysis

            An Ethics Committee will be formed within the legal team. The Ethics Committee will be responsible for conducting a thorough risk/benefits analysis. We have adopted the risk/benefits policy of the International Union of Nutritional Sciences (IUNS). Please follow this guideline. Of particular note, we will be adhering to the incredibly poignant policy description of Anna Lartey, IUNS President:

Public discussions surrounding the development and use of applications of modern biotechnology for agriculture are widespread, particularly discussions about the development of GMFs and GMOs and the safety and efficacy of the new products. Public concerns about gene technology lie in four major areas, namely ethical concerns, socio-economic issues, effects on the environment and food safety and human health. Although acknowledging the importance and the interconnectivity of all these areas, the principal focus of this statement is the scientific basis for assessing the risks and benefits to human health of GMFs and GM crops (IUNS, 2014)

Namely, our risk/benefits analysis shall consist of three main efforts:

·        Food Quality and Human Nutrition

·        Agricultural Practices

·        Industrial Processes

We’d like for the Ethics Committee to also pay particular attention to any possible allergies, toxicities, nutrient imbalances, and potential decreases in diet diversity as outlined in the IUNS policy of risks and benefits of GM food crops (IUNS, 2014). Additionally, a risk/benefits analysis would not be complete without a thorough investigation of the socio-economic aspects of our new crop as well as the societal issues and public attitudes surrounding GM crops in general (IUNS, 2014).”

Concluding Remarks to Departments

We are confident that if we work as a team, we can have Tatertot^tm potatoes on the market within the next 10 years. Please bring any problems or new ideas to our attention as soon as possible. Based on current models (McDougall, 2011), our budget for the project is $150 million over the 10 year project, to be divided among the departments as follows:

·        Research – $10M

·        Development – $75M

·        Marketing – $20M

·        Ethics - $45M

As the time and expense needed to bring this GM crop to market is staggering, we should all strive to resolve any issues at the lowest levels. Please work within your departments to ensure that any potential show-stoppers are brought to our attention as soon as discovered.

Signed:

Tim Steele, Chief Scientist

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