why we do what we do
Ithaca, New York is home to Cornell University. The expansive area of Upstate New York surrounding Ithaca is also home to over 625,000 dairy cows that provide the region and rest of the country with some of the nation’s best dairy products - from homemade cheese to creamy milk to delicious ice cream. Some dairy farms are small and locally supported while others have over 4,000 cows grazing their lands and ship their products all over the nation .
Bovine mastitis is a painful infection of a cow’s mammary glands that is difficult to avoid. Various studies have seen that subclinical mastitis costs the United States dairy industry over $1 billion annually. The losses to farmers are not just in lowered profit numbers but also in the decline of overall health of their cows for the rest of their lives . While the dairy industry has fought back the blow of mastitis with long-treatment antibiotics, the losses from infected cows, lowered quality and quantity of milk, and increased bacterial resistance is something we can no longer ignore.
It’s time to do something Legendairy.
Bovine mastitis is an immune response to a bacterial infection of the teat canal, and the etiology of mastitis is linked to a diverse array of bacterial species. However, recent studies have shown that bacteriocins, antimicrobial peptides like Nisin and Entericidin B used in our project last year, work effectively to inhibit the growth of pathogenic bacteria [3,4]. Thus, Cornell iGEM has aimed to engineer E. coli to regulate the production of several different bacteriocins that we believe will effectively target the top and most harmful mastitis-causing bacterial species. This panel of bacteriocins can be chosen individually to specifically target Gram-positive or Gram-negative bacteria and will provide dairy farmers with a more efficient, sustainable alternative to antibiotics. We also believe our research for Legendairy furthers the study of bacteriocins as treatment options for bacterial infections in both animals and humans.
To prevent mastitis and effectively lower the outbreak of mastitis on farms, our Product Development team has redesigned the milking shell attachments that are placed around a cow's’ teats before they are milked. All the farmers we interviewed agreed the best way to prevent bacterial infection is to keep bacteria out of the mammary gland during the milking process. We’ve maximized the success of this goal by completely redesigning the milking nozzle shell. This novel shell has various modules adding to its functionality, including a temperature sensor and sterilizing UV lights. This new milking shell works with modern industrial tubing and machines by attaching to the top of the current tubing. Throughout the prototyping process we shared our shell prototype with local dairy farmers to welcome feedback so that we could improve our product to better fit their needs.
Finally, to improve upon the detection of mastitis, we have embraced a past iGEM team’s project to incorporate into our own product with their permission. Our software designers have worked to build a smartphone application that will work conjointly with an attachable smartphone microscope. This will allow farmers to count somatic cells in milk samples to accurately determine mastitis outbreaks and treat bacterial infections using the appropriate peptide from our panel of bacteriocins.
Legendairy comes at a critical time when integral food sources will become less dependable if we do not find alternative ways to fight the bacterial species threatening our sources. This project paves the way to building a sustainable future in order to support a growing human population without the presence of antibiotics.
Mastitis: Bovine mastitis is an immune response to bacterial infection inside the mammary glands of cows and is a major disease of dairy cattle triggered by over 200 bacterial pathogens. Mastitis spreads from contact with contaminated milking machines, hands, bedding, and other equipment, as well as from environmental sources. There are two types of mastitis: clinical and subclinical. Clinical mastitis is apparent from significant inflammation in the cow’s teats and a change in texture of the milk produced. However, subclinical mastitis is not as obvious, and the only evident symptom is an increase in the somatic cell count in the cow’s milk. Subclinical mastitis is the most common form of mastitis and often leads to death of the animal or degraded quality of milk throughout the cow’s lifetime. A five-point plan was created in the 1960s to prevent and control mastitis, mastitis has yet to be eradicated due to bacterial resistance .
Dairy Industry: In the heart of New York lies one of the largest dairy industries in the country. Dairy products are vital to providing us with the nutrition we need at every stage of our life. The dairy industry contributes greatly to our diets, producing over 636 million tons of milk per year . The US accounts for 14.4% of the world’s milk production, and the US alone contains over 9 million dairy cows . In recent years, farms have increased in size; modern farms typically contain over 500 cows, which increases the likelihood of cross-contamination between cows once one cow contracts mastitis. This is detrimental to the dairy industry since large farms in the US supply over 60% of the country’s milk. The dairy industry needs our help to ensure that it is able to continue providing us with a vital source of food for future generations.
Local Mastitis Consequences: On average, one case of mastitis costs anywhere from $150 to $300. Annually 16 out of every 100 cows contract mastitis, causing smaller farms to suffer greatly, especially when they are competing against large farm corporations. Up to date, farmers have not been able to determine exactly how costly a single case of mastitis is for the farm since a cow’s health continuously declines upon contracting the disease.
Current Detection and Solution: Dairy farmers currently treat bovine mastitis using chemotherapeutic agents such as antibiotics. After first using the California Mastitis Test to check milk samples for a somatic cell count level that is indicative of mastitis, the farmer will then inject common antibiotics, such as oxytocin or amoxicillin, into the mammary glands of the cow . These antibiotics stay in the milk, so the cow is separated from the herd for a few weeks while the antibiotics diffuse out of her system. Thus, both the cow and the farmer are hurt from the infection since the cow’s health is compromised and the farmer loses profit from discarding unmarketable milk. Keeping cows in such close living quarters provides the ideal environment to select for bacteria that are resistant to the antibiotics introduced in the cow .
The use of antibiotics in agriculture poses a significant threat to human health and food security. Agricultural antibiotic use is directly linked to resistance profile changes in pathogens that affect humans, plants, and animals. The European Union has recently banned the use of some antibiotics in agriculture, and many countries are following suit. Thus, it is important that we pursue future applications of non-antibiotic treatment methods to ensure food security.
Plants: Plant diseases are another potential target. For instance, bacterial stalk rot and Stewart’s disease, both devastating diseases of maize, could theoretically be addressed through the utilization of an antibacterial toxin, delivered through crop dusting. Other potential agricultural solutions abound.
People: While admittedly more ambitious, bacteriocins could be used in the future to treat human infectious diseases. There have been multiple clinical trials of antimicrobial peptides for use in humans, but to our knowledge none of these have been FDA approved . Some of these trials have been promising, and it is likely that antimicrobial peptides will become a regular agent in human health in the near future as research moves away from traditional antibiotics. Moreover, as bacterial species evolve, the bacteriocins will also evolve so that the host can remain competitive in the ecosystem, thus allowing us to always have a new peptide to investigate in the case of any sort of natural bacterial resistance.
Increase Efficiency of the Dairy Industry: Future entrepreneurs should continue working on improving the dairy milking machinery to reduce contamination and increase the efficiency of detecting mastitis-causing bacteria. There is also more to explore in terms of improving the way our peptides work in tandem with industrial tools and potentially creating a more concise device to contain and release our peptides.
In short, we have developed a theoretical means of curing bacterial diseases that does not rely on antibiotics. We believe that our treatment method could be directly applied to multiple bacterial infections. The technique we’ve employed to utilize small antimicrobial peptides to treat disease can be applied to agriculture and human health. With increasing antibiotic resistance, solutions such as ours will have a more prominent role in human health and food security.
 Overton, T. R. The New York Dairy Industry and Cornell. Retrieved from http://ccetompkins.org/resources/the-new-york-dairy-industry-and-cornell.  Ruegg, P. Premiums, Production and Pails of Discarded Milk How Much Money Does Mastitis Cost You? Retrieved from http://milkquality.wisc.edu/wp-content/uploads/2011/09/how-much-money-does-mastitis-cost.pdf.  Cleveland, J., Montville, T., Nes, I., & Chikindas, M. (2001, December 4). Bacteriocins: Safe, natural antimicrobials for food preservation. International Journal of Food Microbiology, 71(1), 1-20. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11764886.  Yang, S., Lin, C., Sung, C. T., & Fang, J. (2014, May 26). Antibacterial activities of bacteriocins: Application in foods and pharmaceuticals. Frontiers in Microbiology. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4033612/.  Mastitis in Dairy Cows. (2016). Retrieved from https://dairy.ahdb.org.uk/technical-information/animal-health-welfare/mastitis/#.V_08UZMrKAw.  World Milk Production. (2015, June 5). Retrieved from https://dairy.ahdb.org.uk/market-information/supply-production/milk-production/world-milk-production/#.V_7D05MrJE4.  Overview of the United States Dairy Industry. (2010, September 22). Retrieved from http://usda.mannlib.cornell.edu/usda/current/USDairyIndus/USDairyIndus-09-22-2010.pdf.  McFadden, M. (2011, April). California Mastitis Test and Milk Quality. Mchigan Dairy Review, 16(2). Retrieved from http://msue.anr.msu.edu/uploads/234/76581/cmt.pdf.  Mastitis Treatment and Control. (n.d.). Retrieved from http://ansci.illinois.edu/static/ansc438/Mastitis/control.html.  Witte, W. (1998). BIOMEDICINE: Medical Consequences of Antibiotic Use in Agriculture. Science, 349(6253), 996-997.