Overview

fishPHARM first started as an iGEM summer project motivated, but has quickly evolved into a novel start-up company with potential for immediate application and long-term impact. We have engaged in several entrepreneurship endeavors to facilitate the growth of fishPHARM as not only a synthetic biology based project, but as a locally-based business venture capable of curing BCWD worldwide. We have also partnered with a variety of fish hatcheries and research institutes in the New York State Finger Lakes Region to help take our discoveries from the lab bench and meet the demands of a growing consumer market. Through conversations with these hatcheries, which deal with bacterial coldwater disease daily, we are able to analyze the safety implications of deploying our product in the fish farming industry and compare the economic costs of our product to current solutions. fishPHARM is designed directly with the needs of your everyday fish farmer in mind. By collaborating with our consumers in the initial stages, we aim to develop a product that is not only safe and effective, but also is practical for treating BCWD in the real-world.

Hatchery Collaborations

Economic Analysis

Oxytetracycline (branded as Terramycin) costs roughly $0.70/gram. Since the total amount of antibiotic required for a 10-day treatment is 25 g/100 lbs, treatment of a fish stock with Terramycin costs about $0.025 per dollar of fish [1]. However, Terramycin is already becoming obsolete as a treatment protocol due to the rapid formation of resistant strains [2]. While the antibiotic may appear cost effective, it cannot be relied upon as a long-term solution due to the rise of antibiotic resistance. Bacterial tolerance of chemotherapeutic agents could obligate fish farmers to use more potent antibiotics, which could have undesirable side effects on their stock. Furthermore, the evolutionary capability of Flavobacterium to overcome antibiotics suggests that reliance on such agents in the future is a questionable proposition.

The total production cost of a fishPHARM has been estimated to be roughly $2.00 per 20-pound fish. This translates to about $.14 per dollar of fish. While this may seem like a nontrivial amount, fishPHARM guarantees users a peace of mind that Terramycin simply cannot match. fishPHARM’S EcnB peptide is biodegradable as well as, and thus does not pose the same environmental and health risks that antibiotics do.

It is clear that the negative consequences of Flavobacterium psychrophilum infection are acute. As reported by the New York Department of Environmental Conservation, an epizootic of BCWD once infected 25% of lake trout raised in New York State hatchery raceways [4]. Given the inedibility of infected salmonids, the organism has the potential to reduce the financial yield of a salmon population from $7/lb to $4.90/lb in this scenario. Since roughly 2.4 million tons of salmon are produced by aquaculturists each year, even a small incidence of BCWD would have dire economic ramifications.

Environmental Impact

Given the relatively benign nature of Entericidin B and its Escherichia coli chassis, the environmental consequences of fishPHARM are negligible compared to that of current mainstream BCWD treatment methods - namely antibiotics. While there is a slight risk of the Entercidin B disrupting the ecological microbiome present at its point of dissemination, the specificity of the toxin makes this unlikely.

EcnB is naturally found in the human gut genome and thus not a hazard to human health. The benign nature of the treatment protocol we have devised provides distinct advantages over oxytetracycline, an antibiotic used to treat BCWD, because abuse of such chemotherapeutic agents fosters resistance among targeted pathogens [5]. In fact, a study conducted between 1994 and 1998 among Danish trout farms recorded an oxytetracycline resistance rate of between 60 and 75 percent of Flavobacterium colonies sampled [6]. Bacterial resistance to agents such as amoxicillin, florfenicol and sulfonamides has also been reported, largely due to the organism’s ability to form extremely hardy biofilms [6]. FishPHARM thus constitutes an effective circumvention of the issue of environmental antibiotic resistance: by eschewing the use of any chemical agents, we prevent the formation of more dangerous pathogens.

Furthermore, FishPHARM has the potential to be a more reliable, enduring solution, as it would be more difficult for Flavobacterium psychrophilum to develop any evolutionary countermeasures to such a system. It should be further noted that agents such as amoxicillin have uses in medicine, and that encouraging the development of strains resistant to such drugs could have deleterious consequences for human health.

Risk Assessment

iGEM Collaborations

This year, Cornell iGEM has collaborated with Yale iGEM by engaging in the team’s discussion about utilizing non-model organisms as part of projects and research. This dialogue was to address the increasing amount of iGEM projects that have centered around these non-model organisms, instead of Escherichia coli or Saccharomyces cerevisiae. Yale iGEM identified our project team as one that was using a non-model organism as part of our project, and have thus asked us to share our experiences working with our non-model organism. We were more than happy to share our experiences working with Flavobacterium psychrophilum, our bacteria of interest that we were trying to tackle with fishPHARM. Because F. psychrophilum is not a bacterial strain commonly worked with, we occasionally had trouble finding necessary information from scientific journals. Luckily, we were able to collaborate with a professor who had worked with F. psychrophilum and was able to provide us much needed insight into the organism. In collaborating with Yale iGEM, we share their sentiments in the hopes that future iGEM teams will be able to utilize a greater variety of non-model organisms for their projects.