Baby sloths at the Sloth Sanctuary of Costa Rica
It is always exciting when seemingly disparate personal passions intersect not only beautifully, but also beneficially. I knew it was only a matter of time before my favorite animal came together with my vocation in such harmony. On January 15, 2014 PLOS ONE published the paper “Sloth Hair as a Novel Source of Fungi with Potent Anti-Parasitic, Anti-Cancer and Anti-Bacterial Bioactivity”. Aside from giving sloths some well-deserved street cred in the research world, this paper identifies new fungi and one with potentially novel antibacterial mechanisms.
The study focuses on the three-fingered sloth (Bradypus variegatus). “Three-fingered sloth” is the updated common name from “three-toed sloth” since all sloths have three-toes, including two-fingered sloths (Choloepus didactylus or hoffmanni). Disappointingly the authors’ describe the three-fingered sloth as an, “arboreal mammal commonly found in the lowland tropical forests of Central America.” Such a terse description does little justice to this amazing animal, but I understand that the word limit constraints of most journals would make it difficult to properly describe the sloth. In turn, I will limit myself here and refer readers to the Sloth Sanctuary of Costa Rica to learn more about both three- and two-fingered sloths. The Sanctuary was officially founded in 1997 as the first sloth rescue center and research institute in the world. In 2010, I volunteered there for two months, learning about and caring for the sloths and leading tours of the facility.
Three-fingered sloths at the Sloth Sanctuary of Costa Rica
In addition to sloths, I am passionate about increasing both basic and therapeutic research into the neglected world of fungi (“Focus on Fungi”, August 19th, 2013) and into the development of novel antibiotics (“Bacteria: from gut to lab to disease”, August 27th, 2013). It is estimated that there are 5 million fungal species on earth, but only 100,000 of these species have been described (Blackwell M., 2011) and a 2013 review in the Annals of Clinical Microbiology and Antimicrobials highlights the need for antibiotics and the tedious progress of the Infectious Diseases Society of America’s (IDSA) 10x’20 Initiative to develop ten new antibiotics by 2020. Fungi are a natural source of antibiotics, including the first antibiotic, penicillin, and cephalosporins. The identification and characterization of potentially millions of fungal species could lead to unimaginable options for the development of antibiotics.
But why sloth hair; what makes it so special (besides the fact that it is on a sloth)? The average human skin microbiome is made up of <0.01 percent fungi. The average three-fingered sloth hair microbiome is made up of 8 percent fungi! Therefore, sloth hair provides an easily accessible rich source of mammal-associated fungi. Easily accessible because, let’s be honest, it isn’t hard to catch a three-fingered sloth (in a tree here, and even slower on the ground here).
In this paper, first author Sarah Higginbotham of the Smithsonian Tropical Research Institute, Republic of Panama, in collaboration with corresponding author, Elizabeth Arnold of the University of Arizona, Tucson, the University of California, Santa Cruz, and the Instituto de Investigaciones Científicas y Servicios de Alta Tecnología, Republic of Panama, isolated 84 fungal strains from the hair of three-fingered sloths in Soberanía National Park in Panama. Four of these isolated species are in understudied or potentially novel groups. The authors then cultured several of these fungal stains and tested their activity against parasites and cancer. 2.5 percent of the culture species are highly active against Plasmodium falciparum, the causative agent of malaria; 12.9 percent are highly active against the etiological agent of Chagas disease, Trypanosoma cruzi; and 20.6 percent are highly active against human breast cancer MCF-7 cells. Intriguingly, there is limited overlap of active strains between the tested pathologies. Furthermore, some of the families of these fungi have established activity against malaria and cancer but the anti-trypanosomal activity is novel.
To test the antibacterial activity of the fungal strains they used BioMAP and examined activity against 15 human pathogenic bacteria. Twenty of the isolated fungi had activity against at least one pathogen and the fungi were more active against Gram-positive than Gram-negative bacteria. Of the fungal strains, F4807, showed activity against Gram-negative bacteria. Intriguingly, the bioactivity profile of F4807 does not match any known antibiotic classes previously tested by BioMAP. This identification of a potential novel mode of action could be a breakthrough for fighting Gram-negative multidrug-resistant bacteria. Currently the majority of research is focused on Gram-positive methicillin-resistant Staphylococcus aureaus, or MRSA.
Hopefully, this paper will catch the eye of mycologists, bacteriologists, and oncologists and the sloth’s value to the rest of the world will finally be accepted and exulted. That’s the world I want to live in.
Two-fingered sloths at the Sloth Sanctuary of Costa Rica
Images by Li Tai Fang
Contract research organizations (CROs) are becoming an integral part of the biotech research and development landscape, especially as big pharma continues to restructure its model for early stage discovery (January 16thpost), and everyone is taking this exploding market seriously. However, the more we hear “CRO” the more confused some of us are as to what constitutes a CRO and how CROs fit into the research-sphere. On Monday, January 27th, the Oxbridge Biotech Roundtable (OBR) Bay Area Chapter hosted “CROs: Partners and Disruptors in Drug Discovery” at the University of California, San Francisco to clarify some of this confusion.
An audience of nearly 200 registered attendees gathered to actively interact with a panel of CRO experts including Ken Meek, director of sales and marketing at Aragen Bioscience; Joe Francisco, Senior Client Services Scientist at Charles River Laboratories; Elizabeth Iorns, cofounder and CEO of Science Exchange; Jesse McGreivy, Chief Medical Officer at Pharmacyclics; and Kitty Yale, Senior Director at Gilead Sciences, Inc. The panel began by summarizing CROs as any entity willing to perform research for a second party for pay. The research includes everything from basic discovery to clinical trials. The panelists emphasized the importance of CROs to the biotech industry at all levels, but particularly startups and early stage ventures. David Rabuka, founder of Redwood Bioscience, did not attend the event but commented prior to his talk at the BioScience Forum event later in the week that CROs are essential to minimizing research costs and keeping startups viable. For the remainder of the organized discussion, panel members fielded questions from attendees including what are the drivers for the growth of CROs, of which increased regulatory challenges topped the list, and how is the perception of PhD scientists accepting jobs with CROs improving as CROs become more common.
As outsourcing increases, established CROs are growing to meet rising demand. Charles River, founded in 1947 on the shores of the Charles River in Boston as a provider of lab animals, has grown to locations in 14 countries, 25 locations in the US alone, offering services from toxicology to pre-clinical services. In addition, larger companies looking to expand their service portfolio are rapidly acquiring smaller providers. Aragen’s 50 or so employees are about to reach a larger market as Aragen’s acquisition by GVK BIO, an India-based CRO, was announced on January 29th. One attendee, perhaps with entrepreneurship on his mind, inquired what is missing in the enormous, but potentially crowded, CRO space? All the panelists agreed that providers of extremely specialized services are difficult to find. This is where the highly specialized research of academic labs becomes a commodity and Science Exchange is working to fill this need. Science Exchange puts consumers in touch with registered contract research providers. According to CEO Dr Iorns, several of the registered providers are academic labs looking to raise money through offering their niche services. Academic labs are realizing this is a perfect platform for fundraising to compensate for the deficits created by reductions in traditional funding. Furthermore, acting as a CRO avoids the complications surrounding crowdsourcing the biological sciences.
After the panel discussion, Sajith Wickramasekara, founder of Benchling, commented, “The increasing use of CROs by researchers highlights a greater trend in life science: an industry that’s embracing collaboration and specialization.” With greater collaboration comes the need for more formal data organization and sharing between team members. Benchling, which provides a cloud-based forum for analyzing and sharing DNA sequences and molecular biology tools is one of many startups capitalizing on these needs.
During the post-panel networking session, attendees, including a diverse mix of graduate students, postdoctoral fellows, and industry scientists, enjoyed food and drinks while making new connections. Benjamin Gaub, a PhD student at the University of California, Berkeley working to restore vision in blind animals through retinal reanimation as well as developing echolocation devices for the blind, appreciated the time as an opportunity to, “expand my network and get some exposure to industry.” It may be fair to assert that by brining people together for these events, OBR is providing a CRO-like service for networking.
For more information on upcoming OBR events visit our site here.