When Ernest Hankin made the first discovery of the activity of bacteriophages in India in 1896, he had no idea that more than 100 years later, a company would be based on the potential use of those "bacteria eaters" to cure contemporary illness.

GangaGen Inc. is looking to bacteriophages and that century-old bacteriophage discovery for its own science. But the company says bacteriophages took a back seat to antibiotics once antibiotics were introduced.

GangaGen, whose executive office is in San Francisco but has research and development facilities in Bangalore, as well as a life sciences subsidiary in Ottawa, Ontario, is banking on bacteriophages in an age of emerging "superbugs" and diminishing effectiveness of modern antibiotics.

GangaGen takes its name from the Ganges River in India, which in the past has been known for carrying human carcasses downstream as well as for being a host to thousands of human bathers. However, it's where Hankin discovered that the river's water killed the cholera bacteria in culture, and today it's also known to some as a great site for gathering bacteriophages.

GangaGen Chairman and CEO David Martin, who was appointed in November, said of bacteriophages: "We coexist with them. They can't bind or adhere to any type of mammalian cell - they only adhere to bacteria. They've been fighting the bacterial wars for millions of years, and as a result, they have never evolved to attack mammalian cells."

Bacteriophages work by attaching to their targets through specific sites on the bacterial surface and injecting their DNA, the company said. The phage DNA then redirects the bacterial cell's biosynthetic machinery to produce hundreds of new phages in a short time, ranging anywhere from 30 to 60 minutes, it said. The newly formed phages break down the cell wall and attack other bacterial cells until they're eliminated. The phage then stops the progress, because it can survive only by devouring the bacteria. Once the bacteria are gone, it's the end of the road for the phage.

"We've got about 1,200 clinical strains of human pathogenic bacteria, and we've got well over 500 bacteriophage isolates," Martin said. "That's quite an extensive library."

Founded in 2001 by the individual Janakiraman Ramachandran, the company has raised just less than $4 million from seed funding and angel investors and is in the process of seeking $10 million. That money would carry the company to clinical trials, Martin told BioWorld Today. He expects to have both an approved product in 2005 as well as a therapeutic product in clinical trials.

Martin brought considerable experience to GangaGen, including most recently having served as CEO and co-founder of Eos Biotechnology Inc., a company focused on genome-based therapeutic antibodies. It was acquired by Protein Design Labs Inc., of Fremont, Calif., in April. He has served as president of Chiron Therapeutics and senior vice president of Chiron Corp., of Emeryville, Calif. In the early 80s, Martin was recruited to become the first vice president of research and development at South San Francisco-based Genentech Inc. GangaGen has 36 employees, 28 of whom are in Bangalore.

"Our business strategy is as follows: We are primarily interested in human therapeutics," Martin said. "However, there's a real funding gap in the development process of human therapeutics. So, accessible cash is pretty good at the research stage [and] it's pretty good after one has a product candidate in clinical trials and has efficacy data. In between is this valley of death where a lot of companies just fold. Our approach is to provide some stepping-stones across that valley of death."

Those stepping-stones, he said, are the "applications of its technology to eliminating human pathogens from the food chain," the source of many human infections and many headlines: E. coli015787.

The company's first product is expected to be "a cocktail of bacteriophage" that attacks that particular strain of E. coli, which makes its way into the food chain when manure-strewn fields ultimately contaminate ground water that is sprayed on crops. GangaGen's Canadian subsidiary, GangaGen Life Sciences Inc., will be developing a bacteriophage product to be added to manure and eliminate the strain before it is used as fertilizer.

Another way E.coli015787 infects humans is when the intestinal contents of cows spill in the slaughterhouse and thus contaminate meat. Based on the same bacteriophage cocktail, GangaGen will be developing an oral pill as a feed additive in an attempt to eliminate the E.coli strain from the animals' gastrointestinal tract.

In human therapeutics, Martin said the company has focused on modifying the bacteriophages so that they have properties making them more desirable than wild-type bacteriophages. Wild-type bacteria can come from sources ranging from animal feces and manure, to hospital sewage and the Ganges, as well as other rivers in India.

The fact that GangaGen has focused on modifying naturally occurring bacteriophage makes them easier to patent, Martin said. He acknowledged that the nature of bacteriophages also represents something of a regulatory challenge.

"What we have done is to engineer the bacteriophage that we will be using so that they cannot replicate in the bacterium they are going to kill," Martin said.

Because the GangaGen bacteriophages are self-limiting, he said he expects "regulatory hurdles will be significantly less" than with naturally occurring bacteriophage, which every time it replicates could do so 100-fold or more. But with no other bacteriophage products on the market, there is the obstacle of being first.

What helps the company is the need to fight antibiotic-resistant germs.

"The FDA and the medical community, as well as society in general, [are] very concerned about what the Brits have now characterized as the perfect storm,' and that is large numbers of antibiotic-resistant bacteria increasing hospital infections [simultaneous with] pharmaceutical companies backing out of antibiotic R&D," Martin said.

So while Martin believes the FDA may be a hurdle, he concludes: "The FDA is creating hurdles all the time for the drug industry, and I think that for biologics with current molecular biology and the ability for us to sequence the genome of the bacteriophage pretty quickly, we can address their concerns, and our concerns, before we do clinical studies and certainly before we have an approved product."