Jascha Hoffman

As bacteria have grown increasingly resistant to standard antibiotics, scientists have begun a desperate search for alternatives to the drugs. In one promising approach, they are trying to harness viruses that naturally evolved to prey on harmful bacteria and to use them as weapons for staving off intruders.

That may sound like a new idea, but it is a revival of an ancient remedy. Therapies that use bacteria-eating viruses -- bacteriophages, or just phage for short -- have been part of traditional cures for centuries in India, and they have been practiced in the former Soviet Union for decades.

They have yet to be properly tested on people, and some researchers are skeptical about unleashing a self-replicating virus into a patient's bloodstream.

As drug companies abandon antibiotics for more reliable products, a handful of start-up companies is developing precision-engineered viruses for medical use. One of the youngest, GangaGen, founded in 2000 and based in San Francisco and Bangalore, uses genetic engineering to control the healing viruses.

GangaGen's name refers to the moment when Western science discovered phage therapies in 1896, when a British chemist noticed that water from the Ganges River in India, traditionally known for its curative properties, was lethal to the cholera bacterium. After gaining attention in Sinclair Lewis's ''Arrowsmith'' in 1925, phage cocktails were marketed by American drug companies for a brief period before being overshadowed by powerful antibiotics developed in World War II.

Phage treatments in the form of oral or topical medications are now poised for a comeback. But they are riskier than drugs. For good results, many strains of virus are often needed; the viruses can multiply quickly in a host; and they may in some cases produce toxic chemicals.

But GangaGen, which will conduct human trials in hospitals in India this year for a virus that attacks staph bacteria, is using genetic engineering to reduce the risks.

Unlike broad-spectrum antibiotics, phages evolved to attack a narrow range of bacteria, so they have traditionally been applied in combinations of three or more. It would be safer to find a single virus that did the job. To that end, GangaGen is pursuing ways to increasing the number of a virus's potential hosts by inserting new genes into its tail.

There is, however, a far more serious problem. The viruses, although they may save lives, can also kill people, ''not just because of the fact that they might be contaminated with something, but also because the viruses themselves can carry toxin genes,'' said Dr. Carl R. Merril, a senior investigator at the National Institutes of Health.

A phage uses its host to make hundreds of copies of itself that then burst out to infect other cells, growing exponentially in dosage. If a phage is allowed to replicate unimpeded, it may acquire a toxin-coding gene from its host, a potentially lethal turn of events.

To eliminate that problem, Dr. Ryland F. Young, a professor of biochemistry at Texas A&M who is also on the GangaGen advisory board, has engineered the first virus that does not burst open its host. [Correction: see below.] This phage kills bacteria like any other, the founder of GangaGen, Dr. Janakiraman Ramachandran, said, but it does not risk unchecked replication or the buildup of toxins.

Some experts said research to modify the viruses was not necessary for effective phage treatments.

''Why would you want to spend a lot of time and money fine tuning phage that already may be out there?'' said Dr. Alexander Sulakvelidze, head of research at Intralytix in Baltimore. The company was an early leader in phage therapy and is developing phage-based food additives to kill salmonella and listeria. ''The beauty is that they're so ubiquitous and natural. Mother Nature has the best genetic engineering lab.''

Although phage therapy has longterm potential as a treatment for illnesses like diarrhea and tuberculosis, Mr. Ramachandran said, GangaGen will focus on medical applications that do not require inserting viruses in the bloodstream.

The companies developing phage products seek money for research and trials. If officials decide that the antibiotics shortage has reached a crisis level or that phage therapy should be integral to biodefense, Dr. Merril said, anything is possible.

—Jascha Hoffman

CORRECTION: An article in Science Times on May 18 about bacteriaphage therapy, which harnesses viruses to fight bacteria, misstated the role of Dr. Ryland F. Young in researching the treatment. Dr. Young studied the way the viruses replicate and burst out of the host cell to invade other cells. His research group was also the first to delete genes in a bacteriphage, preventing the virus from bursting out of the cell after replication. But Dr. Young was not the first researcher to manipulate a phage genetically so that it killed bacteria without bursting out and infecting other cells. Scientists isolated mutant viruses with that property more than four decades ago.

Health on the Web

A Google search for "cancer" returns 299 million results; narrow that to, say, "prostate cancer" and you still get 12.7 million. It's a vast, bewildering world out there, but here's a look at six of the most interesting and potentially useful online health resources. - JASCHA HOFFMAN

PubMed
www.ncbi.nlm.nih.gov/pubmed

Created more than a decade ago by the National Library of Medicine, PubMed includes millions of citations from medical journals dating to the 1950s. Doctors and students have learned to rely on the database to track studies. Patients, on the other hand, may be overwhelmed by the flood of results: more than 500 abstracts crop up when the system translates a naïve query for "causes of bad breath" into "etiology of halitosis." But if you know what you're looking for, and how to make sense of it, PubMed is a power tool without peer. A free log-in allows easier filtering, and a new iPhone application holds the promise of a second opinion right there in the waiting room.

Visualdxhealth.com
visualdxhealth.com

The art of diagnosis is subtle. But when it comes to skin conditions, sometimes the answer is right there in front of your eyes. Enter the Skin Disease Finder at visualdxhealth.com, a kind of Flickr for bites, boils, cysts, moles, rashes, sores, warts and more — even the hard-to-describe skin infections caused by MRSA. Drawn from an even larger visual library sold by Logical Images in Rochester, this free dermatological atlas will satisfy all but the most fiendish amateur skin detective. You can select a location as precise as scalp, cheek, toenail or “finger webspace,” or you can shoot the moon by clicking on “widespread rash.” Presto, a sort of lineup of skin diseases appears, with instantly recognizable mug shots that enable anyone to tell eczema from rosacea, shingles from ringworm, scabies from psoriasis. The whole thing is certainly more thrilling than a visit to the dermatologist’s office — especially if you don’t have a rash.

San Fransisco City Clinic
sfcityclinic.org

San Francisco City Clinic, which offers low-cost testing and treatment for sexually transmitted diseases, is also a bracing and realistic source of information. Its front page comes on gently with a little box marked “About You.” This leads to a customized list of diseases one can get as, say, a middle-age transsexual who sleeps with both men and women. For those who would rather see all the risks at once, a handy chart of “S.T.D. basics” catalogs the infections that can be transmitted by nine kinds of sexual activity. Bay Area residents can consult an exhaustive catalog of local resources. For the rest of us there is the clinic’s “Dr. K,” whose advice columns reveal, for example, that two condoms are not better protection than one.

Clinical Trials
clinicaltrials.gov

Looking for experimental treatment? With more than 25,000 open trials testing a dizzying variety of new drugs, surgeries and vaccines, this site may have something for everyone. The upside is bargain-priced treatment; inpatient volunteers can be well compensated. The downside is that you may be pumped full of an untested drug with serious effects. (You may get a placebo.) By and large, the trials sponsored by universities and the National Institutes of Health are more likely to be monitored for safety than those offered by private companies.

Patients Like Me
patientslikeme.com

If you learned you had a life-changing illness, broadcasting it on the Internet might be the last thing on your mind. But PatientsLikeMe encourages people to do just that. Founded by Ben and James Heywood after their brother Stephen received a diagnosis of Lou Gehrig’s disease, the site is a kind of Facebook for the chronically ill. It holds thousands of profiles of patients living with diseases as diverse as multiple sclerosis, Parkinson’s and H.I.V., with a special section for mood disorders like depression and anxiety. Patients can use slick visual tools to chart their symptoms over time, rate their drugs and treatments, and track their progress against fellow patients with a degree of transparency that borders on the voyeuristic. Users should be aware that the site shares data, stripped of names and other identifying material, with nonprofit groups, research hospitals and pharmaceutical companies.

Mayo Clinic
mayoclinic.com

It may be tough to get an appointment at the Mayo Clinic, which for over a century has set the standard for medical care in America. But it’s much easier to consult its encyclopedic site, which may be the most concise source of medical information on the Web. Unlike many other health sites, Mayo writes its own material, with a tone that manages to be both conversational and precise, straightforward and sympathetic. (“Suicide is the act of taking your own life. ... You may think suicide is a solution when, in fact, it’s not.”) The no-nonsense symptom checker, while remarkably simple to use, should probably be kept away from hypochondriacs. (Wheezing and drooling? You may have epiglottitis. Dizzy and stumbling? Might be ataxia.) The site could be easier to navigate, but the guide to ailments is so terse and authoritative that you may find yourself reading it for pleasure.