Investigator Lawrence Broxmeyer MD sees the possibility of bacteriophages as the antimicrobrials of the future.

Most people do not realize it but there are viruses which infect, live in, and can even destroy their host bacteria. Called bacteriophages or simply "phages", it is just this potential to kill disease causing bacteria that has long intrigued scientists.

Internist/researcher Lawrence Broxmeyer MD relates that "the concept of using bacteriophages to treat human infection has been with us for decades, long before penicillin was known, when doctors carried these bacterial killing viruses as injections and potions and early 1930's drug giants Eli Lilly, ER Squibb and Abbott all manufactured "phage" preparations. But a pivotal, yet poorly designed 1934 US JAMA study by Eaton and Bayne-Jones found systemic phages as having mixed results, concluding that body fluids strongly inhibited and destroyed most bacteriophages before they could reach target tissue."

"Ironically", says Lawrence Broxmeyer, MD, "It was Rene Dubos, the father of modern day antibiotics, who leaped to the defense of treating human illness with phages."

"This was the same Rene Dubos" says Lawrence Broxmeyer, "who's Gramicidin laid the foundation for Fleming and Domagk's penicillin, and the sulfonamide Prontosil, respectively. And it was Rene Dubos, who in 1943, published one of the best early animal studies of phage treatment, supported by the US military, and answering virtually all of the scientific concerns raised in the flawed yet fatal Eaton and Bayne-Jones 1930s JAMA report."

"Dubos's study" Lawrence Broxmeyer MD goes on to say "used concentrated lower abdominal (peritoneal) phage injections to fight bacteria injected into the brains of experimental animals at lethal levels, and showed that there was no problem in the phages reaching and destroying these virulent bacteria, even in this privileged site in the brain."

"In fact" Lawrence Broxmeyer adds, "the phages multiplied rapidly there and remained at substantial levels in the blood as well, as long as there were sensitive bacteria in which they could reproduce. But despite this impressive study, antibiotics, soon thereafter, became seen as a much more general "magic bullet", easily produced and applied, while phage workers in the West became diverted to molecular biology."

"So", relates Lawrence Broxmeyer MD, "by the late 1930s, phages, poorly understood, fell by the wayside as antibiotic use, seemingly infallible, soared. Canadian Felix d'Herelle had stumbled across bacteriophages in 1917 at the Pasteur Institute as accidentally as Fleming came across penicillin. Like many bacteriologists, d'Herelle long noticed clear spots on culture broths otherwise teeming with bacteria. But what he went on to find in further studies, at one time even picking the brain of Albert Einstein who visited his lab, was a virtual killing field as these viral phages decimated their bacterial pray."

"Today", Lawrence Broxmeyer MD reminds us "antibiotics are no longer infallible. Epidemics of drug-resistant (MDR) tuberculosis have been reported and Mycobacterium avium or fowl tuberculosis infections in humans, for which there never was a satisfactory treatment, are described with increasing frequency in non-AIDS populations. A limitation of most antibiotic antimicrobial agents is that their modes of action require having the microbial target in active replication. And pathogens such as tuberculosis and fowl tuberculosis have a latent or dormant phase of infection in humans."

Tuberculosis is a mycobacterium, because it has both bacterial and fungal (myco-) properties. This is why its so deadly and hard to kill. Phages found in TB are called mycobacteriophages.

In October of 2002, TB & Outbreaks Week featured an article that researchers in the United States had developed a novel technique for fighting tuberculosis and other mycobacterial infections. This article, entitled: "Novel phage-based treatment effective against mycobacterial infections", was written by Michael Greer, a senior medical writer. In it was described a innovative technique, developed by Lawrence Broxmeyer MD, whereby the drug resistance and dormant forms of TB could be overcome by the concept of using nonpathogenic mycobacteria to deliver mycobacteriophage or phage viruses to attack infected cells.

Broxmeyer based his entire theoretical underpinning on a phenomena that in nature, is referred to as "lysogeny". Lysogeny is how one colony of bacteria kills another by means of its phage weaponry without itself being harmed.

Such a scenario opened-up the theoretical possibility that bacteria, nonpathogenic to man, but with the capacity to generate phages known to kill virulent pathogens already in the body, could be parenterally injected to cure otherwise difficult to cure diseases – all the while both protecting, nurturing and delivering these beneficial viral phages.

To achieve this Lawrence Broxmeyer MD and colleagues at centers in California and Nebraska used Mycobacterium smegmatis, a relatively benign bacterial species. First identified in 1884, Smegmatis is abundantly found in the secretions that collect in humans under the prepuce of the foreskin of the penis or of the clitoris, called smegma.


"Basically" Broxmeyer explains, "we assessed the antimicrobial efficacy of Mycobacterium smegmatis organisms carrying the lytic TM4 phage virus, a phage already known to have the potential to kill the most virulent strains of human and fowl tuberculosis, introducing these virus-laden microbes into tuberculosis infected macrophage cultures. And the amount of viable intracellular pathogens dropped significantly after phage treatment."

Similar results were seen in cultures of cells infected with fowl tuberculosis or M. avium, study data showed. This organism is responsible for life-threatening opportunistic infections in HIV/AIDS patients. In fact all tuberculosis samples were from AIDS blood.

"Amazingly" says Lawrence Broxmeyer MD "significant phage TM4-induced reductions in bacilli levels were both time- and dose-dependent and the killing had still not ended during the several days that measurements were obtained for the JID study (Killing of Mycobacterium avium and Mycobacterium tuberculosis by a mycobacteriophage delivered by a nonvirulent mycobacterium: a model for phage therapy of intracellular bacterial pathogens. Journal of Infectious Diseases, October 15, 2002;186(8):1155-1160).

"These results suggest a potentially novel concept to kill intracellular pathogenic bacteria such as TB and warrant future development," Lawrence Broxmeyer, MD and colleagues conclude.

Additional information about Lawrence Broxmeyer MD and his on-going research can be found at http://drbroxmeyer.netfirms.com/



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