Old Cures For New Times

It started as a little tickle in the throat, with just the occasional sneeze, or two. It built gradually to an irritating cough that burned her throat each time another spasm took hold. Then the fever kicked in, and the chills, and the Earth's gravity turned up about three notches. Everything felt so heavy she thought she had better go to bed and stay there. The next morning after a restless sleep, she knew that she was really sick, get to the doctor now sick, so she called her MD's office, only to find that they couldn't fit her in. It seemed everyone else in town had come down with this bug too. The receptionist told her not to bother going to the emergency room either. They'd be full up as well, and worse, full of people who were probably sicker than she was. She asked if they could phone in a prescription to her pharmacy, an antibiotic to knock the infection down to size. The receptionist replied that she'd have the nurse phone some time that day.

During an interminable wait, she got sicker and sicker, which surprised her, because she didn't think that was possible. She turned on the TV, hoping to give herself some mental relief, distract herself from her misery. Flipping from channel to channel, she finally settled on a news station, figuring she might as well get caught up with what was going on in the world. What she saw shocked and scared her. They were talking about this bug she had caught as if it were a real news story. Half the country had come down with it, and it was still spreading. Worse, it wasn't responding to treatment. People were dying. None of the antibiotics that should have been working were having any effect. None. Whatever new mutation had brought this thing into being had made it completely immune to the defenses of man. All those years of over-prescribed antibiotics, all that pill popping, "just in case," had finally caught up with medical industry. So few new antibiotics had come out in the last few years, and most of them were simply modifications on the old formulas. They had no way to stop this thing.

Okay, melodrama over. My husband has a work emergency tonight, so I have extra time on my hands. I was just setting you up for the question: Do we have any defenses against antibiotic-resistant bacteria? It's true that very few new antibiotics are finding their way to market. The expense of R&D, coupled with a truckload of regulations are making real breakthroughs more and more rare. Bacteria are getting more resistant, too. Between half-finished prescriptions (stopped when the patient feels better, and not when the infection is really dead), antibiotics prescribed at a patient's insistence (rather than actual need), and disinfectants that kill "most" of the germs they target, what we are doing is making sure the strong survive. The bacteria that come away from the battle with our modern miracles alive, do so because they had some bit of resistance the other bugs didn't, resistance that they pass on to their offspring, who pass it on to the next generation, and so on, until what used to be an easy illness to beat, when antibiotics were the new miracle on the block, is defying treatment and demanding new approaches.

Well, sort of new approaches. Actually, one of them isn't new at all, but has been around at least as long as antibiotics. Daria Vaisman writes at Slate.com about bacteriophages. What are they? According to Vaisman, they are bugs that eat bugs, and were themselves hailed as a breakthrough until antibiotics took some of the effort out of fighting bacteria:

Bacteriophages are viruses found virtually everywhere—from soil to seawater to your intestines—that kill specific, infection-causing bacteria. In the United States, the drug company Eli Lilly marketed phages for abscesses and respiratory infections. (Sinclair Lewis' Pulitzer-winning Arrowsmith is about a doctor who uses phages to prevent a diphtheria epidemic.) But by the 1940s, American scientists stopped working with phages for treatment because they no longer had reason to. Penicillin, discovered by the Scottish bacteriologist Alexander Fleming in 1928, had become widely available thanks to synthetic production and zapped infections without the expertise needed for finicky phages.

American doctors shouldn't have given up on phages altogether. They are flexible little guys. Apparently, just as bacteria mutate, so can the phages. It takes expertise to lead them in the right direction, but Vaisman says that with that expertise, new batches of phages can be grown to meet the challenge of keeping up with the changing bacteria. A sort of "if you build them, they will eat" scenario. Just as scientists come up with a new flu vaccine each year, to meet the demands of mutating flu viruses, new phages can be developed quickly, unlike antibiotics, which take many years, and many millions of dollars to produce.

As the article in Slate continues, Vaisman discusses the work being done at "...Eliava phage research institute, which Stalin helped set up in Tbilisi in 1923, the treatment center offers personalized cures for a host of infections the United States says it can no longer do anything about." You read it right; after antibiotics were all the rage here in the west, phages were still a cheaper alternative, and continued to be used in the former Soviet Union. (Wow, something Stalin did that has endured in a positive way. Who'da thunk it?) Work on phages is still going on there:

The word phage comes from the Greek "to eat." A phage contains genetic material that gets injected into a virus's host. Whereas "bad" viruses infect healthy cells, phages target specific bacteria that then explode. At Eliava, phages are produced as a liquid that can be drunk or injected intravenously, as pills, or as phage-containing patches for wounds. Though few published articles in Western journals report positive clinical trials—most of the recent long-term research on phages comes out of the Soviet Union—some Western scientists say that phages are safe and that they work.

Vaisman says that the treatment center in the former Soviet Georgia takes on cases of infection on which western doctors have given up. She points out that phages were repeatedly shown to be effective at stopping infection in Soviet clinical trials. Georgia has gone into the "medical tourist" business, gaining patients from western countries, where such treatments are less available:

So, why do American patients need to go to all the way to Georgia for treatment? For starters, in their natural state phages are hard to patent, the route by which drug companies lock up future profits. The first company to spend millions of dollars to prove that a particular phage is safe could allow its competitors to capitalize on the results. As important is the difficulty of regulation. There are two ways that phages are currently used in the former Soviet Union, and both pose problems from the point of view of the Food and Drug Administration. At the Tbilisi phage center, phages are personalized: You send your bacterial sample to the lab, and it's either matched up with an existing phage or a phage is cultured just for you. In the United States, by contrast, drugs are mass produced, which makes it easier for the FDA to regulate them.

Phages are also sold over-the-counter in Georgia. People take the popular mixture biobacteriophage, for example, to fight off common infections including staph and strep. These phage mixtures are updated regularly so they can attack newly emerging bacterial strains. In the United States, the FDA would want the phages in each new concoction to be gene sequenced, because regulations require every component of a drug to be identified. To do so would entail prohibitively expensive and lengthy clinical trials.

Leave it to regulation to be a blessing and a curse. Regulations do protect us. Vaisman reports that early bacteriophages killed more people than they cured. The sources for the phages were dirty water. For example, the first phage found came from the Ganges river. There are other dangers, too, for those who don't know what they're doing. Regulations do protect us to a degree from some of the risks inherent to medical research. However, there's the flip side of regulation as well, the side that makes everything prohibitavely expensive, and take a lot of time--the side that makes it impossible to put out a phage cocktail, because the FDA would require gene sequencing that would possibly make the phage obsolete before it came out of clinical trials.

There are workarounds for some of the FDA issues, and there are companies venturing into this arena here in the States, looking to find ways to make phage production a viable alternative to antibiotics. There are agricultural applications as well, that don't have the FDA restrictions. However, options for the widespread use of phages to fight infection here at home, especially as over the counter remedies, are pretty dim at this point. Georgia may be the best option for a while, so that "medical tourism" thing could really take off, for patients wealthy enough to travel the globe in search of a cure for what ails them. On the other hand, I'm betting that if we did see some major outbreak of antibiotic-resistant bacteria, phages would start looking a lot more feasible in a hurry. Regulations serve their purpose, but if any serious percentage of the population became ill with something our doctors couldn't fight, those regulations would become a whole lot less attractive, even to the regulators, especially if they have children. It's comforting to know that there are other options out there, even if the world would have to look like a made-for-TV disaster movie before they were given the nod. I simply have to believe that even bureaucrats aren't so dense as to watch the country die of some horrible disease because they didn't have gene sequencing data available on the cure yet. The Pollyanna in me insists on having hope.

Just so you know. The girl in our story which introduced us to this topic is fine. She recovered after a couple of weeks in bed, and got a big raise when she went back to work, because her bosses discovered they couldn't get along without her. She also finally made it into her doctor's office, and when she filled out her prescription for a cough suppressant, she met a wonderful young pharmacist who asked her out to dinner. They had a lovely time. (Since I made it up, I get to make it a happy ending. The Pollyanna in me likes a happy ending. My husband says I'm going through a phage.)

Note: If you're interested in the topic of antibiotic-resistant bacteria, and the obstacles to developing new drugs, here's an article at TCS Daily by Dr. Henry Miller. It's not particularly cheerful, but it's informative.