Discussing the disappearing miracle

Antibiotics are less than 100 years old. That means there are people alive today who were born when mothers and infants still died of childbed fever, or streptococcal infections. While the risk of infection remains, the use of antibiotics has almost completely eliminated the risk of death due to infection during childbirth.Likewise, before World War II, soldiers didn’t have to receive a mortal wound to die during war. Injuries and illnesses that we now treat with 5-10 days of antibiotics took the lives of soldiers, nurses, doctors, and civilians. In 1936, the son of president Franklin Delano Roosevelt lay on the edge of death, until an experimental treatment with the first commercially produced antibiotic wiped out the streptococcal infection in his body.

Prontosil would earn its discoverer, Gerhard Domagk, a Nobel Prize for Medicine in 1939. Penicillin, the first natural antibiotic (derived from the fungus Penicillium, found growing on a forgotten petri plate in the lab of Alexander Fleming where it inhibited microbial growth), became available in the 1940s. These miracle drugs helped wipe out the terrible scourges that had plagued mankind for centuries, including combating a disease so prevalent it had multiple names based on which symptoms manifested. Infection with Mycobacterium tuberculosis could cause consumption, or phthisis, as so many knew what we call simply TB. It could also cause terrible inflammation in lymph nodes and produce scrofula, creating a chronic mass in the neck that might eventually form a sinus and then an open wound. The introduction in 1946 of streptomycin, an antibiotic for tuberculosis, gave patients an option that wasn’t isolation or surgery to treat their disease. Today, however, streptomycin is no longer an option for TB patients. Though you will hear of patients with penicillin allergies, it is rarely, if ever prescribed. Instead, when doctors and pharmacists refer to penicillin allergies, they’re referring to the class of drugs derived from penicillin, drugs which are chemically similar in structure, but not identical. Allergies aren’t the issue, either. Resistance is.

Let’s address what these two mechanisms are so that you can understand the problem before us. Drug allergies occur when the patient taking a medication has an immunological response to the medication. The patient’s body has inappropriately formed antibodies against the drug (or, if the drug is too small, as with haptens, the body has antibodies against the protein produced when the drug binds to its receptor in the body). These antibodies then attack the body whenever the drug is present – no drug, no reaction. Every time the drug is given, the body overreacts, and every time is worse than the time before. The rule of thumb for allergies is simple: The first time is free, but the price you pay escalates every time after. Resistance, however, occurs within the bacteria, the organisms being targeted by the drug for elimination. All bacteria carry their basic genetic code within them, just like all humans do, and all cows, sheep, dogs, chickens, pigs, ducks, bugs, corn, grass, mushrooms, etc. In that way, we’re all alike. But bacteria have a means of packing extra information inside, little bonuses. These little bonuses are extra pieces of DNA called plasmids, and while they can be packaged in with the rest of the genetic code of the bacteria, they don’t have to be. They can be just tiny little circles of bonus features tucked inside, waiting to be shared. Plasmids carry things like fertility, which is sort of a misleading term, since bacteria don’t reproduce the way people do. All bacteria are clones – they just copy themselves and then bud off the copy, resulting in two identical cells from one. There’s no need for fertility for that. No, fertility plasmids allow a structure called a pili to be extended from one bacteria to another, and the one who sends the pili can then send a plasmid. Now the second bacterium has a plasmid for fertility, too.

Let’s make this a little easier to see. I’m going to rephrase this as an analogy, a story between Sue, Jim, and Sal. Even though all bacteria reproduce asexually and thus are called mother and daughter cells, we’re going to call our bacteria “Sue” ,“Jim”, and “Sal”. Sue is a very happy Streptococcus. She’s living life just like all her mother did and her sister and the mothers and sisters before her – synthesize DNA, transcribe DNA into RNA, translate the RNA into amino acids which assemble into peptides and fold into proteins that Sue can use to do everything Sue needs to survive. Good Sue.

Jim’s a peachy keen Escherichia. He has no idea he smells bad (and poor guy, he reeks). He just goes through life, just like Sue, just like his mother and his sisters, synthesizing DNA, transcribing it, translating it, using his proteins… As Jim happens to be carried past Sue by the current today, Sue’s proteins have made a pili. In and amongst her DNA is a plasmid for pili, and that’s one of the ones she’s expressing. It brushes against Jim, and the two cells connect. As soon as that happens, Streptococcus Sue’s plasmid starts to travel down her pili to Escherichia Jim’s cell. It doesn’t matter that they’re different kinds of cells. She’s got a pili and she’s got a plasmid, and bacteria love to share. The current didn’t stop, of course, and the connection was always tenuous, so it’s not long at all before the pili breaks loose. Sue goes back to drifting along. She’ll probably make contact with some of Jim’s siblings, and her siblings will probably make contact with Jim – bacteria love to share, and they don’t like to be alone.

By the end, Sue’s plasmid has made it not just to Jim but probably to several of his siblings, but we’re going to leave poor Sue behind. Jim finds his new plasmid and plugs it in. This is nifty stuff. Now he can make a pili, too! He practices. As he’s drifting along in the current, extending his new pili, Jim encounters Sal, the Salmonella (Yeah, yeah, on the nose, whatever). Sal also has a pili, but Sal has a different kind of plasmid to share with his pili plasmid. Sal knows how to fight off sulfa-antibiotics. Bacteria like to share. Sal shares this plasmid, this resistance to sulfa-drugs, with Jim, with all of Jim’s siblings, and now, every bacteria Jim encounters will also gain resistance to sulfa antibiotics.

It didn’t matter that Jim and Sal were different kinds of bacteria, or even that Jim didn’t care about Sulfa antibiotics. Jim is a bacteria, and Bacteria Share. In the 90 years since penicillin was discovered, bacteria have shared resistance to it so extensively that it is largely useless. In the 70 years since streptomycin’s introduction, bacteria have shared resistance to it so extensively that it is largely useless. Bacteria Share. They share with every bacteria, and they do it faster than we can fight them, faster than we can find new drugs, terrifyingly fast. But that’s not why we may lose the single greatest weapon we’ve had in the war on disease in the past century. If all we were fighting was the fact that Bacteria Share, we could deal with that. The bigger issue comes when you and I help the bacteria. Stay tuned for “SuperChickens?”, “Quitting when you’re not really ahead”, and “No, the Z-Pack won’t treat the Flu”.