From my perspective there are two kinds of science literacy for non-scientists. The first involves answers to simple questions about the Universe, like “Why is the sky blue?” or “Where do trees get their mass?” The second type of science literacy involves understanding scientific concepts that can be critical to our functioning in modern society, such as understanding observer bias. Very recently I was confronted with a personal failure in my science literacy that added more fear to an already terrifying situation.
Over the course of three days, my son developed an infection that required hospitalization and two surgical procedures. All in all we were in the hospital for eight days – add those original three days and my wife and I had a disturbing week and a half (I won’t speak for my son’s personal experience). Without the last one hundred years of medical advancements in the areas of antibiotics and microsurgery my seven year old would have certainly died. The same would be true if instead of a first world country we lived in a place without access to modern medical care. (I would like to pause here to thank the incredible staff at the University of New Mexico Children’s Hospital, who provided Xavier with the best of care, both medically and emotionally.) I don’t point out that he would have died to be melodramatic, but to emphasize a simple fact: it is only because of medical science that my son is alive today. It is ironic that we were in the hospital (and mostly recovered) on the day of the March for Science, which is when we took the picture at the top of this page.
The reason hospitalization was necessary was because my son’s infection was not responding to antibiotics, but at the same time the doctors were confident that it wasn’t a superbug (an antibiotic-resistant bacteria that brings forth warranted apocalyptic warnings from the medical community). How could it be that a bacterial infection would not respond to antibiotics and not be antibiotic-resistant? The doctors explained to me that some antibiotics only treat certain kinds of infections.
I’ve openly stated in the past that I am not a biologist, and at the time I didn’t understand how an antibiotic might work on one type of bacteria and not another. Suddenly it became very important for me to understand how antibiotics work. This interest went far beyond scientific curiosity and instead spoke to my responsibility as a parent; I was unable to understand what was happening to my son without understanding antibiotics. My lack of knowledge was breeding fear inside me, which was unacceptable and entirely avoidable. You might one day find yourself in a similar situation, though I hope you never do. In that case, and for our general science literacy, let’s learn some biology.
So, how do antibiotics work?
Louis Pasteur (1822-1895), commonly referred to as the “father of microbiology”, remarked that various types of microorganisms “antagonized” one another. What Pasteur observed was essentially a competition for survival on the microscopic scale; some microorganisms appeared to have a defense against other types of microorganisms. Pasteur noted that if that defense mechanism could be identified and harnessed, a great many diseases that were (at the time) fatal could perhaps be conquered. It wasn’t until 1928 when Alexander Fleming identified penicillin that significant progress was made toward realizing Pasteur’s prophecy.
Certain types of mold (which is one type of microorganism) produce a chemical that kills various types of bacteria (another type of microorganism). This allows the mold to spread into an environment without direct conflict with bacteria that are vying for the same resources. Essentially, mold engages in aggressive chemical warfare with bacteria on the microscopic level. Fleming was the first to identify this chemical and named it penicillin, after the common food mold penicillium where he first observed the antibacterial behavior. Not being a chemist, Fleming failed in his attempts to actually isolate penicillin for medical use. This was accomplished by biochemists Ernst Chain and Howard Florey in 1942 when they successfully purified Penicillin G, the world’s first intravenous antibiotic. The culturing of penicillin was not easy or efficient, so the drug saw very little use outside the Allied military during World War II. In 1945 Norman Heatley, a biochemist at Oxford University, developed a technique to successfully produce pure penicillin in bulk, and modern medicine was radically transformed after the War.
How is it that penicillin kills bacteria while not destroying other cells, notably the mold cells that produce it? All antibiotics work by targeting some feature that bacteria possess that “normal” cells don’t. The cells in our bodies are specialized and function as part of a larger organism, whereas bacteria are single celled complete organisms. A bacteria’s single cell must function entirely on its own, meaning it must be different in some respects from cells that make up multicellular organisms like mold or animals. Antibiotics attack these differences.
Bacteria are the simplest organisms known, and exist in every ecosystem on earth, from the desert to radioactive waste containers. Bacteria are sacks of cytoplasm, a gelatinous liquid that contains the cell’s organelles – the specialized components within the cell that are most comparable to our organs. This cytoplasm is contained within a wall called a bacterial cell envelope. Most antibiotics work by either preventing the bacteria from reproducing (a bacteriostat) or by destroying the cell envelope (a bactericide). If the cell envelope is destroyed then there is nothing holding the cell together and the cytoplasm dissipates to be absorbed by the host body (whoever or whatever is infected by the bacteria). Penicillin is a potent bactericide that works in just this way.
Our skin is constantly being regenerated. The outer surface of our skin dies and flakes off (which is where a lot of the dust in our homes comes from), while the deepest layer of our skin is constantly being grown by our bodies. This regeneration process continues throughout our entire lives. Our skin protects us from hazards and is sacrificial in this regard. Bacteria do much the same thing; their cell envelopes are constantly being dissolved and reformed. The key difference is that our skin is a few millimeters thick and composed of countless individual cells, whereas a bacteria’s cell wall is at most a few tens of nanometers thick, or about 0.00001 millimeters, and is composed of short chains of molecules. At that scale, if something goes wrong with the regeneration of the cell envelope then there is no further line of defense for the bacteria.
Bacteria contain a number of enzymes to perform specialized tasks. Enzymes are chemical structures that enable or trigger other chemical reactions. In this case, two particular enzymes are responsible for rebuilding the bacteria’s cell envelope. The first dissolves the cell envelope, recovering the building material for reuse. The second enzyme reconstructs the cell envelope, providing a fresh coat of paint to the bacteria.
Keep in mind that a bacteria has no mouth, instead it absorbs nutrients through osmosis. The cell envelope is constructed so that certain chemicals can penetrate it; this is a necessity for the bacteria to survive. It’s the same way our lungs have to let in air to supply our bodies with oxygen, and can’t stop poison gas from getting in without suffocating us. Penicillin enters the bacteria through the cell envelope and prevents the builder enzyme from functioning properly; the bacteria has no choice but to let the penicillin in. Thanks to the penicillin the builder enzyme stops working while the dissolving enzyme continues to function – the bacteria essentially eats its own skin off until it dies. Penicillin doesn’t kill us because our cells are built differently. We don’t have the same enzymes destroying and rebuilding our cells.
But what happens if the penicillin can’t get through the cell envelope to interfere with the builder enzyme? To return to our metaphor about poisoned air, what if the bacteria is wearing a gas mask?
In 1884, Hans Christian Gram developed a simple test for distinguishing between two major classes of bacteria. The test attempts to stain bacteria with a dye. Whether or not the stain adheres to the bacteria indicates something key about the structure of the cell envelope. The two classes of bacteria came to be known as Gram-positive (bacteria which are stained by Gram’s test) and Gram-negative. When my son’s doctors cultured the bacteria that was causing his infection it turned out to be Gram-negative.
Gram-negative bacteria have an additional outer cell wall. The cell envelope of a Gram-positive bacteria is essentially an inner wall of a Gram-negative bacteria. As a result it is much harder (if not impossible) for traditional antibiotics to penetrate Gram-negative bacteria and interfere with the builder enzyme. The bacterial outer membrane is itself also a problem because it often contains chemical structures called endotoxins that produce strong immune responses in animals, which can lead to swelling and toxic shock.
The outer cell membrane contains porins, which you may have guessed from the name act like the pores in our skin. Porins are chemical structures shaped like short tubes that allow certain types of molecules through – the key words being “certain types.” These porins are the metaphorical gas mask filters and keep many types of antibiotics from entering the bacteria. In order to kill Gram-negative bacteria an antibiotic is needed that can slip through the porin and enter the cell.
Ampicillin was discovered in 1958 and was the first “broad spectrum antibiotic,” meaning it could tackle a wide range of bacterial infections. It works against a lot of nasty bugs, both Gram-positive and negative, and the World Health Organization considers it an essential medicine to have in any national health program. Essentially penicillin with an additional chemical (amino) group attached, Ampicillin is able to penetrate the outer membrane of Gram-negative bacteria thanks to the extra amino. Once inside it functions the same as penicillin to inhibit the builder enzyme.
When we’re is school we sometimes wonder when science or math will ever be important to us. If someone isn’t planning a career in the sciences, what good is it to know anything about them? Rather than wax philosophical, today I will appeal to your base drive to survive. Yes, my son’s doctors knew what they were dealing with far more than I ever will. But when your child is sick and you don’t understand the most basic facts about his or her treatment, then you either educate yourself or add undue fear to an already scary situation. I can testify that a bacterial infection can strike and escalate quickly. Before you find yourself in the situation I was in, wouldn’t it be nice to improve your science literacy? We can do it together.