Viruses
When I was a kid...

one of my favorite rides at Disneyland (other than the Matterhorn) was Monsanto’s Adventures Thru Inner Space. In it, you boarded a vehicle which pretended to gradually shrink you down to the size of molecules. I’m not the only one who remembers it fondly; some guy on the Internet has actually re-created the ride using computer animation and sells it as a download.

Update: Did you know that is article is one of the most common reasons worldwide why people come to our site? I have updated the content for all you far-flung web visitors.  

My Internet research also informed me that since the ride was free, most of the people on it were teenagers looking for a place to make out. Well, that and the occasional science nerd like me.

An adventure through biological inner space would be a great ride. My idea is to take a TV talking head news person, and go up his nose. This might explain, on a molecular level, why antibiotics don’t kill viruses.

As we shrink in size, the droning sound of our talking head interviewing a guest will become louder, but earplugs can take care of that. When we are about 1/8th of an inch, we can easily fit up his nose and see those huge nostril hairs. As we shrink down further, we see the tissue on the inside of the nose is not a smooth uniform sheet but is actually made up of thousands of cells in tight approximation. Continuing to shrink, we find ourselves the size of one of these cells lining his nose. This cell is the target for common cold viruses.

At this level of magnification, we can see bacteria sitting on the cells as well. There are dozens of bacteria, sitting on the outside of the cell, but they are mostly innocent bystanders. Some swim around in the nasal mucous with a whip-like tail, others just wriggle in place. Some are friendly, and by being present they prevent bad bacteria from living up there.

The good bacteria in our talking head’s nose are alive. They move, they divide in two. They eat sugar and give off gas. If you spray them with an antibiotic, they might just keel over and die.

As we shrink, we notice something interesting about the cells lining the nose. Although some look perfectly normal, some look abnormal. One appears broken open. We can’t yet see why, but it has definitely split apart.

Once we shrink down small enough to get inside the cell we see why. There are thousands of tiny particles streaming out of the cell. These are viruses.

Scientists sometimes debate the question of whether viruses are alive or not. Well, they are not alive. This is plainly obvious as we shrink down to the size of a virus. Cells are a hundred times bigger than a bacterium (bacterium = one bacteria), and a bacterium is a thousand times bigger than a virus. If you are down to that size, you are not alive. Why?

If we could feel the signs of life coming froWhy don't antibiotics kill virusesm a human cell or a bacterium, if biochemical processes made a humming noise like the engines on space ships in science fiction movies, then human cells would be humming, as would bacteria. There are all sorts of chemical reactions going on inside. Energy is being consumed, things are happening. But the viruses would appear as cold, dead, inactive objects. They don’t move, they don’t show any signs of life. They are not eating or breathing. There are no chemical reactions taking place.

Antibiotics kill bacteria by targeting their life processes. The goal in developing antibiotics is to find substances which disrupt the chemical reactions of life for bacteria but don’t harm human cells. For example, penicillin blocks the formation of bacteria cell walls, but does not affect human cells because we have cell membranes, not cell walls. Ciprofloxacin makes it impossible for bacterial DNA to divide, but it has no effect on human DNA.

But if no life is going on, if no chemical processes are underway, then an antibiotic cannot do anything.

Human viruses, like their computer cousins, are simply a set of instructions written in DNA or RNA instead of computer code, surrounded by a protective protein covering. A virus is engineered to attach to a cell and then squirt a short strand of DNA or RNA into the cell. Sometimes, a virus is packaged with one or two chemicals to help it get in and out of cells or to make copies of its DNA.

Being inside the cell is like making it past airport security. In theory, everyone has been screened and everyone should be a good guy, so the human cell does not really have much in the way of immunity to protect itself against foreign and evil DNA. It assumes any DNA it sees is its own. The human body is very good at attacking things which are outside cells, but not so good once they get inside a single cell.

The human cell takes the DNA from the virus and starts following the instructions on it. Instead of making nose mucous, which might be your job if you are a cell lining a nose, you stop doing that and start following the new instructions given to you by the virus. Those new instructions, not surprisingly, tell the cell to start making more copies of the virus. So the cell now devotes all its energy to making viruses. Soon, the cell is full of hundreds, if not thousands of virus particles and it bursts open. These viruses, in turn, go to attack other cells.

You can’t kill a virus because it is already dead

When viruses are out in the open, the body’s immune system soon recognizes them and will destroy them. Viruses are pretty defenseless just floating out there. They are inert, inactive, and can’t run away. If we want to get rid of a viral infection, antibiotics don’t do anything because antibiotics target biological processes in living organisms and viruses are not living.

A better approach is a vaccine. This is a shot form of millions of killed virus particles (or parts of them). The body sees this and gears up the immune system. When the real virus comes along, we know what it looks like and are ready to destroy it before it can start infecting cells.

Another method to combat viruses are drugs which target the virus directly. We call these drugs “antiviral” drugs to distinguish them from the antibiotics that work on bacteria. For example, the flu virus is good at getting inside cells and forcing the cell to make lots of copies of the virus, but the flu virus particles have a hard time breaking out of the cell. Instead of filling up the cell and bursting it open, each flu virus forms a tiny bud and pushes through the cell membrane, one at a time. In order to accomplish this task, it  carries a special enzyme called neuraminidase, which sits on the outside of the virus. The job of this enzyme is to punch a hole in the human cell membrane. Tamiflu is an anti-viral drug which blocks neuraminidase. By latching on to the neuraminidase molecule, the smaller Tamiflu molecule prevents the virus from detaching itself from the cell it has infected. This is how it works against influenza. Obviously, you need a virus with this exact biological behavior to be a target for Tamiflu. That is why Tamiflu won’t work against a cold or stomach flu—these viruses don’t bud out of cells and they don’t have neuraminidase molecules on their surface.

Flu viruses are named by the type of neuraminidase they have, they are numbered N1 to N9, and also by one other enzyme they carry, called hemagglutinin. Hemagglutinin also sits on the outside of the virus and allows it to attach to new cells. The first 3 of the 16 types of hemagglutinin easily infect humans. So one virus might be named H1N1, and another H5N1. The “H5” indicates the fifth type of hemagglutinin, and also, by being numbered greater than 3, is a type that does not (yet) easily infect humans. H5N1  is bird flu.

Why don't antibiotics kill virusesAnyway, back on our ride through our talking head’s nose. We see that many of the cells lining his nose are infected with rhinovirus, the most frequent cause of the common cold. An azithromycin (Z-Pak) molecule floats by, prescribed unnecessarily by a doctor. Azithromycin is a specialized molecule which gets inside a bacteria and finds the spot where the bacteria makes protein. Azithromycin needs an active, living, metabolizing bacterium to do its job. Once inside, azithromycin binds to the protein-making machinery of the bacteria (which is sufficiently different from our own that the drug is not harmful to our cells) and it kills the bacterium by preventing protein production. The bacteria cannot make anything, it cannot do anything new, and gradually dies. The azithromycin molecules are busy killing off innocent bacteria that normally live in the nose. “I’m innocent!” they scream, but the azithromycin does not know good from evil. It kills all bacteria in its path. Meanwhile, the viral infection goes on unimpeded. The virus makes no protein on its own and cannot be harmed by the Z-Pak. Of course, we kill off a few people every year with a Z-pack prescription, a point I try to make when patients are demanding unnecessary antibiotics. (Don’t trust me, Google it: “Do Z-Paks kill people?”)

We see that the nose has lost thousands of cells. They’ve all been converted to common cold virus production houses. When the cell is full of copies of this virus, it explodes, alien-like, and thousands of new virus particles burst forth. When our patient sneezes, many virus particles shoot out his nose and into the atmosphere.

Soon, his immune system begins to recognize that these virus particles are a foreign invader and they gobble them up. Then new healthy cells need to grow back to line his nose. This takes a few days and accounts for the long recovery period from many viral infections. Long after we are no longer contagious, we feel lousy because new cells must be made to replace those lost in the viral infection.

Why do doctors so commonly prescribe antibiotics for viruses when they do absolutely nothing and might make people worse? It’s all about doctors being busy, making patients happy, and not getting sued. A typical primary care physician is so rushed during his day that his main goal is to see people as quickly as possible. If a patient has an expectation of receiving an antibiotic, it takes much longer to explain why an antibiotic is not necessary than to just write the prescription. If insurance companies paid doctors an extra $100 for not prescribing antibiotics for viral infections, then the practice would drop off sharply. However, a visit for bronchitis generally pays the same—antibiotics or not—and an extra 10 minutes of discussion generates no added revenue.

The second problem is patient satisfaction. Every physician on the planet has seen the angry, arms folded, sour-faced posture of a patient who hears that he or she is not going to get an antibiotic. Patients feel they are not being taken seriously. They think that somehow a bacterial infection means something is “really wrong” but a viral one means “the doctor said there was nothing wrong with me.” Tell that to a guy hospitalized with viral pneumonia! And by the way, AIDS, hepatitis, bird flu, chicken pox, Ebola, and SARS are all viruses. Influenza kills more old people than strep throat.

But in any event, doctors want their patients to be happy. You can turn a frown into a smile with antibiotics. Every doctor has done this, even the purists among us.

The third reason for unnecessary antibiotic prescribing is lawsuits. The fact is that it can be hard to tell the difference between bronchitis and an early pneumonia. Should we get a chest X-ray on everyone with a cough? Clearly, that is not good medicine. Anyway, the x-ray sometimes lags behind clinical symptoms. Most sinusitis is not bacterial, but sometimes it is. Should we do a needle aspiration of the sinus on all patients? The doctor who prescribes an antibiotic unnecessarily, when there is at least some plausible reason for doing so, is unlikely to be sued successfully if the patient does poorly. But Heaven help the doctor who, using his best judgment, does the right thing and avoids an antibiotic. One in a hundred will turn out to have a bacterial infection. No legal harm in writing 100 or 200 unnecessary antibiotic prescriptions, but many physicians feel they will be crucified for missing that one person who might’ve benefited from an antibiotic a day or two earlier.

If you are seeing a physician who wants to prescribe an antibiotic, you can get much better care by saying, “Doc, do I really need this? I don’t want to take antibiotics unless it’s really necessary. Would you take this antibiotic if this were you?” If patients did this, who knows, doctors might reply by saying, “I actually think this is likely to be a virus. Why don’t we wait a day or two and see.” Or a physician might say, “Sir, the red streaks going up your arm and the fever of 104 tells me this is bacterial!”

In my practice, I treat patients how I would treat myself or my own family. I personally would never take an antibiotic for the various types of viral crud that goes around all winter. It will just give me diarrhea and make me prone to a real bacterial infection. However, my mother demands an antibiotic, and so if patients are adamant, I offer my best opinion, but I won’t withhold antibiotics if patients insist and there is at least some plausible rationale for prescribing.

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