Chapter 5: Cell Structure and FunctionIssues in Biology |
What could 4000-year-old mummies possibly have to do with Christmas Seals? As strange as it seems, tuberculosis (TB), is the connection. Some Egyptian mummies dating from about 2400 B.C. display symptoms of tuberculosis infection, a deadly disease that has plagued humans since that time. In the early 1900s, Christmas Seals were invented as a way to raise money for treating children who suffered from tuberculosis. Although tuberculosis has not been a major cause of death in the United States in the past 45 years, it remains a serious illness in the developing world. Perhaps of more concern, the World Health Organization warns that drug-resistant strains of TB present a serious, worldwide threat to human health.
Tuberculosis is caused by Mycobacterium tuberculosis, a bacterium first identified in 1882 by the great German microbiologist, Robert Koch. (Koch was awarded the 1905 Nobel Prize in medicine for this work.) The evidence of tuberculosis infection in Egyptian mummies indicates that this bacterium has been causing disease in human populations for more than 4000 years. At least 1 billion people have died from TB in the last 200 years alone, including many well-known individuals, such as Frederick Chopin, Robert Louis Stevenson, and Vivien Leigh. Currently, about one-third of the entire human population is infected with Mycobacterium tuberculosis. Although most of these people will not develop a full-blown case of TB, the disease will progress in about 8 million of these infected individuals to an active, infectious case of TB. About 3 million individuals will die this year as a consequence of the resulting damage to lungs or other organs.
A TB infection begins when a person inhales Mycobacterium tuberculosis cells that have been encapsulated in the microscopic particles produced when a person with full-blown TB coughs or sneezes. The particles are so tiny that they get carried deep into the lungs, reaching the tiny alveoli. Usually, the bacteria are engulfed and destroyed by cells of the immune system known as macrophages. In some cases the bacteria are not destroyed but remain inside the macrophage, slowly reproducing. When the macrophage eventually dies, large numbers of bacteria are released, stimulating another immune reaction that walls off the bacteria in hardened nodules known as tubercules, the structures that give the disease its name. There are very few living bacteria in these tubercules; consequently, although a tuberculosis infection is present, the individual does not pass on the infection to others. If the infected person’s immune system is weakened, the TB bacterium can begin to divide and multiply, eventually causing serious damage to the lungs. The patient begins to lose weight, to cough, has a fever, and becomes increasingly weak. These symptoms explain why TB was known for many years as "consumption," since the disease appears to consume its victims.
A revolution in treatment of tuberculosis and other bacterial infections occurred in the middle of this century. Before the 1940s, the best treatment for TB was to send the affected person to a sanitarium for bed rest and fresh air. For some, this treatment allowed the body to rally and fight off the bacteria. For most, though, it did little to stem the course of the infection. In 1944 Selman Waksman was able to isolate an antibiotic from a bacterium called Streptomyces griseus. Believe it or not, the bacterium itself originally came from a chicken coop! The antibiotic, streptomycin, proved to be effective in treating TB, but bacteria that were resistant to streptomycin appeared almost immediately. Consequently, additional antibiotics were developed and used in combined therapy to treat patients with TB. This combined approach actually provided an effective cure for TB!
Today, the standard treatment for TB is a combination of four antibiotics: isoniazid, rifampin, pyrazinamide, and ethambutol or streptomycin. Because each of these drugs targets a different enzyme or protein of the bacterium, it is unlikely that a strain can arise that is simultaneously resistant to all four antibiotics—provided the patient completes the entire 9 to 12 months of antibiotic treatment. This lengthy treatment is needed because Mycobacterium tuberculosis reproduces very slowly, dividing only once about every 20 days. Most antibiotics are effective only against actively growing and reproducing bacteria.
How is it that antibiotics are able to inhibit the growth of bacteria but usually have little effect on the cells of the human patient? Luckily for us, bacterial cells have fundamental differences from our own eukaryotic cells. Streptomycin, for example, targets bacterial ribosomes, thus inhibiting protein synthesis. Because eukaryotic ribosomes are slightly different, this drug is unable to bind to our ribosomes, thus protein synthesis in our cells continues in the presence of streptomycin. Many other antibiotics interfere with specific enzymes in the bacterium that are needed for cell wall production or other essential biochemical reactions. Examples of such antibiotics include penicillin, tetracycline, and vancomycin, as well as the anti-TB antibiotics, isoniazid, pyrazinamide, and ethambutol.
A serious concern is the advent of Mycobacterium tuberculosis strains that are resistant to the major antibiotics typically used for therapy. Multi-drug-resistant strains usually develop in individuals who do not complete their entire antibiotic therapy regime. After a few weeks or months of treatment, the patient feels much better—back to normal, in fact. During this time, the drugs have killed off normal bacteria, leaving only those few that have some degree of resistance to the antibiotics. If the patient stops taking the drugs prematurely, these resistant bacteria now can reproduce. Eventually, the growth of the bacteria cause the symptoms to return, but this time the standard drug cocktail is ineffective, and more toxic drugs must be used to control the infection. These drugs are also much more expensive, costing up to $250,000 for treatment of a single person! In the meantime, the individual may have passed the resistant strain to others. Such multi-drug-resistant bacteria have the potential to turn "conquered" foes such as TB and other bacterial infections into raging epidemics for which there are no effective treatments. It is ironic that, in our sophisticated age of computers and organ transplants, ancient scourges that have ravaged humans for thousands of years may return in new ferocity to once again claim billions of lives. Even more ironic is that our own cavalier attitudes toward bacteria and antibiotics will be the door through which these scourges emerge. Perhaps, next time you see a Christmas Seal, it will serve as a subtle reminder of these serious possibilities.