Those Resilient Germs​—How They Rebound

VIRUSES, bacteria, protozoans, fungi, and other microorganisms have evidently been around since life on earth began. The stunning flexibility of these germs, the simplest of all creatures, has allowed them to survive where nothing else can. They are found in scalding vents on the ocean floor as well as in the freezing waters of the Arctic. Now these germs are repelling the most concentrated of all assaults on their existence​—antimicrobial drugs.

A hundred years ago, some microbes, or microorganisms, were known to cause illness, but no one then living had heard of antimicrobial medicines. So if a person came down with a serious infectious disease, many doctors had little to offer in the way of treatment except moral support. The person’s immune system had to fight off the infection on its own. If the immune system wasn’t strong enough, the consequence was often tragic. Even a minor scratch infected by a microbe all too often led to death.

Thus, the discovery of the first safe antimicrobial drugs​—antibiotics—​revolutionized medicine.a The medical use of sulfa drugs in the 1930’s and of such drugs as penicillin and streptomycin in the 1940’s led to a flood of discoveries in succeeding decades. By the 1990’s, the antibiotic armory had come to include some 150 compounds in 15 different categories.

Anticipation of Victory Smashed

By the 1950’s and 1960’s, some people had begun to celebrate victory over infectious diseases. Some microbiologists even believed that these diseases would soon be a nightmare of the past. In 1969 the U.S. surgeon general testified before Congress that humanity might soon “close the book on infectious disease.” In 1972, Nobel laureate Macfarlane Burnet along with David White wrote: “The most likely forecast about the future of infectious disease is that it will be very dull.” Indeed, some felt that such diseases might be eliminated altogether.

The belief that infectious diseases had, in effect, been defeated resulted in widespread overconfidence. One nurse who was familiar with the dire threat that germs posed before the introduction of antibiotics noted that some younger nurses had become lax in simple hygiene. When she reminded them to wash their hands, they would retort: “Don’t worry, we have antibiotics now.”

Yet, dependence on antibiotics and their overuse have had disastrous consequences. Infectious diseases have persisted. More than that, they have roared back to become the leading cause of death in the world! Other factors that have also contributed to the spread of infectious diseases include the chaos of warfare, widespread malnutrition in developing countries, lack of clean water, poor sanitation, rapid international travel, and global climate change.

Bacterial Resistance

The astounding resilience of everyday germs has proved a major problem, one not generally anticipated. Yet, in hindsight, that germs would develop immunity to drugs should have been anticipated. Why? Consider, for example, something related that happened with the introduction of the insecticide DDT in the mid-1940’s.b At that time dairymen rejoiced as flies essentially disappeared with the spraying of DDT. But a few flies survived, and their offspring inherited immunity to DDT. Soon these flies, unaffected by DDT, multiplied in vast numbers.

Even before DDT was used, and before penicillin became commercially available in 1944, harmful bacteria gave foregleams of their prodigious defensive weaponry. Dr. Alexander Fleming, penicillin’s discoverer, became aware of this. In his laboratory he watched as succeeding generations of Staphylococcus aureus (hospital staph) developed cell walls increasingly impervious to the drug that he had discovered.

This led Dr. Fleming to warn some 60 years ago that harmful bacteria in an infected person could develop resistance to penicillin. So if doses of penicillin did not kill sufficient numbers of the harmful bacteria, their resistant offspring would multiply. As a result, there would be a rebound of the disease that penicillin could not cure.

The book The Antibiotic Paradox comments: “Fleming’s predictions were borne out in a more devastating way than even he surmised.” How so? Well, it was learned that in some strains of bacteria, the genes​—the tiny blueprints in a bacterium’s DNA—​produce enzymes that make penicillin ineffective. As a result, even extensive courses of penicillin often prove useless. What a shock this was!

In an attempt to win the battle against infectious diseases, new antibiotics were regularly introduced into medicine from the 1940’s through the 1970’s, as well as a few during the 1980’s and the 1990’s. These could treat bacteria that defied earlier drugs. But within a few years, strains of bacteria surfaced that defied these new drugs as well.

Humans have come to learn that bacterial resistance is astonishingly ingenious. Bacteria have the ability to change their cell wall to keep the antibiotic out or to alter their own chemistry so that the antibiotic cannot kill them. On the other hand, the bacteria may pump the antibiotic out as fast as it enters, or the bacteria may simply render the antibiotic ineffectual by taking it apart.

As the use of antibiotics has increased, resistant strains of bacteria have multiplied and spread. A total disaster? No, at least not in most cases. If one antibiotic doesn’t work for a particular infection, another usually does. Resistance has been a nuisance, but until recently it has usually been manageable.

Multidrug Resistance

Then, to their horror, medical scientists learned that bacteria exchange genes among themselves. At first it was thought that only bacteria of the same type could exchange genes. But later the very same resistance genes were discovered in completely different types of bacteria. By means of such exchanges, bacteria of various types have accumulated resistance to many different commonly used drugs.

As if all of this were not enough, studies in the 1990’s showed that some bacteria can become drug resistant on their own. Even in the presence of only one antibiotic, some kinds of bacteria develop resistance to multiple antibiotics, both natural and synthetic.

A Foreboding Future

Although most antibiotics today still work in the majority of people, how effective will such drugs be in the future? The Antibiotic Paradox observes: “We can no longer expect that any infection will be cured by the first antibiotic chosen.” The book adds: “In some parts of the world, limited supplies of antibiotics mean that no available antibiotic is effective. . . . Patients are suffering and dying from diseases that some predicted 50 years ago would be wiped off the face of the earth.”

Bacteria are not the only germs that have become resistant to drugs used in medicine. Viruses as well as fungi and other tiny parasites have also shown amazing adaptability, offering the world strains that threaten to nullify all the efforts invested to discover and produce the drugs that fight them.

What, then, can be done? Can resistance be eliminated or at least contained? How can the victories won by antibiotics and other antimicrobials be preserved in a world increasingly beset by infectious diseases?

[Footnotes]

[Box/Picture on page 6]

What Are Antimicrobials?

The antibiotic given you by a doctor falls into a class of medicines called antimicrobials. These come under the general heading “chemotherapy,” which refers to the treatment of disease with chemicals. While the term “chemotherapy” is often used in connection with treating cancer, it originally applied​—and still does—​to the treatment of infectious diseases. In such cases it is called antimicrobial chemotherapy.

Microbes, or microorganisms, are tiny organisms that can be seen only with the help of a microscope. Antimicrobials are chemicals that act against microbes that cause illness. Unfortunately, antimicrobials can also act against microbes that are beneficial.

In 1941, Selman Waksman, codiscoverer of streptomycin, applied the term “antibiotic” to antibacterials that come from microorganisms. Antibiotics as well as other antimicrobials used in medical treatment are valuable because of what is called selective toxicity. This means that they can poison germs without seriously poisoning you.

Actually, however, all antibiotics are at least somewhat poisonous to us too. The margin of safety between the dosage that will affect the germs and the dosage that will harm us is called the therapeutic index. The larger the index, the safer the drug; the smaller, the more dangerous. In fact, thousands of antibiotic substances have been found, but most are not useful in medicine because of being too toxic to people or to animals.

The first natural antibiotic that could be used internally was penicillin, which came from a mold called Penicillium notatum. Penicillin was employed intravenously for the first time in 1941. Shortly thereafter, in 1943, streptomycin was isolated from Streptomyces griseus, a soil bacteria. In time, scores of additional antibiotics were developed, both those that are derived from living things and those that are made synthetically. Yet, bacteria have developed ways of resisting many of these antibiotics, causing a global medical problem.

[Picture]

The penicillin mold colony seen at the bottom of the dish inhibits the growth of the bacteria

[Credit Line]

Christine L. Case/Skyline College

[Box/Pictures on page 7]

Kinds of Germs

Viruses are the tiniest germs. They are the cause of common illnesses such as colds, flu, and sore throats. Viruses also cause terrible diseases such as polio, Ebola, and AIDS.

Bacteria are one-celled organisms so simple that they lack a nucleus and generally have only one chromosome. Bacteria inhabit our bodies by the trillions, mostly in our digestive tract. They help us to digest our food and are the primary source of vitamin K, necessary for the clotting of blood.

Only about 300 out of some 4,600 listed species of bacteria are considered pathogens (disease causing). Still, bacteria are the source of a long list of diseases in plants, animals, and humans. In humans these diseases include tuberculosis, cholera, diphtheria, anthrax, tooth decay, certain kinds of pneumonia, and a number of sexually transmitted diseases.

Protozoans, like bacteria, are single-celled organisms, but they may have more than one nucleus. Included are amoebas and trypanosomes as well as the parasite that causes malaria. About one third of living species are parasites​—there are some 10,000 different kinds—​although only a few of these parasites cause disease in humans.

Fungi too can cause illness. These organisms have a nucleus and form tangled mats of filaments. The most common infections are ringworm, such as athlete’s foot, and candidiasis (Candida). Serious fungal infections usually afflict only people whose defenses have been weakened by malnutrition, cancer, drugs, or viral infections that suppress the immune system.

[Pictures]

Ebola virus

“Staphylococcus aureus” bacteria

“Giardia lamblia” protozoan

Ringworm fungus

[Credit Lines]

CDC/C. Goldsmith

CDC/Janice Carr

Courtesy Dr. Arturo Gonzáles Robles, CINVESTAV, I.P.N. México

© Bristol Biomedical Image Archive, University of Bristol

[Picture on page 4]

Alexander Fleming, who discovered penicillin