Can We Wipe Out Disease?

There's no doubt that we are smart enough to conquer many diseases. But like it or not, we are also part of the process that produces them.

By Jerold M. Lowenstein|Sunday, November 01, 1992
RELATED TAGS: INFECTIOUS DISEASES
The elimination of disease is one of the great dreams of mankind. Indeed, heaven is often depicted as a kind of blissful, disease-free sanatorium. Is the longed-for state of perpetual health destined to remain nothing more than a dream?

Are health and sickness, like life and death, inevitable antitheses that will always circumscribe our fate as humans? Or will a diseaseless society one day be within our reach on Earth?

Certainly the prospects of finding cures for most of our ills have never looked better. The history of medicine until fairly recently was a deplorable tale of ignorance, hocus-pocus, and guesswork. In the 1800s physicians were still starving, purging, and bleeding their patients to cure nearly any disease, much as physicians had done in ancient Greece. (The Greeks believed that such treatments evacuated the excessive humors, or body fluids, that were upsetting the healthy equilibrium of the body.) Patients were still operated on without anesthesia. Many, if they survived that ordeal, died of sepsis because surgeons, operating in ignorance of germs, plunged into their patients with unsterilized instruments and filthy hands. With the exception of digitalis for heart failure and quinine for malaria, there were almost no effective drugs. Oliver Wendell Holmes, the nineteenth-century Boston physician and sage, commented that if all the medicines then known were thrown into the ocean, it would be the better for the human race and the worse for the fish.

Looked at from this perspective, the high-tech medicine with which we’re rocketing into the twenty-first century seems astounding. To what do we owe this giant leap forward? The answer lies in the application of science to the understanding and treatment of diseases over the past 150 or so years. Microscopes of increasing power led to the identification of bacteria, parasites, and eventually viruses as the agents of such familiar diseases as diphtheria, malaria, and influenza. Learning how these germs were transmitted and how our bodies defended themselves against them provided the rational basis for vaccines, drugs, and public health measures that have effectively doubled the average human life span. Thanks to vaccines, smallpox has been wiped off the face of the Earth, and polio has been tamed. Thanks to antibiotics, which came into routine use only in the 1950s, parents no longer commonly fear losing children to pneumonia, streptococcal infections, or meningitis. Removing a child’s inflamed appendix--once a risky operation in the bacteria-filled gut--now seems almost ordinary.

In just the last 20 years medicine has changed beyond recognition. Who would have imagined that coronary artery disease would be treated on a come-and-go basis by the threading of a balloon catheter into narrowed arteries to prize them open? Who would have thought that powerful scanners could peer into and display the inner sanctum of the living human brain?

The discovery of DNA’s double helix in 1953 began an even more exciting chapter in our attack on disease. Finding the structure of DNA, the stuff that genes are made of, and cracking the code used to convey its instructions ushered in a new age of molecular medicine. For the first time we are beginning to understand the diseases that come from the genes inside our very own cells--inherited disorders and genetic anomalies that make up a major share of the still unconquered scourges of humankind. In fact, we’ve come so far so fast that some medical researchers predict that the next couple of decades will be a mopping-up operation for those diseases not yet overcome--cancer, AIDS, malaria, Alzheimer’s, and schizophrenia. But will it be that simple? Let’s consider for a moment two of those problems: AIDS, a lethal viral infection, and malaria, caused by a protozoan.

AIDS is one of the newest infectious diseases of humankind and malaria one of the oldest. AIDS has killed close to a million people since it was first observed about ten years ago. Malaria is still responsible for at least one to two million deaths every year. Why haven’t we developed a vaccine against AIDS or a chemical that can eradicate the persistent and deadly parasite that causes malaria?

This question introduces a new variable into our task of controlling disease--the evolutionary factor. Retroviruses like the human immunodeficiency virus (HIV) of AIDS evolve at about a million times the rate of most other viruses. As a result, they change their protein coat fast enough to present a moving target to the human immune system that is charged with destroying them. Meanwhile the virus attacks and destroys the immune system, leaving the body defenseless, and the victim usually dies of opportunistic infections like Pneumocystis pneumonia.

As for malaria-causing parasites, like many bacteria they initially seemed to succumb to our chemical warfare: for a few years drugs like chloroquine were effective in preventing and curing the disease. Then in the 1950s drug-resistant strains of parasites evolved. Whatever new drugs or drug combinations we have employed since, some varieties of malaria have found a way to sidestep their effects.

So when we think about eliminating disease, we must consider that the evolutionary process practically guarantees an endless conflict between the defenders and the would-be invaders of the human body--with the tide of battle surging first one way and then the other. Having said that, however, it’s heartening to realize that we humans have never been better equipped to gain the upper hand. The more we know of the life cycles, genetics, and biochemistry of infectious agents like HIV and malaria parasites, the more likely it seems that our science will triumph over their evolutionary evasiveness and keep us one step ahead in the evolutionary rat race.

Cancer and genetic diseases, the enemies that bore from within, will be harder nuts to crack, though we are getting a grip on them too. In 1989 Michael Bishop and Harold Varmus of the University of California at San Francisco received a Nobel Prize for their discovery of cancer-causing oncogenes in humans. Oncogenes are normal genes gone wild because of mutations or dislocations in the DNA. If we can find the mistakes in their molecular structure--the keys to their ability to stimulate abnormal cell growth--then we should be able to correct them. Similarly several hundreds of gene defects are known to cause inherited illnesses, ranging from sickle-cell disease to Huntington’s chorea.

But once more we encounter an evolutionary paradox, for sickle cells are actually a rather successful defense against killer malaria. These red blood cells, with their odd scimitar shape, are resistant to the malaria parasite. Ten percent of African Americans have some protective sickle cells in their blood, a result of inheriting a sickling gene from one parent. It’s only when children inherit the gene from both parents that they develop sickle-cell disease, which may involve anemia, impaired growth, and painful crises when the spiky cells form clumps in their blood vessels.

In 1949 Linus Pauling traced sickle-cell disease to a tiny defect in the molecular structure of hemoglobin, the oxygen-carrying pigment in red blood cells. A single mutation in the long DNA chain that codes for hemoglobin results in a single amino acid change that causes sickling. We now know of more than 300 other abnormal hemoglobins that occur in various ethnic groups and even sporadically. Many don’t transport oxygen as well as normal hemoglobin and shorten the life of red cells. But they confer no known advantage or resistance to malaria or other diseases.

What these many variations on the hemoglobin theme show once again is how busy evolution is at the molecular level. And all that change provides the raw material for potential defenses against new diseases. If, say, hemoglobin D, one of the variant blood pigments, were to prove resistant to a lethal disease not yet inflicted on our species, future populations would doubtless show a huge increase in the hemoglobin D gene.

From the perspective of molecular evolution, then, it is not so easy to distinguish between disease, normal variation, and adaptation to changing circumstances. Ridding the gene pool of sickle hemoglobin would be beneficial to African Americans because in this country the trait has become a liability. But it would be decidedly harmful to Africans, who still have to cope with malaria.

Questions like these are still hypothetical, but they soon may not be if genetic engineering becomes a reality. If, say, sickle-cell disease is diagnosed prenatally, it might be possible to replace part of a baby’s bone marrow, the organ that makes red cells, with borrowed bone marrow cells that have the normal hemoglobin gene. In this way children destined to have genetic abnormalities might be able to avoid their fate. But suppose by genetic engineering we could successfully purge the human population of all its hemoglobinopathies? Might we not then be in the same situation as food crops during the green revolution of the 1960s, when the widespread planting of superior monocultures of rice and other grains made them particularly vulnerable to fungi and insects? No longer faced with a diversity of resistant variants, plant diseases swept through crops worldwide.

The very concept of a static healthy human population runs contrary to the incessant mobility of evolutionary history. Based on the common genetic language of DNA and the many genes shared by all living organisms, it is virtually certain that the 10 million or more species on Earth today descended from a common one-celled ancestor that emerged from the hot broths of the early planet some 3.5 billion years ago. Obviously tremendous changes had to take place just to get from a single-celled organism to a multicellular one, let alone to the complicated creatures we’ve become.

The cells of humans and other animals bear witness to one of the earliest and most extraordinary of these changes. They are permanently infected by mitochondria, small bodies that originated as bacterial invaders of those ancient unicellular organisms. The aerobic invaders enabled their previously anaerobic hosts to capitalize on oxygen as a new energy source. Now we’re completely dependent on these prehistoric trespassers. Mitochondria are the batteries that power our cells.

At any point in this evolutionary history, a perfectly healthy, perfectly adapted species would have been unlikely to evolve into something different. After all, why change if you’re doing well? It takes changes in environment and climate, overcrowding, and disease to drive the evolutionary process, to encourage new adaptations such as the movement from life in the water to life on land, or back from land to water. Genetic abnormalities, maladaptive to the old environment but adaptive to the new, made these movements possible. This process of flux is going on all the time, though mostly at the unseen molecular level. Organisms are constantly changing their relationship to one another and to the environment, and what we call diseases are part of that process. Whether we like it or not, we humans are part of it, too.

More than 2 billion years ago, photosynthesizing plants altered Earth’s atmosphere by converting carbon dioxide into oxygen. Oxygen allowed life as we know it to flourish. During our lifetime, a veritable instant in Earth’s history, human activity has changed the atmosphere by adding large amounts of carbon dioxide and other gases, like fluorocarbons, that threaten to produce profound climatic and environmental disturbances and weaken the ozone layer that screens out ultraviolet light from the sun.

If you picture Earth and its inhabitants as a single self- sustaining organism, along the lines of the popular Gaia concept, then we humans might ourselves be seen as pathogenic. We are infecting the planet, growing recklessly as cancer cells do, destroying Gaia’s other specialized cells (that is, extinguishing other species), and poisoning our air supply.

From a subjective human perspective, it would be good to eliminate infectious diseases, cancer, and genetic defects. From a Gaian perspective, as many pointed out at the recent Earth Summit in Rio de Janeiro, the main disease to be eliminated is us. From the evolutionary perspective, perhaps humanity can be considered another agent of global change, like glaciation or the asteroid that wiped out the dinosaurs. But in this case, we are both the asteroid and the dinosaurs.

Paradoxically, some of the worst calamities facing humankind stem from our reproductive success. Our large population and runaway consumption degrade our planet, poison our oceans, and foul our atmosphere--threatening our crops, our water supply, and our health. The intelligence that produced agriculture and antibiotics seems unable so far to restrain the uncontrolled multiplication of a species that has thrown Earth’s homeostasis out of balance. So we find ourselves in a bind. The more success we have at fighting disease and extending human life, the greater looms the possibility of hastening our own extinction.

It was the scientific approach, the use of our uniquely evolved human brains, that sparked our fantastic progress against disease in the last 150 years. The question now is no longer whether we have the skill to subdue most infectious diseases and repair many genetic disorders--for we clearly do. The critical question for the coming centuries is whether our species is smart enough to deal with its own explosive success.
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