In contrast, molecular biologists typically take a bottom-up approach to evaluating the human condition, working from first principles. Nucleotide sequences and genetic mutations that predispose the individual or the population to diseases are the primary focus. Neither approach is correct nor incorrect. The simultaneous top-down and bottom-up approaches to evaluating the human condition are common research methods of virtually every field. A bottom-up approach starts at the most detailed level, and seeks the big picture from the details. For instance, the examination of DNA sequences to study the human organism is analogous to studying alphabets to research written language. Eventually, the interrelated works converge on some greater understanding of the underlying culture (the human organism)—the point of expressing thought and feelings through language.
The dual top-down and bottom-up views of the human condition illustrate the interrelatedness of high- level observations and nucleotide sequences as well as the practical significance of perspective. For example, many animals, plants, and insects directly affect human health in ways that may not be obvious from first principles derived from human nucleotide sequences. Many plants produce
beneficial compounds, while animals and insects are common vectors for parasites and pathogens. An individual's genetic constitution may provide information on what is best for his or her survival, but it may not indicate what is best for the population as a whole. For example, there are times when individuals must suffer so that the general population can survive and thrive.
Consider the interrelatedness of public health and molecular biology. Public health officials rely on population statistics, education levels, vaccination compliance, and other predictors of disease prevention. For example, thanks to efforts orchestrated in part by the World Health Organization, smallpox was eradicated from the general population in the last century through vaccination. For the sake of protecting the entire population, the health of a subset of the population was jeopardized. Many children were subject to side effects of the smallpox vaccine, which ranged from fever to death. From a slightly different perspective, consider that while smoking is considered detrimental to the health of the population as a whole, there are exceptions. For individuals at risk for developing Parkinson's Disease, smoking can reduce the risk of developing this neurologic disorder. This protective effect of smoking is only present with patients with a genetic profile that makes them susceptible to developing Parkinson's. Individuals without genetic susceptibility can increase their chances of contracting Parkinson's if they smoke. Given the relatively low incidence of Parkinson's Disease (less than 1 person per 1,000, predominantly in their 50s), prescribing smoking for the general population would have a negative effect on public health overall.
Another example of the need for simultaneous top-down and bottom-up approach to studying the human organism is the interrelatedness of personal and public health. A significant issue worldwide is the interrelatedness of sickle-cell anemia and the Plasmodium falciparum parasite responsible for malaria. Sickle-cell anemia is caused by a change in the chemical composition of the hemoglobin protein that carries the oxygen inside of the red blood cells. These chemical changes in hemoglobin cause the molecule to elongate, distorting the shape of the whole red blood cell. These sickle-shaped red blood cells can damage the capillaries around them and the tissues that depend on the vessels for oxygen and nourishment, resulting in clotting, and, in some cases, death of surrounding tissues. The homozygous form of sickle-cell disease that is associated with an anemia is universally fatal; few individuals suffering from sickle-cell disease live beyond 20. What's more, in a population free of Anopheline mosquitoes carrying the Plasmodium falciparum parasite, individuals with the sickle-cell trait (heterozygotes) are also at a distinct disadvantage to those without the trait. However, in malaria-infested areas of the world, the sickle-cell trait has a protective effect against the malaria parasite. Women with the trait have more offspring, compared to women without the trait, and more of their offspring reach maturity because they are relatively unaffected by malaria.
Although malaria can be cured by drug therapy, treatment is extensive and usually associated with numerous side effects. However, because the DNA of the Plasmodium falciparum parasite was sequenced in 2002, there is increased likelihood of an engineered drug that will free those infected from extensive medical regimens.
The pharmaceutical industry provides additional examples of the tension between bottom-up and top- down approaches to evaluating the human condition. Consider that when the antibiotic penicillin was discovered by Alexander Fleming, he observed, by chance, that bacterial growth on a piece of bread was inhibited by a contaminating mold. When it was first used as an antibiotic, penicillin was effective against the majority of bacterial infections. To a practicing clinician, there was no need to understand penicillin's mechanism of action. All that mattered was whether the antibiotic was effective in
inhibiting or eradicating a particular pathogen, and the potential side effects, such as allergic reactions.
As soon as penicillin was introduced into the general patient population, bacteria developed a resistance through mutation and the natural selection process. As a result, many patients were unable to benefit from penicillin as an antibiotic, and the market for synthetic pharmaceuticals was born. Since the 1950s, many synthetic derivatives of penicillin have been widely used for a variety of diseases. For example, ampicillin is one of the most useful of these derivatives and serves as a highly effective agent against bacterial infections. As with penicillin, the side effects are normally relatively minor, and usually limited to minor allergic reactions.
Because bacteria can mutate faster than pharmaceutical firms can create engineered antibiotics, newly introduced antibiotics have shorter useful lifetimes than their predecessors. Clinicians attempt to minimize the growing of resistant strains of bacteria by using analogs of penicillin and other first- generation antibiotics whenever possible. However, because antibioticresistant bacteria are
increasing in relative numbers, more powerful drugs have to be introduced to the market frequently. For example, the cephalosporin class of synthetic antibiotics has a much wider spectrum of activity against pathogens than penicillin and its derivatives.
Synthetic, engineered antibiotics such as the cephalosporins are resistant to the penicillinases produced by penicillin-resistant bacteria and are therefore useful in treating bacterial infections that don't respond to penicillin derivatives. However, bacteria are also developing resistance to the cephalosporins. In addition, these later-generation antibiotics also tend to have more significant side effects than penicillin-based drugs. For example, common side effects of cephalosporins range from stomach cramps, nausea, and vomiting, to headache, fainting, and difficulty breathing.
Molecular biologists are in a constant time-limited battle with mutating bacteria. One of the latest trends in the pharmaceutical industry is the synthesis of drugs that interfere with the bacteria at multiple sites. As a result, for a pathogen to survive, it must develop multiple mutations in one generation—an unlikely event. A dual-site antibiotic interferes with two or more processes that not only function independently within the bacteria but aren't linked in any way. However, developing these next-generation antibiotics requires the use of new visualization techniques, simulations, and other computationally intensive processes—as well as the data on a pathogen's nucleotide sequence. The relevance and relatedness of the pharmaceutical industry's rush to bring product to market to address bacterial resistance and other issues can be appreciated from an information flow