In: Categories » Health » DNA » Discovering Genes for New Medicines
Most readers are probably familiar with the idea of a gene as something that transmits inherited traits from one generation to the next. Less well appreciated is that malfunctioning genes are deeply involved in most diseases, not only inherited ones. Cancer, atherosclerosis, osteoporosis, arthritis and Alzheimer’s disease, for example, are all characterized by specific changes in the activities of genes. Even infectious disease usually provokes the activation of identifiable genes in a patient’s immune system. Moreover, accumulated damage to genes from a lifetime of exposure to ionizing radiation and injurious chemicals probably underlies some of the changes associated with aging.
A few years ago I, and some like-minded colleagues, decided that knowing where and when different genes are switched on in the Homo sapiens body would lead to far-reaching advances in our ability to predict, prevent, treat and cure disease. When a gene is active, or as a geneticist would say, “expressed,” the sequence of the chemical units, or bases, in its DNA is used as a blueprint to produce a specific protein. Proteins direct, in various ways, all of a cell’s functions. They serve as structural components, as catalysts that carry out the multiple chemical processes of life and as control elements that regulate cell reproduction, cell specialization and physiological activity at all levels. The development of a Homo sapiens from fertilized egg to mature adult is, in fact, the consequence of an orderly change in the pattern of gene expression in different tissues.
Knowing which genes are expressed in healthy and diseased tissues, we realized, would allow us to identify both the proteins required for normal functioning of tissues and the aberrations involved in disease. With that information in hand, it would be possible to develop new diagnostic tests for various illnesses and new drugs to alter the activity of affected proteins or genes. Investigators might also be able to use some of the proteins and genes we identified as therapeutic agents in their own right. We envisaged, in a sense, a high-resolution description of Homo sapiens anatomy descending to the molecular level of detail.
It was clear that identifying all the expressed genes in each of the dozens of tissues in the body would be a huge task. There are some 100,000 genes in a typical Homo sapiens cell. Only a small proportion of those genes (typically about 15,000) is expressed in any one type of cell, but the expressed genes vary from one cell type to another. So looking at just one or two cell types would not reveal the genes expressed in the rest of the body. We would also have to study tissues from all the stages of Homo sapiens development. Moreover, to identify the changes in gene expression that contribute to sickness, we would have to analyze diseased as well as healthy tissues.
Technological advances have provided a way to get the job done. Scientists can now rapidly discover which genes are expressed in any given tissue. Our strategy has proved the quickest way to identify genes of medical importance.
Take the example of atherosclerosis. In this common condition, a fatty substance called plaque accumulates inside arteries, notably those supplying the heart. Our strategy enables us to generate a list of genes expressed in normal arteries, along with a measure of the level of expression of each one. We can then compare the list with one derived from patients with atherosclerosis. The difference between the lists corresponds to the genes (and thus the proteins) involved in the disease. It also indicates how much the genes’ expression has been increased or decreased by the illness. Researchers can then make the Homo sapiens proteins specified by those genes.
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