Wednesday, March 19, 2008

The Future of Molecular Biology

The discovery, in 1953, of the double-helical structure of DNA sparked a revolution in the biological sciences, the full impact of which is only now beginning to be appreciated. The structure immediately suggested how genetic information might be replicated and soon led to the deciphering of the genetic code. Together with the discovery of methods for determining the amino acid sequences of proteins and for sequencing DNA and RNA, it paved the way for emergence of recombinant DNA technology that, in turn, spawned the biotechnology industry and rapidly transformed the fields of molecular biology and molecular genetics that today inform almost every aspect of biomedical science.

Given the quite extraordinary progress of the past forty years, what might we look forward to as we approach the twenty-first century? Launched in the 1980s, the international genome initiative has as its stated goal the cloning and sequencing of the 50,000 or more genes that constitute the human genome and, concurrently, the genomes of a number of other organisms, including the plan aradopsis, yeast, the nematode worm, the fruit fly, and the mouse. Clinical medicine will undoubtedly be the principal beneficiary of this work. Already well over one thousand disease-related genes have been identified, often leading, as in the case of cystic fibrosis, phenylketonuria, muscular dystrophy, and colon cancer, to new DNA-based diagnostic procedures and beginning attempts at gene therapy.

The general field of developmental biology is likely to be the other major beneficiary of the advances in molecular biology and genetics. With the new tools that are now available, rapid progress is being made in elucidating the molecular mechanisms involved in such processes as gametogenesis, fertilization, the establishment of body-plan, differential gene expression and cell-fate determination, and the control of cell proliferation and cell death. The availability of techniques for transferring genes from one organism to another or eliminating specific genes by homologous recombination is contributing to the rapid progress in our understanding of the development of even very complex systems such as the mammalian hematopoietic and immune systems.

In the long term, the greatest challenge remaining to biologists is to understand how the human brain works. Every aspect of human behavior-including our ability to perceive the world around us, to carry out appropriate motor acts, to speak and understand written or spoken language, and to feel and to express our emotions-is due to the integrated actions of the nerve cells in our brains. We are far from understanding how such high-level functions "emerge" from such low-level activities as the conduction of nerve impulses and their transmission at synaptic junctions. The "mind-brain" problem, which for centuries has been exclusively the domain of philosophers and theologians, is now awaiting the concerted efforts of research biologists. Its elucidation will undoubtedly be the greatest triumph of the human intellect and as revolutionary (and with as many societal consequences) as the discovery of evolution by natural selection in the mid-19th century and of the nature of genes in the mid-20th century.

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