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Molecular Biology

MOLECULAR BIOLOGY

MOLECULAR BIOLOGY is the science, or cluster of scientific activities, that seeks to explain the phenomena of life through investigation of the molecules found in living things. The term was apparently invented in the late 1930s by Warren Weaver, a mathematician-turned official of the Rockefeller Foundation, who from 1933 through World War II (1939–1945) channeled much of this philanthropy's considerable resources into a program to promote medical advances by making the life sciences more like physics in intellectual rigor and technological sophistication. There is considerable debate about the extent to which Weaver successfully altered the intellectual direction of the wide range of life sciences with which he interacted. However, there can be little doubt that his program made important new instruments and methods available for biologists. For instance, Rockefeller support greatly furthered the development of X-ray crystallography, ultracentrifuge and electrophoresis instrumentation, and the electron microscope, all used for analyzing the structure and distribution in organisms of proteins, nucleic acids, and other large biomolecules. In the 1930s and 1940s, these biological macromolecules were studied not mainly by biochemists, since the traditional methods of biochemistry were adequate only for the study of compounds orders of magnitude smaller (with molecular weights in the hundreds), but rather by scientists from the ill-defined fields known as "biophysics" and "general physiology."

A general postwar enthusiasm for science made rich resources available to biologists from federal agencies such as the National Science Foundation and the National Institutes of Health. Thanks to this new funding, and also to a postatomic urge to make physics benefit mankind peacefully, the research topics and methods of biophysicists made great headway in the 1950s. New radioisotopes and accelerators spurred radiobiology. Electron microscopes were turned on cells and viruses. Protein structure was probed by crystallography, electrophoresis, and ultracentrifugation; furthermore, chemical methods were developed allowing determination of the sequence of the string of amino acids making up smaller proteins. This kind of macromolecule-focused research in the 1950s has been described as the "structural school of molecular biology" (or biophysics). In the immediate postwar era, another approach also developed around Max Delbrück, a physicist-turned-biologist fascinated since the 1930s with explaining the gene, who attracted many other physicists to biology. Now regarded as the beginning of molecular genetics, this style has been called the "informational school of molecular biology," since during the 1940s and 1950s the school probed the genetic behavior of viruses and bacteria without any attempt to purify and characterize genes chemically. To the surprise of many, largely through the combined efforts of James Watson and Francis Crick—a team representing both schools—in the mid-1950s, the gene was found to be a double-helical form of nucleic acid rather than a protein. From this point through the early 1960s, molecular geneticists concentrated much of their efforts on "cracking" the "code" by which sequences of nucleic acid specify the proteins that carry out the bulk of biological functions. After the "coding" problem was settled in the mid-1960s, they turned mainly to the mechanisms by which genes are activated under particular circumstances, at first in viruses and bacteria, and from the 1970s, in higher organisms. While the extent to which physics actually influenced the development of molecular biology is controversial, some impact can clearly be seen in the use of cybernetic concepts such as feedback in explaining genetic control, as well as in early thinking about genetics as a cryptographic problem.

Although many projects associated with biophysics flourished in the 1950s, the field as a whole did not. Rather, some areas pioneered by biophysicists, such as protein structure, were partly absorbed by biochemistry, while others split off in new disciplines. For example, electron microscopists studying cell structure split when they established cell biology, and radiobiologists largely left biophysics to join (with radiologists) in the newly emerging discipline of nuclear medicine. By the later 1960s, departments bearing the name "molecular biology" were becoming more common, typically including molecular genetics as well as certain types of "structural" biophysics. In the 1970s a new generation of convenient methods for identifying particular nucleic acids and proteins in biological samples (RNA and DNA hybridization techniques, monoclonal antibodies) brought the study of genes and their activation to virtually all the experimental life sciences, from population genetics to physiology to embryology. Also in the 1970s, methods to determine the sequence of nucleic acids making up genes began to be developed—culminating during the 1990s in the government-funded, international Human Genome Project—as well as methods for rearranging DNA sequences in an organism's chromosomes, and then reintroducing these altered sequences to living organisms, making it possible for molecular geneticists to embark upon "genetic engineering." In the early twenty-first century, there is virtually no branch of life science and medicine that is not "molecular," in that all explain biological phenomena partly in terms of nucleic acid sequences and protein structure. Thus, from its beginnings, molecular biology has resisted definition as a discipline. But however defined—as a style of investigation, a set of methods or questions, or a loosely knit and overlapping set of biological fields based in several disciplines—the enterprise of explaining life's properties through the behavior of its constituent molecules has, since its origins in the interwar era, become one of the most intellectually fruitful and medically useful movements ever to engage the life sciences.

BIBLIOGRAPHY

Abir-Am, Pnina. "The Discourse of Physical Power and Biological Knowledge in the 1930's: A Reappraisal of the Rockefeller Foundation's 'Policy' in Molecular Biology," Social Studies of Science 12: 341–382 (1982).

———. "Themes, Genres and Orders of Legitimation in the Consolidation of New Scientific Disciplines: Deconstructing the Historiography of Molecular Biology." History of Science 23 (1985): 73–117.

Chadarevian, Soraya de. Designs for Life: Molecular Biology After World War II. Cambridge, UK: Cambridge University Press, 2002.

Creager, Angela N. H. The Life of a Virus: Tobacco Mosaic Virus As an Experimental Model, 1930–1965. Chicago: University of Chicago Press, 2002.

Kay, Lily E. The Molecular Vision of Life: Caltech, the Rockefeller Vision, and the Rise of the New Biology. New York: Oxford University Press, 1993.

———. Who Wrote the Book of Life?: A History of the Genetic Code. Stanford, Calif.: Stanford University Press, 2000.

Keller, Evelyn Fox. Refiguring Life: Metaphors of Twentieth-Century Biology. New York: Columbia University Press, 1995.

Kohler Jr., Robert E. "The Management of Science: The Experience of Warren Weaver and the Rockefeller Foundation Program in Molecular Biology." Minerva 14 (1976): 279–306.

Olby, Robert C. The Path to the Double Helix. Seattle: University of Washington Press, 1974.

Pauly, Philip. "General Physiology and the Discipline of Physiology, 1890–1935," in G. L. Geison, ed., Physiology in the American Context, 1850–1940. Baltimore: American Physiological Society, 1987, 195–207.

Rasmussen, Nicolas. "The Midcentury Biophysics Bubble: Hiroshima and the Biological Revolution in America, Revisited." History of Science 35 (1997): 245–293.

———. Picture Control: The Electron Microscope and the Transformation of Biology in America, 1940–1960. Stanford, Calif.: Stanford University Press, 1997.

NicolasRasmussen

See alsoDNA ; Genetic Engineering ; Genetics ; Human Genome Project .

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Molecular Biology

Molecular Biology

Deoxyribonucleic acid, better known as DNA, is located in the nucleus of all living cells. DNA dictates which creatures walk, fly, or bore through the soil. Each DNA strand is made up of four nucleotides or "building blocks": adenine, cytosine, guanine, and thymine. These nucleotides, in turn, are made up of a variety of proteins, called amino acids. The strands of DNA, made up of bonded nucleotide pairs, are very long. Molecular biologists have worked toward breaking the genetic code by identifying the nucleotides in order and searching for patterns.

Nature gave scientists one big hint: adenine always bonds with thymine, and guanine always bonds with cytosine. In the past, researchers found fluorescent molecules that mimic the natural nucleotides. When the known fluorescent molecule bonded with an unknown nucleotide, scientists could identify that particular bonded pair of the DNA strand. The process took a decade or more. Researchers hope to speed up this painstaking work with help from computers, so they can accomplish such tasks in hours instead of years.

The challenges are formidable. Scientists must find a way to isolate and copy genes. Sensitive equipment must be developed to allow DNA sequences to be "read" as they are drawn through some kind of microscopic portal. The monitoring equipment must be fast enough, or the process slowed enough, to allow for an accurate identification of these bonded molecules. Finally, researchers must have algorithms to help them process the multitude of data they would receive from even one single strand of DNA, which could have 70,000 nucleotides. Computers are then needed to transmit and compare the sequence of the genes being studied with known gene sequence databases, a monumental task for which computers are particularly well suited.

The benefits of such research are profound. The study of human genetics is the first most obvious benefit, since these findings will aid research in fields as diverse as inherited diseases and anthropology. Since DNA holds the key to every aspect of the human body, genetic studies could potentially be used to mimic the way different cells work. This would allow researchers to develop and experiment with the effect of medications on the body without using living subjects. Disease processes, such as various forms of cancer, could potentially be duplicated in an electronic model and studied. This kind of understanding would aid in the development of successful treatments. Scientists also hope to use DNA sequences to identify and classify organisms, from the discovery of new bacteria to tracing the evolution of animals. Models of bacterial DNA could help in the study of the spread of diseases.

Gene therapy is a field in which the genes of living things are manipulated and even exchanged with one another to provide a beneficial result. For instance, spider silk, one of the strongest materials on Earth, has been produced by potatoes. Frogs and earthworms have been made to glow in the dark. A type of corn has been modified to fight tooth decay effectively. Vitamin A has been added to rice, making the grain more nutritious. Many of these applications of gene therapy have met controversy, since the long-term effects of gene manipulation in food are unknown.

Bioinformatics is the field in which software is developed to aid in the study of molecular biology. Many of the studies currently being done in molecular biology would be impossible without the help of computers and computer software. This software comes from various places. One researcher developed a basic bioinformatics software application and posted it on the web for others to download and improve upon, as did the creators of the Linux operating system , resulting in a versatile software application. Other firms have hired professionals to develop and copyright applications, which are then sold to researchers and private firms.

The U.S. government has played a pivotal role in the quest for information by establishing the National Center for Biotechnology Information, or NCBI. The NCBI is a division of the National Library of Medicine (NLM), which stores biomedical (such as gene sequence) databases. The NLM itself is a division of the National Institutes of Health (NIH). With all of the resources of the NIH, it is considered the largest biomedical research facility in the world. The NCBI is the result of a cooperative effort. Researchers, academic institutions, and similar agencies from other countries around the world access and contribute to the databases available at the NCBI.

Molecular biology and computers are also finding uses within the medical field. For example, scientists have developed a device that electronically smells the presence of bacterial infections in the lungs. Breath samples are taken from patients and put into an aroma-detection device. The machine measures the electrical resistance of the molecules in the sample of air. The results are then displayed in a two-dimensional "map." Different bacteria produce distinct characteristics on this map. This is a potentially life-saving tool because it allows physicians to treat patients immediately with the correct antibiotic for pneumonia instead of waiting two or three days for sample cultures of the bacteria to be grown and identified.

Although the use of computers is rapidly advancing the field of molecular biology, there is growing evidence that molecular biology is also important to computer science. Researchers at Syracuse University in New York are working with a purple protein called bacteriorhodopsin, produced by a type of bacteria native to salt marshes. This protein is quite stable, readily produced, and easily processed. Many believe it will eventually replace silicon microchips. Bacteriorhodopsin changes shape upon exposure to light. One shape is designated as binary 0, and the other shape is designated as binary 1. Bacteriorhodopsin is suspended in organized layers within a polymer gel. Because an individual protein changes shape upon reacting to different colors of lasers, the shape of an individual protein within the cube can be manipulated.

Floppy drives, CD-ROMs (compact disc-read only memory), and hard drives are different forms of memory that operate on a two-dimensional basis. The bacteriorhodopsin gel would be a type of three-dimensional memory. Researchers believe that one cubic centimeter of this bacteriorhodopsin protein/gel will be able to store between eight and ten gigabytes of information.

Experts agree that future molecular biology studies would be unthinkable without computers. Perhaps in the future, computers will be equally dependent upon molecular biology.

see also Binary Number System; Biology; Image Analysis; Molecular Computing; Pattern Recognition.

Mary McIver Puthawala

Bibliography

Cimino, Daniela. "Modeling a Drug." Software Magazine 18, no.1 (1998): 12(1).

Cooke, Robert. "Brave New Bacterial World." MIT Technology Review 100, no. 3 (1997): 14(2).

Levin, Carol. "High Protein Computers." PC Magazine 14, no. 10 (1995): 29(1).

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Molecular Biology

Molecular biology

Molecular biology is the study of life at the level of atoms and molecules. Suppose, for example, that one wishes to understand as much as possible about an earthworm. At one level, it is possible to describe the obvious characteristics of the worm, including its size, shape, color, weight, the foods it eats, and the way it reproduces.

Long ago, however, biologists discovered that a more basic understanding of any organism could be obtained by studying the cells of which that organism is made. They could identify the structures of which cells are made, the way cells change, the substances needed by the cell to survive, products made by the cell, and other cellular characteristics.

Molecular biology takes this analysis of life one step further. It attempts to study the molecules of which living organisms are made in much the same way that chemists study any other kind of molecule. For example, they try to find out the chemical structure of these molecules and the way this structure changes during various life processes, such as reproduction and growth. In their research, molecular biologists make use of ideas and tools from many different sciences, including chemistry, biology, and physics.

The Central Dogma

The key principle that dominates molecular biology is known as the Central Dogma. (A dogma is an established belief.) The Central Dogma is based on two facts. The first fact is that the key players in the way any cell operates are proteins. Proteins are very large, complex molecules made of smaller units known as amino acids. A typical protein might consist, as an example, of a few thousand amino acid molecules joined to each other end-to-end. Proteins play a host of roles in cells. They are the building blocks from which cell structures are made; they act as hormones (chemical messengers) that deliver messages from one part of a cell to another or from one cell to another cell; and they act as enzymes, compounds that speed up the rate at which chemical reactions take place in cells.

The second basic fact is that proteins are constructed in cells based on master plans stored in molecules known as deoxyribonucleic acids (DNA) present in the nuclei of cells. DNA molecules consist of very long chains of units known as nucleotides joined to each other end-to-end. The sequence in which nucleotides are arranged act as a kind of code that tells a cell what proteins to make and how to make them.

Words to Know

Amino acid: An organic compound from which proteins are made.

Cell: The basic unit of a living organism; cells are structured to perform highly specialized functions.

Cytoplasm: The semifluid substance of a cell containing organelles and enclosed by the cell membrane.

DNA (deoxyribonucleic acid): The genetic material in the nucleus of cells that contains information for an organism's development.

Enzyme: Any of numerous complex proteins that are produced by living cells and spark specific biochemical reactions.

Hormone: A chemical produced in living cells that is carried by the blood to organs and tissues in distant parts of the body, where it regulates cellular activity.

Nucleotide: A unit from which DNA molecules are made.

Protein: A complex chemical compound that consists of many amino acids attached to each other that are essential to the structure and functioning of all living cells.

Ribosome: Small structures in cells where proteins are produced.

The Central Dogma, then, is very simple and can be expressed as follows:

DNA mRNA proteins

What this equation says in words is that the code stored in DNA molecules in the nucleus of a cell is first written in another kind of molecule known as messenger ribonucleic acid (mRNA). Once they are constructed, mRNA molecules leave the nucleus and travel out of the nucleus into the cytoplasm of the cell. They attach themselves to ribosomes, structures inside the cytoplasm where protein production takes place. Amino acids that exist abundantly in the cytoplasm are then brought to the ribosomes by another kind of RNA, transfer RNA (tRNA), where they are used to construct new protein molecules. These molecules have their structure dictated by mRNA molecules which, in turn, have structures originally dictated by DNA molecules.

Significance of molecular biology

The development of molecular biology has provided a new and completely different way of understanding living organisms. We now know, for example, that the functions a cell performs can be described in chemical terms. Suppose that we know that a cell makes red hair. What we have learned is that the reason the cell makes red hair is that DNA molecules in its nucleus carry a coded message for red-hair-making. That coded message passes from the cell's DNA to its mRNA. The mRNA then directs the production of red-hair proteins.

The same can be said for any cell function. Perhaps a cell is responsible for producing antibodies against infection, or for making the hormone insulin, or assembling a sex hormone. All of these cell functions can be specified as a set of chemical reactions.

But once that fact has been realized, then humans have exciting new ways of dealing with living organisms. If the master architect of cell functions is a chemical molecule (DNA), then that molecule can be changed, like any other chemical molecule. If and when that happens, the functions performed by the cell are also changed. For these reasons, the development of molecular biology is regarded by many people as one of the greatest revolutions in all of scientific history.

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Molecular Biology

Molecular Biology

Molecular biology is the study of life processes on a small scale. As a whole organism is composed of cells, so are these cells composed of tightly regulated molecular machinery that keep them alive and functioning. Molecular biologists use chemical and biological tools to study DNA, RNA, proteins, and the interactions between them.

These tools have allowed scientists to have a far more detailed understanding of cellular processes than was imagined possible a century ago. One of the most groundbreaking developments in this field has been the polymerase chain reaction (PCR), first conceived by Kary B. Mullis in the 1970s. This technique, which uses DNA-copying polymerases derived from bacteria found in hot springs, can be used to isolate a tiny needle of DNA from a nucleic haystack and copy it many times over. Today, PCR is used in nearly every molecular biology lab to reproduce genes and obtain enough copies of them to study the genes efficiently. This allows scientists to put the genes in other cells, to activate them, or to match them to their protein products.

Molecular biologists also study proteins. They frequently do this through electrophoresis, in which proteins are separated by size as they drift through a thickened gel, propelled by electric current. Once the proteins are separated out by size, a scientist may "probe" the proteins with antibodies specific for only one protein shape and determine if that particular protein is present. The antibody will be radioactive or have some visual marker for easy detection. This technique is called a Western blot. One can also run DNA and RNA through electrophoretic gels and probe with complementary nucleic acids. The double-stranded DNA or RNA is split, and an exact negative copy of the gene is introduced to the gel. The negative copy will stick fast to the positive copy, so if the gene is on the gel, its presence is quickly identified.

With these techniques, and others, such as growing cells in culture and the purification and harvesting of bioactive proteins , molecular biologists are among the best researchers to examine health, disease, and development in animals and humans. While ecology and behavior are useful for large-scale understanding of long-ranging processes in biology, molecular biologists are able to study and manipulate organisms on an individual level and study the mechanisms by which they operate. As molecular biology improves, more and more life processes are seen as the product of biochemical interactions, and scientists are more and more able to paint a complete picture of the physical interactions that make life work.

see also Cells; PCR.

Ian Quigley

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molecular biology

molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller Foundation. In 1950 W. T. Astbury of the Univ. of Leeds used the term in its now accepted sense, to describe the area of research, closely related to and often overlapping biochemistry, conducted by biologists whose approach to and interest in biology are principally at the molecular level of organization. The field of molecular biology has grown with the increasing sophistication of available techniques and has quickly built upon its own increases in the understanding of biological processes. In the 1930s, with the help of the technique of ultracentrifugation, the macromolecules were first studied in detail and their crystalline properties described. In the 1940s the process by which individual genes produce their unique products began to be understood as resulting from the different sequences of the base pairs that make up the genes. In the 1950s Linus Pauling described the three-dimensional structure of proteins, and James Watson and Francis Crick described the double helix of the DNA molecule. Further advances were made in understanding DNA, protein, and virus synthesis and the regulation of genes, and by the 1970s, the techniques of genetic engineering were enabling molecular biologists to study higher plants and animals, opening up the possibility of manipulating plant and animal genes to achieve greater agricultural productivity. Such techniques also opened the way for the development of gene therapy.

See A. Darbre, Introduction to Practical Molecular Biology (1988).

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molecular biology

molecular biology is a branch of biological science that investigates how genes govern the activity of cells, tissues, and organisms. It evolved by the coming together of the sciences of genetics, biochemistry, and cell biology. Its cardinal rule is that DNA makes RNA makes protein.

Alan W. Cuthbert


See cell; genetics, human.

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molecular biology

molecular biology The study of the structure and function of large molecules associated with living organisms, in particular proteins and the nucleic acids DNA and RNA. Molecular genetics is a specialized branch, concerned with the analysis of genes (see DNA sequencing).

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molecular biology

molecular biology Biological study of the make-up and function of molecules found in living organisms. Major areas of study include the chemical and physical properties of proteins and of nucleic acids such as DNA. See also biochemistry

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molecular biology

molecular biology (mŏ-lek-yoo-ler) n. the study of the molecules that are associated with living organisms, especially proteins and nucleic acids.

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