Dictionary:

genetics

  (jə-nĕt'ĭks)

1. (used with a sing. verb) The branch of biology that deals with heredity, especially the mechanisms of hereditary transmission and the variation of inherited characteristics among similar or related organisms.
2. (used with a pl. verb) The genetic constitution of an individual, group, or class.

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Concept

Genetics is the area of biological study concerned with heredity and with the variations between organisms that result from it. It demands an understanding of numerous terms, such as DNA (deoxyribonucleic acid), a molecule in all cells that contains blueprints for genetic inheritance; genes, units of information about particular heritable traits, which are made from DNA; and chromosomes, DNA-containing bodies, located in the cells of most living things, that hold most of the organism's genes. The vocabulary of genetics goes far beyond these three terms, as we shall see, but these are the core concepts. Among the areas in which genetics is applied is forensic science, or the application of science to matters of law—specifically, through "DNA fingerprinting," whereby samples of skin, blood, semen, and other materials can be used to prove or disprove a suspect's innocence. Another fascinating application of genetics is the Human Genome Project, an effort whose goals include the location and identification of every gene in the human body.

How It Works

Genetics and Heredity

Genetics and heredity, the subject of another essay in this book, are closely related ideas. Whereas heredity is the transmission of genetic characteristics from ancestor to descendant through the genes, genetics is concerned with hereditary traits passed down from one generation to the next. It is very hard, if not impossible, to separate the two concepts completely, yet the entire body of knowledge encompassed by these topics is so large and so complex that it is best to separate them as much as possible. For this reason, the Heredity essay is concerned with such issues as how traits are passed on and why they appear in a particular generation but not another. That essay addresses the topics of alleles, dominant and recessive genes, and so on. It also briefly discusses the history of studies in areas that encompass genetics, heredity, and the mechanics thereof. In general, the Heredity essay is concerned with the larger patterns of inheritance over the generations, while the present one examines inheritance at a level smaller than the microscopic—that is, from the molecular or biochemical level.

Somatic and Germ Cells

Heredity begins with the cell, the smallest basic unit of all life. The information for heredity is carried within the cell nucleus, which is the control center not only in physical terms (it is usually located near the middle of the cell) but also because it contains the chromosomes. Within these threadlike structures is the genetic information organized in DNA molecules.

There are two basic types of cell in a multicellular organism: somatic, or body, cells, and germ, or reproductive, cells. The somatic cells are the primary components of most organisms, making up everything except some of the the cells in reproductive organs. The somatic cells of humans have 23 pairs of chromosomes, or 46 chromosomes overall, and are thus known as diploid cells. As the cells grow, they reproduce themselves by a process called mitosis, whereby a diploid cell splits to produce new diploids, each of which is a replica of the original. Thus cells grow and are replaced, making possible the formation of specific tissues and organs, such as muscles and nerves. Without mitosis, an organism's cells would not regenerate, resulting not only in cell death but possibly even the death of the entire organism. Mitosis is also the means of reproduction for organisms that reproduce asexually (see Reproduction).

A germ cell, by contrast, undergoes a process of cell division known as meiosis, whereby it becomes a haploid cell—a cell with half the basic number of chromosomes, which for a human would be 23 unpaired chromosomes. The sperm cells in a male and the egg cells in a female are both haploid germ cells: each contains only 23 chromosomes, and each is prepared to form a new diploid by fusion with another haploid. Sperm cells and egg cells are known as gametes, mature male or female germ cells that possess a haploid set of chromosomes and are prepared to form a new diploid by undergoing fusion with a haploid gamete of the opposite sex.

When egg and sperm fuse, they form a zygote, in which the diploid chromosome number is restored, with the zygote possessing the same chromosomes as both the sperm and the egg. This cell carries all the genetic information needed to grow into an embryo and eventually a full-grown human, with the specific traits and attributes passed on by the parents. Not all offspring of the same parents are the same, of course, and this is because the sperm cells and egg cells vary in their genetic codes—that is, in their DNA blueprints.

The Dna Blueprint

To understand genes and their biological function in heredity, it is necessary to understand the chemical makeup and structure of DNA. The complete DNA molecule often is referred to as the blueprint for life, because it carries all the instructions, in the form of genes, for the growth and functioning of organisms. This fundamental molecule is similar in appearance to a spiral staircase, which also is called a double helix. The sides of the DNA ladder are made up of alternate sugar and phosphate molecules, like links in a chain. The rungs, or steps, of DNA are made from a combination of four different chemical bases. Two of these, adenine and guanine, are known as purines, and the other two, cytosine and thymine, are pyrimidines. The four letters designating these bases—A, G, C, and T—are the alphabet of the genetic code, and each rung of the DNA molecule is made up of a combination of two of these letters.

Dna Sequences

In this genetic code A always combines with T and C with G, to form what is called a base pair. Specific sequences of these base pairs make up the genes. Although a four-letter alphabet may seem rather small for constructing the extensive vocabulary that defines the myriad life-forms on Earth, in practice, the sequences of these base pairs make for almost limitless combinations. For any sequence, there are four possibilities as to the first two letters (AT, TA, CG, or GC) and four more possibilities for the second two letters. Thus, just for a four-letter sequence, there are 16 possibilities, and for each pair of letters added to the sequence, the total is multiplied by four. Given the long strings of base pairs that form DNA sequences, the numbers can be extremely large.

The more complex an organism, from bacteria to humans, the more rungs, or genetic sequences, appear on the ladder. The entire genetic makeup of a human, for example, may contain three billion base pairs, with the average gene unit being 2,000-200,000 base pairs long. Each one of these combinations has a different meaning, providing the code not only for the type of organism but also for specific traits, such as brown hair and blue eyes, dimples, detached earlobes, and so on and on. Except for identical twins, no two humans have exactly the same genetic information.

Dna Replication, Protein Synthesis, and Rna

Genetic information is duplicated during the process of DNA replication, which is initiated by proteins in the cells. To produce identical genetic information during cell mitosis, the DNA hydrogen bonds between the two strands arebroken, splitting the DNA in half lengthwise. This process begins a few hours before the initiation of cell mitosis, and once it is completed, each half of the DNA ladder is capable of forming a new DNA molecule with an identical genetic code. It can do this because of specific chemical catalysts (a substance that enables a chemical reaction without taking part in it) that help synthesize the complementary strand.

Catalysts formed from proteins are known as enzymes, and the functioning of specific cells and organisms is conducted by enzymes synthesized by the cells. Cells contain hundreds of different proteins, complex molecules that make up more than half of all solid body tissues and control most biological processes within and among these tissues. A cell functions in accordance with the particular protein—one of thousands of different types—it contains. It is the genetic base-pair sequence in DNA that determines, or "codes for," the specific arrangement of amino acids to build particular proteins.

Since the sites of protein production lie outside the cell nucleus, coded messages pass from the DNA in the nucleus to the cytoplasm, the material inside the cell that is external to the nucleus. This transfer of messages is achieved by RNA, or ribonucleic acid, and specifically by messenger RNA, or mRNA. Other types of RNA molecules are involved in linking the amino-acids together in a sequence form to shape the protein. (For more about amino acids, proteins, and enzymes, see the respective essays devoted to each subject.)

Mutation

Once a protein has been created for a specific function, it cannot be changed. This is why the theory of acquired characteristics (the idea that changes in an organism's overall anatomy, as opposed to changes in its DNA, can be passed on to offspring) is a fallacy. People may have genes that make it easier for them to acquire certain traits, such as larger muscles or the ability to play the piano through exercise or practice, respectively, but the traits themselves, if they are acquired during the life of the individual and are not encoded in the DNA, are not heritable.

There is only one way in which changes that take place during the life of an organism can be passed on to its offspring, and that is if those changes are encoded in the organism's DNA. This is known as mutation. Suppose lung cancer develops in a man as a result of smoking; unless a tendency to cancer is already a part of his genetic makeup, he cannot genetically pass the disease on to his unborn children. But if the tobacco has acted as a mutagen, a substance that brings about mutation, it is possible that his DNA can be altered in such a way as to pass on either the tendency toward lung cancer or some other characteristic.

Because DNA is extremely stable chemically, it rarely mutates, or experiences an alteration in its physical structure, during replication. But because there are so many strands of DNA in the world, and so much material in the strands, mutation is bound to happen eventually—and, to an extent, at least, this is a good thing. Mutation is the engine that drives evolution, and a certain amount of genetic variation is necessary if species are to adapt by natural selection to a changing environment. If it were not for mutation, neither humans nor the many millions of other species that exist would ever have appeared.

Mutation often occurs when chromosome segments from two parents physically exchange places with each other during the process of meiosis. This is known as genetic recombination. Genes also can change by mutations in the DNA molecule, which take place when a mutagen alters the chemical or physical makeup of DNA. The mutations that result are of two types, corresponding to the two basic varieties of cell: somatic mutations, which occur solely within the affected individual, and germinal mutations, which happen in the DNA of germ cells, producing altered genes that may be passed on to the next generation.

The odd thing about mutations is that while most of them are harmful, the few that are beneficial are, as we have noted, the driving force behind the evolution of life-forms that successfully adapt to their environments. Thus, while most germinal mutations bring about congenital disorders (birth defects) ranging from physical abnormalities to deficiencies in body or mind to diseases, every once in a while a germinal mutation results in an improvement, such as a change in body coloring that acts as camouflage. If the trait improves an individual organism's chances for survival within a particular environment, it may become a permanent trait of the species, because the offspring with this gene have a greater chance of survival and thus will pass on the trait to succeeding generations. (For more about mutation, see the essay by that title. See also Evolution for a discussion of the role played by mutation and natural selection in the evolution of species.)

Real-Life Applications

The Genetics Revolution

In the modern world genetics plays a part in more dramatic breakthroughs than any other field of biological study. These breakthroughs have an impact in a wide variety of areas, from curing diseases to growing better vegetables to catching criminals. The field of genetics is in the midst of a revolution, and at the center of this exciting (and, to some minds, terrifying) phenomenon is the realm of genetic engineering: the alteration of genetic material by direct intervention in genetic processes. In agriculture, for instance, genes are transplanted from one organism to another to produce what are known as transgenic animals or plants. This approach has been used to reduce the amount of fat in cattle raised for meat or to increase proteins in the milk produced by dairy cattle. Fruits and vegetables also have been genetically engineered so that they do not bruise easily or have a longer shelf life.

Not all of the work in genetics is genetic engineering per se; in the realm of law, for instance, the most important application of genetics is genetic fingerprinting. A genetic fingerprint is a sample of a person's DNA that is detailed enough to distinguish it from the DNA of all others. The genetic fingerprint can be used to identify whether a man is the father of a particular child (i.e., to determine paternity), and it can be applied in the solving of crimes. If biological samples can be obtained from a crime scene—for example, skin under the fingernails of a murder victim, presumably the result of fighting against the assailant in the last few moments of life—it is possible to determine with a high degree of accuracy whether that sample came from a particular suspect. The use of DNA in forensic science is discussed near the conclusion of this essay.

The Revolution in Medicine

Some of the biggest strides in genetic engineering and related fields are taking place, not surprisingly, in the realm of medicine. Genetic engineering in the area of health is aimed at understanding the causes of disease and developing treatments for them: for example, recombinant DNA (a DNA sequence from one species that is combined with the DNA of another species) is being used to develop antibiotics, hormones, and other disease-preventing agents. Vaccines also have been genetically re-engineered to trigger an immune response that will protect against specific diseases. One approach is to remove genetic material from a diseased organism, thus making the material weaker and initiating an immune response without causing the disease. (See Immunity and Immunology for more about how vaccines work.)

Gene therapy is another outgrowth of genetics. The idea behind gene therapy is to introduce specific genes into the body either to correct a genetic defect or to enhance the body's capabilities to fight off disease and repair itself. Since many inherited or genetic diseases are caused by the lack of an enzyme or protein, scientists hope one day to treat the unborn child by inserting genes to provide the missing enzyme. (For more about inherited disorders, see the essays Disease, Noninfectious Diseases, and Mutation.)

The Human Genome Project

One of the most exciting developments in genetics is the initiation of the Human Genome Project, designed to provide a complete genetic map outlining the location and function of the 40,000 or so genes that are found in human cells. (A genome is all of the genetic material in the chromosomes of a particular organism.) With the completion of this map, genetic researchers will have easy access to specific genes, to study how the human body works and to develop therapies for diseases. Gene maps for other species of animals also are being developed.

The project had its origins in the 1990s, with the efforts of the United States Department of Energy (DOE) and the National Institutes of Health (NIH). The NIH connection is probably clear enough, but the DOE's involvement at first might seem strange. What, exactly, does genetics have to do with electricity, petroleum, and other concerns of the DOE? The answer is that the DOE grew out of agencies, among them the Atomic Energy Commission (AEC), established soon after the explosion of the two atomic bombs over Japan in 1945. Even at that early date, educated nonscientists understood that the radioactive fallout produced from nuclear weaponry can act as a mutagen; therefore, Congress instructed the AEC to undertake a broad study of genetics and mutation and the possible consequences of exposure to radiation and the chemical by-products of energy production.

Eventually, scientists in the AEC and, later, the DOE recognized that the best way to undertake such a study was to analyze the entire scope of the human genome. The project formally commenced on October 1, 1990, and is scheduled for completion in the middle of the first decade of the twenty-first century. Upon completion, the Human Genome Project will provide a vast store of knowledge and no doubt will lead to the curing of many diseases.

Still, there are many who question the Human Genome Project in particular, and genetic engineering in general, on ethical grounds, fearing that it could give scientists or governments too much power, unleash a Nazi-style eugenics (selective breeding) program, or result in horrible errors, such as the creation of deadly new diseases. In fact, it is impossible to search "genetic engineering" on the World Wide Web without coming across the Web sites of literally dozens and dozens of agencies, activist groups, and individuals opposed to genetic engineering and the mapping of the human genome. For more about the Human Genome Project, genetic engineering, and their opponents, see Genetic Engineering.

Genetics in Forensic Science

Forensic science, as we noted earlier, is the application of science to matters of law. It is based on the idea that a criminal always leaves behind some kind of material evidence that, through careful analysis, can be used to determine the identity of the perpetrator—and to exonerate someone falsely accused. Among those forms of material evidence of interest to forensic scientists working in the field of genetics are blood, semen, hair, saliva, and skin, all of which contain DNA that can be analyzed. In addition, there are areas of forensic science that rely on biological study, though not in the area of genetics: blood typing as well as the analysis of fingerprints or bite marks, both of which have patterns that are as unique to a single individual as DNA is.

One of the first detectives to use science, including biology and medicine, in solving crimes was a fictional character: Sherlock Holmes, whose creator, the British writer Sir Arthur Conan Doyle (1859-1930), happened to be a physician as well. The first full-fledged (and real) police practitioner of forensic science was the French police official Alphonse Bertillon (1853-1914), who developed an identification system that consisted of a photograph and 11 body measurements, including dimensions of the head, arms, legs, feet, hands, and so on, for each individual. Bertillon claimed that the likelihood of two people having the same measurements for all 11 traits was less than one in 250 million. In 1894 fingerprints, which were easier to use and more unique than body measurements, were added to the Bertillon system.

Fingerprints, unlike DNA, are unique to the individual; indeed, identical twins have the same DNA but different fingerprints. Mark Twain (1835-1910) could not have known this in 1894, when he published The Tragedy of Pudd'nhead Wilson, and the Comedy of Those Extraordinary Twins. Nonetheless, the story involves a murder committed by one man and blamed on his twin, who eventually is exonerated on the basis of fingerprint evidence—still a new concept at the time. In some situations, however, fingerprint evidence may be unavailable, and though law-enforcement agencies have developed extraordinary techniques for analyzing nearly invisible (i.e., latent) prints, sometimes this is still not enough.

The Simpson Case and the Controversy Over Dna Evidence

For example, in the infamous murder of Nicole Brown Simpson and Ron Goldman on June 12, 1994, fingerprint evidence would have been ineffective in the case against the suspect, the former football star and actor O. J. Simpson. Since Nicole Simpson was his ex-wife, the appearance of his prints at the scene of her murder in her Los Angeles home could be explained away easily, even though she had taken out a restraining order against her former husband (who she had accused of spousal abuse) some time before the murder. Rather than fingerprints, the prosecution in his murder trial used DNA evidence connecting blood at the crime scene with blood found in Simpson's vehicle. (Some of this blood was apparently his own, since he had mysterious cuts on his hands that he could not explain to police officers.)

A jury found Simpson not guilty on October 3, 1995, and jurors later claimed that the prosecution had failed to make a strong case using DNA evidence. Furthermore, they cited police contamination of the DNA evidence, which had been established in their minds by Simpson's defense team, as a cause for reasonable doubt concerning Simpson's guilt. In fact, assuming that the defense was fully justified in this claim, that would have meant only that the DNA samples would have been less (not more) likely to convict Simpson.

At the same time, a number of legitimate concerns regarding the use of DNA evidence were raised by experts for the defense in the Simpson trial. Samples can become contaminated and thus difficult to read; small samples are difficult for analysts to work with effectively; and results are often open to interpretation. Furthermore, the outcome of the Simpson case illustrates the fact that findings based on DNA evidence are not readily understood by non-specialists, and may not make the best basis for a case-particularly in one so fraught with controversy. The prosecution based its case almost entirely on extremely technical material, explained in excruciating detail by experts who had devoted their lives to studying areas that are far beyond the understanding of the average person. Attempting to wow the jurors with science, the prosecution instead seemed to create the impression that DNA evidence was some sort of hocus-pocus invented to frame an innocent man. Simpson went free, though the jury in a 1996 civil trial (which took a much simpler approach, eschewing complicated DNA testimony) found him guilty.

Dna Evidence Success Stories

Because of the Simpson case, the use of DNA evidence gained something of a bad name. Nonetheless, it has been successful in less high profile cases, beginning in 1986, when English police tracked down a rapist and murderer by collecting blood samples from some 2,000 men. One of them, named Colin Pitchfork, paid another man to provide a sample in his place. This attracted the attention of the police, who tested his DNA and found their man.

Since that time, DNA evidence has been used in more than 24,000 cases and has aided in the conviction of about 700 suspects. The DNA in such cases is not always obtained from a human subject. In the investigation of the May 1992 murder of Denise Johnson in Arizona, a homicide detective found two seed pods from a paloverde tree in the bed of a pickup truck owned by the suspect, Mark Bogan. The accused man admitted having known the victim but denied ever having been near the site where her body was found. It so happened that there was a paloverde tree at the site, and testing showed that the DNA in the pods on his truck bed matched that of the tree itself. Bogan became the first suspect ever convicted by a plant.

On the other hand, in some cases, DNA evidence has cleared a suspect falsely accused. Such was the case with Kerry Kotler, convicted in 1981 for rape, robbery, and burglary and sentenced to 25-50 years in jail. In 1988, Kotler began petitioning for DNA analysis, which subsequently showed that his DNA did not match that of the rapist, who had left a semen sample in the victim's underwear. Kotler was released in December 1992 and in March 1996 was awarded $1.5 million in damages for his wrongful imprisonment. The story does not end there, however. Kotler's case turned out to be one of the more bizarre in the annals of forensic DNA testing. Perhaps he did not commit the first rape, but a month after he received the damage award, he was on his way back to prison for the August 1995 rape of another victim. This time prosecutors showed that Kotler's semen matched samples taken from his victim's clothing—and to prove their case, they used DNA testing.

Where to Learn More

Department of Energy Human Genome Program (Web site). <http://www.ornl.gov/hgmis/>.

The DNA Files/National Public Radio (Web site). <http://www.dnafiles.org/>.

Fridell, Ron. DNA Fingerprinting: The Ultimate Identity. New York: Franklin Watts, 2001.

Genetics Education Center, University of Kansas Medical Center (Web site). <http://www.kumc.edu/gec/>.

Henig, Robin Marantz. The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, the Father of Genetics. Boston: Houghton Mifflin, 2000.

Lerner, K. Lee, and Brenda Wilmoth Lee. World of Genetics. Detroit: Gale Group, 2002.

National Human Genome Research Institute (Web site). <http://www.nhgri.nih.gov>.

Schwartz, Jeffrey H. Sudden Origins: Fossils, Genes, and the Emergence of Species. New York: John Wiley and Sons, 1999.

Tudge, Colin. The Impact of the Gene: From Mendel's Peas to Designer Babies. New York: Hill and Wang, 2001.

Virtual Library on Genetics, Oak Ridge National Laboratory (Web site). <http://www.ornl.gov/TechResources/Human_Genome/genetics.html>.

The science of biological inheritance, that is, the causes of the resemblances and differences among related individuals.

Genetics occupies a central position in biology, for essentially the same principles apply to all animals and plants, and understanding of inheritance is basic for the study of evolution and for the improvement of cultivated plants and domestic animals. It has also been found that genetics has much to contribute to the study of embryology, biochemistry, pathology, anthropology, and other subjects. See also Biochemistry; Embryology; Pathology; Physical anthropology.

Genetics may also be defined as the science that deals with the nature and behavior of the genes, the fundamental hereditary units. From this point of view, evolution is seen as the study of changes in the gene composition of populations, whereas embryology is the study of the effects of the genes on the development of the organism. See also Gene action; Population genetics.

The field of molecular genetics describes the basis of inheritance at the molecular level. It focuses on two general questions: how do genes specify the structure and function of organisms, and how are genes replicated and transmitted to successive generations? Both questions have been answered. Genes specify organismal structure and function according to a process described by the central dogma of molecular biology: DNA is made into messenger ribonucleic acid (mRNA), which specifies the structure of a protein; the mRNA molecule then serves as a template for protein synthesis, which is carried out by complex machinery that comprises a particle called a ribosome and special adapter RNA molecules called transfer RNA. See also Deoxyribonucleic acid (DNA); Ribonucleic acid (RNA); Ribosomes.

The structure of DNA provides a simple mechanism for genes to be faithfully reproduced: the specific interaction between the nucleotides means that each strand of the double helix carries the information for producing the other strand. See also Genetic code; Genetic engineering; Molecular biology; Mutation.

The science that deals with the origin of the characteristics of an individual.

The role of genetics in medicine and public health came to broad public consciousness quite dramatically in June 2000, when President Bill Clinton and Prime Minister Tony Blair jointly sponsored the announcement by government, academic, and industrial scientists that a "first draft" of the human genome sequence had been completed. Then, in early 2001, the announcement of the full sequencing and a revised estimate of the number of genes in the human genome was released. No doubt many people were mystified by the term "genome," even if they had some idea about what genes and proteins are. The genome is the complete set of genes of each individual in any species. In humans, there are an estimated 30,000 to 100,000 genes in the forty-six chromosomes of, essentially, all human cells. In early 2001, the same scientific groups reported a nearly complete sequence for the human genome, with an estimated 30,000 to 40,000 genes distributed on twenty-three pairs of chromosomes.

The Molecular Nature of Genes

DNA (deoxyribonucleic acid) molecules carry the code for genetic information and its transmission from one generation to the next. For decades it was thought that DNA was a most unlikely candidate for this role, due to its presumed simplicity (compared with proteins). DNA consists of a string of just four different nucleotide bases (A, T, G, C—for adenine, thymine, guanine, cytosine) held together by a sugar (deoxyribose)—phosphate backbone. In contrast, proteins are polypeptide chains of twenty different amino acids, offering much more variation for coding. In a classic experiment in 1944, scientists at the Rockefeller Institute in New York City working with bacteria that cause pneumococcal pneumonia showed that inherited transformation of the surface characteristics of the bacteria could be accomplished with DNA and not with protein.

In 1953, James Watson and Francis Crick, at Cambridge University in England, published the stunning hypothesis that two intertwined strands of DNA, running in opposite directions, could be joined in a double helix through hydrogen bonds linking the nucleotide bases in the specific combinations of A-T and G-C. This model was justified by available X-ray pictures of the molecular patterns of DNA. Linear sets of three nucleotide bases generate a "triplet code," with sixty-four combinations, more than enough to code for the twenty amino acids. We now know that the double helix of DNA can separate, through actions of enzymes that facilitate unwinding, so that one strand of the double-stranded DNA can be transcribed into messenger RNA (mRNA) molecules. The mRNA is then translated into polypeptides, which assume highly folded three-dimensional structures to function as enzymes, antibodies, and structural components of cells. Other RNA molecules are involved in supporting the formation of the polypeptides and in delivering the right amino acid to the growing polypeptide chain as directed by the triplet code in the mRNA.

This flow of information from DNA to RNA to protein is a general phenomenon throughout living organisms. There are exceptions, such as viruses (including HIV/AIDS [human immodeficiency virus/acquired immunodeficiency syndrome]) which use RNA as their genetic material. When these viruses infect human (or plant or animal) cells, they must first convert their RNA message into DNA to join the flow of information in the cell from DNA to RNA to protein. Similar "reverse transcription" can occur in cancer cells and during embryological development. Experimental conversion of mRNA to DNA is utilized very extensively to clone and sequence individual genes, key techniques in the field of biotechnology.

The Basis for Inheritance

Long DNA molecules are carried on structures called chromosomes in the nucleus inside each cell. Human chromosomes occur in pairs, one derived from the mother and one from the father in sexual reproduction. Humans have twenty-three pairs of chromosomes, of which twenty-two are similar in males and females. These are numbered 1 through 22, according to chromosome size (1 is the largest). One chromosome pair is different between females and males: XX in females (one X from each parent) and XY in males (X from the mother and Y from the father).

When ordinary cells divide (during fetal development, normal growth, and the regeneration of skin, other organs, and cells lining the lung, intestine, and uterus), the chromosomes must be duplicated and then be distributed to daughter cells so that every cell gets a full set of twenty-three pairs of chromosomes. When the chromosomes are duplicated, the DNA must be replicated, as well.

Egg-forming cells in the ovary and sperm-forming cells in the testes are unique. They are duplicated in a more complex pattern so that they contain only one each of the twenty-three pairs of chromosomes; when egg and sperm then combine, their aggregate of chromosomes is the expected twenty-three pairs.

Something else important can happen during duplication of chromosomes and replication of DNA. There may be recombination across the pairs of chromosomes between the DNA strands, so that genes (information) from the mother are combined at the molecular level with information from the father, and vice versa. Also, there may be mistakes. Mistakes in an individual gene occurring during replication, or when triggered by X-rays, ultraviolet radiation, or chemical reactions, are called "mutations." The complementary double-stranded structure of DNA is a defense against loss of information when DNA is damaged or broken; the damaged strand is repaired using the complementary strand to direct the repair. Mistakes that occur when chromosomes are duplicated can lead to translocations of part of one chromosome onto another, loss of a chromosome or part of a chromosome, or failure of separation of duplicated chromosomes (gaining a third copy of that chromosome, as in Down syndrome, where there are three copies of chromosome 21). In addition, some genes are actually carried outside the nucleus in the energy factories called mitochondria; these can be passed on only by the mother, in the egg cell, and are associated with certain diseases of muscle and brain.

Mapping Genes on Chromosomes

Very effective methods have been developed to identify which genes for specific traits or diseases are located on which chromosomes, and to pinpoint the location on the relevant chromosome. The smallest genes consist of only a few hundred bases of DNA; the largest known human gene, which is mutated in Duchenne muscular dystrophy, is 2 million base pairs in length. A surprising feature of all nonbacterial genes is their organization into "introns" and "exons." Introns are noncoding stretches of DNA within the gene which are transcribed into RNA but then spliced out before the RNA is translated into protein. There are also untranslated noncoding regions at each end of the gene. There are lots of signals built into the sequence of the DNA—for initiation, stopping, splicing, and other functions crucial to defining the genes in the lengthy DNA molecules; for regulating their expression as mRNA and proteins; and for coordinating regulation of related genes. Some genes have only a single exon; others have up to one hundred interruptions with introns. The reasons are still quite obscure.

Gene mapping before 1950 was limited to the X chromosome, deduced by mother-to-son transmission in pedigrees (diagrams of family histories) for X-linked diseases (e.g., hemophilia) or traits (e.g., color blindness). A few genes were located on abnormal chromosomes by careful clinical correlations. Improved chromosomal analyses permitted formation of double-stranded DNA between fluorescent-labeled probe DNA and the DNA in a particular chromosome. Another method used mouse/human hybrid cells with one each of the different human chromosomes—if a human gene could be detected in the presence of the mouse genes, that gene must be coded for on the single human chromosome present. Once one gene is located, another gene which is linked in transmission from generation to generation can be deduced to be on the same chromosome. For example, the gene for cystic fibrosis was placed near linked markers on chromosome 7. This is truly a needle-in-the-haystack approach, since there are some 30,000 to 40,000 genes, distributed on the 23 pairs of chromosomes.

Everything changed with the new methods of recombinant DNA and the polymerase chain reaction—a way to produce millions of copies of a particular DNA molecule isolated or synthesized in tiny amounts. Increasingly, genes are being identified without the benefit of an initial chromosomal localization. A scan of the entire genome (across all chromosomes) is performed in a search for linkage to fairly common variants of genes that serve as well-spaced markers, even without knowing their function. Many steps in this approach are now automated, thousands of samples can be processed, and powerful computer programs sift through hundreds or thousands of markers to find clues for localization of the presumed gene or genes for a disease. Segments of DNA from the suspected chromosomal region can be cloned into specialized vectors. Linking together all such fragments permits scientists to assemble the genome sequence of humans or of many other organisms (e.g., yeast, fruitfly, bacteria, earthworm, mouse). A much more complicated mapping process is helpful in locating multiple genes for complex diseases like diabetes, high blood pressure, or depression.

The Human Genome Project

According to Francis Collins, director of the National Human Genome Research Institute, "mapping the human genetic terrain may rank with the great expeditions of Lewis and Clark, Sir Edmund Hillary, and the Apollo Program." In the early 1970s, obtaining sequence information on DNA or RNA was arduous, typically requiring an entire year to deduce about fifteen nucleotides. Advances in laboratory methods triggered hope in the mid-1980s that a massive scale-up could eventually sequence the entire 3 billion base pairs of human DNA. The project was officially launched in October 1990 in the United States and soon became international, with major efforts in Britain, France, Scandinavia, and Japan. Specific goals, by chromosome, were set to achieve the mapping of genes to chromosomes, the physical map of DNA fragments, and then the DNA sequence. By 1994 there were 5,000 highly useful markers for the genetic map, and overlapping cloned fragments of DNA to create physical maps, using various techniques. Many clever schemes have been put to use to assure sufficient overlaps to orient the location and direction of DNA sequence fragments. Powerful sequencing methods accelerated the target completion date from 2005 to 2003, and then to 2001. Work to "clean-up" the sequence is ongoing.

Nevertheless, having the entire sequence has been likened to having the complete works of William Shakespeare as a sequence of the twenty-six English letters with no punctuation of any kind. Figuring out where the genes are and how they are turned on and off, or up and down, during life's events is a huge remaining task. In reality, the work of understanding the genome has only just begun. Computer algorithms, including one called "GRAIL," have been designed to find and use characteristics that may distinguish coding regions from the other 95 percent of the DNA sequence. Working backward from the mRNA molecules by forming double-stranded complementary DNA with the enzyme reverse transcriptase, and then sequencing the cDNA or even partial cDNA as expressed sequence tags, has accelerated this work.

Another powerful approach has utilized the theme of "unity in diversity" that characterizes all living things. There are amazing homologies between genes in humans and genes for similar functions in mice, earthworms, fruitflies, and even yeast cells, all of which have smaller genomes than humans. Computer databases available to scientists throughout the world permit "virtual experiments" using knowledge of a disease-related gene in the mouse, for example, to deduce what gene might account for a similar disease in humans.

Regulation of gene expression is a crucial feature of differentiated cells in complex organisms and of development from the single fertilized egg cell. Except for red blood cells, which have no nucleus, all other cells in any individual have a nucleus, chromosomes, and DNA—the same DNA. So the information content is essentially the same in all cells, yet quite different sets of genes are active in the blood, liver, kidney, brain, heart, and other organs and in cancer cells. Much is being learned about the ways in which genes are regulated in health and disease.

Interaction of Genes and Environmental Factors

For many decades there were disputes about whether inheritance or environment were more important in determining health status. The debate was framed as genetics versus environment, or nature versus nurture. That kind of thinking is no longer appropriate. It is firmly established that genes act by generating a molecular framework in cells and organisms, including people, that environmental factors act upon. Thus, people are exposed to many kinds of radiation; noise; chemicals and infectious agents in air, water, food, consumer products, cigarettes, alcohol, and drugs; as well as to physical and psychosocial stresses—all of which may interfere with normal cellular functioning. For example, chemicals called polycyclic aromatic hydrocarbons are produced in the combustion of gasoline, oil, cigarettes, and various industrial processes; these chemicals are breathed in through the lungs, enter the circulating blood, are activated in the liver and other organs into very reactive intermediates, and attack the DNA, forming chemical adducts with the DNA. These adducts cause the DNA code letters to be misread, generating mutations in the genetic information of these cells and increasing the risk that these cells will evade normal growth controls and become cancers. Behavioral follow-up studies in Scandinavia of adults who were adopted as infants have provided potent evidence that genetics and biology are crucial to future risks for alcoholism, depression, schizophrenia, and even criminal actions. There is now evidence of relevant inherited variation in dopamine receptors in depression, cigarette-smoking behaviors, and dysfunctional alcoholic intake. Such genetic variation may account for predisposition or resistance to these behavioral disorders.

Many pharmaceutical agents have variable therapeutic effects and variable adverse effects in different patients. In many cases we understand the reason: the drugs are metabolized (changed by enzyme action) into more active, or less active, molecules, depending on the inherited form of the gene coding for that particular metabolizing enzyme. Other chemicals from the external environment may undergo similar variable steps due to the same genes. Interactions of infectious agents with their "hosts," like infected people, may vary with genetic variation in the microbe and genetic variation in the infected person. Responses to high cholesterol foods or to cigarette smoking are subject to marked variation in people with different patterns of relevant genes. The study of these genetic-environmental interactions is called "ecogenetics."

Significance of Genetics in Clinical Medicine

There are well-recognized patterns of inheritance involving particular disease genes. If a disorder occurs in a grandparent, parent, and child, such vertical transmission in the pedigree is called dominant (caused by an abnormal gene from just one of the grandparents), and can involve either the X chromosome or any of the twenty-two autosomal chromosomes. Examples are Marfan's syndrome and Huntington's disease. If both parents appear normal, yet carry a recessive mutation, disease may occur when a child receives the mutant gene from each parent; examples include sickle-cell anemia and cystic fibrosis. Finally, the recessive gene may be carried on the X chromosome without manifestation in the female, but with full manifestation in the XY male, who has no normal second X gene; examples are hemophilia and Duchenne muscular dystrophy.

For common diseases like coronary heart disease, diabetes mellitus, breast cancers, depression, cleft lip and palate, and high blood pressure, multiple genes are involved; the heterogeneous causes vary within any group of diagnosed patients. Identical twins are much more likely than nonidentical (fraternal) twins to have the same disease; siblings and other close relatives have higher risks than unrelated individuals. In all cases, environmental factors, maturation factors, and other genes influence the age of onset of disease and the specific manifestations.

It is quite miraculous that such a high proportion of babies appears to be "normal"—within the broad range of normal physical and mental development. Nevertheless, about 3 percent of newborns have major malformations affecting the heart, colon, bones, or other organs. Some 2 to 5 percent have severe or moderate mental retardation or developmental disabilities. Chromosomal abnormalities account for many of the malformations, and various gene mutations contribute to the disabilities. Major chromosomal abnormalities are particularly common in spontaneously aborted fetuses (up to 50%). Variations within the normal range influence height, body habitus, propensity to weight gain, and mental development and temperament.

One of the important concepts in genetic medicine is "inborn errors of metabolism," a phrase introduced by Sir Archibald Garrod in 1908. Specific mutations, usually involving both the maternal and the paternal forms of the gene (autosomal recessive pattern of inheritance, with 25% risk for each offspring), cause deficiency of a key enzyme—as in mental retardation due to a block in the metabolism of the amino acid phenylalanine, which becomes toxic to the developing brain. The effects of this disorder (phenylketonuria, or PKU) can be prevented by diagnosing the condition at birth through newborn screening of a heel-stick blood sample and putting the child on a diet low in phenylalanine for the first five years of life, while the brain is growing rapidly. The special diet can be less stringent (but should, it now seems, be sustained) during childhood and adolescence. For women, it is crucial that they be back on a stringent low-phenylalanine diet during pregnancy; otherwise, the high circulating levels will definitely damage the fetus (100% risk of mental retardation).

Autosomal dominant diseases, like those which affect collagen in bone, cartilage, skin, and teeth, typically distort key proteins that have two or more polypeptides, such that a mutation in one makes the whole protein complex malfunction.

Knowledge from the Human Genome Project should allow identification of susceptibility genes for a broad array of diseases, thereby permitting testing before symptoms become manifest. If a single gene is responsible, testing during pregnancy or at any other appropriate time of life for the particular disease may predict a high risk or eliminate worry about that specific disease. For example, a person found to carry an inherited mutation in one of the colon cancer mutation repair genes could benefit from annual colonoscopy beginning at age thirty, so that any polyps would be detected and removed long before they progress to a potentially invasive cancer. In more complicated inherited conditions, multiple genes will be tested using new microarray and protein expression methods, answers will be couched in terms of increased or decreased risk and the likelihood of favorable responses to treatment. In other situations, the value of testing is limited due to lack of effective treatments, as for Huntington's disease. Of course, it is hoped that research will lead to effective therapies and preventive interventions and patients and families do value having the correct diagnosis, even if therapy is not (yet) available.

The Human Genome Project Elsi Program

One of the distinctive and important features of the Human Genome Project is its Ethical, Legal, and Social Implications (ELSI) program. James Watson committed a part of the annual appropriation from Congress to such matters from the start of the project. Three major categories of issues that have been examined in conferences, workshops, commissioned papers, and surveys are fairness, privacy, and safety.

Fairness. In the use of genetic information, fairness is especially important in preventing discrimination in access to affordable health care and life insurance and in employment. Many Americans fear genetic testing will identify a predisposition that will be (unfairly) considered a "preexisting condition" by insurance companies. As a result, genetic counselors advise that patients and families have good insurance in place before seeking counseling and testing. Even so, many individuals seek to be tested anonymously.

Privacy. Medical records and insurance health exams are not secure. In the state of Michigan, a 1999 report from the Governor's Commission on Genetic Privacy and Progress led to enactment of seven model statutes in 2000. Federal legislation is pending.

Safety and Efficacy of the Tests. Many new tests emerging from research labs need to be converted to high throughput, less expensive methods, with reliable quality-assurance programs. In general, people will be tested only once, and the test results carry implications for relatives. Autonomy of the individual has been the explicit policy for genetic counseling and informed participation in genetic screening for many years; testing must be conducted with similar respect for individual preferences and decisions.

Significance of Genetics in Public Health

The sequencing of the human genome and the subsequent demonstration of variation in numerous genes in health and disease will surely stimulate a golden age for the public health sciences. It will be essential to investigate and link data about microbial, chemical, and physical exposures; about nutrition, metabolism, growth, and development; about lifestyle behaviors; and about diagnoses, medications, and health care utilization to information about genetic variation. Such studies must be conducted on a population basis in order to interpret the significance of the genetic variation. Laboratory scientists, clinician-investigators, and health care professionals will rely upon epidemiologists, biostatisticians, environmental health scientists, behavioral scientists, health economists, and health-policy analysts for the collaborative research that will inform evidence-based, cost-effective medical care and public health interventions.

In research, practice, and policy, both genetics and public health focus on populations. Both are interested in clinical preventive services and in prevention of environmental and behavioral risks. Both fields explicitly recognize cultural, societal, ethnic, and racial contexts. Geneticists are particularly sensitive to the legacy of the eugenics movement of several decades ago and to the conundrum of making medical decisions when no treatment or preventive intervention is yet known. So long as the United States lacks universal health insurance, discriminatory use of genetic information by insurers and by employers must be guarded against, as noted above.

More knowledge is needed about the heterogeneity of genetic predispositions, environmental exposures, and disease risks. Unfortunately, most public health research on infectious disease and environmental chemical risks has paid little attention to inherited susceptibility in people, focusing only on the environmental-disease agents. Similarly, heterogeneity of study populations has often been neglected in epidemiologic studies in the effort to generate sufficient numbers to justify the analysis statistically. For quantitative traits, pharmacologists, toxicologists, and psychologists have generally emphasized means and standard errors of the means, and neglected potentially informative people with values outside two standard deviations from the mean. Nevertheless, genetics is now at the core of research on cancers, coronary heart disease, high blood pressure, neurological and psychiatric conditions, and a host of other common conditions.

Complete genome sequences are now available for Mycobacterium tuberculosis, HIV, and hepatitis B virus; sequences will soon be available for cholera, malaria, and other agents. The ability to promptly identify disease-causing strains of these infectious agents has been a boon to epidemiologic surveillance in the community and to clinical management of patients. Genetic variation in both the agents and exposed persons interact. For both HIV and malaria, there are cell-surface variants of blood cells in humans that protect some people from infection. These host-parasite relationships will be a fertile area for new knowledge in public health and for drug development.

Nutrition and genetics interact extensively. Individuals with similar elevated levels of cholesterol have a variety of underlying conditions for which different dietary and pharmacologic approaches are needed. Another important risk factor for coronary heart disease is the amino acid homocysteine, whose level is greatly influenced by folic acids and vitamins B12 and B6, as well as genetic variation in enzymes metabolizing these vitamins. One common disorder, hereditary hemochromatosis, results from an overload of iron from the diet, leading to damage from iron deposition in the heart, liver, pancreas (diabetes), testes (infertility), skin, and joints (arthritis). Simple blood donation can reduce iron burdens in the body and prevent these serious complications. It is easy to test for elevated iron levels and for the gene mutations that predispose to the retention of excess iron. Unfortunately, the American Red Cross refuses to accept blood from these otherwise normal potential donors, and the Centers for Disease Control has been extremely cautious about undertaking screening programs on a population basis.

In the arena of environmental health, variation in susceptibility has been recognized as one of the three key components in assessment of risks, together with the dose-response relationship and the levels of exposure in relevant settings. The U.S. government has mounted an Environmental Genome Initiative to direct emerging knowledge of genes and genetic variation from the Human Genome Project and develop powerful new methods of chip technology for testing lots of genes simultaneously as an aid in identifying and preventing health risks from environmental exposures.

Across all of these fields, genetics will surely contribute to a scientifically sound strategy for improving health, preventing disease, and reducing disparities, the overarching missions of public health.

(SEE ALSO: Autonomy; Environmental Determinants of Health; Eugenics; Genes; Genetic Disorders; Human Genome Project; Medical Genetics; Nutrition; Retrovirus; and articles on specific diseases mentioned herein)

Bibliography

Andrews, L. B.; Fullerton, J. E.; Holtzman, N. A.; and Motulsky, A. G., eds. (1994). Assessing Genetic Risks. Implications for Health and Social Policy. Washington, DC: National Academy Press.

Eaton, D. L.; Farin, F.; Omiecinski, C. J.; and Omenn, G. S. (1998). "Genetic Susceptibility." In Environmental and Occupational Medicine, 3rd edition, ed. W. A. Rom. Philadelphia, PA: Lippincott-Raven.

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Khoury, M. J.; Burke, W.; and Thomson, E. J. (2000). Genetics and Public Health in the 21st Century: Using Genetic Information to Improve Health and Prevent Disease. New York: Oxford University Press.

McKusick, V. A. (1997). Mendelian Inheritance in Man: A Catalog of Human Genes and Genetic Disorders, 12th edition. Baltimore, MD: Johns Hopkins University Press.

McNicholl, J. M., and Cuenco, K. T. (1999). "Host Genes and Infectious Diseases: HIV, Other Pathogens, and a Public Health Perspective." American Journal of Preventive Medicine 16:2415–2419.

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—— (2000). "The Genomic Era: A Crucial Role for the Public Health Sciences." Environmental Health Perspectives 108:160–161.

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U.S. Congress, Office of Technology Assessment (1988). Mapping Our Genes: The Genome Projects: How Big, How Fast? Washington, DC: U.S. Government Printing Office.

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Watson, J. D., and Crick, F. H. C. (1953). "A Structure for Deoxyribose Nucleic Acid." Nature 171:737–738.

— GILBERT S. OMENN

Genetics is the scientific study of the structure, function, and transmission of genes in living things. The field of genetics includes many disciplines and uses many different techniques. Historically, genetic scientists (geneticists) investigated patterns of inheritance in whole organisms by observing the distribution and segregation of physical characteristics across several generations of breeding. This type of genetic research, called classical or Mendelian genetics, is still conducted today and remains invaluable for identifying and describing inheritance patterns and traits. The development of modern molecular biology and biochemistry has facilitated the growth of a different but complementary branch of genetic research, known as molecular genetics. This branch focuses on understanding the detailed molecular mechanisms that govern the transmission of genetic material from one generation to the next.

The observable characteristics that describe any organism (for example, height or eye color in humans, or flower size and color in plants) can be broadly grouped into two categories: those that are acquired because of environmental effects, and those that are inherited. Genetics is concerned with this second category—that is, inherited characteristics. Gregor Mendel, an Augustinian monk of the mid-nineteenth century, observed that characteristics such as shape and color in peas were passed from parent to offspring regardless of the environment the plants grew in. He meticulously counted and documented thousands of crosses between different pea varieties to deduce the principles that governed this inheritance. In the end, his work was so influential and vital to the development of genetics that the term "Mendelian" genetics is now a synonym for classical genetics.

Several key concepts put forward by Mendel have been expanded, as the science of genetics has grown. It is now known that genetic information is passed on as a series of discrete units known as genes, each of which is associated with specific traits. Furthermore, most organisms (including humans) get two copies of their genetic information, one from each parent. This means that most living things have two copies of each gene, and that these two copies are not necessarily the same, since they came from different parents. When an organism reproduces, it passes only one of its two copies to an offspring. Importantly, copies of different genes separate (segregate) randomly into the next generation, which means that an offspring can receive either of the two copies that the parent has, and that the set of copies that is passed is different from offspring to offspring.

A growing interest in the biochemical basis of life led geneticists of the twentieth century to attempt to identify the substance that carries genetic information from one generation to the next. Intense research led to the discovery of DNA (deoxyribonucleic acid), the molecule that encodes the genetic information of almost all organisms (a few viruses use RNA—ribonucleic acid—to encode their genes). Understanding the relationship between observable, inherited traits and the structure and organization of the genetic material (DNA) is the primary focus of molecular genetic research. The powerful combination of classical genetics and molecular genetics has led to many important advances in biological and health-care research and continues to be a major force in the advancement of science in the twenty-first century.

—Daniel J. Tomso

For more information on genetics, visit Britannica.com.

Genetics, the science of heredity, includes the interrelated fields of cytology, biochemistry, evolutionary theory, and molecular biology. Today the impact of genetic research is far-reaching, affecting medical diagnosis and therapeutics, agriculture and industry, criminal prosecution, and privacy, as well as ideas regarding individuality, ethics, and responsibility. Studied since antiquity, heredity remained a puzzle until the late twentieth century even though many of its essential physical components—such as chromosomes and "nuclein" (later identified as deoxyribonucleic acid (DNA)—were known by the late nineteenth century. Indeed, genetics did not become a "science" in a contemporary empirical sense until the rediscovery of Gregor Mendel's laws in 1900. Mendel, an Austrian monk who experimented with patterns of inheritance in studies of peas and flowers, determined laws of heredity regarding the integration and assortment of inherited traits. These original principles underwent considerable refinement and expansion throughout the twentieth century as scientists uncovered the physical and chemical mechanisms of heredity. This recent history of genetics can be divided into three general periods: classical genetics, molecular genetics, and applied or modern genetics, each of which benefited greatly from American researchers and institutions.

Classical and Molecular Genetics

The rediscovery of Mendel's laws led to the flowering of classical genetics in the early twentieth century. Population studies, breeding experiments, and radiation were among the early tools in genetic research as scientists looked to uncover the patterns and basic unit of heredity as well as the causes of variation. In 1902, a mere two years after the rediscovery of Mendel's laws, the American biologist Walter S. Sutton observed similarities between Mendel's genetic "units" and chromosomes. Additional research by his Columbia University colleague Edmund Beecher Wilson confirmed the link and identified the "X" sex chromosome in butterflies, while another American, the cytologist Nettie Stevens, independently identified the "Y" chromosome in beetles. The existence of sexlinked genetic traits, such as white eyes in fruit flies (Drosophila melanogaster), was shown by the American biologist Thomas Hunt Morgan in 1910 in studies capable of locating a specific gene on a specific chromosome. Using light-microscope observations, Morgan and his students Alfred Henry Sturtevant, Hermann Joseph Muller, and Calvin Blackman Bridges studied the phenomenon of crossing-over, the process by which chromosomes exchange genes, and as a result were able to construct chromosome maps. Their research proceeded quickly; in 1915, the "Drosophila" group at Columbia University published The Mechanism of Mendelian Heredity—a seminal work that demonstrated the linear arrangement of genes in the chromosome and helped explain abnormal genetic ratios and variation. However, explanations for genetic variation remained unsatisfactory until the pioneering work of Hermann Muller at the University of Texas. Muller experimented with radiation and high temperatures to measure rates of mutation, eventually determining that genes, while generally stable, can be externally induced to mutate. (This discovery also opened the possibility of genetic engineering.) His Artificial Transmutation of the Gene, published in 1927, also hinted at the gene's ability to control metabolism and morphology, leading biochemists and other scientists to investigate the physical composition of the gene and the chemical basis of heredity.

Beginning in the 1940s, techniques such as bacterial vectors and X-ray diffraction analysis led to the development of both biochemical genetics and molecular genetics. In 1941, the Stanford biologist George Wells Beadle and biochemist Edward Lawrie Tatum proposed the one gene–one enzyme theory after experimenting on the nutritional requirements of mutated bread mold, ushering in the field of biochemical genetics by providing an introductory blueprint for the chemical synthesis of enzymes. A few years later, in 1944, the American geneticists Oswald Avery, Colin MacLeod, and Maclyn McCarty transformed bacteria through the introduction of foreign DNA, thereby determining that DNA was the primary heredity material. This indicated that DNA, rather than the previously suspected class of proteins, was the actual carrier of genetic information. Further proof came in 1952 when the American geneticists Alfred D. Hershey and Martha Chase, working at the Cold Spring Harbor Biological Station in New York, demonstrated that viral DNA was responsible for replication within infected bacteria. Using a bacteriophage (a bacterial virus) as a vector, the scientists showed that it was the virus's DNA, not a protein, that infected the host bacteria. However, while DNA was clearly the molecule of heredity, questions on the structure and mechanisms of DNA remained that could only be solved by molecular biology.

By 1950, geneticists had adopted the method of X-ray diffraction analysis pioneered by the American chemist Linus Pauling at the California Institute of Technology to determine the three-dimensional structure of the DNA molecule. Pauling proposed both single-and triple-helix models, but in 1953 the American biochemist James Watson and British biophysicist Francis Crick correctly determined that the DNA molecule was a double helix. The two men proposed that DNA was transcribed into RNA, then translated or expressed as a protein, a method of genetic replication later proven by the American molecular biologists Matthew Stanley Meselson and Franklin William Stahl and now known as the "central dogma" of molecular genetics. In 1961, Crick and Sidney Brenner determined that codons, groups of three nucleotides (adenine, cytosine, guanine, uracil and thymine), were responsible for the synthesis of proteins, while the National Institutes of Health researchers Marshall W. Nirenberg and Johann H. Matthaei showed in 1965 that certain codon combinations also lead to the production of amino acids. A final piece of the genetic puzzle—the means by which genes are activated or deactivated—was resolved by the operon model of genetic regulation. Proposed by the Frenchman Jacques Monod, the operon model requires that regulatory nucleotides, which account for a substantial portion of the DNA molecule, repress the function of other genes by disrupting RNA transcription under certain conditions.

Modern Applied Genetics

The study and sophistication of genetics increased rapidly in the last quarter of the twentieth century, as scientists, aided by advances in technology and industry and government funding, concentrated on both pure and applied genetics. Recombinant DNA engineering and prenatal genetic screening for some inherited diseases became possible in the early 1970s, leading to public concern over potential misuse and eventual governmental regulation. At the same time, the central dogma expanded to include the phenomenon of reverse transcription after American virologist David Baltimore demonstrated that retroviruses were capable of reproducing themselves by copying their own RNA. Perhaps the greatest advancement in pure genetic research came in the form of the Human Genome Project. Launched in 1988 by the U. S. Department of Energy and the National Institutes of Health, the Human Genome Project succeeded in sequencing a human genome in 2000 and represents the new state of "big" biology—an international partnership of government, academic, and industrial research institutions. Although researchers expect that the project will deliver remarkable medical and biological applications, some outside observers worry about the potential for genetic discrimination, genetic racial typing (see Racial Science), and the revitalization of Eugenics, demonstrating both the promise and the danger of contemporary genetics.

Today genetics permeates both the biological sciences and American culture, surfacing in research laboratories, congressional hearings, and courtrooms as well as popular movies and books. Genetics has unified the biological sciences and led to the modern synthesis of evolutionary theory and biology by demonstrating that organisms share the same basic genetic materials and processes. DNA fingerprinting plays a vital role in criminal investigations and the establishment of paternity, while genetic screening and therapy provide hope for those suffering from inherited diseases like sickle-cell anemia, cystic fibrosis, or Huntington's disease. Entering the twenty-first century, transgenic crops may provide the best window into the future impact of genetics, as the rise of a transgenic agricultural industry, which produces crops with an increased pesticide resistance and shelf life, has also led to a counter industry based on organic, or non-genetically enhanced, crops.

Bibliography

Caulfield, Timothy A., and Bryn Williams-Jones, eds. The Commercialization of Genetic Research: Ethical, Legal, and Policy Issues. New York: Kluwer, 1999.

Kohler, Robert E. Lords of the Fly. Chicago: University of Chicago Press, 1994.

Olby, Robert. The Path to the Double Helix. Seattle: University of Washington Press, 1974. Reprint, New York: Dover, 1994.

Ridley, Matt. Genome: The Autobiography of a Species in 23 Chapters. New York: Harper Collins, 1999.

Sarkar, Sahotra. Genetics and Reductionism. Cambridge, U. K., and New York: Cambridge University Press, 1998.

Sturtevant, A. H. A History of Genetics. New York: Cold Spring Harbor Laboratory Press, 2001.

—J. G. Whitesides