Human Genome Project
Human Genome Project
Human Genome Project
The worldwide effort, originally named the Human Genome Initiative but later known as the Human Genome Project or HGP, began in 1987 and was celebrated as complete in 2001. When begun, HGP was dubbed "big science" comparable to placing human beings on the moon. It was international in scope, involving numerous laboratories and associations of scientists around the world and receiving public funding in the United States of $200 million per year with a scheduled fifteen year timeline. The U.S. Department of Energy (DOE) began funding the project in 1987, followed by the National Institutes of Health (NIH) in 1990.
History and goals
The scientific goal was to map the genes and sequence human DNA. Mapping would eventually reveal the position and spacing of the then predicted one hundred thousand genes in each of the human body's cells; sequencing would determine the order of the four base pairs—the A (adenine), T (thymine), G (guanine), and C (cytosine) nucleotides—that compose the DNA molecule. The primary motive was that which drives all basic science, namely, the need to know. The secondary motive was perhaps even more important, namely, to identify the four thousand or so genes that were suspected to be responsible for inherited diseases and prepare the way for treatment through genetic therapy. This would benefit society, HGP architects thought, because a library of DNA knowledge would jump start medical research on many fronts. Many early prophecies found their fulfillment. Some did not.
What was not anticipated was the competition between the private sector and the public sector. J. Craig Venter (b. 1946) led the private sector effort. While on a grant from NIH, Venter applied for nearly three thousand patents on Expressed Sequence Tags (ESTs). The ESTs located genes but stopped short of identifying gene function. A furor developed when researchers working with government money applied for patents on data that merely reports knowledge of what already exists in nature—knowledge of existing DNA sequences—and this led to the 1992 resignation of James Watson (b. 1928) from the directorship of NIH's National Center for Human Genome Research (NCHGR). Watson, who along with Francis Crick (b. 1916) is famed for his discovery of the double helix structure of DNA, was the first to head the NCHGR
Venter then established The Institute for Genomic Research (TIGR) and began using Applied Biosystems automatic sequencers twenty-four hours per day to speed up nucleotide sequencing and the locating of ESTs. By 1998 Venter had established Celera Genomics with sequencing capacity fifty times greater than TIGR, and by June 17, 2000, he concluded a ninety percent complete account of the human genome. It was published in the February 16, 2001, issue of Science.
Francis Collins (b. 1950) took over NCHGR leadership from Watson and found himself driving the public sector effort, racing with Venter toward the mapping finish line. Collins drew twenty laboratories worldwide with hundreds of researchers into the International Human Genome Sequencing Consortium, which he directed from his Washington office. Collins repudiated patenting of raw genomic data and sought to place DNA data into the public domain as rapidly as possible so as to prevent private patenting. His philosophy was that the human genome is the common property of the whole human race. The public project finished almost simultaneously with the private, and the ninety percent complete Collins map appeared one day prior to Venter's on February 15, 2001, in Nature.
Human DNA, as it turns out, is largely junk—that is, 98.6 percent does not code for proteins. Half of the junk DNA consists of repeated sequences of various types, most of which are parasitic elements inherited from our distant evolutionary past. Only 1.1 percent to 1.4 percent constitute sequences that code for proteins that function as genes.
Of dramatic interest is the number of genes in the human genome. At the time of the announcement, Collins estimated there are 31,000 protein-encoding genes; he could actually list 22,000. Venter could provide a list of 26,000, to which he added an estimate of 10,000 additional possibilities. For round numbers, the estimate in 2001 stood at 30,000 human genes.
This is philosophically significant, because when the project began in 1987 the anticipated number of genes was 100,000. It was further assumed that human complexity was lodged in the number of genes: the greater the number of genes, the greater the complexity. So, confusion appeared when, nearing the completion of HGP, scientists could find only a third of the anticipated number. Confusion was enhanced when the human genome was compared to a yeast cell with 6,000 genes, a fly with 13,000 genes, a worm with 26,000 genes, and a rice cell with 50,000 genes. On the basis of the previous assumption, a grain of rice should be more complex than Albert Einstein.
With the near completion of HGP, no longer could human uniqueness, complexity, or even distinctiveness be lodged in the number of genes. Collins began to speculate that perhaps what is distinctively human could be found not in the genes themselves but in the multiple proteins and the complexity of protein production. Culturally, DNA began to lose some of its magic, some of its association with human essence.
The theology and ethics of HGP
At the outset, HGP scientists anticipated ethical and public policy concerns; they were acutely aware that their research would have an impact on society and were willing to share responsibility for it. When in 1987 James Watson counseled the U.S. Department of Health and Human Services to appropriate the funds for what would become HGP, he recommended that three percent of the budget be allotted to study the ethical, legal, and social implications of genome research. Watson insisted that society learn to use genetic information only in beneficial ways; if necessary, the government should pass laws at both the federal and state levels to prevent invasions of privacy and discrimination on genetic grounds. Moral controversy broke out repeatedly during the near decade and a half of research.
Religious responses to the advancing frontier of genetic knowledge emerge mainly from people's concern to relieve human suffering and employ science to improve human health and wellbeing. A statement prepared by the National Council of Churches under the leadership of Union Seminary ethicist Roger L. Shinn affirms that churches in the United States must be involved with genetic research and therapy. "The Christian churches understand themselves as communities dedicated to obeying the will of God through service to others. The churches have a particular concern for those who are hurt or whose faith has been shaken, as demonstrated by the long history of the churches in providing medical care .… Moreover, the churches have a mission to prevent suffering as well as to alleviate it."
In 1990 the Center for Theology and the Natural Sciences (CTNS) at the Graduate Theological Union (GTU) in Berkeley, California, obtained one of the first grants offered by the Ethical, Legal, and Social Issues (ELSI) division of NCHGR. A team of molecular biologists, behavioral geneticists, theologians, and bioethicists monitored the first years of HGP research to articulate theological and ethical implications of the new knowledge. Many religious and ethical issues eventually became public policy concerns. These are adumbrated below.
Genetic discrimination. When Watson recommended the establishment of ELSI, the first public policy concern was what he called privacy, here called genetic discrimination. An anticipated and feared scenario took the following steps. As researchers identify and locate most if not all genes in the human genome that either condition or, in some cases, cause disease, the foreknowledge of an individual's genetic predisposition to expensive diseases could lead to loss of medical insurance and perhaps loss of employment opportunities. As HGP progressed, the gene for cystic fibrosis was found on chromosome seven, and Huntington's chorea on chromosome four. Alzheimer's disease was sought on chromosome twenty-one, and colon cancer on chromosome two. Disposition to muscular dystrophy, sickle-cell anemia, Tay Sachs disease, certain cancers, and numerous other diseases turned out to have locatable genetic origins. More knowledge is yet to come. When it comes, it may be accompanied by an inexpensive method for testing the genome of each individual to see if he or she has any genes for any diseases. Screening for all genetic diseases may become routine for newborns just as testing for phenylketonuria (PKU) has been since the 1960s. A person's individual genome might become part of a data bank to which each person, as well as health care providers, would have future access. The advantage is clear: Medical care from birth to grave could be carefully planned to delay onset, appropriately treat, and perhaps even prevent or cure genetically-based diseases.
Despite the promise for advances in preventative health care, fear arises due to practices of commercial insurance. Insurance works by sharing risk. When risk is uncertain to all, then all can be asked to contribute equally to the insurance pool. Premiums can be equalized. Once the genetic disorders of individuals become known, however, this could justify higher premiums for those demonstrating greater risk. The greater the risk, the higher the premium. Insurance may even be denied those whose genes predict extended or expensive medical treatment.
Some ethicists are seeking protection from discrimination by invoking the principles of confidentiality and privacy. They argue that genetic testing should be voluntary and that the information contained in one's genome be controlled by the patient. This argument presumes that if information can be controlled, then the rights of the individual for employment, insurance, and medical care can be protected. There are grounds for thinking this approach will succeed. Title VII of the 1964 Civil Rights Act restricts pre-employment questioning about work-related health conditions. Paragraph 102.b.4 of the Act potentially protects coverage for the employee's spouse and children. Legislative proposals during the 1990s and early 2000s seem to favor privacy.
Other ethicists argue that privacy is a misguided cure for this problem. Privacy will fail, say its critics, because insurance carriers will press for legislation fairer to them, and eventually protection by privacy may slip. In addition, computer linkage makes it difficult to prevent the movement of data from hospital to insurance carrier and to anyone else bent on finding out. Most importantly, the privacy argument overlooks the principle that genome information should not finally be restricted. The more society knows, the better the health care planning can be. In the long run, what society needs is information without discrimination. The only way to obtain this is to restructure the employment-insurance-health care relationship. The current structure makes it profitable for employers and insurance carriers to discriminate against individuals with certain genetic configurations—that is, it is in their best financial interest to limit or even deny health care. A restructuring is called for so that it becomes profitable to deliver, not withhold, health care. To accomplish this the whole nation will have to become more egalitarian—that is, to think of the nation itself as a single community willing to care for its own constituents.
The Abortion controversy. Given the divisiveness of the abortion controversy in the United States and certain other countries, fears arise over possible genetic discrimination in the womb or even prior to the womb in the petri dish. Techniques have been developed to examine in vitro fertilized (IVF) eggs as early as the fourth cell division in order to identify so-called defective genes, such as the chromosomal structure of Down syndrome. Prospective parents may soon routinely fertilize a dozen or so eggs in the laboratory, screen for the preferred genetic make up, implant the desired zygote or zygotes, and discard the rest. What will be the status of the discarded embryos? Might they be considered abortions? By what criteria does one define "defective" when considering the future of a human being? Should prospective parents limit themselves to eliminating "defective" children, or should they go on to screen for enhancing genetic traits such as blue eyes or higher intelligence? If so, might this lead to a new form of eugenics, to selective breeding based upon personal preference and prevailing social values? What will become of human dignity in all this?
Relevant here is that the legal precedent set by Roe v. Wade (1973) would not serve to legitimate discarding preimplanted embryos. This Supreme Court case legalized the use of abortion to eliminate a fetus from a woman's body as an extension of a woman's right to determine what happens to her body. This would not apply to preimplanted embryos, however, because they are life forms outside the woman's body.
The Roman Catholic tradition has set strong precedents regarding the practice of abortion. The Second Vatican Council document Gaudium et spes (1965) states the position still held today: "… from the moment of its conception life must be guarded with the greatest care, while abortion and infanticide are unspeakable crimes." The challenge to ethicists in the Roman Catholic tradition in the near future will be to examine what transpires at the preimplantation stage of the embryo to determine if the word abortion applies. If it does, this may lead to recommending that genetic screening be pushed back one step further, to the gamete stage prior to fertilization. The genetic make up of sperm and ovum separately could be screened, using acceptable gametes and discarding the unacceptable. The Catholic Health Association of the United States pushes back still further by recommending the development of techniques of gonadal cell therapy to make genetic corrections in the reproductive tissues of prospective parents long before conception takes place—that is, gametocyte therapy.
Genetic determinism, human freedom, and the gene myth. Religious thinkers must deal not only with laboratory science but with the cultural interpretations of science, as well as public policy influenced by both. A cultural myth has grown up with media coverage of the Human Genome Project that assumes "it's all in the genes." DNA has emerged as a cultural icon, holding the "blueprint" for humanity or being thought of as the "essence" of what makes a person a person. Even though molecular biologists withdraw from such extreme forms of genetic determinism, a cultural myth has arisen. Some commentators refer to it as the strong genetic principle ; others call it the gene myth.
Genes, sin, crime, and racial discrimination. The belief in determinism promulgated by the gene myth raises the question of moral and legal culpability. Does a genetic disposition to antisocial behavior make a person guilty or innocent before the law? Over the next decade legal systems will have to face a rethinking of the philosophical planks on which concepts such as free will, guilt, innocence, and mitigating factors have been constructed. There is no question that research into the connection between genetic determinism and human behavior will continue and new discoveries will become immediately relevant to the prosecution and defense of those accused of crimes. The focus will be on the concept of free will, because the assumption of the Western philosophy coming down from Augustine that underlies understanding of law is that guilt can only be assigned to a human agent acting freely. The specter on the genetic horizon is that confirmable genetic dispositions to certain forms of behavior will constitute compulsion, and this will place a fork in the legal road: Either the courts declare the person with a genetic disposition to crime to be innocent and set him or her free, or the courts declare him or her so constitutionally impaired as to justify incarceration and isolation from the rest of society. The first fork would jeopardize the welfare of society; the second fork would violate individual rights.
That society needs to be protected from criminal behavior, and that such protection could be had by isolating individuals with certain genetic dispositions, leads to further questions regarding insanity and race. The issue of insanity arises because the genetic defense may rely upon precedents set by the insanity defense. The courts treat insanity with a focus on the insane person's inability to distinguish right from wrong when committing a crime. When a defendant is judged innocent on these grounds, he or she is incarcerated in a mental hospital until the medical evaluators judge that the individual is cured. Once cured, the person may be released. In principle, such a person might never be judged "cured" and may spend more time in isolation than the prison penalty prescribed for the crime, maybe even the rest of his or her life. Should the genetic defense tie itself to the insanity defense, and if one's DNA is thought to last a lifetime, then the trip to the hospital may become the equivalent of a life sentence. In this way the genetic defense may backfire.
With this prospect, we have returned to the specter of genetic discrimination. The current discussion of possible genetic influence on antisocial behavior is riddled with fears of discrimination, especially its racial overtones. Because the percentage of black men among the population of incarcerated prisoners is growing, society could invoke the gene myth to associate genes with criminal predispositions and with race. A stigma against black people could arise, a presumption that they are genetically predisposed to crime. University of California sociologist Troy Duster fears that if we identify crime with genes and then genes with race, we may inadvertently provide a biological support for prejudice and discrimination.
The gay gene. Theological and ethical debate has arisen over the 1993 discovery of a possible genetic disposition to male homosexuality. Dean H. Hamer and his research team at the U.S. National Cancer Institute announced that they discovered evidence that male homosexuality—at least some male homosexuality—is genetic. Constructing family trees in instances where two or more brothers are gay combined with actual laboratory testing of homosexual DNA, Hamer located a region near the end of the long arm of the X chromosome that likely contains a gene influencing sexual orientation. Because men receive an X chromosome from their mother and a Y from their father (women receive two X's, one from each parent), this means that the possible gay gene is inherited maternally. Mothers can pass on the gay gene without themselves or their daughters being homosexual. A parallel study of lesbian genetics is as yet incomplete; and the present study of gay men will certainly require replication and confirmation. Scientists do not yet have indisputable proof.
The ethical implications, should a biological basis for homosexuality be confirmed, could point in more than one direction. The scientific fact does not itself determine the direction of the ethical interpretation of that fact. The central ethical question is this: Does the genetic disposition toward homosexuality make the bearer of that gene innocent or guilty? Two answers are logically possible.
On the one hand, a homosexual man could claim that because he inherited the gay gene and did not choose a gay orientation by his own free will, he is innocent. The biological innocence position could be buttressed by an additional argument that homosexual activity is not itself sinful; it is simply one natural form of sexual expression among others. One could go still further to say that because it is biologically inherited that it is God's will; that a person's homosexual predisposition is God's gift.
On the other hand, one could follow the opposite road and identify the gay gene with a carnal disposition to sin. Society could claim that the body inherited by each person belongs to who they are—people are determined at least in part by what their parents bequeathed them—and that an inherited disposition to homosexual behavior is just like other innate dispositions such as lust or greed, which are shared with the human race generally; all this constitutes the state of original sin into which we are born. Signposts point in both ethical directions.
Beyond the question of guilt or innocence ethicists anticipate another issue, namely, the risk of stigma. Might the presence of the gay gene in an unborn fetus be considered a genetic defect and become grounds for abortion? Would routine genetic testing lead to a wholesale reduction of gay men in a manner parallel to that of children with Down Syndrome? Would this count as class discrimination?
Somatic therapy versus germline enhancement. The debate over two distinctions—somatic versus germline intervention and therapy versus enhancement intervention—involves both secular and religious discussions. The term somatic therapy refers to the treatment of a disease in the body cells of a living individual by trying to repair an existing defect. The term germline therapy refers to intervention into the gametes, perhaps for the purpose of eliminating a gene such as that for cystic fibrosis so that it would not be passed along to future generations. Both somatic and germline therapies are conservative when compared to genetic enhancement. Enhancement goes beyond mere therapy for existing genes that may be a threat to health by selecting or adding genes to make an individual "superior" in some fashion. Enhancement might involve genetic engineering to increase bodily strength or intelligence or other socially desirable characteristics.
Ethical commentators almost universally agree that somatic therapy is morally desirable, and they look forward to the advances HGP will bring for expanding this important work. Yet they stop short of endorsing genetic selection and manipulation for the purposes of enhancing the quality of biological life for otherwise normal individuals or for the human race as a whole. New knowledge gained from HGP might locate genes that affect the brain's organization and structure so that careful engineering might lead to enhanced ability for abstract thinking or to other forms of physiological and mental improvement.
Religious ethicists argue that somatic therapy should be pursued, but enhancement through germline engineering raises cautions about protecting human dignity. In a 1982 study, the World Council of Churches stated: "Somatic cell therapy may provide a good; however, other issues are raised if it also brings about a change in germline cells. The introduction of genes into the germline is a permanent alteration .… Nonetheless, changes in genes that avoid the occurrence of disease are not necessarily made illicit merely because those changes also alter the genetic inheritance of future generations .… There is no absolute distinction between eliminating defects and improving heredity" (quoted in Peters, ed., 1998, pp. 6–8). The primary caution raised by the WCC here has to do with the lack of knowledge regarding the possible consequences of altering the human germline. The present generation lacks sufficient information regarding the long term consequences of a decision today that might turn out to be irreversible tomorrow. Thus, the WCC does not forbid forever germline therapy or even enhancement; rather, it cautions people to wait and see.
The Catholic Health Association is more positive: "Germline intervention is potentially the only means of treating genetic diseases that do their damage early in embryonic development, for which somatic cell therapy would be ineffective. Although still a long way off, developments in molecular genetics suggest that this is a goal toward which biomedicine could reasonably devote its efforts" (p. 19)
Another reason for caution regarding germline enhancement, especially among the Protestants, is the specter of eugenics. The word eugenics connotes the ghastly racial policies of Nazism, and this accounts for much of today's mistrust of genetic science in Germany and elsewhere. No one expects a resurrection of the Nazi nightmare; yet some critics fear a subtle form of eugenics slipping in the cultural back door. The growing power to control the design of living tissue will foster the emergence of the image of the "perfect child," and a new social value of perfection will begin to oppress all those who fall short.
Gene patenting. A controversy exploded in 1991 over gene patenting prompted by the filing for intellectual property rights by J. Craig Venter on nearly three thousand ESTs, expressed sequence tags. Each of these ESTs consisted of three hundred to five hundred base pairs made from cDNAs, copies of DNA sequences produced by polymerase chain reaction. ESTs are gene fragments, not whole genes; hence they mark the location of a gene but cannot identify gene function. Two issues became the focus of controversy. First, should the U.S. Patent and Trademark Office grant patents on genomic data? Even though the patents applied for were on copies of DNA sequences, their only value was to report raw genomic information. It appeared to critics that these applications failed to meet the three patenting criteria: novelty, utility, and nonobviousness. Second, should the U.S. government apply for and receive such patents in competition with the private sector? Venter's first patent applications were filed while he was working on a government grant; later he moved to the private sector and continued filing for intellectual property rights on his discoveries. James Watson followed by Francis Collins at the NIH both opposed patenting raw genomic data.
Cloning. Technically known as "somatic cell nuclear transfer," cloning techniques were developed in 1996 by Ian Wilmut at the Roslin Institute near Edinburgh, Scotland. Wilmut announced the cloning of Dolly the sheep in February 1997. The scientific breakthrough consisted of returning an already differentiated DNA nucleus to its pre-differentiated state and then transferring it to an ennucleated oocyte to make an embryo. The new embryo thus contains the genome of the donor nucleus. In the worldwide controversy that broke out in 1997 and continues in bioethical discussion, the debate seems to bypass the science of nuclear transfer; rather, the focus is on producing multiple human beings with duplicate genomes. Critics of reproductive cloning argue that children produced by cloning would suffer from loss of individuality, identity, and dignity. Roman Catholic critics along with Wilmut himself oppose human reproductive cloning on the grounds of safety—that is, the imperfect technology would lead to the destruction of many early embryos. Defenders of nuclear transfer research distinguish sharply between reproductive cloning, which they oppose, and therapeutic cloning, which is necessary for stem cell research.
Stem cells. The isolation of human embryonic stem cells (hES cells) was accomplished in August 1997 by James Thomson at the University of Wisconsin on funds from the Geron Corporation. The hES cells are removed from the inner mass of the blastocyst, an embryo at four to six days old. When isolated and placed on a feeder tray, hES cells become immortal—that is, they divide indefinitely. In addition, they are pluripotent and able to differentiate into any and every tissue. The research goal is to control gene expression so as to make designated tissue for rejuvenating human organs. Some progress in gene control has been achieved. The next hurdle to jump is histocompatibility, namely, to avoid organ rejection by matching donor and recipient genetic codes. It is likely that experiments with somatic cell nuclear transfer will be required to attain histocompatibility. Ethical objections to stem cell research from Roman Catholics center on destruction of blastocysts for research purposes. Ethical support for stem cell research stresses beneficence; it emphasizes the marvelous advances in human health and wellbeing that this medical science might offer the human race.
Conclusion: theological commitments to human dignity
Virtually all Roman Catholics and Protestants who take up the challenge of the new genetic knowledge seem to agree on a handful of theological axioms. First, they affirm that God is the creator of the world and, further, that God's creative work is ongoing. God continues to create in and through natural genetic selection and even through human intervention in the natural processes. Second, the human race is created in God's image. In this context, the divine image in humanity is tied to creativity. God creates; so do human beings. With increasing frequency, humans are described by theologians as co-creators with God, making their human contribution to the evolutionary process. In order to avoid the arrogance of thinking that humans are equal to the God who created them in the first place, people must add the term created to make the phrase created co-creators. This emphasizes human dependency on God while pointing to human opportunity and responsibility. Third, these religious documents place a high value on human dignity.
By dignity they mean what eighteenth-century German philosopher Immanuel Kant meant, namely, that each human being is treated as an end, not merely as a means to some further end. As church leaders respond responsibly to new developments in HGP, one thing can be confidently forecast: This affirmation of dignity will become decisive for thinking through the ethical implications of genetic engineering. Promoting dignity is a way of drawing an ethical implication from what the theologian can safely say, namely, that God loves each human being regardless of his or her genetic makeup and, therefore, people should love one another according to this model.
See also Behavioral Genetics; Biotechnology; Cloning; DNA; Eugenics; Freedom; Gene Patenting; Gene Therapy; Genetic Determinism; Genetic Engineering; Genetics; Genetic Testing; Nature versus Nurture; Playing God; Sin; Sociobiology; Stem Cell Research
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Human Genome Project
Human Genome Project
The genome represents the entire complement of DNA in a cell. The Human Genome Project is the determination of the entire nucleotide sequence of all 3 billion + bases of DNA within the nucleus of a human cell. It is one of the greatest scientific undertakings in the history of mankind. The first draft of the human genome sequence was completed in the year 2001 and published simultaneously in the British journal Nature and the American journal Science.
The data obtained from sequencing the human genome promise to bring unprecedented scientific rewards in the discovery of disease-causing genes, in the design of new drugs, in understanding developmental processes and cancer, and in determining the origin and evolution of the human race. The Human Genome Project has also raised many social and ethical issues with regard to the use of such information.
Origins of the Human Genome Project
One could say that the Human Genome Project really began in 1953, when James Watson and Francis Crick deduced the molecular structure of DNA, the molecule of which the genome is made. (Watson and Crick were awarded the Nobel Prize for this work in 1962.) Since that time, scientists have wanted to know the complete sequence of a gene, and even dreamed that some day it would be possible to determine the complete sequence of all of the genes in any organism, including humans.
The original impetus for the Human Genome Project came almost a decade earlier, however, from the U.S. Department of Energy (DOE) shortly after World War II. The atomic bombs that were dropped on Hiroshima and Nagasaki, Japan, left many survivors who had been exposed to high levels of radiation. The survivors of the bomb were stigmatized in Japan. They were considered poor marriage prospects, because of the potential for carrying mutations, and the rest of Japanese society often ostracized them. In 1946 the famous geneticist and Nobel laureate Hermann J. Muller wrote in the New York Times that "if they could foresee the results [mutations among their descendants] 1,000 years from now …, they might consider themselves more fortunate if the bomb had killed them."
Muller had firsthand experience with the devastating effects of radiation, having studied the biological effects of radiation on the fruit fly Drosophila melanogaster. He predicted similar results would follow from the human exposure to radiation. As a consequence, the Atomic Energy Commission of the DOE set up an Atomic Bomb Casualty Commission in 1947 to address the issue of potential mutations among the survivors. The problem they faced was how to experimentally determine such mutations. At that time there were no suitable methods to study the problem. Indeed, it would be many years before the appropriate technology was available.
During the 1970s molecular biologists developed techniques for the isolation and cloning of individual genes. Paul Berg was the first to create a recombinant DNA molecule in 1972, and within a few years gene cloning became a standard tool of the molecular biologist. Using cloning techniques, scientists could generate large quantities of a single gene, enabling researchers
|MODEL ORGANISMS SEQUENCED|
|Date sequenced a||Species||Total bases b|
|7/28/1995||Haemophilis influenzae (bacterium)||1,830,138|
|10/30/1995||Mycoplasma genitalium (bacterium)||580,073|
|5/29/1997||Saccharomyces cerevisiae (yeast)||12,069,247|
|9/5/1997||Escherichia coli (bacterium)||4,639,221|
|11/20/1997||Bacillus subtillis (bacterium)||4,214,814|
|12/31/1998||Caenorhabditis elegans (round worm)||97,283,371|
|3/24/2000||Drosophila melanogaster (fruit fly)||~137,000,000|
|12/14/2000||Arabidopsis thaliana (mustard plant)||~115,400,000|
|1/26/2001||Oryza sativa (rice)||~430,000,000|
|2/15/2001||Homo sapiens (human)||~3,200,000,000|
|First publication date.|
|Data excludes organelles or plasmids. These numbers should not be taken as absolute. Scientists are confirming the sequences; several laboratories were involved in the sequencing of a particular organism and have slightly different numbers; and there are some strain variations. Data were obtained from the (NCBI) Web site.|
|The first number was originally published, and the second is a correction as of June 2000.|
to study its structure and function. In 1977 Drs. Walter Gilbert and Fred Sanger independently developed methods for the sequencing of DNA, for which they received the 1980 Nobel Prize along with Berg. Sanger's group in England was the first to completely sequence a genome, identifying all 5,386 bases of the bacterial virus φχ174.
Another technological breakthrough occurred in 1985, when the polymerase chain reaction method was developed by Dr. Kary Mullis and colleagues at Cetus Corp. This team devised a method whereby minute samples of DNA can be multiplied a billion-fold for analysis. This technique, which has many applications in diverse fields of biology, is one of the most important scientific breakthroughs in gene analysis. Mullis received the Nobel Prize for this work in 1993.
At this time, however, DNA sequencing was still done by hand. At best, a researcher could manually sequence only a few hundred bases per day. To be able to sequence the human genome, machines would be needed that could sequence a million or more bases per day. In 1986 Leroy Hood developed the first generation of automated DNA sequencers, thereby dramatically increasing the speed with which bases could be sequenced. Thus, by the mid-1980s the stage was set.
With these new techniques, molecular biologists now felt that it might be feasible to sequence the entire human genome. The first serious discussions came in June 1985, when Robert Sinsheimer, chancellor of the University of California at Santa Cruz, called a meeting of leading scientists to discuss the possibility of sequencing the human genome. Sinsheimer was inspired by the success of the Manhattan Project, which was the concerted effort of many physicists to develop atomic weapons during World War II. That project led to rapid development and a massive influx of funding for physicists. Sinsheimer wanted a "Manhattan Project" for molecular biology, to enhance and expand human genome research.
Meanwhile, the DOE continued to be interested in the problem of identifying mutations caused by radiation exposure. Led by associate director Charles DeLisi, the DOE became a strong supporter of the genome-mapping initiative, for it understood that sequencing the entire genome would provide the best way to analyze such mutations. Thus the DOE became the first federal agency to begin funding the Human Genome Project.
Mapping the human genome came to be called the "Holy Grail of Molecular Biology," and many biologists were interested in the project. Most notable among them was Nobel laureate Gilbert who, through his interest, personality, and academic ties, developed enormous enthusiasm for the project. The initial goals set out for the Human Genome Project were threefold: to develop genetic linkage maps; to create a physical map of ordered clones of DNA sequences; and to develop the capacity for large-scale sequencing, because faster and cheaper machines along with other great leaps in technology would be needed to get the job done.
In 1988 the National Institutes of Health (NIH) set up an Office of the Human Genome, and Watson agreed to head the project. It had an estimated budget of approximately $3 billion, and 3 percent of the funding was devoted to the study of the social and ethical issues that would arise from the endeavor. A target date for completion of the project was set for September 30, 2005. By 1990 the Human Genome Project had received the additional endorsement of the National Academy of Sciences, the National Research Council, the DOE, the National Science Foundation, the U.S. Department of Agriculture, and the Howard Hughes Medical Institute. Sequencing of the human genome had now officially begun.
While sequencing the human genome was a primary goal, other sequencing projects were just as important. Many scientists established projects that sought to sequence several organisms of genetic, biochemical, or medical importance (see Table 1). These so-called model organisms, with their smaller genomes, would be useful in testing sequencing methodologies and for providing invaluable information that could be used to identify corresponding genes in the human genome. Sequence databases were established, and computer programs to search these databases were written.
Competition between the Public and Private Sectors
Dr. Craig Venter, a scientist at the NIH, felt that private companies could sequence genomes faster than publicly funded laboratories. For this reason he founded a biotechnology company called the Institute for Genomic Research (TIGR). In 1995 TIGR published the first completely sequenced genome, that of the bacterium Haemophilus influenzae. TIGR was soon joined by other biotechnology companies that competed directly with the publicly funded Human Genome Project.
Among these other biotech firms is Celera Genomics, founded in 1998 by Venter in conjunction with the Perkin-Elmer Corporation, manufacturer of the world's fastest automatic DNA sequencers. Celera's goal was to privately sequence the human genome in direct competition with the public efforts supported by the NIH and DOE and the governments of several foreign countries. Using 300 Perkin-Elmer automatic DNA sequencers along with one of the world's most powerful supercomputers, Celera sequenced the genomes of several model organisms with remarkable speed and, in April 2000, announced that it had a preliminary sequence of the human genome.
In order eventually to make a profit, these biotech companies were patenting DNA sequences and intended ultimately to charge clients, including researchers, for access to their databases. This issue of patenting had already caused controversy. Watson felt strongly that the sequence data flowing from the Human Genome Project should remain within the public domain, freely available to all. Meeting opposition to this view, he stepped down from his position as director of the NIH-sponsored project in 1992 and was succeeded by Francis Collins.
Other researchers shared Watson's view, and in 1996 the international consortium of publicly funded laboratories agreed at a meeting in Bermuda to release all data to GenBank, a genome database maintained by NIH. The agreement reached by these scientists came to be known as "The Bermuda Principles," and it mandated that sequence data would be posted on the Internet within 24 hours of acquisition. Because the information is freely available to the public, the sequences can not be patented. The dispute between Celera Genomics and the International Human Genome Consortium continues, as scientists now begin the task of searching the genome for valuable information.
Progress in the Human Genome Project
Sequencing the human genome has led to some surprising results. For example, we once thought that highly evolved humans would need a great many genes to account for their complexity, and scientists originally estimated the number of human genes to be about 100,000. The draft of the human genome, however, indicates that humans may have only about 30,000 genes, far fewer than originally expected. Indeed, this is only about one-third more than the number of genes found in the lowly roundworm, Caenorhabditis elegans (approximately 20,000 genes), and roughly twice the number of genes in the fruit fly Drosophila melanogaster (approximately 14,000 genes). Subsequent estimates have placed the number of human genes closer to 70,000; the true number is unknown as of mid-2002. Scientists have learned that most of the genome does not code for proteins, but rather contains "junk DNA" of no known function. In fact, only a small percentage of human DNA actually encodes a gene.
The complete human genome consists of twenty-two pairs of chromosomes plus the X and Y sex chromosomes. On December 2, 1999, more than 100 scientists working together in laboratories in the United Kingdom, Japan, the United States, Canada, and Sweden announced the first completely sequenced human chromosome, chromosome 22, the smallest of the autosomes . To assure the accuracy of the sequence data, each segment must be sequenced at least ten times.
Thousands of scientists, working in more than 100 laboratories and 19 different countries around the world, have contributed to the Human Genome Project since its inception. Thanks to the development of later generations of high-speed automatic sequencers and supercomputers to handle the enormous amount of data generated, work on the project progressed well ahead of schedule and well under budget, a rare phenomenon in government-sponsored projects. In 2001 the first draft of the complete human genome was published. However, considerable work remained to be done, particularly in the sequence of regions of repetitive DNA.
Whose Genome Is It?
Although all humans share more than 99.99 percent of their genome sequences, each human is unique. Geneticists estimate that each person carries many mutations, perhaps hundreds or even thousands of them. Therefore, one of the major questions that has arisen in the Human Genome Project is "whose genome is it?" The final catalog of sequences, whenever it is complete, will have to take into account these individual variations, and ultimately there will be a "consensus sequence," but it will represent no one specific individual.
A related issue arises from the distinct differences that scientists anticipate will occur among different populations. Which sequences should be considered "normal," and which ones should be classed as "mutated"? The Human Genome Diversity Project was proposed in 1997 to catalog and study naturally occurring sequence variations among racial and geographic groups. This project never gained much support, however, because of the social and ethical ramifications to such a catalog. On the other hand, a Human Cancer Genome Anatomy Project was initiated to catalog all the genes that are expressed in cancer cells in order to aid in the detection and treatment of cancers. This project enjoyed much more support.
Patenting the Genome
From the outset there has been considerable debate among scientists, politicians, and entrepreneurs as to whether the human gene sequences can or should be patented. Indeed, this debate was the reason that Watson resigned as the first director of the NIH Human Genome Project program in 1992. Watson's position was opposed by many biotechnology companies, which hoped to recover the cost of their genome research and began patenting short segments of sequenced DNA without any idea as to their function. As of 2000, the U.S. Patent and Trademark Office (PTO) changed its policy, and began granting patents only to genes that have been identified, rather than just the random sequenced fragments. The data that flow from genome sequencing will be an invaluable scientific resource, particularly in the area of developing new medical treatments, but its use will be restricted if individual organizations can claim exclusive use rights to large segments of it. It is thus clear that debate on the patenting of genes will continue for years to come.
At present much of data from genome research are available to scientists and other interested parties. The data generated by participants in the Bermuda Principles agreement can be accessed on-line at the National Center for Biotechnology Information (NCBI) Web site, at <www.ncbi.nlm.nih.gov/genome/guide/human>. The International Human Genome Consortium Web site provides a current list of genome sites that offer links to most genome databases at <www.ensembl.org/genome/central>. Information about all the genomes that have been sequenced, as well as information on the sequencing of cancer genes, can be found on the Internet at <http://www.ncbi.nlm.nih.gov>.
Genomics and Proteomics
The Human Genome Project has given rise to new fields of research. One of these is genomics . This new field combines information science with molecular biology. It is resulting in the "mining of the genome" for valuable sequence data.
An even more recent development is the field of proteomics , the study of protein sequences. Research in this field is rapidly expanding, as protein sequences can be predicted from the gene sequence. The folding of the proteins (secondary and tertiary structures) can be predicted by computers, leading to a three-dimensional view of the protein encoded by a particular gene. Proteomics will be the next big challenge for genetics research. Indeed, Celera is already gearing up for massive protein sequencing.
From the very beginning of the Human Genome Project, many from both the scientific and public sector have been concerned with ethical issues raised by the research. These issues include preserving the confidentiality of an individual's DNA information and avoiding the stigmatization of individuals who carry certain genes. Some fear that insurers will deny coverage for "preexisting" conditions to people carrying a gene that predisposes them to particular diseases, or that employers might start demanding genetic testing of job applicants.
There are also concerns that prenatal genetic testing could lead to genetic manipulation or a decision to abort based on undesirable traits disclosed by the tests. In addition, some raise concerns that a full knowledge of the human genome could raise profound psychological issues. For example, individuals who know that they carry detrimental genes may find the knowledge to be too great a burden to bear. All of these ethical issues will ultimately have to be addressed by society as a whole.
see also Automated Sequencer; Bioinformatics; Cancer; Cloning Genes; Genome; Genomics; Genomics Industry; Model Organisms; Muller, Hermann; Polymerase Chain Reaction; Polymorphisms; Repetitive DNA Elements; Sequencing DNA; Watson, James; Yeast.
Ralph R. Meyer
Collins, Francis S., and Karin G. Jegalian. "Deciphering the Code of Life." Scientific American 281, 6 (1999): 86-91.
Cook-Deegan, Robert. The Gene Wars: Science, Politics and the Human Genome Project. New York: Norton, 1994.
Davies, Kevin. Cracking the Genome: Inside the Race to Unlock Human DNA. New York: Free Press, 2001.
Ezzell, Carol. "Special Report: Beyond the Human Genome Project." Scientific American 283, no. 1 (2000): 64-69.
Kevles, Daniel J., and Leroy Hood, eds. The Code of Codes: Scientific and Social Issues in the Human Genome Project. Cambridge, MA: Harvard University Press, 1992.
Koshland, Daniel E. Jr. "Sequences and Consequences of the Human Genome." Science 246 (1989): 189.
Nature. "The Human Genome." Special Issue 409 (Feb. 15, 2001): 860-921.
Science. "The Human Genome." Special Issue 291 (Feb. 16, 2001): 1145-1434.
Shostak, Stanley. Evolution of Sameness and Difference. Perspectives on the Human Genome Project. Amsterdam: Harwood Academic Publishers, 1999.
Sloan, Phillip R., ed. Controlling Our Destinies: Historical, Philosophical, Ethical, and Theological Perspectives on the Human Genome Project. South Bend, IN: Notre Dame Press, 2000.
Watson, James D., and Robert M. Cook-Deegan. "Origins of the Human Genome Project." FASEB Journal 5 (1991): 8-11.
In 2002 Craig Venter announced that Celera had sequenced his personal genome, not a composite as originally claimed.
"Human Genome Project." Genetics. . Encyclopedia.com. (October 20, 2016). http://www.encyclopedia.com/medicine/medical-magazines/human-genome-project
"Human Genome Project." Genetics. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/medicine/medical-magazines/human-genome-project
Human Genome Project
Human Genome Project
The Human Genome Project is the scientific research effort to construct a complete map of all of the genes carried in human chromosomes. The finished blueprint of human genetic information will serve as a basic reference for research in human biology and will provide insights into the genetic basis of human disease.
Fifteen-year federal project
The human "genome" is the word used to describe the complete collection of genes found in a single set of human chromosomes. It was in the early 1980s that medical and technical advances first suggested to biologists that a project was possible that would locate, identify, and find out what each of the 100,000 or so genes that make up the human body actually do. After investigations by two United States government agencies—the Department of Energy and the National Institutes of Health—the U.S. Congress voted to support a fifteen-year project, and on October 1, 1990, the Human Genome Project officially began. It was to be coordinated with the existing related programs in several other countries. The project's official goals are to identify all of the approximately 50,000 genes in human deoxyribonucleic acid (DNA) and to determine the sequences of the 3.2 billion base pairs that make up human DNA. The project will also store this information in databases, develop tools for data analysis, and address any ethical, legal, and social issues that may arise.
Makeup of the human chromosome
In order to understand how mammoth an undertaking this ambitious project is, it is necessary to know how genetic instructions are carried on the human chromosome. Humans have forty-six chromosomes, which are coiled structures in the nucleus of a cell that carry DNA. DNA is the genetic material that contains the code for all living things, and it consists of two long chains or strands joined together by chemicals called bases or nucleotides (pronounced NOO-klee-uh-tides), all of which are coiled together into a twisted-ladder shape called a double helix. The bases are considered to be the "rungs" of the twisted ladder. These rungs are made up of only four different types of nucleotides—adenine (A), thymine (T), guanine (G), and cytosine (C)—and are critical to understanding how nature stores and uses a genetic code. The four bases always form a "rung" in pairs, and they always pair up the same way. Scientists know that A always pairs with T, and G always pairs with C. Therefore, each DNA base is like a letter of the alphabet, and a sequence or chain of bases can be thought of as forming a certain message.
Words to Know
Chromosome: Structures that organize genetic information in the nucleus of a cell.
DNA (deoxyribonucleic acid): Large, complex molecules found in the nuclei of cells that carry genetic information for an organism's development.
Gene: A segment of a DNA (deoxyribonucleic acid) molecule contained in the nucleus of a cell that acts as a kind of code for the production of some specific protein. Genes carry instructions for the formation, functioning, and transmission of specific traits from one generation to another.
Nucleotide: The basic unit of a nucleic acid. It consists of a simple sugar, a phosphate group, and a nitrogen-containing base. (Pronounced NOO-klee-uh-tide.)
The human genome
The human genome, which is the entire collection of genes found in a single set of chromosomes (or all the DNA in an organism), consists of 3.2 billion nucleotide pairs or bases. To get some idea about how much information is packed into a very tiny space, a single large gene may consist of tens of thousands of nucleotides or bases, and a single chromosome may contain as many as one million nucleotide base pairs and four thousand genes. What is most important about these pairs of bases is the particular order of the As, Ts, Gs, and Cs. Their order dictates whether an organism is a human being, a bumblebee, or an apple. Another way of looking at the size of the human genome present in each of our cells is to consider the following phone book analogy. If the DNA sequence of the human genome were compiled in books, 200 volumes the size of the Manhattan telephone book (1,000 pages) would be needed to hold it all. This would take 9.5 years to read aloud without stopping. In actuality, since the human genome is 3.2 billion base pairs long, it will take 3 gigabytes of computer data storage to hold it all.
Two types of maps
In light of the project's main goal—to map the location of all the genes on every chromosome and to determine the exact sequence of nucleotides of the entire genome—two types of maps are being made. One of these is a physical map that measures the distance between two genes in terms of nucleotides. A very detailed physical map is needed before real sequencing can be done. Sequencing is the precise order of the nucleotides. The other map type is called a genetic linkage map and it measures the distance between two genes in terms of how frequently the genes are inherited together. This is important since the closer genes are to each other on a chromosome, the more likely they are to be inherited together.
As an international project involving at least eighteen countries, the Human Genome Project was able to make unexpected progress in its early years, and it revised its schedule in 1993 and again in 1998. During December 1999, an international team announced it had achieved a scientific milestone by compiling the entire code of a complete human chromosome for the first time. Researchers chose chromosome 22 because of its relatively small size and its link to many major diseases. The sequence they compiled is over 23 million letters in length and is the longest continuous stretch of DNA ever deciphered and assembled. What was described as the "text" of one chapter of the 23-volume human genetic instruction book was therefore completed. Francis Collins, director of the National Human Genome Research Institute of the National Institutes of Health, said of this success, "To see the entire sequence of a human chromosome for the first time is like seeing an ocean liner emerge out of the fog, when all you've ever seen before were rowboats."
In February 2001, scientists working on the project published the first interpretations of the human genome sequence. Previously, many in the scientific community had believed that the number of human genes totaled about 100,000. But the new findings surprised everyone: both research groups said they could find only about 30,000 or so human genes. This meant that humans have remarkably few genes, not that many more than a fruit fly, which has 13,601 (scientists had decoded this sequence in March 2000). This discovery led scientists to conclude that human complexity does not come from a sheer quantity of genes. Instead, human complexity seems to arise as a result of the structure of the network of different genes, proteins, and groups of proteins and the dynamics of those parts connecting at different times and on different levels.
Private sector competition
The Human Genome Project typically is called "big science," usually referring to a large, complex, and, above all, expensive operation that can only be undertaken by a government. That is why the emergence of private sector (non-governmental) competition in 1998 was such a surprise. During that year, J. Craig Venter, the founder of Celera Genomics, announced that his company planned to sequence the human genome on its own. He said he could achieve this because Celera Genomics was using the largest civilian supercomputer ever made to produce the needed sequences. When Celera began to show real progress, it appeared to many that a race between the public and private sectors would occur. However, once Venter met with Francis Collins, the director of the Human Genome Project, it was agreed that cooperation would achieve more than competition. Therefore, when what was called the "draft sequence" was completed and announced on June 26, 2000, Venter and Collins appeared together and gave the public its first news of this achievement. They stated that the project had compiled what might be called a rough draft of the human genome, having put together a sequence of about 90 percent.
Total project completion—meaning that all of the remaining gaps will be closed and its accuracy improved, so that a complete, high-quality reference map is available—is expected in 2003. This will coincide with the fiftieth anniversary of the description of the molecular structure of DNA, first unraveled in 1953 by American molecular biologist James Watson (1928– ) and English molecular biologist Francis Crick (1916– ). When the genome is completely mapped and fully sequenced in 2003, two years earlier than planned, biologists can for the first time stand back and look at each chromosome as well as the entire human blueprint. They will start to understand how a chromosome is organized, where the genes are located, how they express themselves, how they are duplicated and inherited, and how disease-causing mutations occur. This could lead to the development of new therapies for diseases thought to be incurable as well as to new ways of manipulating DNA.
It also could lead to testing people for "undesirable" genes. However, such a statement leads to all sorts of potential dangers involving ethical and legal matters. Fortunately, such issues have been considered from the beginning. Part of the project's goal is to address these difficult issues of privacy and responsibility, and to use the completely mapped and fully sequenced genome to everyone's benefit.
There is no doubt that the breakthrough in human genome research will mark a revolution in the biology of the twenty-first century. Although we presently have only a glimpse of what the potential benefits of this knowledge may be, there are several good indicators of the fields that may benefit the most. What we have already witnessed is the real beginning of an American biotechnology effort whose genomic research will result in the creation of a multibillion-dollar industry. Many of these new companies that will emerge will develop new DNA-based products and technologies that will improve our health and well-being.
Molecular medicine. First among these new medical applications might be advances in what is known as molecular medicine. With the knowledge gained from the completion of the Human Genome Project, doctors will be less concerned with the symptoms of a disease or how it shows itself than they will with what actually causes the disease. Detailed genome maps will allow researchers to seek and find the genes that are associated with such diseases as inherited colon and breast cancer and Alzheimer's disease. Not only will doctors be able to diagnose these conditions at a much earlier point, but they will have new types of drugs, as well as new techniques and therapies, that will allow them to cure or even prevent a disease. In the near future, it is expected that doctors will know much earlier whether a person has or is predisposed to getting certain diseases,
and to then be able to use certain gene therapies or "custom drugs" to cure these diseases.
New uses for microbes. Microbes are any forms of life that are too small to be seen without a microscope. Bacteria are the most common form of microbes or microorganisms. In the not-too-distant future, we can expect the knowledge gained from the Human Genome Project to result in science being able to sequence and therefore understand the genomes of bacteria as well as of humans. This, in turn, will result in such highly
useful applications as energy production, environmental cleanup, toxic waste reduction, and the creation of entirely new industrial processes or ways in which we manufacture things. Eventually, new "biotechnologies" will be developed that will create bacteria that can "digest" waste material of all sorts, produce energy the way plants do, and improve the way industry makes products from food to clothing. Understanding the genetic sequence of bacteria can also show how harmful bacteria work against the body and perhaps how to combat them as well.
Risk assessment. Biologists know already that certain individuals are more susceptible to certain toxic or poisonous agents than others. They know that the cause for these susceptibilities is found in their genetic makeup or in their genes. Understanding the human genome will lead to science being able to identify, ahead of time, those who are at risk in certain environments, and conversely, those who have a stronger, "built-in" resistance. Such knowledge will help to understand and control the cancer risks of people who might be exposed to radiation or similarly dangerous energy-related materials or processes.
Comparative genomics. Comparative genomics means being able to compare the genetic make-up of individuals, groups, and all forms of life. Understanding the human genome and then the genomes of other life forms will enable scientists to better understand human evolution and to learn how people are connected to all other living things. Once researchers discover what the actual genetic "map" is for all major groups of organisms, there will be greater insight into how all life is connected and related.
Forensic science. Forensic science is the use of scientific methods to investigate a crime and to prepare evidence that is presented in court. Any living thing can be easily identified by examining the DNA sequences of the species to which it belongs. Although identifying an individual by its own DNA sequence is less precise, techniques developed during the Human Genome Project have made it presently possible to create a DNA profile of a person with the assurance that there is an extremely small chance that another individual has the exact same "DNA fingerprint." This not only will allow police to identify suspects whose DNA may match evidence left at a crime scene, but it also can, and has, been used to prove others innocent who were wrongly accused or convicted. DNA fingerprinting can identify victims, prove whether a man is the father of a child, and better match organ donors with recipients.
Better crops and animals. A deeper genetic understanding of plants and animals, as well as humans, will allow farmers to develop crops that can better resist disease, insects, and drought. Such "bioengineered" food would enable farmers to use little or no pesticides on the fruit and vegetables we eat, as well as to reduce waste. They could do the same for the animals farmers breed, and could produce healthier, more disease-resistant livestock.
Altogether, the Human Genome Project has already begun to have a major impact on the life sciences and the quality of our lives. Although it has proven to be a highly successful effort and will certainly achieve all of its stated goals, it really marks only the most basic of beginnings in understanding the genetic secrets of life.
[See also Biotechnology; Genetic disorders; Genetic engineering; Genetics ]
"Human Genome Project." UXL Encyclopedia of Science. . Encyclopedia.com. (October 20, 2016). http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/human-genome-project-3
"Human Genome Project." UXL Encyclopedia of Science. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/science/encyclopedias-almanacs-transcripts-and-maps/human-genome-project-3
Human Genome Project
Human Genome Project
The Human Genome Project (HGP), the determination of the complete nucleotide sequence of all of the more than three billion base pairs of deoxyribonucleic acid (DNA) in the nucleus of a human cell, is one of the greatest scientific undertakings in the history of humankind. The project reached an important milestone in 2001 with the completion of the "first draft" of the entire sequence. The HGP promises to bring unprecedented scientific rewards in the discovery of disease-causing genes , design of new drugs, understanding developmental processes, and determining the origin and evolution of the human race. It has also raised many ethical issues.
The original impetus for the HGP came from the U.S. Department of Energy (DOE) shortly after World War II. In 1945 there were many survivors of the atomic bombs dropped on Hiroshima and Nagasaki who had been exposed to high levels of radiation. In 1946 geneticist and Nobel Prize winner H.J. Müller opined in the New York Times that "if they could foresee the results [mutations among their descendants] 1,000 years from now . . . they might consider themselves more fortunate if the bomb had killed them." Müller, who had studied the biological effects of radiation on the fruit fly Drosophila melanogaster, had firsthand experience with the devastating effects of radiation. The survivors of the bomb were considered poor marriage prospects, because of the potential of carrying mutations and were often ostracized by Japanese society. Thus the Atomic Energy Commission (AEC) of the DOE set up an Atomic Bomb Casualty Commission in 1947 to address the issue of potential mutations among the survivors. The problem they faced, though, was how to experimentally determine such mutations. It would be many years before the technology was developed to do so.
During the mid-1970s, molecular biologists developed techniques for the isolation and cloning of individual genes. In 1977 Walter Gilbert and Fred Sanger independently developed methods for the sequencing of DNA, for which they received the Nobel Prize. In 1980, the polymerase chain reaction (PCR) was invented by a scientist at Cetus Corporation. This technique allowed one to take minute samples of DNA and amplify them a billionfold for analysis. In 1986, an automated DNA sequencer was developed, increasing the number of bases sequenced per day. Thus, by the mid-1980s, there was a feeling among molecular biologists that it might now be feasible to sequence the entire human genome. The first major impetus came in June 1985 when Robert Sinsheimer, chancellor of the University of California at Santa Cruz, called a meeting among leading scientists to discuss the possibility of sequencing the human genome. Meanwhile, the DOE, led by Charles Delisi, was a strong supporter of the initiative, for the DOE had a continuing interest in identifying radiation-caused mutations. Sequencing the entire genome would clearly provide the best way to analyze such mutations.
Many biologists were interested in this "Holy Grail of Molecular Biology." Most notably was Walter Gilbert who, through his interest, personality, and academic ties, developed enormous enthusiasm for the project. The initial goals were to develop:
- genetic linkage maps
- a physical map of ordered clones of DNA sequences
- the capacity for large-scale sequencing, as faster and cheaper machines and great leaps in technology would be necessary.
By 1990 the Human Genome Project had received the endorsement of the National Academy of Sciences, the National Research Council, the DOE, the National Institutes of Health (NIH), the National Science Foundation, the U.S. Department of Agriculture, and the Howard Hughes Medical Institute. Sequencing of the human genome was now officially begun. Nobel Prize winner James Watson agreed to head the project at the NIH. It was estimated to cost $3 billion and be completed by September 30, 2005. However, Watson resigned as the director of the HGP over the issue of patenting the genome. Francis Collins succeeded him as director. Just as important was the establishment of projects seeking to sequence several model organisms, that is, those organisms of genetic, biochemical, or medical importance.
Thousands of scientists, in more than one hundred laboratories in nineteen different countries around the world, are contributing to the HGP. The sequencing progressed well ahead of schedule and well under budget, a rare phenomenon in government-sponsored endeavors. In 1995, the first complete genome, that of the bacterium Haemophilus infuenzae, was published by the biotech company TIGR (The Institute for Genome Research). Several of the model organisms have subsequently been completed, including the yeast Saccharomyces cerevisiae, the first eukaryote sequenced.
The human genome consists of twenty-two pairs of chromosomes plus the X and Y sex chromosomes. On December 2, 1999, more than one hundred scientists working together in laboratories in the United Kingdom, Japan, United States, Canada, and Sweden announced the complete sequence of the first human chromosome, chromosome #22, the smallest of the autosomes. In 1998, J. Craig Venter, along with Perkin Elmer (PE) Corporation, founded the private biotech company Celera Genomics with the goal of privately sequencing the human genome, in direct competition with the public efforts supported by the NIH and DOE. Celera had available three hundred of the world's fastest PE automatic DNA sequencers along with one of the world's most powerful supercomputers. With remarkable speed Celera sequenced several of the model genomes and, in April 2000, announced that it had preliminary sequence of the human genome. In February 2001 Celera and the public consortium jointly announced completion of the draft human sequence.
To assure the accuracy of the sequence, each segment will be sequenced at least ten times. Although all humans share a 99.99 percent or more of their sequences, each human is unique. Geneticists estimate that each person carries many, perhaps hundreds or thousands, mutations. Moreover, it is anticipated that there will be distinct differences among different populations. No single person's genome will be identical to that in the databank as "the human genome." The Human Genome Diversity Project was proposed in 1997 to catalog such variations among racial and/or geographic groups. Samples from four thousand to eight thousand individuals in dozens of populations are to be analyzed. Similarly, a Human Cancer Genome Anatomy Project was initiated in 1997 to catalog all genes expressed in cancer cells to aid in the detection and treatment of cancers.
Most of the genome does not code for proteins . Indeed, perhaps only 5 percent of the DNA will be found to encode a gene. Estimates by scientists of the number of genes in the human genome have ranged from 35,000 to 140,000. Using the sequence data already available, scientists can anticipate that the final number will be approximately 120,000.
Patenting the Genome
From the outset there has been considerable debate among scientists, politicians, and entrepreneurs as to whether the human gene sequences can or should be patented. As of the year 2000, the U.S. Patent and Trademark Office is granting patents to genes that have been identified, rather than just random sequenced fragments. The data will be an invaluable resource, particularly in the area of developing new medical treatments. This has given rise to the new field of genomics (the study of gene sequences), and is resulting in the "mining of the genome" for valuable sequence data. Similarly, proteomics (the study of protein sequences) is a new, rapidly expanding field, as protein sequences can be predicted from the gene sequence. The folding of the proteins (secondary and tertiary structures) can be predicted by computers as well, leading to a three-dimensional view of the protein encoded by a particular gene.
From the outset, many have been concerned with ethical issues raised by the HGP, which need to be addressed by society as a whole. These including the following:
- confidentiality of an individual's DNA information
- insurance denial for pre-existing conditions if a person carries a gene that predisposes one to a particular disease
- stigmatization due to carrying certain genes
- genetic testing required for employment
- prenatal testing and abortion issues
- genetic manipulation
- challenges to self-understanding, given the knowledge of one's genes
- psychological burdens resulting from the knowledge that one carries a detrimental gene.
see also Bioinformatics; DNA Sequencing; Genome; Genomics
Collins, Francis S., and Karin G. Jegalian. "Deciphering the Code of Life." Scientific American 281, no. 6 (1999): 86–91.
Cook-Deegan, Robert. The Gene Wars: Science, Politics and the Human Genome Project. New York: Norton, 1994.
Kevles, Daniel J., and Leroy Hood, eds. The Code of Codes: Scientific and Social Issues in the Human Genome Project. Cambridge, MA: Harvard University Press, 1992.
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"Human Genome Project." Biology. . Encyclopedia.com. (October 20, 2016). http://www.encyclopedia.com/science/news-wires-white-papers-and-books/human-genome-project
"Human Genome Project." Biology. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/science/news-wires-white-papers-and-books/human-genome-project
Human Genome Project
HUMAN GENOME PROJECT
The Human Genome Project (HGP) is an international research program that aims to spell out the complete genetic inheritance of human beings and selected experimental animals. The HGP's goal is to decode the complete DNA inheritance, or genome, of human beings by 2003; following completion of a draft in 2000 that charted 90 percent of the human DNA inheritance. In addition to decoding human and animal DNA, the HGP trains scientists, develops techniques for analyzing genomes, and examines the ethical, legal, and social implications of human genetics research.
DNA is the long thread of a molecule that carries genes. Each strand of DNA, packaged as a chromosome, bears thousands of genes. Each gene contains the instructions for making a single component of the body, usually a protein. The hereditary instructions embedded in DNA are written with a four-letter alphabet (A, G, C, and T). A single misspelling in the DNA code can lead to the production of a defective protein, which can cause disease.
Understanding the human genome, the complete set of genes, sheds light on how the human body works at the fundamental level of molecules. Genes orchestrate the many fantastic and elegant features of life, like the development of embryos, while variations in gene sequence influence each person's susceptibility to diseases, including common illnesses like cancer and heart disease. The HGP will ultimately answer a wide range of scientific and medical questions, including: How do cells work? How do complex organisms develop from single cells? How are living beings related to each other? How do diseases arise?
The HGP was officially launched in 1990, as a joint project of the U.S. government and international partners. It was established as a large-scale, coordinated research project, marshaling the collaborative effort of hundreds of researchers. Between 1990 and 2003, the HGP is expected to reveal the sequence of approximately 3 billion "letters" that make up human DNA to identify all of the approximately 100,000 genes in human DNA, and to make all this information accessible to anyone with access to the Internet. The tools the HGP has built, including increasingly detailed maps of the human genome, helped genetic researchers navigate the genome and discover scores of disease genes in the 1990s. By 2003, a 99.99 percent– accurate listing of the letters that make up the DNA in all the human chromosomes is expected; that readout of the human genome, along with catalogs showing how DNA sequences vary among individuals, will help scientists tease out the genetic basis for complex diseases like diabetes, Alzheimer's disease, cancer, and heart disease— illnesses whose origins can be traced to the effects of multiple genes, as well as social and environmental factors.
By helping reveal the molecular foundations of disease, the HGP is expected by some to transform health care. Genetic technologies are becoming increasingly available. For example, genetic tests are being used to confirm diagnoses for some conditions, and to help define prognoses. Other tests predict the risk for future health problems. In time, more detailed understanding of the molecules involved in disease is expected to promote more rational drug design, making for increasingly precise, in some cases individualized, pharmacologic therapies that will minimize side effects or even avoid them altogether. Ultimately, understanding the molecular origins of disease may reveal ways of preventing many diseases entirely, perhaps by circumventing molecular glitches that can lead to illness or by repairing the altered molecules outright.
While genetic information and technology are likely to create great opportunities for promoting health and preventing disease, some risks are likely to accompany these powerful technologies. Genetic information can be misinterpreted or misused. As knowledge about individuals' genetic backgrounds becomes increasingly widespread, some insurers and employers may use predictions about future health to limit or deny access to health care or employment. Therefore, protecting the privacy of genetic information and preventing genetic discrimination will be crucial. To tap the full benefits of genetics, the medical profession and the public will need to become better equipped to evaluate the meaning of genetic information and to make decisions about the use of the new genetic technologies. At the same time, proper oversight will be necessary to ensure that gene tests and technologies are valid and reliable, sensitive, and specific, and used in appropriate situations.
Genetics, which was largely confined to research laboratories during the twentieth century, is expected to pervade everyday life in the twenty-first century. In the arena of public health, it may be used to access individuals' risks for health problems and to develop programs of preventive health care. Knowing their susceptibility to various health risks, individuals may be able to adopt a schedule of surveillance, perhaps take medications that will prevent health problems, and ideally become motivated to adopt lifestyle measures that will minimize their risks.
Most observers argue that the goal of public health genetics programs should be phenotypic prevention—preventing the emergence of disease—rather than genotypic prevention which is trying to change the genes people inherit. To attempt to prevent the transmission of particular genetic traits to future generations as a public health measure would tread into eugenic territory. Instead, public health goals should be designed to forestall the clinical manifestations of genetic risks.
Francis S. Collins
(see also: Genes; Genetic Disorders; Genetics and Health; Medical Genetics )
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National Human Genome Research Institute site on the World Wide Web: http://www.nhgri.nih.gov.
"Human Genome Project." Encyclopedia of Public Health. . Encyclopedia.com. (October 20, 2016). http://www.encyclopedia.com/education/encyclopedias-almanacs-transcripts-and-maps/human-genome-project
"Human Genome Project." Encyclopedia of Public Health. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/education/encyclopedias-almanacs-transcripts-and-maps/human-genome-project
Human Genome Project
HUMAN GENOME PROJECT
HUMAN GENOME PROJECT. The Human Genome Project (HGP) is an ambitious international effort to understand the hereditary instructions that make each human being unique. Its original goal was to locate the 100,000 or so human genes and read the entire genetic script—all three billion bits of information—by the year 2005, although technological advances moved up the expected completion date to 2003 and allowed the project to release a "working draft" of the human genome sequence in June 2000.
Launched in 1990, the project is supported in the United States by the National Institutes of Health and the Department of Energy. The HGP expects to identify the genes involved in both rare and common diseases, perhaps enabling early detection and treatment of disease and new approaches to prevention. In addition, gene discovery might predict someone's likelihood of getting a disease long before symptoms appear. In some cases, preventive actions can then be undertaken that may avert disease, as with familial breast cancer; or they can detect disease at its earliest stages, when treatment tends to be more successful. Errors in human genes cause an estimated three thousand to four thousand clearly hereditary diseases, including Huntington's disease, cystic fibrosis, sickle-cell anemia, neurofibromatosis, and Duchenne muscular dystrophy. Moreover, altered genes play a part in cancer, heart disease, diabetes, Alzheimer's disease, and many other common illnesses.
The HGP is designed to provide tools and techniques to enable scientists to find genes quickly. The first of these tools are maps of each chromosome. The ultimate goal is to decode, letter by letter, the exact sequence of all 3 billion nucleotide bases that make up the human genome—a daunting task that spurred researchers from many fields (biology, physics, engineering, and computer science, to name a few) to develop automated technologies to reduce the time and cost of sequencing. The ability to probe genes could be a double-edged sword, however. For some diseases, for example, ability to detect a nonfunctional gene has outpaced doctors' ability to do anything about the disease it causes. Huntington's disease is a case in point. Although a test for high-risk families has been available for years, only a handful of individuals have decided to be tested. The reason seems to be that, because there is no way to cure or prevent Huntington's disease, some would rather live with uncertainty than with the knowledge that they will be struck some time in midlife with a fatal disease. There is also the uncertainty of what might happen if a health insurance company or a potential employer learns that an individual is destined to develop Huntington's disease. Might that person be denied coverage or turned down for a job? Because of such concerns, the HGP has, since its inception, devoted about 5 percent of its $3 billion budget to inquiry aimed at anticipating and resolving the ethical, legal, and social issues likely to arise from its research. This marks one of the first times scientists are exploring the consequences of their research before crises arise.
Controversy enveloped the HGP in 1998 when Craig Venter's Celera Genomics, a private corporation, announced its attention to compete with the governmentfunded project and to beat it in the race to decode the human genome. Some observers doubted the value of the private effort, pointing to duplication of effort between Celera and the HGP. Others criticized Celera's goal of seeking patents on individual genes. Despite a joint 2000 statement by U.S. President Bill Clinton and British Prime Minister Tony Blair declaring that the basic information on the human genome should be considered public property, by June 2000 the U.S. Patent and Trademark Office had granted some two thousand gene patents and was considering twenty-five thousand more.
On 12 February 2001 HGP and Celera issued a joint statement stating that they had learned that humans have about thirty thousand genes—many fewer than scientists had anticipated—and that the final decoding might be possible within a few years.
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"Human Genome Project." Dictionary of American History. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/history/dictionaries-thesauruses-pictures-and-press-releases/human-genome-project
Human Genome Project
Human Genome Project, international scientific effort to map all of the genes on the 23 pairs of human chromosomes and, to sequence the 3.1 billion DNA base pairs that make up the chromosomes (see nucleic acid). Begun in 1990 with the goal of enabling scientists to understand the basis of genetic diseases and to gain insight into human evolution, the project was largely completed in 2000 when 85% of the human genome was decoded, and ended in 2003 with 99% decoded; detailed analyses of all the pairs were published by 2006. In the process, scientists identified genes for cystic fibrosis, neurofibromatosis, Huntington's disease, and an inherited form of breast cancer. In addition, the project decoded the genome of the bacterium E. coli, a fruit fly, and a nematode worm (see phylum Nematoda), in order to study genetic similarities among species, and a mouse genome was also decoded.
The Human Genome Project involved laboratories in the United States, France, Great Britain, Germany, and Japan. It was financed in the United States by the National Institutes of Health and by the Department of Energy and in Great Britain by the Wellcome Trust of London. A comparable project using new DNA-sequencing machines was begun as a private industry venture in the United States in 1998, with a stated goal of completing the mapping of the genome in three years.
Early in 2001 scientists from both teams jointly announced the "completion" of the mapping of the human genome, indicating that they had identified an estimated 30,000 genes (instead of the expected 100,000), constituting just 1% of the total human DNA. Subsequent comparison of the two teams' data has indicated that, because of differences in the genes identified by the teams, there may in fact be as many as 40,000 human genes. A subsequent, more refined estimate (2004) based on additional work on the genome was that there are between 20,000 and 25,000 genes. Work continues on further refining the sequencing of the genes on the chromosomes, eliminating the remaining gaps in the genome map, and identifying the extent of variation in the human genome. In 2007 the first sequences of human individuals (James D. Watson and J. Craig Venter, who led the public and private human genome sequencing efforts, respectively) were released; Venter's genome was the first full (diploid) individual human genome. The NIH's National Center for Biotechnology Information maintains GenBank, a database of publicly available genetic sequences from the genomes of plants and animals, including some extinct species.
See studies by J. Sulston and G. Ferry (2003) and J. Shreeve (2004).
"Human Genome Project." The Columbia Encyclopedia, 6th ed.. . Encyclopedia.com. (October 20, 2016). http://www.encyclopedia.com/reference/encyclopedias-almanacs-transcripts-and-maps/human-genome-project-0
"Human Genome Project." The Columbia Encyclopedia, 6th ed.. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/reference/encyclopedias-almanacs-transcripts-and-maps/human-genome-project-0
Human Genome Project
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"Human Genome Project." A Dictionary of Biology. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/science/dictionaries-thesauruses-pictures-and-press-releases/human-genome-project
Human Genome Project
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Human Genome Project
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"Human Genome Project." The Oxford Dictionary of Phrase and Fable. . Retrieved October 20, 2016 from Encyclopedia.com: http://www.encyclopedia.com/humanities/dictionaries-thesauruses-pictures-and-press-releases/human-genome-project