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Charting the Map of Life.



Explorers have traditionally set out from familiar ports toward the unknown, creating maps of where they have been for others to follow. With time, these rough drawings are refined by those who come in their wake so that coastlines are charted, mountains measured, and rivers delineated to the mile. Today, scientists are grappling with a new map--that of the human genome--but unlike the one you can barely fold in your car, this map describes a landscape that remains almost a complete mystery: the 3.2 billion letters of DNA DNA: see nucleic acid.
DNA
 or deoxyribonucleic acid

One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes.
 that code for the creation of a human being. The human genome is the total amount of DNA spooled into a set of 23 chromosomes found in the nucleus of every human cell. It's formed when the chromosomes of the male's sperm fuse with those of the female's egg to form a single-celled embryo, and it contains the genetic "instructions" that allow the embryo to grow into a fully formed person.

When scientists announced they had mapped a rough draft of the human genome--identified 85-90% of the ordered sequence of DNA on each chromosome--the event was lauded around the world as the greatest scientific achievement since the Apollo 11 moon landing. Some scientists called the accomplishment nothing less than the beginning of a true understanding of biology. At a 27 June 2000 White House ceremony featuring the heads of the two teams responsible for the feat--J. Craig Venter, president and chief scientific officer of the Rockville, Maryland-based Celera Genomics, a privately funded biotechnology company, and Francis S. Collins, director of the publicly funded National Human Genome Research Institute--President Clinton said, "Today we are learning the language in which God created life."

The map of the human genome points to a vast uncharted territory, much of it a wasteland. Only 3-5% of the genome--corresponding to between 30,000 and 100,000 functional genes--is thought to be biologically functional. The remainder is so-called junk DNA junk DNA
n.
DNA that does not code for proteins or their regulation but is thought to be involved in the evolution of new genes and in gene repair, and constitutes approximately 95 percent of the human genome.
 that may someday be shown to have biologic merit, but that for now is largely seen as filler that remains in the genome for unknown reasons. Scientists expect that mapping the genome will lead to a host of innovations in biology and research. For example, DNA microarrays, devices that analyze the level of expression of thousands of genes at a time, could be used to accurately diagnose cancer and infectious disease Infectious disease

A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions.
 subtypes and to predict clinical outcomes. Scientists will also use the genome to look at the interactions of the environment, genetic makeup, and toxic exposures, including the ability of certain genes to detoxify de·tox·i·fy
v.
1. To counteract or destroy the toxic properties of a substance.

2. To remove the effects of poison from something, such as the blood.

3.
 the body and promote disease resistance.

The genome will provide tremendous resources for understanding human diversity and evolution. All humans on the planet are roughly 99.9% genomically identical, not surprising considering a common ancestry thought to date back 150,000 years to a tiny band of people in Africa. Within the remaining 0.1% of the genome are the 3 million letters of DNA that govern our physical differences. Many portions of the human genome, particularly those coding for metabolic processes, are identical to those of other species. Comparative genomics studies will provide insight into how metabolic and other physiologic systems evolved in different species.

But despite the great potential of genomics, scientists caution that public expectations need to be tempered with reality. Decrying what she calls the "media inflation of genetic technology," Lily Kay, an associate of the museum of comparative zoology The Museum of Comparative Zoology is located on the grounds of Harvard University in Cambridge, Massachusetts, and is one of three museums which collectively comprise the Harvard Museum of Natural History. The director of the museum is Dr.  at Harvard University in Cambridge and author of Who Wrote the Book of Life? A History of the Genetic Code, says, "We are bombarded daily by media reports of the genetic revolution. And the usual approach is to absorb uncritically these scientific forecasts as fait accompli." The fact is, she says, people are as much a product of their environment as they are of their genes. And to suggest that genetics is the sole determinant that defines us as individuals, writes Eric Lander, director of the Whitehead Center for Genome Research in Cambridge, in a 12 June 2000 editorial in The New York New York, state, United States
New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of
 Times, "stretches the science far beyond the data."

The Nuts and Bolts nuts and bolts
pl.n. Slang
The basic working components or practical aspects: "[proposing]
 

Mapping the human genome is the most recent event in a genetic time line dating back to Gregor Mendel, who discovered the basic principles of heredity heredity, transmission from generation to generation through the process of reproduction in plants and animals of factors which cause the offspring to resemble their parents. That like begets like has been a maxim since ancient times.  in the mid-1800s. Mendel introduced the concept of the gene as a unit of information through which hereditary information is passed from one generation to the next. Later, the concept became less abstract with the discovery that genes are made of the substance DNA. The three-dimensional structure of DNA and its method of replication was discovered by James Watson, an American postdoctoral fellow, and British graduate student Francis Crick at Cambridge University in England. In their classic paper titled "Molecular Structure of Nucleic Acids The Molecular structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid was an article published by James D. Watson and Francis Crick in the scientific journal Nature in its 171th volume on page 737-738 (dated April 25, 1953). . A Structure for Deoxyribose Nucleic Acid nucleic acid, any of a group of organic substances found in the chromosomes of living cells and viruses that play a central role in the storage and replication of hereditary information and in the expression of this information through protein synthesis. ," published in Nature in 1953, the two scientists described the double-helical form of the molecule, shaped like a twisted ladder, in which each rung is made up of four nucleotides: adenine adenine (ăd`ənĭn, –nīn, –nēn), organic base of the purine family. Adenine combines with the sugar ribose to form adenosine, which in turn can be bonded with from one to three phosphoric acid units, yielding the three , thymine thymine (thī`mēn), organic base of the pyrimidine family. Thymine was the first pyrimidine to be purified from a natural source, having been isolated from calf thymus and beef spleen in 1893–4. , cytosine cytosine (sī`tōsēn'), organic base of the pyrimidine family. It was isolated from the nucleic acid of calf thymus tissue in 1894. , and guanine guanine (gwä`nēn), organic base of the purine family. It was reported (1846) to be in the guano of birds; later (1879–84) it was established as one of the major constituents of nucleic acids.  (typically abbreviated as A, T, C, and G). The nucleotides are arranged in a series of base pairs, in which A bonds with T, and C with G. In the years that followed, researchers discovered that genes code for amino acid amino acid (əmē`nō), any one of a class of simple organic compounds containing carbon, hydrogen, oxygen, nitrogen, and in certain cases sulfur. These compounds are the building blocks of proteins.  sequences, which themselves comprise the proteins that make life possible.

A genome map is essentially a representation of where genes are located on the chromosome. At the coarsest level of resolution are genetic linkage maps, which describe gene locations based on their patterns of inheritance, for instance as observed in mating experiments with Drosophila Drosophila: see fruit fly.
drosophila

Any member of about 1,000 species in the dipteran genus Drosophila, commonly known as fruit flies but also called vinegar flies. Some species, particularly D.
 melanogaster (fruit fly). The first such map was developed in 1913 by Alfred Sturtevant while he was an undergraduate in zoology at New York's Columbia University. Working with embryologist em·bry·ol·o·gist
n.
A specialist in embryology.



embryologist

an expert in embryology.
 Thomas Hunt Morgan in the legendary "fly room" at Columbia, Sturtevant arranged the ordered sequence of genes for eye color, wing shape, body size, and other characteristics based on their appearance in consecutive generations of Drosophila. Morgan himself was the first to associate a specific gene with a specific chromosome; again experimenting with fruit flies, Morgan found that the mutant gene mutant gene
n.
A gene that has lost, gained, or exchanged some of the material it received from its parent, resulting in a permanent transmissible change in its function.
 for white eyes (most fruit flies have red eyes) is found only in male progeny and is located exclusively on the X chromosome--a discovery for which he won the Nobel Prize Nobel Prize, award given for outstanding achievement in physics, chemistry, physiology or medicine, peace, or literature. The awards were established by the will of Alfred Nobel, who left a fund to provide annual prizes in the five areas listed above.  for Medicine in 1933.

Gene mapping gene mapping
n.
The determination of the sequence of genes and their relative distances from one another on a specific chromosome.
 (and indeed, the whole field of molecular biology molecular biology, scientific study of the molecular basis of life processes, including cellular respiration, excretion, and reproduction. The term molecular biology was coined in 1938 by Warren Weaver, then director of the natural sciences program at the Rockefeller ) hit its stride in the late 1960s with the discovery that restriction enzymes could be used to cut DNA into specific sequences. In nature, restriction enzymes protect bacteria by slicing up invading viral DNA. But in the laboratory, they can be used as molecular "scissors scissors

Cutting instrument or tool consisting of a pair of opposed metal blades that meet and cut when the handles at their ends are brought together. Modern scissors are of two types: the more usual pivoted blades have a rivet or screw connection between the cutting ends
" that recognize a highly specific DNA sequence DNA sequence Genetics The precise order of bases–A,T,G,C–in a segment of DNA, gene, chromosome, or an entire genome. See Base pair, Base sequence analysis, Chromosome, Gene, Genome. , or type of sequence, and then cut the DNA at the same site in the sequence. Over 3,000 restriction enzymes have been identified to date, affording scientists great specificity when chopping DNA into isolated fragments. The fragments can be cloned (usually in bacteria) or duplicated using a variety of biochemical techniques to provide the unlimited genetic material needed for experimental studies.

These techniques have been used to generate higher-resolution physical maps that describe the biochemical structure of DNA and the ordered sequence of the genes themselves. By the early 1990s, scientists were constructing physical maps of model organisms using a procedure called map-based sequencing. The process involves cutting DNA into fragments of about 200,000 base pairs called bacterial artificial chromosomes (BACs), taking note to record the position of the BACs on the genome, cloning the BACs in bacteria (such as Escherichia coli Escherichia coli (ĕsh'ərĭk`ēə kō`lī), common bacterium that normally inhabits the intestinal tracts of humans and animals, but can cause infection in other parts of the body, especially the urinary tract. ), determining the sequence of the base pairs, and then reassembling the BACs in their original order using a computer.

Map-based sequencing is the technique of choice for the Human Genome Project (HGP See Human Genome Project. ), a consortium of research centers funded by the National Institutes of Health, the U.S. Department of Energy, and the Wellcome Trust, a medical philanthropy based in London. The HGP was formed in 1990, with the goal of mapping the human genome by 2005, a date shortened by five years by politics, competition, and a variety of technical innovations. In addition to mapping the human genome, the project aims to store the information in databases, address the ethical, legal, and social issues raised by the project, and develop tools for data analysis and better sequencing technologies.

Scientists had still not completed a genome map for any organism by 1994, the year Venter venter /ven·ter/ (ven´ter) pl. ven´tres   [L.]
1. a fleshy contractile part of a muscle.

2. abdomen.

3. a hollowed part or cavity.


ven·ter
n.
 and Nobel Prize-winning molecular biologist Hamilton O. Smith Dr. Hamilton Othanel Smith (born August 23, 1931) is an American microbiologist.

Smith was born on August 23, 1931, and graduated from University Laboratory High School of Urbana, Illinois.
 proposed speeding up the process with an alternative method they called whole-genome shotgun sequencing. In contrast to the HGP's method, in which the order of the BACs is known before they are each sequenced individually and then reassembled, the shotgun method involves cutting the DNA into small, random, overlapping pieces that are then sequenced and reassembled using a computer that compares all the pieces and matches the overlaps, thus assembling the whole genome. In 1995, with this technique, Venter and Smith mapped the genome of the disease-causing bacterium Haemophilus influenzae--the first completed genome of any single organism.

The period from 1995 to 2000 gave rise to a stunning series of technologic advancements, including computer automation and robotics, that accelerated the rate of genome mapping. At the forefront was a machine called the ABI Abi (ā`bī) [short for Abijah], in the Bible, King Hezekiah's mother.


(Application Binary Interface) A specification for a specific hardware platform combined with the operating system.
 Prism 3700 DNA Analyzer, introduced in 1998 by the Perkin-Elmer Corporation. This machine is involved in the last step of the sequencing pipeline. Its job is to separate fluorescently labeled DNA fragments by size to determine the sequence of nucleotide bases found on a strand of DNA. Now used by major DNA sequencing laboratories around the world, the Prism 3700 increased the rate of genome sequencing by approximately 20-fold.

The equipment used by both Celera and the HGP to draft the map of the human genome was virtually identical. The only difference between the two organizations was their basic methodology: the HGP used map-based sequencing while Celera used shotgun sequencing. The physical map they produced, the "language in which God created life," is an eye-numbing series of As, Ts, Cs, and Gs stretching into the billions.

Scientists acknowledge that much work on the human genome remains to be done. Since announcing the completion of the rough draft in June, Celera has moved on to other more lucrative pursuits befitting be·fit·ting  
adj.
Appropriate; suitable; proper.



be·fitting·ly adv.

Adj. 1.
 a biotechnology company, such as identifying and patenting gene sequences. Meanwhile, the HGP advances toward a final map, expected to be completed by 2003. At the present time, the BACs covering the two smallest chromosomes, numbers 21 and 22, are essentially complete. Chromosome 22 is particularly noteworthy: it's packed with over 545 known genes (at least 300 more are suspected) ranging in size from 1,000 to 583,000 bases of DNA. Gene variations on chromosome 22 are thought to be associated with at least 27 human disorders including brain cancers, schizophrenia, and multiple birth defects birth defects, abnormalities in physical or mental structure or function that are present at birth. They range from minor to seriously deforming or life-threatening. A major defect of some type occurs in approximately 3% of all births. . Other BACs on other chromosomes are still in various states of disassembly dis·as·sem·ble  
v. dis·as·sem·bled, dis·as·sem·bling, dis·as·sem·bles

v.tr.
To take apart: disassemble a toaster.

v.intr.
1.
, and there are still significant gaps to be filled. Nevertheless, the working draft is considered to be of great value for researchers looking for Looking for

In the context of general equities, this describing a buy interest in which a dealer is asked to offer stock, often involving a capital commitment. Antithesis of in touch with.
 genes, and it represents a major accomplishment. Says Collins, "The completion of the human genome sequence will have a profound effect on understanding genetic contributions to human disease and the development of strategies for minimizing and preventing disease altogether."

Gene-Environment Interactions

One of the most exciting applications for genomics is in the area of gene-environment interactions. Now light-years beyond the theories of evil spirits and "bad blood" espoused by our ancestors, modern science views illness as the outcome of three related factors: genetics, environmental exposures, and aging. Like death and taxes, aging is a certainty. But within the complex interplay of genes and the environment lies a range of potential targets for disease prevention and treatment--particularly for cancer, pulmonary diseases, neurodegenerative disorders, developmental disorders, birth defects, reproductive function, and autoimmune diseases Autoimmune diseases
A group of diseases, like rheumatoid arthritis and systemic lupus erythematosus, in which immune cells turn on the body, attacking various tissues and organs.

Mentioned in: Complement Deficiencies, Premature Menopause
, all of which have been shown to be influenced by environmental agents. In fact, in a paper published in the 13 July 2000 issue of the New England Journal of Medicine The New England Journal of Medicine (New Engl J Med or NEJM) is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It is one of the most popular and widely-read peer-reviewed general medical journals in the world. , Paul Lichtenstein of the Karolinska Institute in Stockholm, Sweden, and colleagues state, "Inherited genetic factors make a minor contribution to susceptibility to most types of [cancers]. This finding indicates that the environment has the principal role in causing sporadic cancer."

One group spearheading the effort to elucidate gene-environment interactions is the Environmental Genome Project genome project 1 The Human Genome Project, see there 2. A general term for a coordinated research initiative for mapping and sequencing the genome of any organism  (EGP (1) (Exterior Gateway Protocol) A broad category of routing protocols that are designed to span different autonomous systems. Contrast with IGP.

(2) (Exterior Gateway P
), headquartered at the NIEHS NIEHS National Institute of Environmental Health Sciences (NIH, DHHS) . Maynard Olson, director of the University of Washington Genome Center in Seattle, where much EGP research is conducted, describes gene mapping as an "extremely powerful tool for furthering investigations into human biology and its interactions with the environment." Many of the enzymes and proteins involved in toxicity have already been identified in classical cell biology studies, he says. What genomic information allows researchers to do is build on this knowledge by identifying how many types of these proteins are expressed, and in what specific tissues they are found.

The mission of the EGP is to identify genes already mapped by other programs (the organization is continually soliciting candidate genes), and then to resequence the genes in an exhaustive search for the variations that augment resistance or susceptibility to environmental exposures. Most variants of interest are called single nucleotide polymorphisms, or SNPs, which are genes whose ordered DNA sequence is mixed up in ways that alter protein expression. If these proteins are involved in metabolizing or detoxifying chemical agents, it's likely that exposure will cause greater harm. For example, a protein called p53 participates in cell signaling processes related to DNA repair, which is important because DNA is continually bombarded by carcinogens Carcinogens
Substances in the environment that cause cancer, presumably by inducing mutations, with prolonged exposure.

Mentioned in: Colon Cancer, Rectal Cancer
 from inside and outside the body. If p53 detects chromosomal damage, it signals the cell to stop DNA synthesis or even undergo cell death. A person with a genetically inherited mutation that alters the function of the p53 gene may be highly susceptible to cancer. Not surprisingly, the EGP has focused its initial efforts largely on finding SNPs among genes that, like p53, participate in DNA repair. Other processes of interest include cell cycle control, xenobiotic xen·o·bi·ot·ic
adj.
Foreign to the body or to living organisms. Used of chemical compounds.

n.
A xenobiotic chemical.



xenobiotic

any substance, harmful or not, that is foreign to the animal's biological system.
 metabolism, and immune and inflammatory reactions.

The most recent addition to environmental genomics at the NIEHS is a newly formed National Center for Toxicogenomics, announced in December 2000 [see NIEHS News, p. A22]. Jose Velazquez, a program administrator for the NIEHS Division of Extramural extramural /ex·tra·mu·ral/ (-mur´il) situated or occurring outside the wall of an organ or structure.

extramural

situated or occurring outside the wall of an organ or structure.
 Research and Training, says the center will complement the activities of the EGP by investigating patterns of gene expression and protein function in response to chemicals. "It's not enough just to understand the expression of the gene," he says. "You also have to understand the function of the protein." The problem is that protein function--particularly in the context of environmental exposure--is extremely difficult to characterize. The way the genome reacts to chemicals is highly dependent on timing and dose. Either of these parameters can exert a major influence on gene expression. Furthermore, chemicals trigger biochemical cascades within cells in which some proteins are turned off, others are turned on, and some aren't affected at all. It's really more a question of genome expression than gene expression. And indeed, many genomic scientists say the key to the future of genomics is actually found in functional genomics, or proteomics, which seeks to understand the global activity of proteins in a cell at any given time. Understanding how all the pieces fit together is as much a computational challenge as it is a biochemical mystery. For this reason, the center has also proposed the improvement of mathematical paradigms for the study of protein function as a major agenda item for the future.

The EGP's ultimate goal is to sponsor and support epidemiologic studies of gene-environment interactions, both at the NIEHS and by outside researchers funded through the institute's extramural grants program. Empowered by databases with useful information about genes and gene functions, researchers in the genomic era will be able to more clearly determine how specific populations respond to their environment. The activities now under way at the EGP constitute a critical step in that direction.

Comparative Genomics

Although the public's attention has been captured by human genomics, mapping and studying the genomes of other organisms--or comparative genomics--is also important. Jonathan King, a professor of molecular biology at the Massachusetts Institute of Technology Massachusetts Institute of Technology, at Cambridge; coeducational; chartered 1861, opened 1865 in Boston, moved 1916. It has long been recognized as an outstanding technological institute and its Sloan School of Management has notable programs in business,  in Cambridge and a board member of the Council for Responsible Genetics The Council for Responsible Genetics (CRG) is a public interest group with a focus on biotechnology.

Founded in 1983, CRG "fosters public debate about the social, ethical and environmental implications of genetic technologies.
, says, "Most genes evolved long ago, and there is enormous homology for essential functions like metabolism." Therefore, he says, the amino acid sequences of many proteins are identical throughout all the higher species, a phenomenon known as genetic conservation. Comparative genomics is generally undertaken for two reasons: to provide road maps that help researchers locate genes for inherited characteristics and behavior in humans and other creatures, and to advance the study of genomic evolution. As the maps become available, blocks of human DNA will be compared to other species to understand not only sequencing gaps but also genetic conservation. To date, physical maps of yeast, the soil worm Caenorhabditis elegans, and the fruit fly (in addition to numerous bacteria and viruses) have been completed. Scientists are also mapping the genomes of the mouse, rat, cat, dog, pig, cow, goat, zebrafish, rainbow trout rainbow trout

Species (Oncorhynchus mykiss) of fish in the salmon family (Salmonidae) noted for spectacular leaps and hard fighting when hooked. It has been introduced from western North America to many other countries.
, tilapia tilapia (təlä`pēə) or St. Peter's fish, a spiny-finned freshwater fish of the family Cichlidae, native chiefly to Africa and the Middle East.  fish, medaka me·da·ka  
n.
A small Japanese fish (Oryzias latipes) commonly found in rice fields and often used in biological research or in stocking aquariums.
 fish, rabbit, chicken, sheep, and horse.

Researchers at the Laboratory of Genomic Diversity (LGD LGD Loss Given Default
LGD Livestock Guardian Dog
LGD Low-Grade Dysplasia (abnormal cells, such as those found when doing a biopsy)
LGD Laboratory of Genomic Diversity
LGD Lou Gehrig's Disease
) at the National Cancer Institute's Frederick Cancer Research and Development Center in Frederick, Maryland, are mapping the cat genome, which apparently shares more order homology (meaning similar order of genes on the chromosome) with the human than any other nonprimate species that has been studied. According to William Murphy, a geneticist ge·net·i·cist
n.
A specialist in genetics.



geneticist

a specialist in genetics.

geneticist 
 with the LGD, this means that genomes of both cats and humans have changed relatively little during the 90 million years since mammals diverged from their parent ancestor. Comparing the genome to a deck of cards, he says the genes of other laboratory species including mice, rats, and dogs have been substantially reshuffled over time, making them more challenging than the cat for studying genomic evolutionary history.

Comparative genomics is also useful for identifying models of human hereditary disease. There are a multitude of genetic diseases that show up in humans and other animals. Cats, for example, carry genes for hemophilia, polycystic kidney disease Polycystic Kidney Disease Definition

Polycystic kidney disease (PKD) is one of the most common of all life-threatening human genetic disorders.
, and hypertrophic cardiomyopathy Hypertrophic Cardiomyopathy Definition

Cardiomyopathy is an ongoing disease process that damages the muscle wall of the lower chambers of the heart.
. According to an article by Stephen J. O'Brien and colleagues from the LGD published in the 15 October 1999 issue of Science, nearly every human gene has a mouse homologue homologue /ho·mo·logue/ (hom´ah-log)
1. any homologous organ or part.

2. in chemistry, one of a series of compounds distinguished by addition of a CH2 group in successive members.
, making this traditional laboratory animal highly amenable to the study of genetic illnesses. Studies in mice have already identified mutated genes for multiple disorders that are also present in humans. In the best known example, a mutated gene involved in metabolism is present in both overweight mice and morbidly obese humans. Similarly, comparative mapping studies of hypertension in rats have uncovered candidate genes for the same disease in humans. Within the year, scientists with the HGP expect to complete working drafts of the mouse and rat genomes, which will expand the potential for comparative inference relating to human health. As this occurs, scientists will use rodent models, and those of other species as well, to identify candidate genes for analogous functions in humans and to define their interactions with other genes in the context of mutation, environmental exposure, infectious disease, sex, aging, and more.

The Myth of Determinism

Ironically, even as gene-environment interactions grow in scientific prominence, scientists worry that the recent media hype is helping to resurrect an outdated theory of "genetic determinism," which suggests that individual phenotypes are governed wholly by genetic makeup. The danger, they say, is that people will take a fatalistic fa·tal·ism  
n.
1. The doctrine that all events are predetermined by fate and are therefore unalterable.

2. Acceptance of the belief that all events are predetermined and inevitable.
 attitude toward disease and discount the effects of environment and lifestyle. David Page, chair of the Whitehead Task Force on Genetics and Public Policy and a professor of biology at the Massachusetts Institute of Technology, attributes the problem to a tendency among scientists to simplify genomics for the press, which have adopted "Gene X Causes Disease Y" as their standard headline. Without efforts to dispel some of the fuzziness surrounding genetic mechanisms, he says, the public will believe the truth is as simple as the headlines would suggest.

And just as the genome isn't deterministic in the context of the entire organism, neither is it deterministic with respect to the structure of individual proteins. Knowledge of the genome makes it possible to describe a protein's amino acid sequence, but not to predict its three-dimensional shape. A host of internal factors within the cell contribute to protein "folding," which governs the protein's receptor chemistry and therefore all of its functionality. This is a major problem for biotechnology and pharmaceutical companies hoping to use genomics to create new classes of drugs--a fact that is rarely appreciated by the public. "This is why gene-based biotechnology is in trouble," says Kay. "Gene-based biotechnology lost $5 billion last year. One hundred seventy-six drugs were proposed; one was approved, and the others faltered in the second stage of clinical trials."

Ultimately, some suggest, genomics will be more useful as a research and diagnostic tool than as an agent that lifts medical treatment to new heights. However, efforts to use genomics for these purposes are increasingly hamstrung by a new application for the law in biology: gene patents and intellectual property protection for gene products [see Spheres of Influence]. Private-sector companies are increasingly patenting gene sequences, cell lines, genetically modified organisms ge·net·i·cal·ly modified organism
n. Abbr. GMO
An organism whose genetic characteristics have been altered by the insertion of a modified gene or a gene from another organism using the techniques of genetic engineering.
, and even natural species--a practice that has angered many prominent scientists. Leveling sharp criticism at what he calls a "radical extension of patent law," King says, "Genes are the products of millions of years of evolution and are in the deepest sense products of nature. They are not the inventions of individuals, corporations, or institutions." King predicts that gene patents will retard research because investigators won't share information for fear of undermining the ability to file patents later, and will impede health care delivery because providers will need to pay licensing fees to use gene products. In addition, he says, such patents provide a legal mechanism for companies to charge excessive sums for genetic screening (in the event they own the patent to the gene sequences of interest to the patient) and even more for gene therapy (in the event the screen shows the patient's own gene is defective).

But, illustrating the contentious nature of the debate, these concerns were rejected by Philip Reilly, the chairman of the board and chief executive officer of Interleukin interleukin

Any of a class of naturally occurring proteins important in regulation of lymphocyte function. Several known types are recognized as crucial constituents of the body's immune system (see immunity).
 Genetics, a biotechnology company located in Waltham, Massachusetts. Reilly says that without legal protection for intellectual property, the $20 billion in research dollars spent annually by biotechnology and pharmaceutical companies would dry up overnight. "I'm the CEO (1) (Chief Executive Officer) The highest individual in command of an organization. Typically the president of the company, the CEO reports to the Chairman of the Board.  of a very small biotech company," he says, "and I have never seen a more Darwinian process than trying to bring a biotech product forward. The vast majority of these companies fail, and the return on investment is very low." He also charges that it is false to assume that biotechnology companies are looking to establish a "captive population for gene therapy." Responding to negative publicity following the September 1999 death of 18-year-old Jesse Gelsinger, who died following experimental gene therapy for a rare metabolic disorder, he says, "Venture capital companies are running scared from gene therapy."

And so, even as genomics promises to play a vital role in the future of biologic research, the overriding question facing society is how to use the information in ways that benefit the common good. Clearly, the answers to these questions remain unknown. What seems apparent is that genomics must be placed in the context of the whole human experience, including the environment in which we live. "Poverty is the main source of disease in the world," says Olson. "It's not genetic variation [that degrades public health] as much as it is economic variation. And we shouldn't forget that."
COPYRIGHT 2001 National Institute of Environmental Health Sciences
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2001, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Author:Schmidt, Charles W.
Publication:Environmental Health Perspectives
Date:Jan 1, 2001
Words:3967
Previous Article:Environmental Genome Project: A Positive Sequence of Events.
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