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A Revolution in Genetics: Changing Medicine, Changing Lives.

The sequencing of the human genome is only the tip of the iceberg tip of the iceberg
n. pl. tips of the iceberg
A small evident part or aspect of something largely hidden: afraid that these few reported cases of the disease might only be the tip of the iceberg. 
. It is the beginning of a revolution that many predict will transform medicine. How will genetics research affect physicians and patients and the practice of medicine? When investigators identify the function and association of human genes with common chronic diseases, diagnosis, treatment, and classification of human diseases will be changed forever. Genetic susceptibility testing allows patients to know their predisposition to disease long before symptoms appear. Physicians can intervene with customized advice so that the patient can prevent, modify, or avoid the predisposed condition by better understanding both his or her genetic and environmental risk for disease. The promise of a genetic approach to drug therapy involves moving from one size fits all to personalized medicine tailored to the individual patient. Physicians will become mentors and counselors, advising patients on the best treatment path given their unique genetic predisposit ion--even in this sophisticated, high tech field, the physician-patient relationship physician-patient relationship Medical malpractice A formal or inferred relationship between a physician and a Pt, which is established once the physician assumes or undertakes the medical care or treatment of a Pt; the establishment of a PPR is 'automatic' in  is likely to improve, highlighted by individualized therapies and personal attention.


* Genetics Transforming Medicine

* The Human Genome Project

* Advances in Medicine

* Improving Disease Classification

* Genetic Susceptibility Testing

* New Therapies and Customized Pharmaceuticals

HOW WILL GENETICS transform medicine? The sequencing of the human genome is spurring investigators from all parts of the world to uncover the function of each human gene. Since most diseases have a genetic component, genetics will increasingly play a pivotal role in predicting, preventing, diagnosing, treating, and classifying all human diseases. The practice of medicine will be revolutionized and hundreds of millions of people will be affected.

The basics of genetics

In the nucleus of each somatic cell somatic cell
Any cell of a plant or an animal other than a germ cell.
 in the body there are two sets of the human genome, one from the mother and one from the father. Each set of the genome contains the same genes on the same 23 chromosomes. The genetic information is contained in the double helix double helix
The coiled structure of a double-stranded DNA molecule in which strands linked by hydrogen bonds form a spiral configuration. Also called DNA helix, Watson-Crick helix.
 molecule of DNA DNA: see nucleic acid.
 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.
, composed of nucleotide base pairs. Almost everything in the human body is composed of proteins that are manufactured using the genetic instructions in the genes through a process of replication and translation that is mediated by messenger RNA mes·sen·ger RNA
See mRNA.
. The biochemical reactions in the body are facilitated by proteins called enzymes and hormones that turn genes on and off.

Matt Ridley in Genome: The Autobiography of a Species in 23 Chapters comments on the relationship between genes and proteins: "A protein is just a gene's way of making another gene; and a gene is just a protein's way of making another protein. Cooks need recipes, but recipes also need cooks." [1]

Although we traditionally think in terms of one gene, one messenger RNA, one protein, and one disease if there is a mutation, we now know it can be far more complicated. Alkaptonuria is an example of the simple model of genetic disease. This mild disease that causes arthritis and black urine is due to a single base pair substitution at either the 690th or the 901st position of nucleotides making up the third human chromosome. When a patient has such a mutation, he or she manufactures a defective version of the protein homogentisate dioxygenase and, thus, suffers from alkaptonuria. [1]

Unlike the straightforward alkaptonuria gene, there appears to be no single asthma gene. There are at least 15 different asthma genes that are implicated im·pli·cate  
tr.v. im·pli·cat·ed, im·pli·cat·ing, im·pli·cates
1. To involve or connect intimately or incriminatingly: evidence that implicates others in the plot.

 in some forms of the disease, in some people, some of the time. A genetic marker genetic marker
A gene phenotypically associated with a particular, easily identified trait and used to identify an individual or cell carrying that gene.
 on chromosome 11, for example, explains only 15 percent of asthma sufferers, and other candidate genes for asthma are being examined on chromosome 5, 6, 13, and 14. And it gets even more complicated. [1] Marsh found that ten out of 11 gene candidates for susceptibility to asthma were unique to only one racial or ethnic group. [2] Many believe that most of the most common chronic diseases--diabetes, rheumatoid arthritis rheumatoid arthritis

Chronic, progressive autoimmune disease causing connective-tissue inflammation, mostly in synovial joints. It can occur at any age, is more common in women, and has an unpredictable course.
, heart disease, depression, dementia, and common cancers-- are genetically more like asthma than alkaptonuria.

Realizing that many common diseases do not exhibit a one-to-one relationship between a single gene mutation and the expression of the disease, investigators are developing new research tools to study diseases like asthma. The traditional approach featured geneticists This is a list of people who have made notable contributions to genetics. The growth and development of genetics represents the work of many people. This list of geneticists is therefore by no means complete. Contributors of great distinction to genetics are not yet on the list.  performing linkage analysis linkage analysis Genetics A gene-hunting technique that traces patterns of heredity in large, high-risk families, in an attempt to locate a disease-causing gene mutation by identifying traits co-inherited with it; the formal study of the association between the  studies that examined the relationships between inheritance and genetic markers in families affected by the disease. This approach located the genes for Huntington's disease Huntington's disease, hereditary, acute disturbance of the central nervous system usually beginning in middle age and characterized by involuntary muscular movements and progressive intellectual deterioration; formerly called Huntington's chorea.  and cystic fibrosis cystic fibrosis (sĭs`tĭk fībrō`sĭs), inherited disorder of the exocrine glands (see gland), affecting children and young people; median survival is 25 years in females and 30 years in males. , but proved to be unsuccessful in studying diseases like asthma.

Researchers searching for functions of genes are increasingly employing association studies of unrelated affected patients and controls, instead of the more traditional linkage studies concentrating on hereditary diseases in families. These association studies of complex multigenic diseases require large numbers of participants from around the world to differentiate between genetic and environmental causes. Searching for these genotypic-phenotypic associations requires access to well phenotyped, properly consented DNA and tissue samples and medical histories from diverse patients.

Genetics transform diagnosis

How does knowing the function of a human gene lead to new ways of diagnosing, treating, and classifying disease? When we know the function of a gene or, in some cases, how the genes do not function properly, we can develop genetic susceptibility tests. Some genetic susceptibility testing is being developed based on the use of biochips to detect genetic differences in a single nucleotide building block of DNA, known as single nucleotide polymorphisms (SNPs). The patient's sampled cheek cell yields up its chromosomes made up of a double-stranded DNA molecule. The extracted DNA is separated, duplicated, and placed on a testing chip containing artificial DNA with a known composition of bases. On the chip, as the patient's DNA binds with the artificial DNA, the SNPs become apparent as differences from the expected binding.

This testing allows patients to know their predisposition to disease long before symptoms appear. Health care providers are able to intervene with individual customized advice so that the patient can prevent, modify, or avoid the predisposed condition by better understanding both his or her genetic and environmental risk for disease. Every one of us has thousands of these genetic differences or SNPs, and most of them do not have clinical significance. However, the SNPs of interest are those that are in crucial positions on the chromosome, such that the translation into protein is abnormal or the amount of protein produced is impaired. Associating these genetic differences with specific diseases and determining the function of the proteins they encode will result in new ways to diagnose patients with disease.

These tests can tell us if individuals are predisposed to a disease, allowing earlier intervention by health care providers. The genetic differences may also predict the likely outcome of a disease, which can direct physicians towards recommending more aggressive or more conservative treatments as appropriate.

New approaches to therapy

Treatment will also be revolutionized by the new knowledge derived from genetic research. Understanding the function of the protein produced by the gene associated with disease can lead to new treatments in several ways. In some cases, the faulty protein can provide a target against which existing libraries of small-molecule compounds can be tested for therapeutic effect. In other cases, the protein may be a novel compound that can be used to treat the disease.

Pharmaceutical companies are also investigating the use of SNPs to predict which drugs will be most effective for which patients. Some of the SNP SNP Scottish National Party

Noun 1. SNP - (genetics) genetic variation in a DNA sequence that occurs when a single nucleotide in a genome is altered; SNPs are usually considered to be point mutations that have been evolutionarily
 genetic differences are associated with adverse reactions adverse reactions, unfavorable reactions resulting from administration of a local anesthetic; responsible factors include the drug used, concentration, and route of administration.
 to certain drugs or increased metabolism; the genetic profile of a patient will allow pharmacologists to tailor-make drugs for the individual patient.

A recent study published in the Proceedings of the National Academy of Sciences The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences.  showed that patient response to the asthma drug albuterol albuterol /al·bu·ter·ol/ (al-bu´ter-ol) a ß agonist used as the base or sulfate salt as a bronchodilator.

 is affected by several genetic polymorphisms of the beta-2 receptor. [3] Such findings could become the basis for simple blood tests that will predict which patients will benefit from a drug like albuterol and which will not respond. Presently, a drug that is effective in only 50 to 70 percent of the patients who receive it is considered a success.

The promise of a genetic approach to drug therapy involves moving from one size fits all to personalized medicine tailored to the individual patient.

Gene therapy can be thought of as inserting a functioning gene into a target tissue to replace a defective gene; it should allow physicians to treat the underlying causes of diseases like cystic fibrosis, asthma, and cancer rather than just the symptoms. Drug companies like Novartis invested almost $1 billion in this revolutionary approach, and advocates predicted early success that did not materialize.

The biggest challenge so far has been to identify a vector that can safely deliver the normal genes to the diseased cells in the body for a long enough time to cure the disease. An adenovirus adenovirus

Any of a group of spheroidal viruses, made up of DNA wrapped in a protein coat, that cause sore throat and fever in humans, hepatitis in dogs, and several diseases in fowl, mice, cattle, pigs, and monkeys.
 was used as a vector in the University of Pennsylvania (body, education) University of Pennsylvania - The home of ENIAC and Machiavelli.

Address: Philadelphia, PA, USA.
 gene therapy trial that resulted in the death of the young patient who had a rare liver disease Liver Disease Definition

Liver disease is a general term for any damage that reduces the functioning of the liver.

The liver is a large, solid organ located in the upper right-hand side of the abdomen.
. This unexpected death has resulted in a re-evaluation of all gene therapy programs in the United States, and nobody is predicting effective gene therapy the next few years. [4]

The classification of disease will also be transformed by the new genetic information. When we discover the genes associated with a disease code for a specific enzyme, we will have a better way to classify and understand human diseases. Researchers are starting to realize that many common diseases represent collections of different conditions that may each have their own genetic cause. Articles are starting to appear that predict the classification of diseases like hematopoietic hematopoietic /he·ma·to·poi·et·ic/ (-poi-et´ik)
1. pertaining to hematopoiesis.

2. an agent that promotes hematopoiesis.


1. pertaining to or affecting the formation of blood cells.
 malignancies on the basis of genetic profile, rather than morphologic appearance under the microscope or the expression of immunologic markers by immunoperoxidase staining immunoperoxidase staining

a technique of histological staining that provides morphological details and immunological identification. Analogous to immunofluorescence techniques, but uses peroxidase conjugated to immunoglobulin instead of fluorescent dyes.

Cautionary note

Craig Venter, 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 Celera, said, "As a civilization, we know far less than one percent of what will be known about biology, human physiology, and medicine. My view of biology is 'We don't know Don't know (DK, DKed)

"Don't know the trade." A Street expression used whenever one party lacks knowledge of a trade or receives conflicting instructions from the other party.
 shit."' [5] It is good to remember that the promise of the genomics revolution is just that-a promise; no one knows how it will all work out, and it is wise to remember all that we do not know at the present time.

We do not even know how many genes a human has. Three estimates published in the journal Nature Genetics ranged from 28,000 to 120,000, and scientists at a meeting at the Cold Spring Harbor Laboratory The Cold Spring Harbor Laboratory  opened a sweepstakes with bets ranging from 27,462 to 200,000. The winner will be determined at the annual meeting of geneticists in 2003. [6]

It is important to remember that environment plays a role in human disease, and all of this investigation of genetics may highlight the role of environmental factors. If one identical twin develops juvenile diabetes juvenile diabetes
Insulin-dependent diabetes.
, the other twin with essentially the same genetic inheritance develops the disease less than 50 percent of the time. A recent 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.  twin study from Scandinavia concluded that inherited genetic factors make a minor contribution to susceptibility to most types of cancer. The researchers concluded that environment has the principal role in causing sporadic cancer in the 44,788 pairs of twins studied. [7]

There are skeptics who question how much genetics will transform medicine. Professor Richard Lewontin of Harvard has written extensively about the limitations of some theories of genetics. "Were God to appear to me in a dream telling me the heritability heritability /her·i·ta·bil·i·ty/ (her?i-tah-bil´i-te) the quality of being heritable; a measure of the extent to which a phenotype is influenced by the genotype.

 of, say, coronary artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. , to the fourth decimal place, I could not use that information for any program of amelioration a·me·lio·ra·tion  
1. The act or an instance of ameliorating.

2. The state of being ameliorated; improvement.

Noun 1.
, prevention, or cure, because it would tell me nothing useful about the pathways of mediation." [8]

The British medical historian Roy Porter is quoted 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, "Nowadays, with the 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 , people might say that all diseases have a genetic basis. In 20 years, they'll realize it was a gigantic mistake, in the way that throughout history almost all obsessional monocausal theories about how there's one model for disease-they're all due to the humors or all due to the devil or all due to bacteria or genetics-turn out to be wrong because the human body is so complex." [9]


The sequencing of the human genome by the Human Genome Project and Celera is only the beginning of a revolution that many predict will transform medicine. When investigators identify the function and association of human genes with common chronic diseases, diagnosis, treatment, and classification of human diseases will be changed forever.

Practicing physicians are in a unique position to facilitate this important linking of genes to common diseases. Because the association studies of unrelated patients require thousands of research subjects and controls to differentiate between genetic and environmental affects, DNA and tissue samples have emerged as a rate limiting step. Physicians can play an important role in encouraging their patients to take part in such research and in requiring that the research be conducted ethically and with sensitivity toward the research subjects. Such participation represents a shift from the usual doctor-patient relationship doctor-patient relationship,
n in-teraction between a physician and a patient.
 with its more immediate rewards and benefits; the rewards of genetic association studies will not be immediate, but rather long term and for the benefit of all patients.

Many patients have become disenchanted dis·en·chant  
tr.v. dis·en·chant·ed, dis·en·chant·ing, dis·en·chants
To free from illusion or false belief; undeceive.

[Obsolete French desenchanter, from Old French,
 with modern medicine because more sophisticated technology has often been associated with impersonal encounters that lack intimacy and the special relationship with a caring, empathetic em·pa·thet·ic  

empa·theti·cal·ly adv.
 physician. Genetic susceptibility testing is sophisticated technology that will require a close relationship with providers who can deal with the psychosocial, ethical, and legal issues associated with inherited susceptibility. It is ironic and encouraging that this most advanced technology may lead us back to a more traditional doctor-patient relationship featuring individualized therapies and personal attention.

Norton Zinder puts where we are in perspective: "This is the beginning of the beginning. The human genome alone doesn't tell you crap. This is like Vesalius. Vesalius did the first human anatomy. Before Vesalius, people didn't even know they had hearts and lungs. With the human genome, we finally know what's there, but we still have to figure out how it all works. Having the human genome is like having a copy of the Talmud but not knowing how to read Aramaic."

Kent Battles, MD, is President of the Genomics Repository of Genomics Collaborative, Inc., in Cambridge, Massachusetts.


(1.) Ridley, M. Genome: The Autobiography of a Species in 23 Chapters. New York: Harper collins, 1999.

(2.) Marsh, D.G., et al. Linkage Analysis of IL4 and other chromosome 5q31.1 Markers and Total Serum Immunoglobulin-E concentrations. Science. 264: 1152-6, 1994.

(3.) Drysdale, et al. Proceedings of the National Academy of Sciences, September 12, 2000.

(4.) Langreth, R, Moore, S.D. Delivery Shortfall: Gene Therapy, Touted As a Breakthrough, Bogs Down in Details: Human Tests Prove, at Best, Inconclusive; Novartis Reins in Its Investments: 'Not Proud of It Right Now.' The Wall Street Journal. October 27, 1999.

(5.) Preston, R. The Genome Warrior, The New Yorker June 12, 2000, pp. 66-83.


(7.) Lichtenstein, P., et al. Environmental and Heritable her·i·ta·ble
1. Capable of being passed from one generation to the next; hereditary.

2. Capable of inheriting or taking by inheritance.
 Factors in the causation of cancer: Analyeses of cohorts of Twins from Sweden, Denmark, and Finland. New England Journal of Medicine. 343: 78-85, 2000.

(8.) Lewontin, R. It Ain't Necessarily So: The Dream of the Human Genome and Other Illusions. New York: New York Review of Books, 2000.

(9.) Lyall, S. A Historical Alchemist Turns Medicine into Gold. New York Times, April 24, 1999.

Genomic Biotech Companies

Drug development companies

Millennium Pharmaceuticals

Cambridge, Massachusetts

Milestones: Partnerships with Bayer, Monsanto, Pfizer, Eli Lily, American Home Products, Astra, and Roche.

Human Genome Sciences Human Genome Sciences NASDAQ: HGSI is a biopharmaceutical corporation founded in 1992. Its stated purpose is to "discover, develop, manufacture and market innovative drugs that serve patients with unmet medical needs, with a primary focus on protein and antibody drugs.  

Rockville, Maryland

Milestones: Partnership with SmithKline Beecham. Drugs in clinical trials

Data subscription companies

Celera Genomics Group

Rockville, Maryland

Milestones: Partnerships with Novartis, Pharmacia and Upjohn, Amgen.

EST EST electroshock therapy.

electroshock therapy
 Shotgun sequencing of human genome.

Incyte Pharmaceuticals

Palo Alto, California “Palo Alto” redirects here. For other uses, see Palo Alto (disambiguation).
Palo Alto (IPA: /ˌpæloʊˈʔæltoʊ/, from Spanish: palo: "stick" and alto: "high", i.e.

Milestones: More than 25 subscriptions.

Drug discovery platform company

Genomics Collaborative

Cambridge, Massachusetts

Milestones: Global physician collection network, global repository, GCI GCI Ground Circuit Interrupter
GCI Getty Conservation Institute
GCI Global Commerce Initiative
GCI Green Cross International (non-profit international environmental organization)
GCI Growth Competitiveness Index
GCI Great Cities Institute
 Discovery Technology.

Genomic Resources

Genome: The Autobiography of a Species in 23 Chapters

Matt Ridley

New York: Harper Collins, 1999

A delightful, well-written, and scientifically accurate account of the human genome. This is the best starting place for the non-geneticist who wants an overview of genetics.

It Ain't Necessarily So: The Dream of the Human Genome and Other illusions

Richard Lewontin

New York: New York Review of Books, 2000

A thought-provoking discussion of the difficulties medicine will face in realizing the promise of the genomics revolution.

Section, F. The New York Times, June 27, 2000. Ten excellent overview articles published on the day of the White House announcement.

This website of Genomics Collaborative of Cambridge, Massachusetts, contains general introductory material and a discussion of ethical issues.

Profiles: The Genome Warrior

Richard Preston

The New Yorker, June 12, 2000, pages 66-83.

An irreverent and highly revealing account of the behind the scenes jockeying for position to receive 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 the sequencing of the human genome. Preston manages to get both the science and the gossip right.
COPYRIGHT 2001 American College of Physician Executives
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:Bottles, Kent
Publication:Physician Executive
Geographic Code:1USA
Date:Mar 1, 2001
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