March 2003: A Half-Century of DNA
March 2003: A Half-Century of DNA
A half-century ago, Francis Crick and James Watson walked into a pub in Cambridge, England, and announced, in not-so-precise words, that they had discovered the structure of DNA. The journey on the road to this solution, however, was traveled by more than just the British Crick and the American Watson -- it was a collaborative effort, shaped by social and political aspects, that drew on the contributions of Rosalind Franklin and Maurice Wilkins, and others as well. In the end, the world, and science, were, in effect, changed forever. The elucidation of the DNA molecule as a double helix, comprising polynucleotide chains bound by complementary pairing between the nitrogen-containing bases, also helped underscore speculation that DNA was the carrier of hereditary information. Its very structure suggested a mechanism by which the molecule could essentially "unzip" and replicate itself, and therefore create "new life."
The understanding that DNA contained the genetic information necessary to program the living cell appropriately sparked efforts to translate this code, and ushered in the very early steps in the genome era. Frederick Sanger established a method, albeit difficult, of sequencing strands of DNA, a method that was further refined and automated by other scientists in the ensuing years. However, it was the invention of the polymerase chain reaction (PCR) by Kary Mullis that perhaps had the greatest impact on the field of molecular genetics. PCR, which is essentially a primer extension reaction, allowed for the amplification of specific and discrete stretches of DNA in vitro by up to billions-fold. This process solved a fundamental problem in genetic science -- how to obtain sufficient quantities of a target DNA sequence efficiently, rapidly, and cost-effectively.
Fulfillment of the goal of understanding living creatures in terms of their DNA began with J. Craig Venter and his team's decoding of the first genome: that of the bacterium Haemophilus influenzae. By extension, all of these efforts converged on the ultimate goal of mapping the human genome. In the subsequent "race" to this end, both public and private, we now have the Human Genome Project, headed by Francis Collins, a complex multidisciplinary scientific initiative that is charged with the tasks of mapping and sequencing all of the human genetic code and determining aspects of its function. A working draft of the human DNA sequence was announced in June 2000, and elucidation of the full genome sequence is anticipated in spring 2003.
How does this discussion lead us back to Gastroenterology? Well, we can begin by viewing the above in the broader context of medicine. The use of gene technology and molecular biology (and discovery of disease genes) has elevated our understanding of human disease, and, in so doing, has created a new branch of research: Molecular Medicine. Our enhanced knowledge of human biology and pathophysiology that began with that fundamental revelation 50 years ago in Cambridge has helped make possible the significant progress in the understanding -- and thus, prevention, diagnosis, and treatment -- of human disease that we have witnessed in the subsequent decades.
How has medical science bridged this gap? It was primarily through the application of research involving gene therapy/technology, gene manipulation, genetic epidemiology, and molecular and clinical pharmacology that our enhanced precision and understanding of disease processes was achieved. The basic knowledge imparted by that DNA molecule laid the foundation for our understanding of gene structure, regulation of expression, and function; organization of the genome; the role of DNA modification; and to the ability to develop animal models of disease; as well as identify and define the consequence of defects (mutations) in the genetic code.
Of course, all of these broader concepts regarding the application of genetic science to clinical medicine lead us to the more granular level and cause us to ask more focused questions. How, for example, has the field of gastroenterology been influenced by the application of genetic/molecular technology? "For now," says Howard J. Worman, MD, Associate Professor of Medicine and Anatomy and Cell Biology, and Director, Division of Digestive and Liver Diseases, College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, New York, NY, "we have identified the genes for many chronic liver disorders, including hereditary hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, and congenital hyperbilirubinemias. We have identified mutations in several genes that predispose to colon cancer. [Additionally,] therapeutic agents from recombinant DNA technology, such as recombinant interferon-alfa and antibodies against tumor necrosis factor, are used to treat viral hepatitis and Crohn's disease, respectively."
However, this response regarding the here-and-now status of genetic applications in the field of gastroenterology led us to ask Dr. Worman to consider one additional question: As we enter a new decade and century, what, in his view, are the specific areas within the field that are likely to be most affected by the application of molecular/DNA science? "The great challenge for the future," Worman added, "is how to identify susceptibility and modifying genes for various digestive diseases. For example, what are the genetic factors that predispose [an individual] to inflammatory bowel disease or celiac disease? Or, why do some people with chronic viral hepatitis go on to develop cirrhosis [whereas] others do fine? What genes are involved? Gene therapy may also become a practical reality."
Indeed, these concepts in basic science continue to evolve toward clinical application. Regardless of the status, the impact of DNA technology on our understanding of disease processes is undeniable, and is reflected strongly by the significant focus on clinical genetics at the major meetings in the field. Stephen B. Hanauer, MD, for example, provided insight regarding the genetic underpinnings of inflammatory bowel disease in his recent report based on key sessions presented during Digestive Disease Week 2002, "Inflammatory Bowel Disease: Novel Aspects of Clinical Genetics and Potential for Probiotic Therapy." Additionally, the role of genomics in the setting of colorectal cancer was emphasized by Douglas K. Rex, MD, in his discussion on "Colorectal Cancer: Issues in Prevention," based on proceedings of the American College of Gastroenterology 67th Annual Scientific Meeting this past fall. As a final point of note, the role of genetic technology in identifying potential targets for future drug development in the setting of hepatitis C virus infection was well addressed by David Bernstein, MD, in his recent report, "New Concepts and New Therapies in Hepatitis C," as derived from key sessions presented at the 53rd Annual Meeting of The American Association for the Study of Liver Diseases in November 2002.
I hope that the above discussion conveys an appropriate appreciation for how the knowledge of the genetic mechanisms underlying human disease (specifically digestive and liver diseases), as derived from developments in DNA science, has irrevocably influenced the course of clinical medicine. A single, pivotal scientific event that occurred 50 years ago has clearly altered our perspective of human disease. While we should not overestimate the potential of genome science, nor disregard societal and ethical concerns, we should likewise not understate its potential in enhancing the detection, diagnosis, and treatment of these disease processes.
I invite and encourage your continued feedback as we move forward with our mission to provide our audience with the most topical and relevant information in clinical gastroenterology. You may contact me directly at gastroeditor@webmd.net. (If your concern is technical, however, please contact our customer support staff at medscapecustomersupport@webmd.net)
A half-century ago, Francis Crick and James Watson walked into a pub in Cambridge, England, and announced, in not-so-precise words, that they had discovered the structure of DNA. The journey on the road to this solution, however, was traveled by more than just the British Crick and the American Watson -- it was a collaborative effort, shaped by social and political aspects, that drew on the contributions of Rosalind Franklin and Maurice Wilkins, and others as well. In the end, the world, and science, were, in effect, changed forever. The elucidation of the DNA molecule as a double helix, comprising polynucleotide chains bound by complementary pairing between the nitrogen-containing bases, also helped underscore speculation that DNA was the carrier of hereditary information. Its very structure suggested a mechanism by which the molecule could essentially "unzip" and replicate itself, and therefore create "new life."
The understanding that DNA contained the genetic information necessary to program the living cell appropriately sparked efforts to translate this code, and ushered in the very early steps in the genome era. Frederick Sanger established a method, albeit difficult, of sequencing strands of DNA, a method that was further refined and automated by other scientists in the ensuing years. However, it was the invention of the polymerase chain reaction (PCR) by Kary Mullis that perhaps had the greatest impact on the field of molecular genetics. PCR, which is essentially a primer extension reaction, allowed for the amplification of specific and discrete stretches of DNA in vitro by up to billions-fold. This process solved a fundamental problem in genetic science -- how to obtain sufficient quantities of a target DNA sequence efficiently, rapidly, and cost-effectively.
Fulfillment of the goal of understanding living creatures in terms of their DNA began with J. Craig Venter and his team's decoding of the first genome: that of the bacterium Haemophilus influenzae. By extension, all of these efforts converged on the ultimate goal of mapping the human genome. In the subsequent "race" to this end, both public and private, we now have the Human Genome Project, headed by Francis Collins, a complex multidisciplinary scientific initiative that is charged with the tasks of mapping and sequencing all of the human genetic code and determining aspects of its function. A working draft of the human DNA sequence was announced in June 2000, and elucidation of the full genome sequence is anticipated in spring 2003.
How does this discussion lead us back to Gastroenterology? Well, we can begin by viewing the above in the broader context of medicine. The use of gene technology and molecular biology (and discovery of disease genes) has elevated our understanding of human disease, and, in so doing, has created a new branch of research: Molecular Medicine. Our enhanced knowledge of human biology and pathophysiology that began with that fundamental revelation 50 years ago in Cambridge has helped make possible the significant progress in the understanding -- and thus, prevention, diagnosis, and treatment -- of human disease that we have witnessed in the subsequent decades.
How has medical science bridged this gap? It was primarily through the application of research involving gene therapy/technology, gene manipulation, genetic epidemiology, and molecular and clinical pharmacology that our enhanced precision and understanding of disease processes was achieved. The basic knowledge imparted by that DNA molecule laid the foundation for our understanding of gene structure, regulation of expression, and function; organization of the genome; the role of DNA modification; and to the ability to develop animal models of disease; as well as identify and define the consequence of defects (mutations) in the genetic code.
Of course, all of these broader concepts regarding the application of genetic science to clinical medicine lead us to the more granular level and cause us to ask more focused questions. How, for example, has the field of gastroenterology been influenced by the application of genetic/molecular technology? "For now," says Howard J. Worman, MD, Associate Professor of Medicine and Anatomy and Cell Biology, and Director, Division of Digestive and Liver Diseases, College of Physicians and Surgeons, Columbia-Presbyterian Medical Center, New York, NY, "we have identified the genes for many chronic liver disorders, including hereditary hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, and congenital hyperbilirubinemias. We have identified mutations in several genes that predispose to colon cancer. [Additionally,] therapeutic agents from recombinant DNA technology, such as recombinant interferon-alfa and antibodies against tumor necrosis factor, are used to treat viral hepatitis and Crohn's disease, respectively."
However, this response regarding the here-and-now status of genetic applications in the field of gastroenterology led us to ask Dr. Worman to consider one additional question: As we enter a new decade and century, what, in his view, are the specific areas within the field that are likely to be most affected by the application of molecular/DNA science? "The great challenge for the future," Worman added, "is how to identify susceptibility and modifying genes for various digestive diseases. For example, what are the genetic factors that predispose [an individual] to inflammatory bowel disease or celiac disease? Or, why do some people with chronic viral hepatitis go on to develop cirrhosis [whereas] others do fine? What genes are involved? Gene therapy may also become a practical reality."
Indeed, these concepts in basic science continue to evolve toward clinical application. Regardless of the status, the impact of DNA technology on our understanding of disease processes is undeniable, and is reflected strongly by the significant focus on clinical genetics at the major meetings in the field. Stephen B. Hanauer, MD, for example, provided insight regarding the genetic underpinnings of inflammatory bowel disease in his recent report based on key sessions presented during Digestive Disease Week 2002, "Inflammatory Bowel Disease: Novel Aspects of Clinical Genetics and Potential for Probiotic Therapy." Additionally, the role of genomics in the setting of colorectal cancer was emphasized by Douglas K. Rex, MD, in his discussion on "Colorectal Cancer: Issues in Prevention," based on proceedings of the American College of Gastroenterology 67th Annual Scientific Meeting this past fall. As a final point of note, the role of genetic technology in identifying potential targets for future drug development in the setting of hepatitis C virus infection was well addressed by David Bernstein, MD, in his recent report, "New Concepts and New Therapies in Hepatitis C," as derived from key sessions presented at the 53rd Annual Meeting of The American Association for the Study of Liver Diseases in November 2002.
I hope that the above discussion conveys an appropriate appreciation for how the knowledge of the genetic mechanisms underlying human disease (specifically digestive and liver diseases), as derived from developments in DNA science, has irrevocably influenced the course of clinical medicine. A single, pivotal scientific event that occurred 50 years ago has clearly altered our perspective of human disease. While we should not overestimate the potential of genome science, nor disregard societal and ethical concerns, we should likewise not understate its potential in enhancing the detection, diagnosis, and treatment of these disease processes.
I invite and encourage your continued feedback as we move forward with our mission to provide our audience with the most topical and relevant information in clinical gastroenterology. You may contact me directly at gastroeditor@webmd.net. (If your concern is technical, however, please contact our customer support staff at medscapecustomersupport@webmd.net)
