You Say Tomato and I Say Tomahto: Human Genetics and Gene Therapy
Authors: H F Willard
Journal: Molecular Therapy (2001)

Based in Part on a Presidential Address Delivered October 13, 2001, At the Annual Meeting of the American Society of Human Genetics in San Diego, CaliforniaThere can hardly be a better time to be in human genetics.We have witnessed dramatic advances over the past few decades in our understanding of the role of genes in disease and in our ability to dissect genetically complex pathways and phenomena. We have seen the hopeful beginnings of “translational genetics,” taking fundamental discoveries from the laboratory and applying them to new advances in medicine. In the past year, we have seen the unveiling of the human genome and have begun to sense the magnitude of its contribution to human biology and disease. And, after a period of much hand-wringing and even self-doubt, we have at last witnessed the very first and long-anticipated demonstrations of clinical efficacy in gene therapy.The purview of human genetics spans pure basic scientific inquiry into formal genetics as well as molecular genetics of both Homo sapiens and a variety of versatile model organisms, disease-oriented and patient-oriented research into the basis for human disease, and translational and clinical research at the bedside. It is a tapestry wide enough to cover both the most fundamental advances in basic science and the most potentially meaningful applications in treating and curing human disease. Human geneticists have long had a special interest in the treatment of genetic disease, ranging from inborn errors of metabolism approached from a strong foundation in basic biochemical genetics, to lysosomal storage diseases treated by organ and tissue transplantation, to new “molecular diseases” whose hoped-for treatment comes from the fields of cell and gene therapy. The fields of human genetics and gene therapy, therefore, have much in common, and our respective societies—the American Society of Human Genetics (ASHG) and the American Society of Gene Therapy (ASGT)—have much to learn from each other.The practical imperative and endpoint of disease treatment unites the fields of human genetics and gene therapy under the same tent. But both are and continue to be firmly rooted in basic genetic and genomic science as well, and there lies the greatest opportunity for collaboration. Gene therapy encompasses far more than inherited disease, of course. But whether one focuses on gene therapy in cancer, complex adult-onset diseases of either genetic or non-genetic etiology, or classic monogenic diseases, effective treatment depends on a thorough understanding of both genetic and epigenetic mechanisms of gene regulation, as well as the role of genomic sequences that potentially modulate or extinguish long-term gene expression. All of this is the stuff of human genetics. It is not so much a matter of being in “our” tent or “your” tent; we are both under the same tent!There are other opportunities for enlarging the tent. Our societies stand for the open presentation and discussion of data and ideas, and we should openly welcome scientists from the pharmaceutical and biotechnology industries to participate fully. My sense is that the ASGT (with its journal, Molecular Therapy) does a more effective job at this than we have done in human genetics. An open invitation to participate is critical if academic societies such as ours are to retain our vitality, because it is the leaders of many of these companies who will increasingly drive the revolution in medicine and biology that we all hope to be part of. To be sure, an alliance between academic societies and the for-profit sector is potentially an uncomfortable one. After all, the two cultures are founded on very different principles and beliefs, and the potential for conflicts of interest must be carefully considered and managed. But within that context, societies such as ours can provide a common meeting ground, where scientists with a shared interest in the science can openly present their findings and discuss their implications.There is another reason to consider enlarging our tent. Genetics (and certainly genomics), including gene therapy, is now “big science.” To be sure, human genetics in general and gene therapy in particular—with their breadth of focus on basic science, practical applications to medicine, and increasingly important social policy implications—represent enormously complex problems. To successfully tackle such problems almost certainly will require input of energy and resources from a diverse set of organized units in both the academic and commercial worlds.These are two different cultures, but the gulf between them can be bridged. This is where the ASHG and the ASGT can come in, if we are both willing. None of this will happen without a sense of a shared mission, and our societies can help to catalyze this as agents of change. We are two sides of the same coin. We have in common a focus on the same no-longer-quite-so-distant horizon. It is the same tent we share, and there is plenty of room for all. Based in Part on a Presidential Address Delivered October 13, 2001, At the Annual Meeting of the American Society of Human Genetics in San Diego, CaliforniaThere can hardly be a better time to be in human genetics.We have witnessed dramatic advances over the past few decades in our understanding of the role of genes in disease and in our ability to dissect genetically complex pathways and phenomena. We have seen the hopeful beginnings of “translational genetics,” taking fundamental discoveries from the laboratory and applying them to new advances in medicine. In the past year, we have seen the unveiling of the human genome and have begun to sense the magnitude of its contribution to human biology and disease. And, after a period of much hand-wringing and even self-doubt, we have at last witnessed the very first and long-anticipated demonstrations of clinical efficacy in gene therapy.The purview of human genetics spans pure basic scientific inquiry into formal genetics as well as molecular genetics of both Homo sapiens and a variety of versatile model organisms, disease-oriented and patient-oriented research into the basis for human disease, and translational and clinical research at the bedside. It is a tapestry wide enough to cover both the most fundamental advances in basic science and the most potentially meaningful applications in treating and curing human disease. Human geneticists have long had a special interest in the treatment of genetic disease, ranging from inborn errors of metabolism approached from a strong foundation in basic biochemical genetics, to lysosomal storage diseases treated by organ and tissue transplantation, to new “molecular diseases” whose hoped-for treatment comes from the fields of cell and gene therapy. The fields of human genetics and gene therapy, therefore, have much in common, and our respective societies—the American Society of Human Genetics (ASHG) and the American Society of Gene Therapy (ASGT)—have much to learn from each other.The practical imperative and endpoint of disease treatment unites the fields of human genetics and gene therapy under the same tent. But both are and continue to be firmly rooted in basic genetic and genomic science as well, and there lies the greatest opportunity for collaboration. Gene therapy encompasses far more than inherited disease, of course. But whether one focuses on gene therapy in cancer, complex adult-onset diseases of either genetic or non-genetic etiology, or classic monogenic diseases, effective treatment depends on a thorough understanding of both genetic and epigenetic mechanisms of gene regulation, as well as the role of genomic sequences that potentially modulate or extinguish long-term gene expression. All of this is the stuff of human genetics. It is not so much a matter of being in “our” tent or “your” tent; we are both under the same tent!There are other opportunities for enlarging the tent. Our societies stand for the open presentation and discussion of data and ideas, and we should openly welcome scientists from the pharmaceutical and biotechnology industries to participate fully. My sense is that the ASGT (with its journal, Molecular Therapy) does a more effective job at this than we have done in human genetics. An open invitation to participate is critical if academic societies such as ours are to retain our vitality, because it is the leaders of many of these companies who will increasingly drive the revolution in medicine and biology that we all hope to be part of. To be sure, an alliance between academic societies and the for-profit sector is potentially an uncomfortable one. After all, the two cultures are founded on very different principles and beliefs, and the potential for conflicts of interest must be carefully considered and managed. But within that context, societies such as ours can provide a common meeting ground, where scientists with a shared interest in the science can openly present their findings and discuss their implications.There is another reason to consider enlarging our tent. Genetics (and certainly genomics), including gene therapy, is now “big science.” To be sure, human genetics in general and gene therapy in particular—with their breadth of focus on basic science, practical applications to medicine, and increasingly important social policy implications—represent enormously complex problems. To successfully tackle such problems almost certainly will require input of energy and resources from a diverse set of organized units in both the academic and commercial worlds.These are two different cultures, but the gulf between them can be bridged. This is where the ASHG and the ASGT can come in, if we are both willing. None of this will happen without a sense of a shared mission, and our societies can help to catalyze this as agents of change. We are two sides of the same coin. We have in common a focus on the same no-longer-quite-so-distant horizon. It is the same tent we share, and there is plenty of room for all. There can hardly be a better time to be in human genetics. We have witnessed dramatic advances over the past few decades in our understanding of the role of genes in disease and in our ability to dissect genetically complex pathways and phenomena. We have seen the hopeful beginnings of “translational genetics,” taking fundamental discoveries from the laboratory and applying them to new advances in medicine. In the past year, we have seen the unveiling of the human genome and have begun to sense the magnitude of its contribution to human biology and disease. And, after a period of much hand-wringing and even self-doubt, we have at last witnessed the very first and long-anticipated demonstrations of clinical efficacy in gene therapy. The purview of human genetics spans pure basic scientific inquiry into formal genetics as well as molecular genetics of both Homo sapiens and a variety of versatile model organisms, disease-oriented and patient-oriented research into the basis for human disease, and translational and clinical research at the bedside. It is a tapestry wide enough to cover both the most fundamental advances in basic science and the most potentially meaningful applications in treating and curing human disease. Human geneticists have long had a special interest in the treatment of genetic disease, ranging from inborn errors of metabolism approached from a strong foundation in basic biochemical genetics, to lysosomal storage diseases treated by organ and tissue transplantation, to new “molecular diseases” whose hoped-for treatment comes from the fields of cell and gene therapy. The fields of human genetics and gene therapy, therefore, have much in common, and our respective societies—the American Society of Human Genetics (ASHG) and the American Society of Gene Therapy (ASGT)—have much to learn from each other. The practical imperative and endpoint of disease treatment unites the fields of human genetics and gene therapy under the same tent. But both are and continue to be firmly rooted in basic genetic and genomic science as well, and there lies the greatest opportunity for collaboration. Gene therapy encompasses far more than inherited disease, of course. But whether one focuses on gene therapy in cancer, complex adult-onset diseases of either genetic or non-genetic etiology, or classic monogenic diseases, effective treatment depends on a thorough understanding of both genetic and epigenetic mechanisms of gene regulation, as well as the role of genomic sequences that potentially modulate or extinguish long-term gene expression. All of this is the stuff of human genetics. It is not so much a matter of being in “our” tent or “your” tent; we are both under the same tent! There are other opportunities for enlarging the tent. Our societies stand for the open presentation and discussion of data and ideas, and we should openly welcome scientists from the pharmaceutical and biotechnology industries to participate fully. My sense is that the ASGT (with its journal, Molecular Therapy) does a more effective job at this than we have done in human genetics. An open invitation to participate is critical if academic societies such as ours are to retain our vitality, because it is the leaders of many of these companies who will increasingly drive the revolution in medicine and biology that we all hope to be part of. To be sure, an alliance between academic societies and the for-profit sector is potentially an uncomfortable one. After all, the two cultures are founded on very different principles and beliefs, and the potential for conflicts of interest must be carefully considered and managed. But within that context, societies such as ours can provide a common meeting ground, where scientists with a shared interest in the science can openly present their findings and discuss their implications. There is another reason to consider enlarging our tent. Genetics (and certainly genomics), including gene therapy, is now “big science.” To be sure, human genetics in general and gene therapy in particular—with their breadth of focus on basic science, practical applications to medicine, and increasingly important social policy implications—represent enormously complex problems. To successfully tackle such problems almost certainly will require input of energy and resources from a diverse set of organized units in both the academic and commercial worlds. These are two different cultures, but the gulf between them can be bridged. This is where the ASHG and the ASGT can come in, if we are both willing. None of this will happen without a sense of a shared mission, and our societies can help to catalyze this as agents of change. We are two sides of the same coin. We have in common a focus on the same no-longer-quite-so-distant horizon. It is the same tent we share, and there is plenty of room for all.