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ARTICLE |

Biotechnology and Medicine of the Future FREE

Leroy Hood, MD, PhD
[+] Author Affiliations

Based on a lecture given at the presentation of the Albert Lasker Clinical Medical Research Award, New York, Nov 18, 1987.

Reprint requests to Division of Biology, California Institute of Technology, Pasadena, CA 91125 (Dr Hood).


JAMA. 1988;259(12):1837-1844. doi:10.1001/jama.1988.03720120041033
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The practice of biology and medicine has been revolutionized during the past ten years by the advent of three biotechnologies—recombinant DNA techniques, the monoclonal antibody technology, and the development of microchemical instrumentation, machines that permit the rapid and effective synthesis and sequence analysis of proteins and genes. In this article, these powerful biotechnologies will be discussed, with particular emphasis on microchemical instrumentation, a major focus of my efforts for the past 15 years. I will also discuss two fundamental problems in modern medicine that are being explored in my laboratory using these techniques—genetic engineering of the nervous system and the mapping and sequencing of the human genome.

(JAMA 1988;259:1837-1844)

REFERENCES

Early P, Hood L:  Mouse immunoglobulin genes , in Setlow JK, Hollaender A (eds): Genetic Engineering . New York, Plenum Publishing Corp, 1981;, vol 3, pp 157-188.
Steinmetz M, Hood L:  Genes of the major histocompatibility complex in mouse and man. Science 1983;;222:727-733.
Kronenberg M, Siu G, Hood LE, et al:  The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Ann Rev Immunol 1986;;4:529-591.
Hood L, Kronenberg M, Hunkapiller T:  T-cell antigen receptors and the immunoglobulin supergene family. Cell 1985;;40:225-229.
Hunkapiller T, Hood L:  The growing immunoglobulin gene superfamily. Nature 1986;;323:15-16.
Hunkapiller T, Hood L:  Diversity of the immunoglobulin gene superfamily. Adv Immunol , in press.
Maniatis J, Fritsch EF, Sambrook J: Molecular Cloning . Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1982;.
Hunkapiller M, Kent S, Caruthers M, et al:  A microchemical facility for the analysis and synthesis of genes and proteins. Nature 1984;;310:105-111.
Horvath SJ, Firca JR, Hunkapiller T, et al:  An automated DNA synthesizer employing deoxynucleoside 3, phosphoramidites. Methods Enzymol 1987;;154:314-326.
Caruthers MH:  Gene synthesis machines: DNA chemistry and its uses. Science 1985;;230:281-285.
Edman P:  Method for determination of the amino acid sequence in peptides. Acta Chem Scand 1949;;4:283-293.
Hunkapiller MW, Hood L:  A new protein sequenator with increased sensitivity. Science 1980;;207:523-525.
Hewick RM, Hunkapiller MW, Hood LE, et al:  A gas-liquid solid phase peptide and protein sequenator. J Biol Chem 1981;;256:7990-7997.
Merrifield RB:  Solid phase peptide synthesis: I. The synthesis of a tetrapeptide. J Am Chem Soc 1963;;85:2149-2154.
Kent S, Clark-Lewis I:  Modern methods for the chemical synthesis of biologically active peptides , in Alitalo K, Partanen P, Vaheri A (eds): Synthetic Peptides in Biology and Medicine . Amsterdam, Elsevier Science Publishers, 1985;, pp 29-57.
Kent SB, Hood LE, Beilan H, et al:  A novel approach to automated peptide synthesis based on new insights into solid phase chemistry , in Isymiya N (ed): Peptide Chemistry 1984: Proceedings of the Japanese Peptide Symposium . Osaka, Japan, Protein Research Foundation, 1984;, pp 217-222.
Clark-Lewis I, Aebersold R, Ziltener H, et al:  Automated chemical synthesis of a protein growth factor for hemopoietic cells, interleukin-3. Science 1986;;231:134-139.
Bruist MF, Horvath SJ, Hood LE, et al:  Synthesis of a site-specific DNA binding peptide. Science 1987;;235:777-780.
Lerner RA:  Tapping the immunological repertoire to produce antibodies of predetermined specificity. Nature 1982;;299:592-596.
Morell P (ed): Myelin , ed 2. New York, Plenum Publishing Corp, 1984;.
Chernoff GH:  Shiverer: An autosomal recessive mutant mouse with myelin deficiency. J Hered 1981;;72:128.
Roach A, Boylan K, Horvath S, et al:  Characterization of cloned cDNA representing rat myelin basic protein: Absence of expression in brain of shiverer mutant mice. Cell 1983;;34:799-806.
Roach A, Takahashi N, Pravtcheva D, et al:  Chromosomal mapping of the mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 1985;;42:149-155.
Takahashi N, Roach A, Teplow DB, et al:  Cloning and characterization of the myelin basic protein gene from mouse: One gene can encode both 14 kd and 18.5 kd MBPs by alternate use of exons. Cell 1985;;42:139-148.
Early P, Rogers J, Davis M, et al:  Two mRNAs can be produced from a single immunoglobulin μ gene by alternative RNA processing pathways. Cell 1980;;20:313-319.
Readhead C, Popko B, Takahashi N, et al:  Expression of a myelin basic protein gene in transgenic shiverer mice: Correction of the dysmyelinating phenotype. Cell 1987;;48:703-712.
Popko B, Puckett C, Lai E, et al:  Myelin deficient mice: Expression of myelin basic protein and generation of mice with varying levels of myelin. Cell 1987;;48:713-721.
Smith L, Sanders J, Kaiser R, et al:  Fluorescence detection in automated DNA sequence analysis. Nature 1986;;321:675-679.
Sanger F, Nicklin S, Coulson AR:  DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977;;74:5463-5467.
Connell C, Fung S, Heiner C, et al:  Automated DNA sequence analysis. BioTechniques 1987;;5: 342-348.
Hood L, Smith L:  Sequencing the human genome. Issues Sci Technol 1987;;3:35-46.
Gilbert W:  Genome sequencing: Creating a new biology for the 21st century. Issues Sci Technol 1987;;3:26-35.
Baltimore D:  Genome sequencing: A small science approach. Issues Sci Technol 1987;;3:48-50.
Smith L, Hood L:  Mapping and sequencing the human genome: How to proceed. BioTechnology 1987;;5:933-939.
Hood L, Hunkapiller MW, Smith LM:  Automated DNA sequencing and analysis of the human genome. Genomics , in press.

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Early P, Hood L:  Mouse immunoglobulin genes , in Setlow JK, Hollaender A (eds): Genetic Engineering . New York, Plenum Publishing Corp, 1981;, vol 3, pp 157-188.
Steinmetz M, Hood L:  Genes of the major histocompatibility complex in mouse and man. Science 1983;;222:727-733.
Kronenberg M, Siu G, Hood LE, et al:  The molecular genetics of the T-cell antigen receptor and T-cell antigen recognition. Ann Rev Immunol 1986;;4:529-591.
Hood L, Kronenberg M, Hunkapiller T:  T-cell antigen receptors and the immunoglobulin supergene family. Cell 1985;;40:225-229.
Hunkapiller T, Hood L:  The growing immunoglobulin gene superfamily. Nature 1986;;323:15-16.
Hunkapiller T, Hood L:  Diversity of the immunoglobulin gene superfamily. Adv Immunol , in press.
Maniatis J, Fritsch EF, Sambrook J: Molecular Cloning . Cold Spring Harbor, NY, Cold Spring Harbor Laboratory, 1982;.
Hunkapiller M, Kent S, Caruthers M, et al:  A microchemical facility for the analysis and synthesis of genes and proteins. Nature 1984;;310:105-111.
Horvath SJ, Firca JR, Hunkapiller T, et al:  An automated DNA synthesizer employing deoxynucleoside 3, phosphoramidites. Methods Enzymol 1987;;154:314-326.
Caruthers MH:  Gene synthesis machines: DNA chemistry and its uses. Science 1985;;230:281-285.
Edman P:  Method for determination of the amino acid sequence in peptides. Acta Chem Scand 1949;;4:283-293.
Hunkapiller MW, Hood L:  A new protein sequenator with increased sensitivity. Science 1980;;207:523-525.
Hewick RM, Hunkapiller MW, Hood LE, et al:  A gas-liquid solid phase peptide and protein sequenator. J Biol Chem 1981;;256:7990-7997.
Merrifield RB:  Solid phase peptide synthesis: I. The synthesis of a tetrapeptide. J Am Chem Soc 1963;;85:2149-2154.
Kent S, Clark-Lewis I:  Modern methods for the chemical synthesis of biologically active peptides , in Alitalo K, Partanen P, Vaheri A (eds): Synthetic Peptides in Biology and Medicine . Amsterdam, Elsevier Science Publishers, 1985;, pp 29-57.
Kent SB, Hood LE, Beilan H, et al:  A novel approach to automated peptide synthesis based on new insights into solid phase chemistry , in Isymiya N (ed): Peptide Chemistry 1984: Proceedings of the Japanese Peptide Symposium . Osaka, Japan, Protein Research Foundation, 1984;, pp 217-222.
Clark-Lewis I, Aebersold R, Ziltener H, et al:  Automated chemical synthesis of a protein growth factor for hemopoietic cells, interleukin-3. Science 1986;;231:134-139.
Bruist MF, Horvath SJ, Hood LE, et al:  Synthesis of a site-specific DNA binding peptide. Science 1987;;235:777-780.
Lerner RA:  Tapping the immunological repertoire to produce antibodies of predetermined specificity. Nature 1982;;299:592-596.
Morell P (ed): Myelin , ed 2. New York, Plenum Publishing Corp, 1984;.
Chernoff GH:  Shiverer: An autosomal recessive mutant mouse with myelin deficiency. J Hered 1981;;72:128.
Roach A, Boylan K, Horvath S, et al:  Characterization of cloned cDNA representing rat myelin basic protein: Absence of expression in brain of shiverer mutant mice. Cell 1983;;34:799-806.
Roach A, Takahashi N, Pravtcheva D, et al:  Chromosomal mapping of the mouse myelin basic protein gene and structure and transcription of the partially deleted gene in shiverer mutant mice. Cell 1985;;42:149-155.
Takahashi N, Roach A, Teplow DB, et al:  Cloning and characterization of the myelin basic protein gene from mouse: One gene can encode both 14 kd and 18.5 kd MBPs by alternate use of exons. Cell 1985;;42:139-148.
Early P, Rogers J, Davis M, et al:  Two mRNAs can be produced from a single immunoglobulin μ gene by alternative RNA processing pathways. Cell 1980;;20:313-319.
Readhead C, Popko B, Takahashi N, et al:  Expression of a myelin basic protein gene in transgenic shiverer mice: Correction of the dysmyelinating phenotype. Cell 1987;;48:703-712.
Popko B, Puckett C, Lai E, et al:  Myelin deficient mice: Expression of myelin basic protein and generation of mice with varying levels of myelin. Cell 1987;;48:713-721.
Smith L, Sanders J, Kaiser R, et al:  Fluorescence detection in automated DNA sequence analysis. Nature 1986;;321:675-679.
Sanger F, Nicklin S, Coulson AR:  DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 1977;;74:5463-5467.
Connell C, Fung S, Heiner C, et al:  Automated DNA sequence analysis. BioTechniques 1987;;5: 342-348.
Hood L, Smith L:  Sequencing the human genome. Issues Sci Technol 1987;;3:35-46.
Gilbert W:  Genome sequencing: Creating a new biology for the 21st century. Issues Sci Technol 1987;;3:26-35.
Baltimore D:  Genome sequencing: A small science approach. Issues Sci Technol 1987;;3:48-50.
Smith L, Hood L:  Mapping and sequencing the human genome: How to proceed. BioTechnology 1987;;5:933-939.
Hood L, Hunkapiller MW, Smith LM:  Automated DNA sequencing and analysis of the human genome. Genomics , in press.
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