1、Technology, Science, Money, and Health,A Policy History of GenomicsRobert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome Sciences and Policy,Outline of the talk,Some histories Some data Some interpretation Some stories A few more data Some interpretation,Technology,Re
2、combinant DNA 1975-7 DNA sequencingDesktop PC (1984 Macintosh) 1983 PCR (1986 Cold Spring Harbor talk)Automated DNA sequencing 1989 World Wide WebMicro-arraysSNPs (1999 SNP Consortium) 2001 Haplotype map (2003 officially launched),Science,1950s Phage group 1960s Emergence of molecular biology 1970s
3、Dominance of molecular biology 1980s Scale-up of molecular biology 1990s Capital-intensive biology 2000 Draft sequence 2003 Reference sequence 2004 Genetic variation Next? Integration with organismal biology and clinical research (beyond lip service?),Policy issues,1985-88 To fund or not to fund Big
4、 Science v cottage industry Human genetics or worm-yeast sociology 1989-1993 Launch phase Getting maps done NIH-DOE leadership competition; international collab. 1993-2003 Public-private competition Sequencing 2004 Making information useful,ELSI priorities,Early Genetic discrimination, genetic priva
5、cy Transition from gene discovery to genetic test Eugenics history Middle Health professional education Regulation of tests, “screening” use Newer Race, diversity, health disparities Intellectual property Next Reimbursement, coverage, cost, cost-effectiveness,Money,1940 Industry philanthropy govt 19
6、50-60 Fed industry philanthropy 1990 Industry fed philanthropy19976-80 first wave of biotech startups 1981 Applied Biosystems founded 1992-3 first wave of genomics startups Incyte, Human Genome Sciences, Millennium, Mercator, Myriad, etc. 1998 Celera 2000 peak of genomics bubble 2004 continued R&D i
7、ncreases, but market cap decline,NIH Appropriations 1940-2003,National Health Expenditures,Health R&D as Percent National Health Expenditures,Health Research Funding,Industry,Philanthropy,Government,Intellectual property,1980 Diamond v Chakrabarty 1980 Cohen-Boyer 1980 Bayh-Dole; Stevenson-Wydler 19
8、82 Court of Appeals for the Federal Circuit 1991 EST controversy 1994 Eisenberg-Merges; Varmus abandons EST patents 1995 OTA dies before publishing DNA patenting report 1995 ten-sequence rule 1995 TRIPS 1999 Examination guidelines (utility; written description) 1999 NIH guidelines on research tools
9、2000 US adopts 18-month publication rule 2004 NIH draft guidelines on patent licensing,Which of these histories matters?,Scientific, practical, and commercial value of DNA information Analysis, networking and distributed work through computers and telecomm Stronger patents Tighter links between acad
10、eme and pharma/biotech,Which policies mattered?,Health research (and genomics) funding? Availability of capital for high-tech, whiz-bang science Stronger patent protection Tech transfer policy,Translation of Delphion Search Algorithm1. Search US Patent classes 047 (plant husbandry), 119 (animal husb
11、andry), 260 (organic chemistry), 426 (food), 435 (molecular biology and microbiology), 514 (drug, bio-affecting and body treating compositions), 536/subclasses 22 through 23.1 (nucleic acids, genes, etc., but not peptides or proteins), subclasses 24 and 25 (various nucleic acids, variants, and relat
12、ed methods), and class 800 (multicellular organisms).,2. Select patents from that group that include one or more of the following terms in their claims: antisense cDNA centromere deoxyoligonucleotide deoxyribonucleic deoxyribonucleotide DNA (with or without following letters, such as DNAs) exon gene
13、 or genes (exact match only) genetic genome genomic genotype haplotype intron mtDNA (with or without following letters such as mtDNAs)exact case match only nucleic nucleotide,List of terms continued oligonucleotide oligodeoxynucleotide oligoribonucleotide plasmid polymorphism polynucleotide polyribo
14、nucleotide ribonucleotide ribonucleic recombinant DNA (exact match for case and words only) RNA (all upper case only, with or without following letters such as RNAs) mRNA (exact case match only, with or without following letters such as mRNAs) rRNA (exact case match only, with or without following l
15、etters such as rRNAs) siRNA (exact case match only, with or without following letters such as siRNAs) snRNA (exact case match only, with or without following letters such as snRNAs) tRNA (exact case match only, with or without following letters such as tRNAs) ribonucleoprotein hnRNP (exact case matc
16、h only, with or without following letters such as hnRNPs) snRNP (exact case match only, with or without following letters such as snRNPs) SNP (exact case match only, with or without following letters such as SNPs)Terms were tested for specificity and sensitivity,Sir John Sulston and the Open Genomic
17、s of the Worm,The Worm Project,Coming: Rachel Ankeny: The Conqueror Worm,Another Story,The Third Way,Celera: Data by subscription,Spectrum of data access,Bermuda rules: 24-hour data release Merck EST database, cancer Genome Anatomy Program, Mammalian Gene Collection, mouse mutant collections Apply f
18、or patent and abandon: SNP Consortium Celera: data by subscription Universities: genes for a license fee Incyte: high-priced multilateralism Pharma: publish occasionally HGS: trade secrecy plus patent,Yellow = private R White = public $,Policy story: cDNA sequencing,Incorporated into OTA budget plan
19、 (1987 “costs” workshop) Omitted from NIH initial 5-year plan 1990 EST patent controversy 1991 Incyte, HGS based on cDNA sequencing 1992-3 Merck EST index 1994-5 Cancer genome anatomy program, Mammalian gene collection 1996Lesson: govt mistake, private sector adaptation,Policy story: whole-genome sh
20、otgun sequencing,Sulston refined sequence out April 2003 “reference sequence” to coincide with DNA 50thLesson: public sector spurred to action by private sector threat,Is the genome project a success?,Ask a scientist Ask a doctor or patient Ask a lawyer Ask an anthropologist Ask someone worried abou
21、t health disparities Ask a legislator or governor Ask an economist,Genomics Funding: privatepublic (Year 2000),Source: World Survey of Funding for Genomics Research Stanford in Washington Program http:/www.stanford.edu/class/siw198q/websites/genomics/,Growth of Commercial Genomics,Data through Year
22、2000 Market Cap figures for end of year Number of firms at end of each year,R&D v Market Cap,When did the market have the economic value of genomics right?,Early 1990s (near-zero investment) 1993-1995 first wave of genomics firms 1998-2001 euphoria and hype: the bubble Very high valuation of IP 2002
23、-2004 conversion to pharma model very low valuation of IP,Making assumptions explicit,Genome data and technologies are a Big Deal in science, and will work their way into applications Time scale is over a decade hence Not a revolution but a foundation Chokepoint is clinical utility, not fundamental knowledge A robust scientific commons is immensely important to capturing social benefit,
