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Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome Sciences and Policy
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Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Mar 31, 2015

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Page 1: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Technology, Science, Money, and Health

A Policy History of Genomics

Robert Cook-Deegan, MDCenter for Genome Ethics, Law, and PolicyInstitute for Genome Sciences and Policy

Page 2: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Outline of the talk

• Some histories

• Some data

• Some interpretation

• Some stories

• A few more data

• Some interpretation

Page 3: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Technology

1973 Recombinant DNA1975-7 DNA sequencing1981 Desktop PC (1984 Macintosh)1983 PCR (1986 Cold Spring Harbor talk)1986 Automated DNA sequencing1989 World Wide Web1995 Micro-arrays1996 SNPs (1999 SNP Consortium)2001 Haplotype map (2003 officially launched)

Page 4: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Science

• 1950s Phage group• 1960s Emergence of molecular biology• 1970s 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?)

Page 5: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Policy issues

• 1985-88 To fund or not to fund– Big 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

Page 6: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

ELSI priorities

• Early– Genetic discrimination, genetic privacy– 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

Page 7: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Money

• 1940 Industry > philanthropy > gov’t• 1950-60 Fed > industry > philanthropy• 1990 Industry > fed > philanthropy

• 19976-80 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 increases, but market cap decline

Page 8: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

NIH Appropriations 1940-200319

4019

4119

4219

4319

4419

4519

4619

4719

4819

4919

5019

5119

5219

5319

5419

5519

5619

5719

5819

5919

6019

6119

6219

6319

6419

6519

6619

6719

6819

6919

7019

7119

7219

7319

7419

7519

7619

7719

7819

7919

8019

8119

8219

8319

8419

8519

8619

8719

8819

8919

9019

9119

9219

9319

9419

9519

9619

9719

9819

9920

0020

0120

0220

03

S1

0

5

10

15

20

25

30

Year

$ billion (2000 dollars)

Page 9: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

National Health Expenditures

0

200

400

600

800

1,000

1,200

1,400

1960

1962

1964

1966

1968

1970

1972

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

$ B

illi

on

(Y

2000

co

nst

ant

do

llar

s)

National Health Expenditures (billions)

adjusted by Y2000 deflator

Page 10: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Health R&D as Percent National Health Expenditures

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

1960

1962

1964

1966

1968

1970

1972

1974

1976

1978

1980

1982

1984

1986

1988

1990

1992

1994

1996

1998

2000

Pe

rce

nt

Page 11: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Health Research Funding1940

7%

38%

55%

1965

68%

8%

24%

1998

46%

5%

49%

IndustryIndustry

Philanthropy

GovernmentGovernment

Page 12: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Federal Health (budget function 550) v PhRMA R&D 1970-2000Thousand $ (1996 dollars)

-

5,000.00

10,000.00

15,000.00

20,000.00

25,000.00

1970

1971

1972

1973

1974

1975

1976

1977

1978

1979

1980

1981

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

PhRMA

NSF pharma

Fed Health R&D (550)

Page 13: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Intellectual property

1980 Diamond v Chakrabarty1980 Cohen-Boyer1980 Bayh-Dole; Stevenson-Wydler1982 Court of Appeals for the Federal Circuit1991 EST controversy1994 Eisenberg-Merges; Varmus abandons EST patents1995 OTA dies before publishing DNA patenting report1995 ten-sequence rule1995 TRIPS1999 Examination guidelines (utility; written description)1999 NIH guidelines on research tools2000 US adopts 18-month publication rule2004 NIH draft guidelines on patent licensing

Page 14: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

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 academe and pharma/biotech

Page 15: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Which policies mattered?

• Health research (and genomics) funding?

• Availability of capital for high-tech, whiz-bang science

• Stronger patent protection

• Tech transfer policy

Page 16: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Translation of Delphion Search Algorithm

1. Search US Patent classes 047 (plant husbandry), 119 (animal husbandry), 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 related methods), and class 800 (multicellular organisms).

Page 17: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

2. Select patents from that group that include one or more of the following terms in their claims:

antisensecDNAcentromeredeoxyoligonucleotidedeoxyribonucleicdeoxyribonucleotideDNA (with or without following letters, such as DNAs)exongene or genes (exact match only)geneticgenome genomic genotype haplotype intron mtDNA (with or without following letters such as mtDNAs)—exact case match

onlynucleic nucleotide

Page 18: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

[List of terms continued]oligonucleotide oligodeoxynucleotide oligoribonucleotide plasmid polymorphism polynucleotide polyribonucleotide 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 letters 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)ribonucleoproteinhnRNP (exact case match 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

Page 19: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Number of Patents Retrieved by Search Algorithm by Year of Issue

0

500

1000

1500

2000

2500

3000

3500

4000

4500

5000

Year of Issue

Num

ber

of P

aten

ts R

etri

eved

by

Sea

rch

Alg

orith

m

This research was supported by Grant No. R03 HG02683-02, “DNA Patent Policies at Academic Institutions,” from the National Human Genome Research Institute, NIH, and Grant No. DE FG 02 01ER63171, “Enhancing the DNA Patent Database,” from the U.S. Department of Energy; Io Nami Wolk 02-25-04.

Page 20: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Preliminary Data about the 30 Entities Holding the Largest Numbers of DNA-Based Patents (as of 02-05-04)

0 100 200 300 400 500 600 700 800 900 1000

University of CaliforniaUnited States Government

GlaxoSmithKlineIncyte Genomics

AventisChiron

GenentechBayerWyeth

NovartisMerck

University of TexasHuman Genome Sciences

AmgenJohns Hopkins University

AppleraMassachusetts General Hospital

Novo NordiskHarvard University

PfizerStanford University

LillySalk Institute

Cornell UniversityMIT

AffymetrixColumbia University

University of WisconsinWashington University

University of Pennsylvania

Ent

ity N

ame

Number of DNA-Based Patents

Academic Institution Government For Profit Firm

This research was supported by Grant No. R03 HG02683-02, “DNA Patent Policies at Academic Institutions,” from the National Human Genome Research Institute, NIH, and Grant No. DE FG 02 01ER63171, “Enhancing the DNA Patent Database,” from the U.S. Department of Energy. Io Nami Wolk 03-03-04

Page 21: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Sir John Sulston and the Open Genomics of the Worm

Page 22: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

The Worm Project

Coming: Rachel Ankeny: The Conqueror Worm

Page 23: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Another Story

Page 24: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

The Third Way

Celera: Data by subscription

Page 25: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Spectrum of data access

• Bermuda rules: 24-hour data release• Merck EST database, cancer Genome Anatomy

Program, Mammalian Gene Collection, mouse mutant collections

• Apply for 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&D $; White = public $

Page 26: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Policy story: cDNA sequencing

• Incorporated into OTA budget plan (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 1996

• Lesson: gov’t mistake, private sector adaptation

Page 27: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Policy story: whole-genome shotgun sequencing

• Sulston&Waterston propose rapid draft sequencing• Afeyan&Hunkapiller: 96-capillary sequencer for genomic

sequencing• Venter and Celera 1998• Public project concentrates resources, focuses on draft-

first strategy• Celera moves up end-date, incorporates GenBank data• Temporary Truce June 2000; dueling drafts Feb 2001• Celera moves to pharma model; Venter out; refined

sequence out• April 2003 “reference sequence” to coincide with DNA

50th

• Lesson: public sector spurred to action by private sector threat

Page 28: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Is the genome project a success?

• Ask a scientist• Ask a doctor or patient• Ask a lawyer• Ask an anthropologist• Ask someone worried about health

disparities• Ask a legislator or governor• Ask an economist

Page 29: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Genomics Funding: private>public(Year 2000)

Genomics research funding($ million US)

1,653

2,061

900

0

500

1,000

1,500

2,000

2,500

Gov&nonprofit Genomics firms Pharma&biotech

Source: World Survey of Funding for Genomics ResearchStanford in Washington Programhttp://www.stanford.edu/class/siw198q/websites/genomics/

Page 30: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

Genomics firms with publicly traded stock

0

20

40

60

80

Year

# firms 8 10 14 19 25 28 73

1994 1995 1996 1997 1998 1999 2000

0102030405060708090

100

1994 1996 1998 2000

$B market valueGrowth of Commercial Genomics

Data through Year 2000Market Cap figures for end of yearNumber of firms at end of each year

Page 31: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

R&D v Market CapSum of R&D Expenditures for 15 Genomics Firms

-

200

400

600

800

1,000

1,200

1,400

1,600

1,800

2000 2001 2002

Year

R&

D (

Mil

lio

n U

S$

)

-

10,000

20,000

30,000

40,000

50,000

60,000

Ma

rke

t C

ap

(M

illi

on

US

$)

Total R&D Expenditures

Total Market Cap

Page 32: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

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

• 2002-2004– conversion to pharma model– very low valuation of IP

Page 33: Technology, Science, Money, and Health A Policy History of Genomics Robert Cook-Deegan, MD Center for Genome Ethics, Law, and Policy Institute for Genome.

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