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Ethics and Values in Ethics and Values in BiotechBiotech

Thane Kreiner, Ph.D.Thane Kreiner, Ph.D.Senior Vice President, Corporate AffairsSenior Vice President, Corporate Affairs

AffymetrixAffymetrix

The Promise of Genetics –Public Perceptions

1971 1994

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The Genome is Complex The Genome is Complex

3 B base pairs

Only ~1.5% of genome encodes ~30,000 genes

Millions of differences between any two people

Much unknown about “dark matter” of genome

All Disease is a Result of Genes Interacting All Disease is a Result of Genes Interacting with the Environment…with the Environment…

Infectious Disease

Drugs

Lifestyle Choices

Exercise Diet

Exposures

Genetics

Tay-SachsHIV / AIDS

Diabetes

Cystic Fibrosis Heart Disease

Lead ToxicityCancer

Environment

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Packaging Genetic InformationPackaging Genetic Information5”5”

5”5”

Up to ~6,500,000 Up to ~6,500,000 featuresfeatures // chipchip

1.28cm1.28cm

1.28cm1.28cm

5µm5µm

5µm 5µm

*** ***

Millions of identical Millions of identical probesprobes // featurefeature

chips / wafer

Information Capacity is Exploding

CostInformation Capacity

1994 1996 1998 2000 2002 2004

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Clinical Applications of MicroarraysClinical Applications of Microarrays

Pharmacogenetic testing: CYP450– Example: Roche AmpliChipTM

Companion diagnostics: determine safety and efficacy

– Example: Herceptin®

Future? Combined use array: symptom & treatment decisions

Diagnosis Disease Classification

PrognosisTherapeutic Choice

Applications of Genetics Technology

Agricultural biotechAgricultural biotechAgricultural biotech

Livestock diagnosticsor grading

Livestock Livestock diagnosticsdiagnosticsor gradingor grading

Human diagnosticsHuman diagnosticsHuman diagnostics

Environmental testing

Environmental Environmental testingtesting

Food testingFood testingFood testing

Basic ResearchBasic ResearchBasic Research

Identity testingIdentity testingIdentity testing

Personalized medicinePersonalized medicinePersonalized medicine

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Why Care About Ethics in Why Care About Ethics in Biomedical Science?Biomedical Science?

Research and clinical applications are often: – High visibility– High expectation– High potential revenue– Lacking policy and precedent– Tied to “moral values” of society

Why does business care about ethics?– Want to do the right thing– Public perceptions and acceptance ultimately affect bottom line

Companies, Healthcare & SocietyCompanies, Healthcare & Society

“… healthcare providers have a direct effect upon the lives of people in the societies they operate in, and consequently their activities are subject to understandable scrutiny”

“… The pharmaceutical industry is founded on trust, and we must preserve and encourage trust at all times”

- Liz MacGillivray, Novartis Pharma

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Corporate Social ResponsibilityCorporate Social Responsibility

CSR Issues– Stakeholder involvement– Supply chain management– Issues of access

Expanded Responsibilities?– Actively encouraging broad discussion about social issues– Pursuing self-regulation when appropriate– Examination of product use issues

Ethical Questions Ethical Questions

Gene Patenting: Should one firm own the rights to research and development on this gene?

– Ability to control access– Ability to control price

Marketing: should genetic tests be marketed directly to the public?

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Example: The BRCA CaseExample: The BRCA Case

BRCA1 Gene, implicated in some hereditary breast cancers, discovered by Mary Claire King in 1990

Research done by Francis Collins to understand mutations relatedto breast cancer

Patents granted to a single firm

Test available using common laboratory equipment through a single source for ~$2400

Example: Gene PatentingExample: Gene PatentingThe SARS Genome: Who Owns It?The SARS Genome: Who Owns It?

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No One Should Own the GenomeNo One Should Own the Genome

No one should own the genome – Can’t invent around a gene– Many diseases are caused by interactions of multiple

genes and the environment

Some things should not be patentable:– Periodic table of elements– Anatomy maps– Cell structure

Gene patents slow access to tests & treatments

Active Ethics: Currently exploring concept of gene Active Ethics: Currently exploring concept of gene patent pooling patent pooling –– allows all researchers access to allows all researchers access to genetic information for reasonable access feegenetic information for reasonable access fee

DTC Marketing of Health ProductsDTC Marketing of Health Products

Pharmaceutical Marketing– $2.8B in 2001– Appears to influence consumer opinions and physician prescribing– 33% have “asked their doctor” (Weissman et al, Health Affairs, 2003)

Genetic Test Marketing– Range of sources, largely web-based– Ads attempt to simplify complex issues and diseases– Focus on themes:

Powerful hope for better healthDesire for control over health care optionsMotivation to relieve fear

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Is it Appropriate to Market Hereditary Is it Appropriate to Market Hereditary Breast Cancer Testing to the Public?Breast Cancer Testing to the Public?

– The CDC recommends hereditary breast cancer testing for <1% of population

– No special treatment currently exists for women who pre-symptomatically test positive for BRCA1 and BRCA2

American women estimate there is a 40% chance they will get breast cancer, when in fact their overall risk is less than 10%

Harris Poll® #7, Jan 27, 1999. ~1000 adults > age 18

Complicated Social Context Makes Complicated Social Context Makes Marketing Ethically ChallengingMarketing Ethically Challenging

Challenges:– Fears about genetics– Heightened expectations about genetics– Risk information is difficult to understand– Tempting to oversimplify issues

Does the healthcare industry have a greater obligation to consider these issues from an ethics perspective?

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The Promise of Genetics – Hype vs. Hope?

2001 Harris Poll Survey (US): – 84% Americans believe genomics research will have a positive

impactimprovements in detection and treatment of diseaseImprovements in the quality and length of life

Harris Poll® Public Awareness in the Age of Genomics. ~1000 adults > age 18

45% concerned that genetic information will be misused

Words MatterWords Matter

“Genetics” evokes feelings of permanence, accuracy and destiny

– Often tied to the moral values of society

Public perceptions are critical to understanding moral and ethical issues for businesses

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Genetic Discrimination Example: Genetic Discrimination Example: Burlington NorthernBurlington Northern

2000: Burlington Northern began secret genetic testing of its workforce

– The railroad hoped to prove a pre-existing condition, thus reducing their workers compensation costs.

The EEOC sued for discrimination based upon predictive genetic testing

2002: Case settled with Burlington Northern paying $2.2 million to the workers

Genetic Privacy & NonGenetic Privacy & Non--discriminationdiscrimination

2002 Harris Poll Survey (US): – Who should have access to your genetic

information?17% employers25% life insurance39% health insurance

Affymetrix advocates for privacy & non-discrimination protection

– Insurance– Employment

Important for public to be comfortable with genetics and genetics research

Harris Poll® #26, June 5, 2002. ~1000 adults > age 18

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Status of Federal Nondiscrimination BillStatus of Federal Nondiscrimination Bill

Genetic Non-Discrimination legislation – Non-discrimination in health insurance– Non-discrimination in employment

Senate: has passed Senate twice– Current bill, S306 – Passed 98-0

House: has not been brought to a vote– HR 1227

Ethics at AffymetrixEthics at Affymetrix

Social Initiatives– Genetic Age Symposium series is designed to reach the general

public, focused primarily on policy issues (www.geneticage.org)

Internal Initiatives– Ongoing Ethics Speaker Series designed to encourage

employees to think about ethical ramifications of their work, to“de-mystify” ethics and make it accessible

Policy Initiatives– In favor of Federal genetic non-discrimination legislation– Against the patenting of naturally occurring gene sequences

Ethics Advisory Committee

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Affymetrix Ethics Advisory Committee

Formed in March, 1997 to understand how technology can best be used

No approval or veto –advisory role

Diversity of experience and opinion

No conflicts of interest

Advisor names kept confidential – no PR

Law SchoolProfessor

FormerEthics Center

Director

Biochemist(Nobel

Laureate)

Genetic Counselor

Physician Formerly on NBAC

SociologyProfessor

Ethics Advisory

Committee

EAC: Logistical IssuesEAC: Logistical Issues

Minimize conflicts of interest

Payment– Discussed at formation of EAC– Paid “going rate” for consultants to cover their time

2 accept payment, 3 do not, 1 donates funds to charity

Personnel Changes– 2 members stepped down, 1 addition – handled case-by-case

Confidentiality– Advisors are asked to sign a non-disclosure agreement– Do not want to inhibit ongoing research or publications; handled

case-by-case

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Discussion TopicsDiscussion Topics

Any department can bring topics (research, EH&S, legal, collaborations, commercial team)

Two main categories: – Broad topics including ethics positions, company responsibility and

informed consent– Specific topics including contract language, product development

and collaborations

Common Topics:

Corporate vs. social responsibility – how responsible should we be for our customers’ use of our products?

Moving genomics to the clinic – what issues matter in the healthcare realm? What type of PR is appropriate?

EAC Output: Ethical FrameworkEAC Output: Ethical Framework

Based on the analysis of ethical responsibility, the corporation has a number of possible actions:

– Put limitations on use of chips– Make recommendations– Encourage state or federal

legislation– Avoid market entirely– Do nothing

Market Position

Product

Use

Employment or Insurance Discrimination

Non Human Research

Participant MonopolistGeneric

Custom

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ExampleExample

Market Position

Product

Use

Employment or Insurance Discrimination

Non Human Research

Participant MonopolistGeneric

Custom

Hypothetical Example:– Universally applicable

product for research on chickens

Low need for ethical concern

ExamplesExamples

Hypothetical Example:– Test for predisposition to

late-onset disease, similar to other tests on market

Market Position

Product

Use

Employment or Insurance Discrimination

Non Human Research

Participant MonopolistGeneric

Custom

Presence of competition

lessens ethical burden

Potential for misuse

increases ethical burden

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ExampleExample

Hypothetical Example– Low cost smallpox test,

only offered by Affymetrix

Market Position

Product

Use

Employment or Insurance Discrimination

Non Human Research

Participant MonopolistGeneric

Custom

{? Public good

No competition increases

ethical burdenCustom product increases ethical

burden

Real Life ExampleReal Life Example

Potential Diagnostic company wants to offer “ethnically targeted” genetic testing for couples and potentially children

– Single diagnostic product to allow comprehensive diagnosis of ~70 disorders (Carrier frequency above 1:200)

– Will include regions of that gene that are known or may contain potential mutation hot spots, functional or structural domains

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High Ethical ConcernHigh Ethical Concern

Market Position

Product

Use

Employment or Insurance Discrimination

Non Human Research

Participant MonopolistGeneric

Custom

Example Discussion: QuestionsExample Discussion: Questions

Do we have a responsibility to examine which “disorders” are included?

– What if “IQ gene” was included in list?

Do we have a responsibility to curate content (i.e. which polymorphisms are included)?

What if we suspect content is in violation of existing IP?

Content

Quality

Legal

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Ethical Analysis: ActionsEthical Analysis: Actions

Based on the analysis of ethical responsibility, the corporation has a number of possible actions:

– Put limitations on use of chips– Make recommendations– Encourage state or federal legislation– Avoid market entirely– Do nothing

Ethics Informs PolicyEthics Informs Policy

Affymetrix strives to be:– Informed– Involved– Influential– In front

Logical outgrowth of company’s commitment to examining ethical issues

Policy important to company’s future business objectives

Divergence of interests with industry associations

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ConclusionsConclusions

Social contract and public perceptions matter and may obligate “extra” work on the part of the corporation

Compliance framework alone will not work– There are often no regulations or precedents

Ethics may compel you to lobby for regulation of your own industry

QuestionsQuestions