The Ethics of Preclinical Recombinant DNA Research

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The Ethics of Preclinical Recombinant DNA Research

• David Magnus, PhD
• Center for Bioethics
• University of Pennsylvania

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Focus

• Plant Made Pharmaceuticals
• Pharm Animals
• Model Organisms

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Plant Made Pharmaceuticals (PMP)--benefits

• Cheaper, faster way to produce biologics
  (monoclonal antibodies)
• 5-7 years to build biologics plant vs. 1-3 years
  for conventional pharm plant
• Improved delivery of vaccines to impoverished
  populations?

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As Centocor Vice President for Medical Research
Richard McCloskey stated, the top four reseasons
to make MAbs in transgenic plants are capital
avoidance, capital avoidance, capital avoidance,
and capital avoidance. (BIO News)
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Crops used

• Corn
• Rice
• Tobacco
• Safflower

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Why corn?

• Stability (no degradation)
• Well understood
• No compatible weed species in U.S.
• No known endogenous human pathogens
• Several good methods of sterilization
• Easy identifiable markers

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Environmental Risks

• Escape (weed problem)
• Out-crossing
• Horizontal gene transfer
• Impact if consumed by animals, insects

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Risks to Food Supply

• Starlink--Bt protein not approved for human
  consumption entered food supply
• Prodigene--Iowa--155 acres of conventional corn
  burned--Nebraska--500,000 bushels of soybeans
  contaminated

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Management of Risks

• Contained system
• Whole corn harvesting
• Monitoring and training of workers
• Physical confinement
• Temporal confinement
• Bioconfinement
• Monitoring and inspections

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Pharm animals

• Stable, complex molecules that are difficult to
  produce can be produced in milk
• Organ scarcity alleviated through
  xenotransplantation

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Risks

• Milk and carcasses of animals enter food supply
• Animal welfare--some cases result in harm to
  animals
• Clinical trial stage will present many additional
  risks

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Model organisms

• More useful as tools for study, e.g. more
  reliable tumor development in mice
• More like humans in relevant ways to be better
  models, e.g. humanized mice

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Risks

• Escape into environment
• Harm to animals--e.g. oncomouse

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Ethical Values/Issues--beyond risk

• Justice
• Balancing animal versus human welfare
• Playing God

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Justice

• Who is exposed to any risks versus who benefits?
• Who makes decisions?
• Is the regulatory system fair?

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Justice--community input into where to grow PMPs

• Iowa farmers want to grow
• Iowa community wants it grown
• Food producers oppose
• Food consumers?

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How do we weigh the trade-offs between animal
welfare and human benefits?

• Utilitarian
• Animal rights
• Instrumental rights

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Playing God

• Transgressing the integrity of species
• Hubris
• Owning Life
• Commodification of Life

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There is a wisdom in the natural order of things
which reflects the goodness and purposiveness of
the creator. For humans to mix aspects of
different organisms by genetic engineering would
go beyond Gods wise ordering of life. Donald
Bruce
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To contend that we can enhance the telos of an
animal--and thus by extension that we can improve
upon nature--is hubris. Michael W. Fox
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The patenting of animals brings up the central
ethical issue of reverence for life. Will future
generations follow the ethic of this patent
policy and view life as mere chemical manufacture
and invention with no greater value or meaning
than industrial products? (Mark Hatfield)
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The decision to allow the patenting of
genetically engineered animals presents
fundamental dangers to humanitys relationship
with the natural world. Reverence for all life
created by God may be eroded by subtle economic
pressures to view animal life as if it were an
industrial product invented and manufactured by
humans. (R. Hoyle)
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