Human Gene Therapy

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Human Gene Therapy
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Human Gene Therapy

• Background
• September 1990 First approved gene therapy
  procedure
• Severe Combined Immune Deficiency
• Removed white blood cells and infused them with
  genetically modified cells and placed them back
  into the patient
• Not a cure procedure needs to be repeated every
  few months

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Human Gene Therapy

• Background
• Somatic cell gene therapy
• Non-reproductive cells (virtually all cells in
  the body except egg and sperm cells)
• Germ cell gene therapy
• Reproductive cells cells that carry the genes
  to future generations

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Human Gene Therapy

• Background
• Techniques (somatic cell therapy)
• Using blood cells to introduce a normally
  functioning gene into the blood cells and
  returning them to the patient
• Inserting normal genes directly into affected
  cells (e.g., cancer cells)
• Inserting new DNA into affected area using a
  different medium (e.g., cystic fibrosis)

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Human Gene Therapy

• Background
• Techniques (germ line therapy)
• More difficult
• Treating an embryo prior to implantation
• Treating germ cells of affected adults

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Human Gene Therapy

• Background
• Types of diseases treated
• Single gene diseases
• Severe Combined Immune Deficiency
• Hypercholesterolemia
• Cystic fibrosis
• Gauchers disease

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Human Gene Therapy

• Background
• Types of diseases treated
• Criteria for selection
• Disease is incurable
• Tissue and cells types affected by the disease
  have been identified
• Normal counterpart of the defective gene is
  cloned
• Normal gene can be introduced into the target
  tissue
• The gene will produce sufficient quantity of
  normal protein to make a difference
• Safety of procedures are verified

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Human Gene Therapy

• History of Gene Therapy in the United States
• 1967 cells are programmed using synthetic
  techniques in the laboratory
• 1974 Recombinant DNA research is regulated
• Recombinant DNA Advisory (RAC) Board created
• 1974 - The RAC and FDA begin to develop
  regulations for safety and procedures for
  research protocols
• 1980 UCLA researcher performed experiments
  without institutional approval (done in Italy and
  Israel)
• 1984 RAC develops document to guide to those
  applying for approval of gene therapy research

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Human Gene Therapy

• History of Gene Therapy in the United States
• 1988 First protocols are received
• 1990 Severe Combined Immune Deficiency
  protocols approved, and demonstrate success
• 1999 Death of Jesse Gelsinger first fatal
  gene therapy experiment
• Subsequently it was discovered that six other
  deaths had occurred

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Human Gene Therapy

• Arguments in favor of Gene Therapy
• The need to treat desperately ill individuals
• The need to prevent onset of horrible illness
• Analogous to other medical techniques
• Obligation to serve the well-being of patients

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Human Gene Therapy

• Arguments in favor of Gene Therapy
• A strictly therapeutic intervention whose
  explicit objective is the healing of various
  maladies such as those stemming from chromosomal
  defects will, in principle, be considered
  desirable, provided it is directed to the true
  promotion of the personal well-being of the
  individual without doing harm to his integrity or
  worsening his condition of life. Such an
  intervention would indeed fall within the logic
  of the Christian tradition. (John Paul II)

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Human Gene Therapy

• Arguments opposed to Gene Therapy
• This marks a slippery slope.
• How do we distinguish between good and bad
  genes?
• How to follow up on patients long term?
• Many gene therapy candidates are children too
  young to comprehend and give consent.
• Conflicts of interests individual reproductive
  liberties vs. societys interests (costs for
  caring for children with genetic diseases)
• Justice and allocation of resources who gets
  the therapy at what cost?

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Human Gene Therapy

• Arguments in Favor of Germ Line Gene Therapy
• Offers a true cure and not simply symptomatic
  treatment
• May be the only effective way to treat some
  genetic diseases
• Prevention of transmission of disease means that
  somatic gene therapy would not be required by
  future generations
• Responsible response to health needs of
  prospective parents
• Scientific community has a right to free inquiry

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Human Gene Therapy

• Arguments Opposed to Germ Cell Gene Therapy
• Involves too much scientific uncertainty
• Long term effects of such therapy are unknown
• Opens the door to attempts to alter human traits
  not associated with disease (e.g., small stature)
• Involves research on embryos issues of consent
• Offspring are affected without their consent
• Costs are very high

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Human Gene Therapy

• Additional Issues
• What is a disease?
• How do we distinguish between enhancement and
  treatment?
• What truly is therapeutic?