Ethical Challenges of Biotechnology

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Ethical Challenges of Biotechnology

• Pattle P.Pun, Ph.D.
• Professor of Biology,
• Wheaton College,
• Wheaton, IL 60187
• USA

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Biotechnology

• The use of living organisms to solve problems or
  make useful products.

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Human Genome Project
Goals  identify all the approximate 30,000
genes in human DNA, determine the sequences of
the 3 billion chemical base pairs that make up
human DNA, store this information in
databases, improve tools for data analysis,
transfer related technologies to the private
sector, and address the ethical, legal, and
social issues (ELSI) that may arise from the
project.   Milestones 1990 Project initiated
as joint effort of U.S. Department of Energy and
the National Institutes of Health June 2000
Completion of a working draft of the entire human
genome February 2001 Analyses of the working
draft are published April 2003 HGP sequencing
is completed and Project is declared finished two
years ahead of schedule
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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What does the draft human genome sequence tell
us?
By the Numbers The human genome contains 3
billion chemical nucleotide bases (A, C, T, and
G).  The average gene consists of 3000 bases,
but sizes vary greatly, with the largest known
human gene being dystrophin at 2.4 million
bases.   The total number of genes is estimated
at around 30,000--much lower than previous
estimates of 80,000 to 140,000.   Almost all
(99.9) nucleotide bases are exactly the same in
all people.   The functions are unknown for over
50 of discovered genes.
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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What does the draft human genome sequence tell us?
How It's Arranged The human genome's gene-dense
"urban centers" are predominantly composed of the
DNA building blocks G and C.   In contrast, the
gene-poor "deserts" are rich in the DNA building
blocks A and T. GC- and AT-rich regions usually
can be seen through a microscope as light and
dark bands on chromosomes.   Genes appear to be
concentrated in random areas along the genome,
with vast expanses of noncoding DNA between.  
Stretches of up to 30,000 C and G bases repeating
over and over often occur adjacent to gene-rich
areas, forming a barrier between the genes and
the "junk DNA." These CpG islands are believed to
help regulate gene activity.   Chromosome 1 has
the most genes (2968), and the Y chromosome has
the fewest (231).
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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What does the draft human genome sequence tell
us?
The Wheat from the Chaff Less than 2 of the
genome codes for proteins.   Repeated sequences
that do not code for proteins ("junk DNA") make
up at least 50 of the human genome.  
Repetitive sequences are thought to have no
direct functions, but they shed light on
chromosome structure and dynamics. Over time,
these repeats reshape the genome by rearranging
it, creating entirely new genes, and modifying
and reshuffling existing genes.   The human
genome has a much greater portion (50) of repeat
sequences than the mustard weed (11), the worm
(7), and the fly (3).
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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What does the draft human genome sequence tell
us?
How the Human Compares with Other Organisms
Unlike the human's seemingly random distribution
of gene-rich areas, many other organisms' genomes
are more uniform, with genes evenly spaced
throughout.   Humans have on average three times
as many kinds of proteins as the fly or worm
because of mRNA transcript "alternative splicing"
and chemical modifications to the proteins. This
process can yield different protein products from
the same gene.   Humans share most of the same
protein families with worms, flies, and plants
but the number of gene family members has
expanded in humans, especially in proteins
involved in development and immunity.
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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What does the draft human genome sequence tell
us?
Variations and Mutations Scientists have
identified about 3 million locations where
single-base DNA differences (SNPs) occur in
humans. This information promises to
revolutionize the processes of finding
chromosomal locations for disease-associated
sequences and tracing human history.   The
ratio of germline (sperm or egg cell) mutations
is 21 in males vs females. Researchers point to
several reasons for the higher mutation rate in
the male germline, including the greater number
of cell divisions required for sperm formation
than for eggs.
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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How does the human genome stack up?
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Anticipated Benefits of Genome Research
Molecular Medicine improve diagnosis of
disease detect genetic predispositions to
disease create drugs based on molecular
information use gene therapy and control
systems as drugs design custom drugs
(pharmacogenomics) based on individual genetic
profiles Microbial Genomics rapidly detect
and treat pathogens (disease-causing microbes) in
clinical practice develop new energy sources
(biofuels) monitor environments to detect
pollutants protect citizenry from biological
and chemical warfare clean up toxic waste
safely and efficiently
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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Anticipated Benefits of Genome Research-cont.
Risk Assessment evaluate the health risks
faced by individuals who may be exposed to
radiation (including low levels in industrial
areas) and to cancer-causing chemicals and
toxins Bioarchaeology, Anthropology, Evolution,
and Human Migration study evolution through
germline mutations in lineages study migration
of different population groups based on maternal
inheritance study mutations on the Y chromosome
to trace lineage and migration of males compare
breakpoints in the evolution of mutations with
ages of populations and historical events
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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Anticipated Benefits of Genome Research-cont.
DNA Identification (Forensics) identify
potential suspects whose DNA may match evidence
left at crime scenes exonerate persons wrongly
accused of crimes identify crime and
catastrophe victims establish paternity and
other family relationships identify endangered
and protected species as an aid to wildlife
officials (could be used for prosecuting
poachers) detect bacteria and other organisms
that may pollute air, water, soil, and food
match organ donors with recipients in transplant
programs determine pedigree for seed or
livestock breeds authenticate consumables such
as caviar and wine  
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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Anticipated Benefits of Genome Research-cont.
Agriculture, Livestock Breeding, and
Bioprocessing grow disease-, insect-, and
drought-resistant crops breed healthier, more
productive, disease-resistant farm animals grow
more nutritious produce develop biopesticides
incorporate edible vaccines incorporated into
food products develop new environmental cleanup
uses for plants like tobacco
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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Medicine and the New Genetics
Gene Testing ? Pharmacogenomics ? Gene
Therapy

• Anticipated Benefits
• improved diagnosis of disease
• earlier detection of genetic predispositions to
  disease
• rational drug design
• gene therapy and control systems for drugs
• personalized, custom drugs

U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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Sustained Correction of X-Linked Severe Combined
Immunodeficiency by ex Vivo Gene Therapy, NEJM
3461185-1193 April 18, 2002

• Methods CD34 bone marrow cells from five boys
  with X-linked severe combined immunodeficiency
  were transduced ex vivo with the use of a
  defective retroviral vector. Integration and
  expression of the c transgene and development of
  lymphocyte subgroups and their functions were
  sequentially analyzed over a period of up to 2.5
  years after gene transfer.

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Therapy
Enhancement
Somatic
Germ Line
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Behavior is Multifactorial
Sin?
Environment
Genes
Development
Behavior
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Classical Methods for Studying the Relationship
between Genes and Behavior

• Twins
• Same genes different environments
• Adoptees
• Different genes same environment

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Heritability of Various Psychiatric Diseases,
Personality Traits And Behaviors

• Phenotype Heritability
• Schizophrenia .60
• Bipolar disorder .62
• Major depression .40
• Social phobia .52
• Panic disorder .42
• Generalized anxiety disorder .35
• Neuroticism .52
• Extraversion .38
• Novelty Seeking .45
• Cigarette smoking .60
• Divorce .52
• Religious affiliation .00

Heritability is the fraction of total
variability due to genetic differences. It is
determined by studying twins and adoptees.
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Although many behaviors are partially heritable,
most of the genes are unknown

• For example
• Schizophrenia and Bipolar DisorderDozens of
  loci have been identified by linkage mapping, but
  only a few have been replicated in at least one
  study and none in every study. No specific genes
  have been found.
• Personality traits such as Neuroticism and
  Novelty SeekingSpecific genes have been found,
  but they account for only a few percent of total
  variance.

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Behavior Gene Discovery

• Complications
• Multiple genes
• Environment is important
• Plieotropy
• Measurement

Mapping Genes To Traits
Mapping Traits To Genes
Trait 1 Gene Trait 2
Trait 3
Gene 1 Trait Gene 2 Gene 3
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The Number of Genes Involved in Particular
Behaviors is Unknown
gene 1
environment
gene 6
or
?
gene1
environment
gene 100
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Technology of cloning
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• Because of the age of the donor nucleus, the life
  expectancy of Dolly is shorter than a newborn
  sheep. In addition, Dolly has obesity problem. At
  6, she was given a lethal injection after
  veterinarians discovered she had lung cancer.
  Normal life span of sheep is 12 years. These
  symptoms that are associated with premature
  aging are also found in other cloned animals.

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Technology of Stem Cell Research
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• In what stage of embryonic development is the
  fertilized egg accorded the status of a human
  being who is entitled to human right protection?

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• In the context of human transplants, should we
  sacrifice one life in order to save another life?

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• In fact, recent successes with adult stem cells
  make them a non-controversial and promising
  alternative to embryonic stem cells. These
  rapidly dividing adult cells, such as cells
  derived from bone marrow, placenta, cord blood,
  are also capable of developing into totipotent
  cells. They can also pose promises as potential
  source of human transplants.

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Promises of Adult Stem Cell Research
Cells isolated from murine skeletal muscle have a
remarkable capacity for hematopoietic
differentiation
Hematopoietic potential of stem cells isolated
from murine skeletal muscle Kathyjo Ann Jackson,
Tiejuan Mi, and Margaret A. Goode Proc Natl Acad
Sci U S A. 1999 December 7 96(25) 1448214486 -
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Embryonic Stem Cells, Cloning, Are Not
Necessarily Path To Cure

• 1. Embryonic stem cells have produced
  disappointing results for juvenile diabetes
• Because of the difficulty of getting ESCs to
  differentiate into desired tissues, the risk of
  tumor formation, the genetic instability of ESCs
  in culture, and other problems, ESCs cannot be
  expected to provide treatments for juvenile
  diabetes anytime soon.
• S. Sipione et al., Insulin expressing
  cells from differentiated embryonic stem cells
  are not beta cells, 47 Diabetologia 499-508
  (2004).

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Embryonic Stem Cells, Cloning, Are Not
Necessarily Path To Cure

• 2. ADULT islet cells have reversed juvenile
  diabetes in hundreds of patients in clinical
  trial
• of the 250 patients who have received the
  newest version of the transplant, more than 80
  percent have been free from insulin shots or
  insulin pumps for more than a year .
• D. Wahlberg, New islet cells put into
  liver, The Atlanta Journal- Constitution, June
  1, 2003, at www.ajc.com/health/content/health/spec
  ial/0603/01exdiabetic_sidebar.html.

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Embryonic Stem Cells, Cloning, Are Not
Necessarily Path To Cure

• 3. Problems of supply and tissue rejection in the
  Edmonton protocol are being addressed.
• NIH researchers have shown that a prior
  transplant of adult bone marrow stem cells can
  prevent rejection of islet cell transplants in
  mice, without use of anti-rejection drugs
• News Release, American Society of
  Hematology, Researchers Look to Stem Cell
  Therapy and Bone Marrow Transplants to Find a
  Cure for Diabetes, December 8, 2003, at
  www.hematology.org/news/press/press_120903_5.cfm?p
  agemodeprint

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Embryonic Stem Cells, Cloning, Are Not
Necessarily Path To Cure

• 4. ADULT stem cells are advancing to create
  entirely new therapies for juvenile diabetes.
• Researchers in Canada have shown that
  transplanted adult stem cells from bone marrow
  can cause pancreatic tissue to repair itself,
  restoring normal insulin production and reversing
  symptoms of diabetes. 
• Transplanted Bone Marrow Stem Cells
  Reverse Diabetes in Mice, JDRF Countdown, Fall
  2003, p. 6. See D. Hess et al., Bone
  marrow-derived stem cells initiate pancreatic
  regeneration, 21 Nature Biotechnology 763-70
  (2003).

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Embryonic Stem Cells, Cloning, Are Not
Necessarily Path To Cure

• 5. Therapeutic Cloning is Useless in Treating
  Juvenile Diabetes
• autoimmune diseases, including type 1
  diabetes.  In such cases transfer of
  immunologically identical cells to a patient is
  expected to induce the same rejection .
• I. Wilmut, Human cells from cloned
  embryos in research and therapy, 328 British
  Medical Journal 415-6 (2004)

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Nuclear Reprogramming of Somatic Cells After
Fusion with Human Embryonic Stem Cells.
Science2005 vol309 iss5739 pg1369

• The Harvard University team fused lab-grown
  embryonic stem cells with the adult cells to
  create the new stem cell. Researchers believe
  these hybrid embryonic stem cells could help
  disease research without using human embryos.

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Unsociable Cyborgs,David Fletcher, Wheaton
College

• A deliberate integration, called converging
  technology, will unite nanotechnology,
  biotechnology, information technology, and
  cognitive technologies with the goal of enhancing
  human performance.
• Because we are not simply isolated individuals
  who are free to tweak ourselves at will. Other
  people will have to live with us. Individuals
  must content themselves with staying merely human
  and must resist the temptation to change into
  something that is supposed to be superhuman

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• Ethical Challenges of Biotechnology

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ELSI Ethical, Legal, and Social Issues
Privacy and confidentiality of genetic
information. Fairness in the use of genetic
information by insurers, employers, courts,
schools, adoption agencies, and the military,
among others. Psychological impact,
stigmatization, and discrimination due to an
individuals genetic differences. Reproductive
issues including adequate and informed consent
and use of genetic information in reproductive
decision making. Clinical issues including the
education of doctors and other health-service
providers, people identified with genetic
conditions, and the general public about
capabilities, limitations, and social risks and
implementation of standards and quality-control
measures.
U.S. Department of Energy Genome Programs,
Genomics and Its Impact on Science and Society,
2003
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• Would the planting of transgenic
  herbicide/pesticide resistant crops lead to the
  chemical abuse in agriculture and the spread of
  resistant pests (superbugs) and weeds?
• Would the introduction of transgenic organisms
  into the environment endanger desirable wild
  life? (ie. Bt corn)
• What should be the proper regulation of
  genetically modified crops?

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Should there be governmental regulations on Stem
Cell Research? Is Reproductive Cloning
Ethical? What should be the proper treatment of
surplus embryos?
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A. Various Ethical Principles informed by the
Christian Worldview
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1. Divine Law of Aquinas and Augustine

• The Creator has designed purposes and directions
  for His creation. This Divine Law can be
  discovered in Nature. Despite man's sinful
  nature, God still reveals this Law to man through
  the Scripture and the Church. The Divine Law is
  consonant with human nature and can be
  universally applied.

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2. God's Steward in His Creation

• Human's participation in creation as a
  significant part of man's stewardship of God's
  creation demands his respect for nature, not his
  exploitation. Man has to maintain two attitudes
  in exercising his stewardship of nature to be
  grateful towards his Creator, and to be prudent
  towards managing the creation.

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3. The Ethics of Virtue

• A virtuous person is driven to do good deeds not
  by the mores of his institutions, but by his own
  virtuous disposition. The Scriptures define
  virtuous disposition as the internal desire to be
  good and to do good, not only based on ones'
  education and upbringing, but on the freedom from
  the bondage of sin and the fruits of the Holy
  Spirit in a repentant sinner.

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B. Towards a Christian Model of Ethics What
Constitute a Perfect Human Being?

• Therefore you are perfect, as your heavenly
  Father is perfect Mt. 548

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The concept of a Perfect Human Being as defined
by scriptural perspectives should help in the
discussion of the ethics of HGP since it defines
the essence of what is being human as well as the
criteria by which genetic technologies should be
applied particularly in relation to man himself.
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1. Creature of God Confined by Finitude

• There is a limit within which human intervention
  to save life can operate since man is doomed to
  die because of our sin. However, advancement in
  medical and genetic technologies can ultimately
  be the instruments that God uses to manifest His
  work in ameliorating the effects of sin and decay

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2. Created to Enjoy and Glorify God

• Health can be defined more holistically as "the
  strength to be human, not to pursue total
  fulfillment. The paradox of the evils in the
  world under the benevolence of the Creator can
  only be solved in the death and resurrection of
  Jesus Christ. While eliminating human suffering
  is a noble cause, there may be a higher purpose
  for some incurable diseases after all human
  efforts are exhausted.

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3. Made Alive by the Direct Involvement of God

• God's direct involvement in human life is evident
  in the act of breathing into the nostrils of man
  in creation. Genetic engineering of germ cells or
  the cloning of adult human beings cross the
  border line of depriving the offspring yet to be
  born of the freedom to choose the direction of
  his/her life, a gift uniquely given only by the
  Creator Himself.

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4. Created to be God's Steward

• As stewards of God's creation, Christians should
  be the salt and light of the world and actively
  provide leadership in establishing ethical
  principles for the HGP and the applications of
  biotechnology, instead of being the obscurantists
  who oppose technological advance for the sake of
  tradition.

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5. Created in His Image Divine Moral Law

• All human beings are created in the Image of God.
  Although the Fall depraved man's divine
  conscience, the church and the social
  institutions have the obligations to uphold God's
  Divine Moral Laws which are meant to bring
  welfare to individuals and to societies. The
  Golden Rule was meant for the survival and
  stability of human society. The genetic
  information of individuals should be guarded as
  one's private property and is to be protected
  against unjustified intrusion.

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6. Creature Representing Creation to God

• The Fall brought about the three fold alienation
  of man (1) with the Creator, (2) with fellow
  creatures, (3) with the creation, resulting in
  the loss of spiritual, social and physical
  health respectively. Man representing the
  creation in reconciliation in each of these 3
  levels through Jesus Christ brings man into
  harmony with God and the creation in the healing
  process. Without the covenantal relationship of
  reconciliation in each of these 3 levels,
  holistic health and environmental integrity
  cannot be achieved

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7. Conformed to the Image of the Incarnate Word.

• Based on the historical fact of Christ's
  resurrection, the redemption of our bodies at
  Christ's second coming is the consummation of all
  creation, which eagerly awaits its liberation
  from its bondage to decay and deliverance into
  the glorious freedom of the children of God. By
  conforming to the image of Christ, man is
  justified and will be glorified when his lowly
  body is transformed to be like His glorious body.
  It is therefore wrong to look for the domination
  of creation including the elimination of human
  suffering outside the lordship of Christ in other
  earthly powers such as those of the state and
  science and technology

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• A Perfect Human Being
• 1. Creature of God Confined by Finitude
• 2. Created to Enjoy and Glorify God
• 3. Made Alive by the Direct Involvement of God
• 4. Created to be God's Steward
• 5. Created in His Image Divine Moral Law
• 6. Creature Representing Creation to God
• 7. Conformed to the Image of the Incarnate Word.

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1. Prohibition on Genetic Discrimination in
Employment and Insurance.
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2. Establishing Uniform Rule to Protect Genetic
Privacy (i.e. HIPAA)
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HIPAA Health Insurance Portability and
Accountability Act of 1996

• PROTECTING THE PRIVACY OF PATIENTS' HEALTH
  INFORMATION
• The rule does not restrict the ability of
  doctors, nurses and other providers to share
  information needed to treat their patients. In
  other situations, though, personal health
  information generally may not be used for
  purposes not related to health care, and covered
  entities may use or share only the minimum amount
  of protected information needed for a particular
  purpose. In addition, patients would have to sign
  a specific authorization before a covered entity
  could release their medical information to a life
  insurer, a bank, a marketing firm or another
  outside business for purposes not related to
  their health care.
• http//www.hhs.gov/news/facts/privacy.html

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Agriculture Biotechnology

• 108th CONGRESS
• 1st Session
• S. RES. 154
• Expressing the support of the Senate of United
  States efforts in the World Trade Organization to
  end the unwarranted moratorium imposed by the
  European Union on the approval of agricultural
  biotechnology products.
• IN THE SENATE OF THE UNITED STATES
• May 23, 2003
• http//thomas.loc.gov/home/search.html