Defining Human Life: Applications from Bedside to Bench

1
Defining Human Life Applications from Bedside to
Bench

• December 10, 2008
• Patricia Scripko, MS3/MA
• Cleveland Clinic/CWRU

2
History of Present Presentation

• 25y/o female medical student and bioethics
  masters candidate who presents with ideas on
  human life in an attempt to streamline
  controversial policies and practices regarding
  it. Prior to this event, she reports 2yrs
  investigation of this subject both while
  completing a basic science Sarnoff Foundation
  research fellowship at the Harvard Stem Cell
  Institute, and a preceding clinical ethics
  project at the Cleveland Clinic. She denies any
  affiliations or conflicts of interest.

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Overview

• Observation Many arguments against stem cell
  research, human enhancement (ie cosmetic surgery)
  and other clinical and lab practices seem to
  depend on some notion of what is human.
• Previous work to define human based on a trait or
  set of traits
• Findings in Failure
• New approach defining human life
• Clinical criteria for brain death the goods of
  life death lacks brain function
• Common thread of an underlying appreciation for
  human life as dependent on higher cortical
  function, both at the bedside and bench
• Apply higher cortical function as a criterion for
  human life to solve debates

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Previous Work

• Goals
• 1. Define human based on human traits
• 2. Determine if limits on which human traits may
  be enhanced, commodified or manipulated exist
• 3. Determine if ESC research violates the
  essence of what is human by the traits it
  manipulates
• Strategy Literature research questionnaire
  study to create a comparative framework

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Previous Mess
KEY greenaccepted orangemore controversial
redprohibited H Human NHNon-Human
2. PRACTICES
(Insufficient OR Insufficient v. Sufficient to
declare as human)
1. TRAITS
3. SELECTED RULINGS/REGULATION

• 1. In Vitro Fertilization v.
• Generating embryos for the creation of life
• 2. Abortion v.
• In vivo, the mother has control over the embryos
  fate until the 3rd trimester in contrast to the
  lack of control a mother has on an ex vivo
  embryos fate in research or a trash can
• 3. Embryonic Stem Cell Research v.
• Using embryos for the study, and ultimately, the
  preservation of life
• 4. Blood , Sperm , v.
  Embryo
  v. Banking
• 5. Production of Organs and Headless Humans
• 6. Chimera Research Human-Human (H-H)
  Human-Non-Human (H-NH) With
  Microscopic Material
• (H-NH) SCID mice , (H-NH) Teratoma assays,
  (H-NH )Neuron Mouse, v.
• (H-H) Bone Marrow Transplant, (H-NH
  H-H) Fertilization or transfer of an embryo
• With Macroscopic Material
• (H-NH H-H NH-H) Organ Transplant
• Interest in regulation arose from a fear of
  virally transmitted diseases

• 1791 1st Amendment grants the right for chimeras
  used in artwork as freedom of expression, but
  does not grant a right to scientific inquiry may
  pertain to 6 9
• H
  
• 1865 13th Amendment- Anything deemed human
  that is used in research, clinical practice,
  art, etc, may be viewed as stripped of their
  rightsas slaves to research, medicine and art
  (applicable to 1-11)
• 1868 14th Amendment
• 1923 Meyer v. Nebraska- Granted the right to
  acquire useful knowledge (applicable to 3, 6
  8) H
• 1973 Roe v. Wade- Embryo in utero is not a living
  person (applicable to 2) see above
• No position on ex-vivo embryos (applicable to 1,
  3, 4 6) might H
• 1939 American Society of Cosmetic Surgery
  established and recognized NH
• 1970s FDA claims jurisdiction over pig heart
  valves (applicable to 6)
• 1980 Diamond v. Chakrabarty Genetically
  engineered bacterium are patentable (contrast
  with Newman Patent to note difference between
  living and living human) NH
• 1984 Warnock committee of the U.K. Human
  Fertilisation and Embryology Authority
  articulates the "14-day limit," based on the
  distinctions between human embryos which have
  not yet formed the primitive streak, and those
  that are undergoing organogenesis. The U.S. NAS
  guidelines prohibit the mixing of cells of any
  nature with the pre-streak embryo (applicable to
  1, 3-6 7 contrast with 2)
  H
• 1997 Newman Patent was denied because it
  embraced a human being USPTO will not patent
  human life or anything for the process of
  creating a human (applicable to 1, 3, 4, 5)
  H

Microscopic Biological Material Somatic Cells,
DNA, protein products Pluripotent/Adult Stem
Cells Gametes and Cells capable of producing
life (ESCs) Macroscopic Biological
Material Organs (Cerebral Cortex, Brainstem,
Heart, Liver) -can survive independently so long
as they are perfused Body Parts (Legs,
arms) Superficial characteristics
(Face) Physical Function Required to survive
(Breathing, Organ function) -can be sustained
with technology such as pacemakers and
ventilators Required to excel (Athleticism) Ment
al Function Cortical (intrinsic) -characterized
by survival of neurons Cortical (responsive to
the extrinsic) -cognition and social interaction,
not mere function Social attributes,
awareness -able to uphold the values and goodness
of humanity Abstract Qualities Soul Conscious -a
ble to perceive and evaluate the world around
oneself Life is the being of the living it is
self-awareness. Robert Spaeman if one agrees
with this statement, embryos and their
derivatives are placed as is on this posters
hierarchy, but, if one disagrees, the argument
can be made that these life forms may be moved to
the highest position. Mortality Imperfection
With the exception of mortality, traits are
placed in gross hierarchal order. Thus, it may
be assumed that all traits below and above a
given trait are protected as human or deemed
insufficient to declare a being human,
respectively, when the given trait is not
protected.
This work was supported in part by the National
Institutes of Health, National Center for
Research Resources, General Clinical Research
Center Grant M01 RR-018390
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Compared Practices

• At the Bench

• At the Bedside

• Chimeric mice
• Disease models
• Human Neuron Mouse
• Human Ear Mouse
• Genetic engineering
• ESC research
• iPSCs

• Chimeric humans/transplant
• Cosmetic Neurology
• Cosmetic Surgery
• Pre-gestational Diagnosis
• IVF Abortion
• Oocyte, sperm, blood and bone marrow banking and
  donation

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Conclusion 1Particular traits affect our
ethical tolerance of a practice
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Looks Matter Insoo Hyun, PhD

• Human ear mouse

• SCID Mouse

www.livescience.com
Stuart Little
blog.empas.com
So does function
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Limits matter
www.mindhacks.com
www.active.com
http//www.flickr.com/photos/piedmontphoto/2657752
286/
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Potential matters
Potential to create life
A lack of potential to carry on life..
Potential to save lives
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Do beginnings matter?
Induced pluripotent stem cells
Nature 448, 260-262(19 July 2007
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Conclusion 2The sum of the parts is less than
the whole

• There is, of course, nothing novel about
  reductionism, materialism, and determinismthese
  are doctrines with which Socrates contended long
  ago. What is new is that these philosophies seem
  to be vindicated by scientific advance. Here, in
  consequence, would be the most pernicious result
  of the new biology the erosion, perhaps the
  final erosion, of the idea of man as noble,
  dignified, precious, or godlike, and its
  replacement with a view of man, no less than of
  nature, as mere raw material for manipulation and
  homogenization. Leon Kass, 2007

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Human Dignity

• Ubiquitous, intangible, abstract
• Value is independent of the sum of its parts
• Hence my failure to trait seek
• Carries with us from the onset of life past death
• Greater respect for dead body than plastic model
  in anatomy lab
• Cannot be degraded, destroyed
• Can be ignored or devalued, but only by acting on
  the human as a whole (ie slavery, experimentation
  w/o consent )

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Human Life Marking Human Creation

• Identifying onset of human life is identifying
  the moment when human dignity is acquired
• All humans develop from living substrates, and
  thus, are living humans when dignity is acquired
• To have ever been human, one must have been
  alive at some point (cant be human before being
  alive)

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The Human in the Cortex

• Unique
• Personhood
• dementia/schizophrenia/drugs change it
• Sentience The capacity to feel, reflect
• human understanding of pain, self-awareness,
  consciousness
• How we process, remember and respond to love,
  fear, passion and joy
• human interactions
• This can be our criterion for human life

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Death Defining Life at the Bedside

• "The goods of human life are in the act of
  living. Death is the definite elimination of all
  goods of life. - Nagel
• Its simple Death the removal of what defines
  life!
• Death has been defined differently based on
  technology (Daroff, 2006)
• Respiratory (hand to nares)
• Cardiac (stethoscope)
• Brain (ventilators and resuscitation machines)

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Brain Death

• Higher, lower and whole brain theorists
• Higher capacity to think, perceive and
  respond
• Lower capacity to integrate bodily functions
• (Veith, 1977)
• Whole brain criteria enacted in USA, but often
  supported only to ensure higher brain deficit is
  irreversible (Bernat, 2006)
• Appreciation of higher remains (loss of person)
  
• AMA (1990) AAN (1988) show this appreciation in
  their policy making
• Remember Brain function can be reliably tested!

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Defining Life at the Bench

• ESCs pose conservative criteria
• Stem cell exceptionalism
• Two thoughts reign
• 1. Embryo is a living human at time of conception
  or creation
• Precludes use of ESCs, IVF, brain death
• 2. Embryo has potential to create human life
• 14 day rule arbitrary time point for primitive
  streak/gastrulation/beginnings of all organ
  systems including CNS (1990)

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Human Neuron-Mouse Chimera

• Chimeras around for decades in lab and clinic
• SCID mice, transplant patients, etc..
• Any ESC involving chimera receives attention
  (Hyun, 2007), but neuron-mouse chimera is also
  particularly trendy to debate. Why?
• Its too human Our perception of a person, of a
  human is defined by cortically dependent
  functions of interacting and responding to our
  environment (Greely, 2007 review)

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Applicative Example

• 1.iPSCs v. ESCs in the Human-Neuron Mouse
• -The ends matter, not the beginnings as the
  initial substrates (cells) both lack human life
• -Equal ethical tolerance should be exhibited
  towards both means.
• 2.Enhancement of traits
• -So long as autonomy-driven, it does not
  ignore human dignity
• 3.DBS for Depression?

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Conclusions

• 1. The whole is greater than the sum of the parts
• 2. We have a defining trait for the whole, human
  dignity, but need a marker for its presence
  since it is abstract
• 3. The onset of human life serves as a marker
• 4. Human life can be defined by what human death
  lacks (ie brain death)
• 5. Higher cortical function is appreciated at the
  bench and bedside and in the popular media as the
  trait living humans share, and dead humans lack.
• 6. Higher cortical function is a workable
  definition for human life that may be used to
  direct practices and policies.

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Thanks!

• Cleveland Clinic
• Dr Robert Dimeff sports med
• Dr James Young cardiology
• Case Western Reserve
• Dr Insoo Hyun bioethics
• Dr Eric Juengst - bioethics
• Dr Robert Daroff - neurology

MGH HSCI Dr David Greer - neurology Dr David
Scadden co-director Dr Laurence Daheron iPSC
core Scadden Cowan Labs Sarnoff
Foundation Others Mr. Alan Jakimo Sidley
Austin Mr Landon Thorne CC Dr Julian Savalescu
PScripko_at_gmail.com