Defining Human Life Applications from Bedside to Bench by dsp14791


									   December 10, 2008

Patricia Scripko, MS3/MA
 Cleveland Clinic/CWRU
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.
   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
•   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
      KEY: green=accepted; orange=more controversial;
                      H= Human; NH=Non-Human
                                                                                                                   Previous Mess
                                                                                                                                         2. PRACTICES
                    1. TRAITS*                                                                                        (Insufficient OR Insufficient v. Sufficient to declare as ―human‖*)                              3. SELECTED RULINGS/REGULATION
                                                                                                                     1. In Vitro Fertilization                       v.                                                1791: 1st Amendment grants the right for chimeras used in artwork as freedom of expression,
  Microscopic Biological Material:                                                                                   Generating embryos for the creation of life                                                       but does not grant a right to scientific inquiry; may pertain to #6& 9
  Somatic Cells, DNA, protein products
                                                                                                                     2. Abortion                 v.                                                                    1865: 13th Amendment- Anything deemed ―human‖ that is used in research, clinical practice,
  Pluripotent/Adult Stem Cells                                                                                       In vivo, the mother has control over the embryo‘s fate until the 3rd trimester; in contrast to    art, etc, may be viewed as stripped of their rights—as slaves to research, medicine and art
                                                                                                                     the lack of control a mother has on an ex vivo embryo‘s fate in research or a trash can           (applicable to #1-11)
  Gametes and Cells capable of producing life (ESCs***)
                                                                                                                                                                                                                       1868: 14th Amendment
                                                                                                                     3. Embryonic Stem Cell Research                             v.
                                                                                                                                                                                                                       -1923 Meyer v. Nebraska- Granted the right to acquire useful knowledge (applicable to #3, 6
                                                                                                                     Using embryos for the study, and ultimately, the preservation of life                             & 8)                 =H
  Macroscopic Biological Material:                                                                                                                                                                                     -1973 Roe v. Wade- Embryo in utero is not a living person (applicable to #2) see above
                                                                                                                     4. Blood , Sperm ,               v.                                             Embryo            -No position on ex-vivo embryos (applicable to #1, 3, 4 & 6)      might =H
  Organs (Cerebral Cortex, Brainstem, Heart, Liver)                                                                  v.         Banking
  -can survive independently so long as they are perfused                                                                                                                                                              1939: American Society of Cosmetic Surgery established and recognized           =NH

  Body Parts (Legs, arms)                                                                                            5. Production of Organs and Headless ―Humans‖                                                     1970s: FDA claims jurisdiction over pig heart valves (applicable to #6)

  Superficial characteristics (Face)                                                                                 6. Chimera Research: Human-Human (H-H); Human-Non-Human (H-NH)                       With         1980: Diamond v. Chakrabarty: Genetically engineered bacterium are patentable (contrast
                                                                                                                                                                                                                       with Newman Patent to note difference between living and living human) NH=
                                                                                                                     Microscopic Material
                                                                                                                     (H-NH) SCID mice      , (H-NH) Teratoma assays,          (H-NH )Neuron Mouse,            v.       1984: Warnock committee of the U.K. Human Fertilisation and Embryology Authority
  Physical Function:                                                                                                  (H-H) Bone Marrow Transplant,         (H-NH; H-H) Fertilization or transfer of an embryo
                                                                                                                                                                                                                       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
  Required to survive (Breathing, Organ function)                                                                    With Macroscopic Material                                                                         (applicable to # 1, 3-6 & 7; contrast with #2)            =H
  -can be sustained with technology such as pacemakers and ventilators                                               (H-NH; H-H; NH-H) Organ Transplant
                                                                                                                                                                                                                       1997: Newman Patent was denied because it ―embraced a human being‖; USPTO will not
                                                                                                                     Interest in regulation arose from a fear of virally transmitted diseases
  Required to excel (Athleticism)                                                                                                                                                                                      patent human life or anything for the process of creating a human (applicable to # 1, 3, 4, 5)
                                                                                                                     (H-H) Face Transplant                                                                             =H

                                                                                                                                                                                                                       2003: Presidential Council in USA Reproduction and Responsibility Act – Uterus is not an
                                                                                                                     7. Declaring Brain Death                                                                          incubator; no embryos created for purposes other than childbirth; all research performed
  Mental Function:                                                                                                                                                                                                     with the wellbeing of the potential resulting child in mind, but the wellbeing of the embryo
                                                                                                                      On combined loss of cortical and brainstem function          /                                   seems less important (applicable to #1-5, 8)       =H?
  Cortical (intrinsic)                                                                                               In the context of technology‘s current ability to sustain or ‗bring back‘ life (what is dead
                                                                                                                     today may be considered living 20y from now)                                                      2003:H-H, m/f chimera (hermaphrodite) shunned (applicable to #6)          =H
  -characterized by survival of neurons
                                                                                                                        -We can apply this to embryos used in research (see above #3 & 6): we cannot turn
  Cortical (responsive to the extrinsic)                                                                                                                                                                               2004: Presidential Council okayed chimera research when disease prevention is the goal, but
                                                                                                                     them into a viable humans at this point in time, and so, they hold no potential for human
                                                                                                                                                                                                                       recommended that human embryos not be transferred to animals, and no H-NH embryos be
                                                                                                                                                                                                                       formed.       =H
  -cognition and social interaction, not mere function
  Social attributes, awareness                                                                                       8. Manipulation of Microscopic Material                                                           2004- Congress passed bill that that prohibited USPTO from issuing patents on human
                                                                                                                                                                                                                       organisms. The bill does not inhibit patenting of DNA, cell lines, stem cells, tissues and
  -able to uphold the values and goodness of humanity                                                                 Genetic Engineering                                                                              other products of human origin or the processes required to create these biological products
                                                                                                                                                                                                                       (applicable to #3, 6, 8)               =H
                                                                                                                     -For treatment or for enhancement (I.e. reproductive choices that give the mother control
                                                                                                                     over the embryo as in abortion. See #2 above)                                                     **NOTE: No rulings on AAS, Anti-Aging or Cosmetic Surgery have their direct, purported
  Abstract Qualities:                                                                                                                                                                                                  origins in protecting human dignity, but the underlying motivation may be rooted in this. The
                                                                                                                     Anti-aging ―medicine‖**                                                                           stated origins typically are in prevention of physical “harm” (ie FDA withdrawal of silicone
  Soul                                                                                                                                                                                                                 implants and the ban on steroids)

  Conscious                                                                                                          9. Manipulation of Macroscopic Material                                                           Future venues of regulation for #1-11:
  -able to perceive and evaluate the world around oneself; ―Life is the being of the living‖ it is self-                                                                                                               FDA
  awareness. –Robert Spaeman ***if one agrees with this statement, embryos and their derivatives are placed
                                                                                                                     Cosmetic Surgery**
                                                                                                                                                                                                                       -1938 Food Drug Cosmetic Act (drugs)
  as is on this poster’s hierarchy, but, if one disagrees, the argument can be made that these life forms may be
                                                                                                                                                                                                                       -Public Health Service Act (biological materials)
  moved to the highest position.
                                                                                                                     10. Manipulation of Physical Function
  Mortality & Imperfection                                                                                           Anabolic Steroids (for treatment or           enhancement)**                                      UPSTO: Allows patents on anything composed of less than 50% human DNA (applicable to
                                                                                                                                                                                                                       #6 in contrast to #4 &5); allows patents on devices used in manipulating human traits (ie
*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
                                                                                                                     11. Manipulation of Mental Function                                                               cosmetic surgery; applicable to #8-11 and in contrast to the Newman Patent ruling)

  human or deemed insufficient to declare a being “human”, respectively, when the                                     Adderall, Aricept (for treatment or          enhancement)**
                            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
   Chimeric mice             Chimeric

       Disease models          humans/transplant
       Human Neuron Mouse    Cosmetic Neurology

       Human Ear Mouse         Cosmetic Surgery

   Genetic engineering         Pre-gestational
   ESC research                 Diagnosis
   iPSCs                       IVF & Abortion
                                Oocyte, sperm, blood
                                 and bone marrow
                                 banking and donation

                             SCID MOUSE
                                                 Stuart Little

                     So does function…

                                                Potential to create life…

A lack of potential to carry on life..

                               Potential to save lives
Induced pluripotent
     stem cells

       Nature 448, 260-262(19 July 2007
   “There is, of course, nothing novel
    about reductionism, materialism, and
    determinism…these 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
   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 )
   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 (can’t be human before being alive)
   Unique
   Personhood
       dementia/schizophrenia/drugs change it
   Sentience: The capacity to feel, & reflect
       “human” understanding of pain, self-awareness,
   How we process, remember and respond to
    love, fear, passion and joy
       “human” interactions

   This can be our criterion for human life
   "The goods of human life are in the act of living.
    Death is the definite elimination of all goods of life.“
    - Nagel
   It’s simple: Death= the removal of what defines
   Death has been defined differently based on
    technology (Daroff, 2006)
     Respiratory (hand to nares)
     Cardiac (stethoscope)
     Brain (ventilators and resuscitation machines)
    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!
   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)
   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?
       It’s “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)
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

3.DBS for Depression?
   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
   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
Cleveland Clinic                   MGH & HSCI
   Dr Robert Dimeff – sports med      Dr David Greer - neurology
   Dr James Young – cardiology        Dr David Scadden – co-director
                                      Dr Laurence Daheron –iPSC core
                                      Scadden & Cowan Labs
Case Western Reserve
   Dr Insoo Hyun –bioethics        Sarnoff Foundation
   Dr Eric Juengst - bioethics
   Dr Robert Daroff - neurology    Others
                                      Mr. Alan Jakimo – Sidley Austin
                                      Mr Landon Thorne – CC
                                      Dr Julian Savalescu

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