Powerpoint Presentation

Defining Human Life: Applications Defining Human Life: Applications

from Bedside to Benchfrom Bedside to Bench

December 10, 2008

Patricia Scripko, MS3/MACleveland 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

Previous Mess

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)

Mental 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-able 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 poster’s hierarchy, but, if one disagrees, the argument can be made that these life forms may be moved to the highest position.

Mortality & Imperfection

2. PRACTICES (Insufficient OR Insufficient v. Sufficient to declare as “human”*)

3. SELECTED RULINGS/REGULATION1. TRAITS*1. In Vitro Fertilization v.Generating embryos for the creation of life

2. Abortion v.In vivo, the mother has control over the embryo’s fate until the 3 rd trimester; in contrast to the lack of control a mother has on an ex vivo embryo’s 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

(H-H) Face Transplant

7. Declaring Brain Death

On combined loss of cortical and brainstem function /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)

-We can apply this to embryos used in research (see above #3 & 6): we cannot turn them into a viable humans at this point in time, and so, they hold no potential for human life

8. Manipulation of Microscopic Material Genetic Engineering-For treatment or for enhancement (I.e. reproductive choices that give the mother control over the embryo as in abortion. See #2 above)

Anti-aging “medicine”**

9. Manipulation of Macroscopic Material

Cosmetic Surgery**

10. Manipulation of Physical Function

Anabolic Steroids (for treatment or enhancement)**

11. Manipulation of Mental Function

Adderall, Aricept (for treatment or enhancement)**

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 rights—as 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

2003: Presidential Council in USA Reproduction and Responsibility Act – Uterus is not an incubator; no embryos created for purposes other than childbirth; all research performed with the wellbeing of the potential resulting child in mind, but the wellbeing of the embryo seems less important (applicable to #1-5, 8) =H?

2003:H-H, m/f chimera (hermaphrodite) shunned (applicable to #6) =H

2004: Presidential Council okayed chimera research when disease prevention is the goal, but recommended that human embryos not be transferred to animals, and no H-NH embryos be formed. =H

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 other products of human origin or the processes required to create these biological products (applicable to #3, 6, 8) =H

**NOTE: No rulings on AAS, Anti-Aging or Cosmetic Surgery have their direct, purported origins in protecting human dignity, but the underlying motivation may be rooted in this. The stated origins typically are in prevention of physical “harm” (ie FDA withdrawal of silicone implants and the ban on steroids)

Future venues of regulation for #1-11:

FDA

-1938 Food Drug Cosmetic Act (drugs)

-Public Health Service Act (biological materials)

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 cosmetic surgery; applicable to #8-11 and in contrast to the Newman Patent ruling)

*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.

KEY: green=accepted; orange=more controversial; red=prohibited

H= Human; NH=Non-Human

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

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

http://www.music-atlas.com/artists/cher.htm

http://images4.wikia.nocookie.net/starwars/images/thumb/6/6b/Lion_Man.jpg/250px-Lion_Man.jpg

HUMAN EAR MOUSE

SCID MOUSE

So does function…

Stuart Littleblog.empas.com

www.livescience.com

http://www.flickr.com/photos/piedmontphoto/2657752286/

www.mindhacks.com

www.active.com

A lack of potential to carry on life..

Potential to create 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, consciousness

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 life!

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 dignity

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 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.

Cleveland ClinicDr Robert Dimeff – sports

medDr James Young – cardiology

Case Western ReserveDr Insoo Hyun –bioethicsDr Eric Juengst - bioethicsDr Robert Daroff - neurology

MGH & HSCIDr David Greer - neurologyDr David Scadden – co-directorDr Laurence Daheron –iPSC coreScadden & Cowan Labs

Sarnoff Foundation

OthersMr. Alan Jakimo – Sidley AustinMr Landon Thorne – CCDr Julian Savalescu

[email protected]