Transcript Chatterjee A. Neurology 63:968

The Neuroethics of Enhancement
(or, Is All Really Fair In Love And
War?)
NYSAM Annual Meeting
February 5, 2011
Richard N. Rosenthal, MD
Antenucci Professor of Clinical Psychiatry
Columbia University
Chairman, Department of Psychiatry
St. Luke’s Roosevelt Hospital Center, NY
Overview
Neuroethics
Distinctions
Enhancement Domains
Creativity
Physicality
Cognitive Function
Spirituality
Ethics
Neuroethics 101
How It Is
“But exactly because of their impressive powers to
alter the workings of body and mind, the “dual uses”
of the same technologies make them attractive also
to people who are not sick but who would use them
to look younger, perform better, feel happier, or
become more “perfect”.”
Fundamental inquiry into the human and moral
significance of developments in biomedical and
behavioral science and technology
President’s Council on Bioethics. Beyond therapy: Biotechnology and the pursuit
of human improvement, Washington, DC, Dana Press, 2003
Distinctions
““Therapy” … is the use of biotechnical power to treat
individuals with known diseases, disabilities, or
impairments, in an attempt to restore them to a
normal state of health and fitness.” (not questionable)
““Enhancement,” by contrast, is the directed use of
biotechnical power to alter, by direct intervention, not
disease processes but the “normal” workings of the
human body and psyche, to augment or improve their
native capacities and performances.” (questionable)
President’s Council on Bioethics. Beyond therapy: Biotechnology and the pursuit
of human improvement, Washington, DC, Dana Press, 2003
Distinctions
Therapy vs. Medical Enhancement vs. Non-medical
Enhancement (distinction may not be so helpful)
Surgical reconstruction vs. augmentation
Psychopharmacology vs. cosmetic
psychopharmacology
Potential genetic Tx of Type 1 DM vs. cosmetic
genetics
The line between remediable non-disease states,
sub-threshold disorder states (e.g., poor motivation,
indecisiveness) and disease states is unclear.
All therapies are enhancing, even if enhancements
are not necessarily therapeutic
Chatterjee A. Neurology 63:968-974, 2004
Distinctions
What is NORMAL?
Disease-free? If not, then therapy
IQ of 100? If it’s 86, would genetic intervention
that increased it be therapy or enhancement?
What is HEALTH?
Disease-free? If no, then therapy
“A state of complete physical, mental and
social well-being” (WHO definition)
Going beyond natural limits: which aspects of
the human condition call for improvement?
President’s Council on Bioethics. Beyond therapy: Biotechnology and the pursuit of
Human improvement, Washington, DC, Dana Press, 2003
Creativity
Alcohol
In addition to disinhibition, creative people
may get inspiration from alcohol, probably
due to expectation rather than drug effects
(Lapp 1994)
Marijuana
Associations to novel stimuli not enhanced
(Tinklenberg 1978)
Lapp et al., Am J Psychol 107:17-206, 2004. Tinklenberg et al., J Nerv Ment Dis.
166:362-4, 1978
Creativity
Hallucinogens
Common effects: alterations in perception, emotional
range and lability, expansion in individual thought and
identity, and capacity for transcendence of normative
beliefs and values (Sessa 2008)
Zegans and colleagues (1967) LSD vs. placebo control
testing a range of creativity measures, only in subjects
with high baseline creative traits, there was an
increase in novel thoughts and associations.
Some evidence for augmenting the illumination stage
of creativity (Lanni 2008)
Not clear if they make people creative
Sessa B. J Psychopharmacol; 22:821-827, 2008; Zegans LS. Arch Gen Psychiatry
Jun;16(6):740-749, 1967; Lanni et al., Pharm Res 2008
Creativity
Stimulants
May increase creativity through DA, which may
reduce latent inhibition (enables fixing into
sensations), correlated with novelty-seeking
(Swerdlow 2003; Savitz 2004)
N= 16 Subjects with convergent task impairments
given mixed amphetamine salts had enhanced
functioning but with higher range of normal
creativity were unaffected or impaired (Farah
2008).
Swerdlow et al., Psychopharm 169:314-320, 2003; Savitz et al., Am J Med Gen B
Neuropsych Gen 131:20-32, 2004; Farah MJ et al. Psychopharm (Berl). 2008 Nov
15.Epub
Creativity
All that Jazz
“Any musician who says he is playing
better on tea, the needle, or when he is
juiced, is a plain, straight liar”- Charlie
Parker (Keepnews 1988)
Little correlation between creativity and
substance use in writers, artists and
musicians (Kerr 1991)
Keepnews O. The view from within: Jazz writings 1948-1987, New York Oxford
Univ Press, 1988, p 91.; Kerr et al., J Creative Behavior 25:145-153, 1991
Physicality
Amphetamines:
Promote CNS plasticity and accelerate motor
learning in post-stroke patients (Walker-Batson
1995; Grade 1998)
Is there a role for enhancing motor skills
acquisition in normals (skiing, piano, swimming)?
(Chatterjee 2004)
Reboxetine
Enhances motor skill acquisition in a single dose,
but not at steady-state (Lange 2007).
Walker-Batson et al., Stroke 26:2254-2259, 1995; Grade et al., Arch Phys Med
Rehab 79:1047-1050, 1998; Chatterjee A. Neurology 63:968-974, 2004; Lange
et al., J Neural Transm 114:1085-1089, 2007;
Physicality
Sexual Performance
The “ED” diagnosis. Sildenafil, vardenafil, tadalafil,
etc. Is “erectile dysfunction” a part of normal aging
or always pathological?
Is lower free testosterone due to increased SHBG
in aging men pathological or just normal aging?
If it’s normal aging, is it cheating? Have society’s
views changed? Is it due to marketing? Changed
expectancies of male function?
What about enhanced performance in normals?
Cognitive Function
One purpose of medicine is to improve quality
of life
If we could enhance cognition in disease,
should we do it in health?
What is the cost/benefit?
Commercial pilots taking donezepil 5mg
(cholinesterase inhibitor) x 1mo performed better
in flight simulation compared to placebo-treated,
especially in emergency situations (Yesavage
2001)
Chatterjee A. Neurology 63:968-974, 2004; Yesavage et al., Neurology 59:
123-125, 2001
Cognitive Function
Desired caffeine effects - stimulant and ergogenic
properties:
more subjective energy
reduced fatigue
better concentration
increased capacity for mental or physical exertion
(Åkerstedt and Ficca 1997; Ivy et al. 1979; Trice et al.
1995)
Workers who consume more than 220mg of
caffeine/day have about half the risk of frequent/very
frequent cognitive failures (memory, attention, choice
of action) and a similar reduction in risk for accidents
at work (Smith 2005).
Åkerstedt and Ficca Chronobiol Int 14: 145–158, 1997; Ivy et al. Med Sci Sports.
Spring;11(1):6-11. 1979; Trice et al. Int J Sport Nutr 37-44, 1995; Smith AP. Human
Psychopharmacol 20: 441–445, 2005
Cognitive Function
Energy drinks and synergy:
Caffeine increases fluency and capacity for
information processing in the brain
Glucose priming enhances learning and memory
(Sunram-Lea 2002)
Caffeine (40mg) + glucose (60mg) = enhanced
speed, accuracy and sustained selective attention
(Rao, 2005)
Espresso an unfair advantage at work?
Should safety and performance effects make it a
requirement?
Sunram-Lea et al., Behav Brain Res 134: 505-516, 2002
Rao et al., Nutrition Neurosci 8:141-153, 2005
Cognitive Function
Serotonergic Drugs
5-HT involved in memory
SSRI’s may improve verbal memory
consolidation, short-and long-term memory
enhancement
Otherwise, not much evidence of cognitive
enhancement in normals
Ampakines: coming soon
glutamatergic AMPA receptor
Schmitt et al., Curr Pharmaceut Design 12:2473-2486, 2006
Cognitive Function
Stimulants: Methylphenidate
Improve attention, concentration, working memory
in ADHD (Pary 2002)
Improves executive functioning such as working
memory and planning in healthy adults (Eliott
1997; Mehta 2000)
WW II US (and Japanese and German) Military use of
amphetamines
Well-known on college campuses for use as a
‘study aid’ (Maher 2008).
Student use of methylphenidate snorting often at
higher doses before exams or to write term papers
(Babcock 2000; DuPont 2008)
Pary et al., Ann Clin Psychiatry 14:105-111, 2002; Eliott et al. Psychopharmacology
131, 196–2061997; Mehta MA et al., J. Neurosci. 20, RC65, 2000; Maher B. Nature
452(7188):674-675, 2008; Babcock et al., J Am College Health 49:143-45, 2000;
Dupont RL. Am J Addict. May-Jun;17(3):167-71, 2008.
Cognitive Function
Stimulants: Modafinil
Increases arousal and reduces attentional
deficits due to sleep-deprivation (Lagarde
1995; Caldwell 2000; Gill 2006)
In normal adults significantly improves: fatigue
levels, motivation, and vigilance, performance
on digit span, visual pattern recognition
memory, spatial planning and reaction time
(Baranski et al. 2004; Turner et al. 2004)
Lagarde et al., Func Clin Pharm 9:1-9,1995; Caldwell et al., Psychopharm 150:272282, 2000; Gill et al. Acad Emer Med 13:158-65, 2006; Baranski et al., Hum
Psychopharmacol 19:323–332, 2004; Turner et al., Biol Psychiatry 55(10):1031–40,
2004
Cognitive Function
Stimulants: Modafinil
Arrington (2008) in an online technical weblog
states, “…the buzz lately is that it’s the
‘entrepreneur’s drug of choice’ around Silicon
Valley.”
Might higher safety/lower addiction
liability drugs such as modafinil and
atomoxetine be likely to be used off-label?
Arrington M. TechCrunch.com, July 15, 2008.
Cognitive Function
Stimulant drugs
Informal poll of Nature Readers
1400 people from 60 countries
responded: 80% favored adult
discretion over use.
20% positive responses
44% modafinil
62% methylphenidate
15% β-blockers
Source
34% Internet
52% Physician prescription
14% Pharmacy
Maher B, Nature 452(7188):674-5, 2008
Cognitive Function
D-Cycloserine (DCS)
NMDA partial agonist (Ressler 2004)
Enhances learning in rodents, especially learning
underlying the extinction of conditioned fear.
Acute dosing facilitates exposure therapy effects
upon acrophobia (Ressler 2004)
DCS + exposure Tx in social anxiety disorder had
linearly better outcomes over time vs. exposure
alone (Hofman 2006)
Studies in PTSD, anorexia, panic disorder
No effects demonstrated in normal groups
Ressler et al., Arch Gen Psych 61: 1136-1144, 2004
Hofman et al., CNS Drug Rev 12:208-217, 2006
Cognitive Function
Cognition-enhancing Herbs
Gingko biloba
120 mg complexed w/ phosphatidyl serine improved speed of
memory task performance and delayed memory (Kennedy 2007)
Sage (salvia lavandulaefolia/officinalis)
Anti-oxidant, estrogenic, anti-inflammatory
Butyl and acetyl cholinesterase inhibitor (Perry 2002)
Improves mnemonic performance in young healthy and elderly
cohorts (50 μl essential oil)
Lemon balm (melissa officinalis)
CNS nicotinic and muscarinic receptor agonist binding
Extracts with high cholinergic properties enhance memory
functioning
Kennedy et al., Hum Psychopharm Clin Exp 22:199-210, 2007
Kennedy & Scholey, Curr Pharm Design 12:4613-4623, 2006; Perry et al., J Pharm Pharmacol
51:527-534, 1999; Perry et al., Phytomedicine 9:48-51, 2002
Cognitive Function
Transcranial Magnetic Stimulation
Repetitive frontotemporal lobe stimulation
can increase creativity in normals in both
writing and drawing tasks (Snyder 2004)
Enhances declarative memory, drawing,
mathematics, and calendar calculating
(Young 2004)
Snyder et al., J Integr Neurosci 3:31-46, 2004 Young et al., Neurocase 10(3):215-22,
2004
Spirituality
Many case reports and uncontrolled studies
supporting positive effects of hallucinogens on
transcendant experience, 1950-1985
Griffiths (2006, 2008) -- double blind crossover trial
comparing psilocybin to methylphenidate in N=36
healthy subjects:
61% had full mystical experiences (unity, intuitive
knowledge, transcendence of time & space)
79% had increased well-being or life satisfaction
58% rated among top 5 personally meaningful life
experiences at 14 month follow-up
67% rated among top 5 life spiritual experiences @ 14 Mo.
No spiritual gain without personal effort?
Griffiths et al., Psychopharmacology (Berl). Aug;187(3):268-283, 2006; Griffiths et al, J
Psychopharmacol. Aug;22(6):621-632, 2008.
Ethics
Societal vs. Individual needs
Cosmetic psychopharmacology is dehumanizing
and harms both the individual and society
(President’s Council 2003).
Gain without pain cheapens us and dilutes our character
Altering/manipulating our basic chemical makeup will
alter our humanity in a fundamental (not good) way
The activities of human life may seem more amenable to
improvement than they really are
However, little evidence for the government’s
position (Cerullo 2006)
President’s Council on Bioethics. Beyond therapy: Biotechnology and the pursuit of
human improvement, Washington, DC, Dana Press, 2003.; Cerullo MA. Perspect Biol
Med 49:515-523, 2006; Goering S. Phil Pub Pol Q 21:21-27, 2001
Ethics
“It does not follow from the fact that a drug is
being taken solely to satisfy one’s desires that
its use is objectionable”.
A drug used to inhibit memory formation may
sound reasonable to prevent PTSD after a
traumatic event. But what about its use simply
to prevent an unpleasant memory? (Farah
2004)
President’s Council on Bioethics. Washington, DC, Dana Press, 2003
http://www.bioethics.gov/reports/beyondtherapy/ Farah et al., Nat Rev Neurosci.
May;5(5):421-5, 2004
Ethics
Safety: Expected magnitude of the benefits and
weigh them against risks and side effects.
Clearly, in the balance, we treat disorders, with
medications reasonable cost-benefit
The more severe the illness, the higher the tolerance
for cost
So, for non-illness, the cost tolerance should be low.
How should the use of cognitive enhancing drugs be
regulated in healthy people?
Should their use always be monitored by healthcare
professionals?
Sahakian & Morein-Zamir S. Nature 450(7173):1157-9, 2007
Ethics
Competition off the field: Tension between
competitive reality and social contractIntrinsic factors weigh in inequitably, not only
social norms
Symmetry as a natural selection factor (Pashos 2003)
Physically attractive people earn 7.5-15% more in higherlevel jobs than their less attractive peers (Patzer 2008)
What are ‘unfair’ advantages?
Why is psychotherapy/coaching acceptable, but
pharmacological enhancement of adaptive functioning in
school, work or relationships suspect?
Is it something about the work ethic?
What if everyone else is doing it? Won’t the early
adopters win? So, where do you draw the line?
Pashos A, Niemitz C. Anthropol Anz. 61:331-41, 2003; Patzer GL. Looks. Amacom, NY,
2008; Mathes EW. Psychol Rep. 99:502-11, 2006.
Ethics
Coercion
The pressure to succeed, to maintain or
improve one’s position
“The trouble with the rat race is that even if
you win, you’re still a rat” (L. Tomlin)
1/3 of respondents in Nature survey would
feel pressure to give cognition-enhancing
drugs to their kid if the others’ were taking
them (Maher 2008)
Performance demanded by others
Maher B, Nature 452(7188):674-5, 2008
Ethics
Distributive Justice = Access
Who pays?
Should we stand against it because it isn’t
fair?
We already tolerate wide disparities in
education, nutrition, and shelter that impact
cognitive status (Chatterjee 2004)
Chatterjee A. Neurology 63:968-974, 2004
Ethics
Are we Social Dupes or Hypocrites?Views from Critiques of Plastic Surgery
Social dupes are somewhat excused from
their choices because they are externally
controlled without - they unwittingly follow
the direction of outside forces that shape
their desires (Bordo 1998)
Think about direct marketing of stimulants
to parents of school-age children
Bordo S, In Parens et al., Enhancing Human Traits: Ethical and Social Implications
Georgetown U Press, 1998.
Ethics
Are we Social Dupes or Hypocrites?Views from Critiques of Plastic Surgery
Hypocrites understand that to participate in
non-medical enhancement renders undue
advantage and is socially dubious, yet
choose what they see as the lesser of two
evils: to succeed, rather than than fail
(Davis 1995)
Not a zero-sum game –folks at the bottom
may stand to benefit from some of the
advances at the top
Davis K. Reshaping the Female Body: The Dilemma of Plastic Surgery, Routledge, 1995.
Ethics
Inevitability?
What other enhancements have we been able to
successfully avoid?
One fear is a Brave New World of alphas and
deltas, rife with greater and greater social inequity.
However, having smarter people may help the
overall society
The fairness issue is contested and regulated on
the field, where it should be.
If the train has left the station and there is no
conductor, mightn’t we go to the engine room and
start controlling the speed and destination?
Ethics
You have or will be asked to prescribe
medications for not strictly therapeutic
reasons.
What will you do?
http://www.neuroethicssociety.org/