Turn on the spin machine! Here come da drugs. Or: Trial baloon anyone?

[Guest guest]

http://www.redflagsweekly.com/flash.htm

 

 

May 27, 2004

 

BRAIN ENHANCEMENT - STATE OF THE ART?

 

Are you already feeling pressured to give your mental processes a boost? It is

likely that in the foreseeable future many people will be urged - by employers,

by family members - to boost their brain potential, particularly via the drug

route. What about safety? And what will be morally acceptable in this new world?

Of course, you might wonder if much of this is still science fiction. The

article from Nature that is featured here is by no means a perfect look at what

is occurring. RFD does not endorse any particular statements in this piece, but

we chose it because it provides an example of how conventional medicine is

viewing brain enhancement. RFD, in fact, views all forms of drug use in highly

critical terms, assessing risks and benefits and strongly raising major

questions particularly about psychiatric drugs and their vast overuse. This

piece from Nature, however, does raise some important ethical issues that will

become increasingly important to debate. It is worthwhile to read

it in its entirety.

 

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nrn/journal/v5/n5/full/nrn1390_\

fs.html

 

Science and Society

NEUROCOGNITIVE ENHANCEMENT: WHAT CAN WE DO AND WHAT SHOULD WE DO?

Martha J. Farah1, Judy Illes2, Robert Cook-Deegan3, Howard Gardner4, Eric

Kandel5, Patricia King6, Eric Parens7, Barbara Sahakian8 & Paul Root Wolpe9

about the authors

1 Martha Farah is at the Center for Cognitive Neuroscience, University of

Pennsylvania, 3720 Walnut Street, Philadelphia, Pennsylvania 19104, USA

2 Judy Illes is at the Stanford Center for Biomedical Ethics and the Department

of Radiology, 701 Welch Road, Stanford, California 94304-5748, USA

3 Robert Cook-Deegan is at the Center for Genome Ethics, Law and Policy,

Institute for Genome Sciences and Policy and Department of Public Policy

Studies, Duke University, Room 127C, North Building, Research Drive, Box 90141,

Durham, North Carolina 27708-0141, USA

4 Howard Gardner is at the Graduate School of Education, Harvard University, Roy

E. Larsen Hall, 2nd Floor, Appian Way, Cambridge, Massachusetts 02138, USA

5 Eric Kandel is at the Center for Neurobiology and Behavior, Columbia

University and Howard Hughes Medical Institute, 1051 Riverside Drive, New York,

New York 10032, USA

6 Patricia King is at the Georgetown University Law Center, 600 New Jersey

Avenue, NW Washington DC 20001, USA

7 Eric Parens is at the The Hastings Center, 21 Malcolm Gordon Drive, Garrison,

New York 10524-5555, USA

8 Barbara Sahakian is at the Department of Psychiatry, University of Cambridge,

Addenbrooke's Hospital (Box 189), Cambridge CB2 2QQ, UK

9 Paul Root Wolpe is at the Departments of Psychiatry, Medical Ethics, and

Sociology, Center for Bioethics, University of Pennsylvania, 3401 Market Street,

Philadelphia, Pennsylvania 19104-3319, USA

 

correspondence to:

Martha J. Farah mfarah

Judy Illes illes

Our growing ability to alter brain function can be used to enhance the mental

processes of normal individuals as well as to treat mental dysfunction in people

who are ill. The prospect of neurocognitive enhancement raises many issues about

what is safe, fair and otherwise morally acceptable. This article resulted from

a meeting on neurocognitive enhancement that was held by the authors. Our goal

is to review the state of the art in neurocognitive enhancement, its attendant

social and ethical problems, and the ways in which society can address these

problems.

 

Many are predicting that the twenty-first century will be the century of

neuroscience. Humanity's ability to alter its own brain function might well

shape history as powerfully as the development of metallurgy in the Iron Age,

mechanization in the Industrial Revolution or genetics in the second half of the

twentieth century. This possibility calls for an examination of the benefits and

dangers of neuroscience-based technology, or 'neurotechnology', and

consideration of whether, when and how society might intervene to limit its

uses.

 

At the turn of the century, neurotechnology spans a wide range of methods and

stages of development. Brain–machine interfaces that allow direct two-way

interaction between neural tissue and electronic transducers remain in the

'proof of concept' stage, but show substantial promise1. Neurosurgery is

increasingly considered as a treatment for mental illnesses and an array of new

procedures are under development, including the implantation of devices and

tissue2. Non-invasive transcranial magnetic stimulation (TMS) of targeted brain

areas is the basis of promising new treatments for depression and other

psychopathology3.

 

On the leading edge of neurotechnology is psychopharmacology. Our ability to

achieve specific psychological changes by targeted neurochemical interventions,

which began through a process of serendipity and trial and error in the

mid-twentieth century, is evolving into the science of rational drug design. The

psychopharmacopia of the early twenty-first century encompasses both familiar,

and in some cases highly effective, drugs, and a new generation of more

selective drugs that target the specific molecular events that underlie

cognition and emotion4. For the most part, these drugs are used to treat

neurological and psychiatric illnesses, and there is relatively little

controversy surrounding this use. However, psychopharmacology is also

increasingly used for 'enhancement' — that is, for improving the psychological

function of individuals who are not ill.

 

The enhancement of normal neurocognitive function by pharmacological means is

already a fact of life for many people in our society, from elementary school

children to ageing baby boomers. In some school districts in the United States

the proportion of boys taking methylphenidate exceeds the highest estimates of

the prevalence of attention deficit–hyperactivity disorder (ADHD)5, implying

that normal childhood boisterousness and distractibility are being targeted for

pharmacological intervention. The use of prescription stimulants (such as

methylphenidate and dextroamphetamine) as study aids by high school and college

students who do not have ADHD has recently drawn attention, and might include as

many as 16% of the students on some campuses6. Sales of nutritional supplements

that promise improved memory in middle age and beyond have reached a billion

dollars annually in the United States alone7, despite mixed evidence of

effectiveness8. In contrast to the other neurotechnologies

mentioned earlier, whose potential use for enhancement is still hypothetical,

pharmacological enhancement has already begun.

 

What can we do?

 

Many aspects of psychological function are potential targets for pharmacological

enhancement, including memory, executive function, mood, appetite, libido and

sleep9, 10. We will use the first two of these, memory and executive function,

as examples to show the state of the art in psychopharmaceutical enhancement,

the ethical issues raised by such enhancement and the policy implications of

these ethical issues. A brief review of the state of the art in neurocognitive

enhancement is offered here; additional information is freely available to

readers of this article at www.nyas.org/ebrief/neuroethics and in recent

articles by Rose11, Lynch12 and Hall7.

 

Memory enhancement. Memory enhancement is of interest primarily to older adults.

The ability to encode new memories declines measurably from the third decade of

life onwards, and by the fourth decade the decline can become noticeable and

bothersome to normal healthy individuals13. Memory difficulties in middle or old

age are not necessarily a harbinger of future dementia but can be part of the

normal pattern of cognitive ageing, which does not make it any less inconvenient

when we misplace our glasses or forget the name of a recent acquaintance. What

can current and imminent neurotechnologies offer us by way of help?

 

The changes that underlie normal age-related declines in memory probably differ

from those that underlie Alzheimer's disease, indicating that the optimal

pharmacological approaches to therapy and enhancement might also differ.

Although donepezil, a cholinesterase inhibitor that is used to treat Alzheimer's

disease, did enhance performance in one study of healthy middle-aged pilots

after flight simulator training14, drug companies are looking elsewhere for

pharmacological approaches to memory enhancement in normal individuals. Recent

advances in the molecular biology of memory have presented drug designers with

many entry points through which to influence the specific processes of memory

formation, potentially redressing the changes that underlie both normal and

pathological declines in memory. Most of the candidate drugs fall into one of

two categories: those that target the initial induction of long-term

potentiation and those that target the later stages of memory consolidation. In

the first category are drugs that modulate AMPA

(-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors to facilitate

depolarization, including Cortex Pharmaceuticals' Ampakines12. In the second

category are drugs that increase CREB (the cAMP response element-binding

protein), a molecule that in turn activates genes to produce proteins that

strengthen the synapse. One such drug is the molecule MEM1414, which is being

tested by Memory Pharmaceuticals7 (a company co-founded by one of the authors

(E.K)).

 

The pursuit of mastery over our own memories includes erasing undesirable

memories as well as retaining desirable ones. Traumatic events can cause

lifelong suffering by the intrusive memories of post-traumatic stress disorder

(PTSD), and methods are being sought to prevent the consolidation of such

memories by pharmacological intervention immediately after the trauma15. Drugs

whose primary purpose is to block memories are also being developed by the

pharmaceutical industry7. Extending these methods beyond the victims of trauma,

to anyone who wishes to avoid remembering an unpleasant event, is another way in

which the neural bases of memory could be altered to enhance normal function.

 

Enhancement of executive function. Executive function refers to abilities that

enable flexible, task-appropriate responses in the face of irrelevant competing

inputs or more habitual but inappropriate response patterns. These include the

overlapping constructs of attention, working memory and inhibitory control.

Drugs that target the dopamine and noradrenaline neurotransmitter systems are

effective at improving deficient executive function, for example in ADHD, and

have recently been shown to improve normal executive function as well16, 17.

 

For example, one of the authors (B.J.S.) found that healthy young volunteers

performed the Tower of London problem-solving task more accurately after being

given methylphenidate than after being given a placebo when the task was

novel16. Methylphenidate also increased accuracy in a complex spatial working

memory task, and this was accompanied by a reduction in the activation of areas

of the brain that are related to working memory, as shown by positron emission

tomography (PET)17. For the latter task, the amount of benefit was inversely

proportional to the volunteers' working memory capacity as assessed by a

different working memory task, digit span, with little or no benefit to those

with the highest digit span performances. This is of interest in discussions of

enhancement, because it indicates that, for this medication and this cognitive

ability at least, those with lower levels of performance are more likely to

benefit from enhancement than those with higher levels. Indeed, it is

possible that some drugs would compress the normal range of performance in both

directions. One of the authors (M.J.F.) found that the dopamine agonist

bromocriptine improved performance on various executive function tasks for

individuals with lower- than-average working memory capacity, but lowered the

performance of those with the highest working memory capacities18. Whether

enhancement can boost the performance of already high-performing individuals

must be determined empirically for each drug and for each type of cognitive

ability.

 

Newer drugs might improve executive function in different ways, influencing

different underlying processes and interacting in different ways with individual

differences (for example, in working memory capacity) and states (such as

restedness). The newest potential neurocognitive enhancer is the drug modafinil,

which is approved for the treatment of narcolepsy and is increasingly prescribed

off-label for other purposes19. One of the authors (B.J.S.) found that it

increases performance among healthy young adults on a set of executive function

tasks that differs partly from those that are influenced by methylphenidate,

with its effects resulting at least in part from an improved ability to inhibit

impulsive responses20.

 

What should we do?

 

Ethical problems and policy solutions. Neurocognitive enhancement raises ethical

issues for many different constituencies. These include academic and industry

scientists who are developing enhancers, and physicians who will be the

gatekeepers to them, at least initially. Also included are individuals who must

choose to use or not to use neurocognitive enhancers themselves, and parents who

must choose to give them or not to give them to their children. With the advent

of widespread neurocognitive enhancement, employers and educators will also face

new challenges in the management and evaluation of people who might be

unenhanced or enhanced (for example, decisions to recommend enhancement, to

prefer natural over enhanced performance or vice versa, and to request

disclosure of enhancement). Regulatory agencies might find their

responsibilities expanding into considerations of 'lifestyle' benefits and the

definition of acceptable risk in exchange for such benefits. Finally,

legislators

and the public will need to decide whether current regulatory frameworks are

adequate for the regulation of neurocognitive enhancement, or whether new laws

must be written and new agencies commissioned.

 

To focus our discussion, we will dispense with some ethical issues that are

important but not specific to neurocognitive enhancement. The first such issue

is research ethics. Research on neurocognitive enhancement, as opposed to

therapy, raises special considerations mainly insofar as the potential benefits

can be viewed as smaller, and acceptable levels of risk to research subjects

would be accordingly lower. This consideration is largely academic for those

neurocognitive enhancers that come to market first as therapies for recognized

medical conditions, which includes all of the substances that are now available

for enhancement, although this might not be true in the future. Another

important ethical issue concerns the use of neurocognitive enhancement in the

criminal justice system, in which a large proportion of offenders fall in the

lower range of cognitive ability in general21 and executive inhibitory control

in particular22. Although neurocognitive enhancement brings with it

the potential for subtle coercion in the office or classroom, 'neurocorrection'

is more explicitly coercive and raises special issues of privacy and liberty

that will not be discussed here. Finally, the ethical problems that are involved

in parental decision-making on behalf of minor children are complex and enter

into the ethics of neurocognitive enhancement in school children, but will not

be discussed here.

 

The remaining issues can be classified and enumerated in various ways. Four

general categories will be used here to organize our discussion of the ethical

challenges of neurocognitive enhancement and possible societal responses.

 

Safety. The idea of neurocognitive enhancement evokes unease in many people, and

one source of the unease is concern about safety. Safety is a concern with all

medications and procedures, but our tolerance for risk is smallest when the

treatment is purely elective. Furthermore, in comparison to other comparably

elective treatments such as cosmetic surgery, neurocognitive enhancement

involves intervening in a far more complex system, and we are therefore at

greater risk of unanticipated problems. Would endowing learners with

super-memory interfere with their ability to understand what they have learned

and relate it to other knowledge? Might today's Ritalin users face an old age of

premature cognitive decline? The possibility of hidden costs of neurocognitive

enhancement might be especially salient because of our mistrust of unearned

rewards, and the sense that such opportunities can have Faustian results.

 

With any drug, whether for therapy or enhancement, we can never be absolutely

certain about the potential for subtle, rare or long-term side effects. Instead,

our regulatory agencies determine what constitutes a sufficiently careful search

for side effects and what side effects are acceptable in view of a drug's

benefits. Although consensus will have to be developed on these issues in

connection with neurocognitive enhancement, we see no reason that the same

approach cannot be applied here.

 

Coercion. If neurocognitive enhancement becomes widespread, there will

inevitably be situations in which people are pressured to enhance their

cognitive abilities. Employers will recognize the benefits of a more attentive

and less forgetful workforce; teachers will find enhanced pupils more receptive

to learning. What if keeping one's job or remaining in one's school depends on

practicing neurocognitive enhancement? Such dilemmas are difficult but are not

without useful legal precedent. Many of the relevant issues have been addressed

in legislation such as Connecticut's Statute " Policies regarding the

recommendation of psychotropic drugs by school personnel " 23 and case law such as

Valerie versus Derry Cooperative School District24.

 

Of course, coercion need not be explicit. Merely competing against enhanced

co-workers or students exerts an incentive to use neurocognitive enhancement,

and it is harder to identify any existing legal framework for protecting people

against such incentives to compete. But would we even want to? The

straightforward legislative approach of outlawing or restricting the use of

neurocognitive enhancement in the workplace or in school is itself also

coercive. It denies people the freedom to practice a safe means of

self-improvement, just to eliminate any negative consequences of the (freely

taken) choice not to enhance.

 

Distributive justice. It is likely that neurocognitive enhancement, like most

other things, will not be fairly distributed. Ritalin use by normal healthy

people is highest among college students, an overwhelmingly middle-class and

privileged segment of the population. There will undoubtedly be cost barriers to

legal neurocognitive enhancement and possibly social barriers as well for

certain groups. Such barriers could compound the disadvantages that are already

faced by people of low socioeconomic status in education and employment. Of

course, our society is already full of such inequities, and few would restrict

advances in health or quality of life because of the potential for inequitable

distribution. Unequal access is generally not grounds for prohibiting

neurocognitive enhancement, any more than it is grounds for prohibiting other

types of enhancement, such as private tutoring or cosmetic surgery, that are

enjoyed mainly by the wealthy. Indeed, in principle there is no reason

that neurocognitive enhancement could not help to equalize opportunity in our

society. In comparison with other forms of enhancement that contribute to gaps

in socioeconomic achievement, from good nutrition to high-quality schools,

neurocognitive enhancement could prove easier to distribute equitably.

 

Personhood and intangible values. Enhancing psychological function by brain

intervention is in some ways like improving a car's performance by making

adjustments to the engine. In both cases the goal is to improve function, and to

the extent that we succeed without compromising safety, freedom of choice or

fairness we can view the result as good. But in other ways the two are very

different, because modifying brains, unlike engines, affects persons. The fourth

category of ethical issue encompasses the many ways in which neurocognitive

enhancement intersects with our understanding of what it means to be a person,

to be healthy and whole, to do meaningful work, and to value human life in all

its imperfection. The recent report of the President's Council on Bioethics25

emphasizes these issues in its discussion of enhancement.

 

Attempts to derive policies from these considerations must contend with the

contradictory ways in which different values are both challenged and affirmed by

neurocognitive enhancement. For example, we generally view self-improvement as a

laudable goal. At the same time, improving our natural endowments for traits

such as attention span runs the risk of commodifying them. We generally

encourage innovations that save time and effort, because they enable us to be

more productive and to direct our efforts towards potentially more worthy goals.

However, when we improve our productivity by taking a pill, we might also be

undermining the value and dignity of hard work, medicalizing human effort and

pathologizing a normal attention span. The self-transformation that we effect by

neurocognitive intervention can be seen as self-actualizing, or as eroding our

personal identity. Neither the benefits nor the dangers of neurocognitive

enhancement are trivial.

 

In weighing the dangers of neurocognitive enhancement against its benefits, it

is important to note the many ways in which similar tradeoffs are already

present in our society. For example, the commodification of human talent is not

unique to Ritalin-enhanced executive ability. It is probably more baldly on

display in books and classes that are designed to prepare preschoolers for

precocious reading, music or foreign language skills, but many loving parents

seek out such enrichment for their children. Americans admire the effort that

was expended in Abraham Lincoln's legendary four-mile walk to school every day,

but no-one would do that (or want their child to do that) if a bus ride were

available. Medicalization has accompanied many improvements in human life,

including improved nutrition and family planning. And if we are not the same

person on Ritalin as off, neither are we the same person after a glass of wine

as before, or on vacation as before an exam. As these examples show,

many of our 'lifestyle' decisions end up on the right side of one value and the

wrong side of another, but this does not necessarily mean that these decisions

are wrong.

 

Disentangling moral principle and empirical fact. Since pre-Socratic times,

philosophers have sought ways of systematizing our ethical intuitions, to

identify a set of guiding principles that could be applied in any situation to

dictate the right course of action. All of us have ethical intuitions about most

situations; one goal of ethics is to replace case-by-case intuitions with

principled decisions. A practical social advantage of ethical principles is that

they can provide guidance when intuitions are unclear or inconsistent from

person to person. The success of an ethical discussion depends on the

discussants' ability to articulate the relevant principles as well as the

relevant facts about a situation to which the principles apply.

 

In the ethics of neurocognitive enhancement we are still feeling our way towards

the relevant principles and we still have much to learn about the relevant

facts. Is it a matter of principle that 'medicalization' is bad, or that hard

work confers 'dignity'? Or are these moral heuristics, rules of thumb that might

be contradicted in some cases? And is it a matter of fact that Ritalin reduces

our opportunities to learn self-discipline, or could it in fact have no effect

or even help us in some way? Until we have disentangled the a priori from the

empirical claims, and evaluated the empirical claims more thoroughly, we are at

risk of making wrong choices.

 

When not to decide is to decide. Neurocognitive enhancement is already a fact of

life for many people. Market demand, as measured by sales of nutritional

supplements that promise cognitive enhancement, and ongoing progress in

psychopharmacology portend a growing number of people practicing neurocognitive

enhancement in the coming years. In terms of policy, we will soon reach the

point where not to decide is to decide. Continuing our current laissez-faire

approach, with individuals relying on their physicians or illegal suppliers for

neurocognitive enhancement, risks running afoul of public opinion, drug laws and

physicians' codes of ethics. The question is therefore not whether we need

policies to govern neurocognitive enhancement, but rather what kind of policies

we need. The choices range from minimal measures, such as raising public

awareness of the potential practical and moral difficulties of neurocognitive

enhancement, to the wholesale enacting of new laws and the creation of

new regulatory agencies. In between these extremes lie a host of other options,

for example the inclusion of neurocognitive enhancement policies in codes of

ethics of the professional organizations of physicians, scientists, human

resource managers and educators, and short-term moratoria on neurocognitive

enhancement.

 

Francis Fukuyama26 has argued for new legislation to control the use of

neurocognitive enhancement, among other biotechnologies. He characterizes the

work of groups such as the President's Council on Bioethics in the USA and the

European Group on Ethics in Science and New Technology as the " intellectual

spade work of thinking through the moral and social implications of biomedical

research " , and suggests that " it is time to move from thinking to acting, from

recommending to legislating. We need institutions with real enforcement powers. "

 

We admit to being less certain about the right course of action. With respect to

the first three categories of issue, concerning safety, freedom and fairness,

current laws and customs already go a long way towards protecting society. With

respect to the fourth category of issue, we believe that there is much more

'spade work' (in Fukuyama's words) to be done in sorting out the moral and

social implications of neurocognitive enhancement before we move from

recommendations to legislation. We should draw an object lesson from the history

of federal stem cell legislation in the USA, which was enacted hastily in the

wake of reported attempts at human reproductive cloning with limited public

understanding of the issues. That legislation is now viewed by many as a setback

for responsible biomedical research, and two states have now enacted their own

laws to permit a wider range of research activity.

 

The need for more discussion of the issues is a predictable conclusion for an

article like this one, but nevertheless a valid one. One urgent topic for

discussion is the role of physicians in neurocognitive enhancement27. Although

western medicine has traditionally focused on therapy rather than enhancement,

exceptions are well established. Cosmetic surgery is the most obvious example,

but dermatology, sports medicine and fertility treatments also include

enhancement among their goals. Enabling a young woman to bank her eggs to allow

later childbearing, for example, is not therapeutic but enhancing. Will

neurocognitive enhancement join these practices? If so, will it be provided by

specialists or family practitioners? What responsibility will physicians take

for the social and psychological impact of the enhancements they prescribe, and

by what means (for example, informal or formal psychological screening as used

by cosmetic surgeons or fertility specialists)?

 

Beyond these immediate practical issues, we must clarify the intangible ethical

issues that apply to neurocognitive enhancement. This requires interdisciplinary

discussion, with neuroscientists available to identify the factual assumptions

that are implicit in the arguments for and against different positions, and

ethicists available to articulate the fundamental moral principles that apply.

As a society we are far from understanding the facts and identifying the

relevant principles. With many of our college students already using stimulants

to enhance executive function and the pharmaceutical industry soon to be

offering an array of new memory-enhancing drugs, the time to begin this

discussion is now.

 

 

Links

 

 

FURTHER INFORMATION

Martha Farah's homepage | Judy Illes's homepage | Howard Gardner's homepage |

Eric Kandel's laboratory | Patricia King's homepage | Barbara Sahakian's

homepage | Paul Root Wolpe | NYAS e-briefing on neuroethics

 

 

 

 

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Acknowledgements

This paper is based, in part, on a meeting held at the New York Academy of

Sciences in June 2003, supported by a grant to J.I. from the National Science

Foundation with co-sponsorship of a Mushett Family Foundation grant to the

Academy. The writing of this paper was supported by NSF and NIH grants to M.J.F.

and an NIH grant and a Greenwald Foundation grant to J.I.

 

Competing interests statement. The authors declare competing financial

interests.Declaration of competing financial interests

 

Martha J. Farah, Judy Illes, Robert Cook-Deegan, Howard Gardner, Eric Kandel,

Patricia King, Eric Parens, Barbara Sahakian & Paul Root Wolpe

Neurocognitive enhancement: what can we do and what should we do?. Nature

Reviews Neuroscience 5, 421-425 (2004); doi:10.1038/nrn1390

 

 

Declaration: E.K. is a co-founder and Chariman of the scientific board of

directors of Memory Pharmaceuticals.

 

 

 

 

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