ethical, legal and social aspects of brain-implants using nano-scale materials and techniques

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ORIGINAL PAPER Ethical, Legal and Social Aspects of Brain-Implants Using Nano-Scale Materials and Techniques Francois Berger & Sjef Gevers & Ludwig Siep & Klaus-Michael Weltring Received: 29 January 2008 / Accepted: 18 September 2008 / Published online: 11 October 2008 # Springer Science + Business Media B.V. 2008 Abstract Nanotechnology is an important platform technology which will add new features like improved biocompatibility, smaller size, and more sophisticated electronics to neuro-implants improving their therapeutic potential. Especially in view of possible advantages for patients, research and development of nanotechnologi- cally improved neuro implants is a moral obligation. However, the development of brain implants by itself touches many ethical, social and legal issues, which also apply in a specific way to devices enabled or improved by nanotechnology. For researchers developing nanotech- nology such issues are rather distant from their daily work in the lab, but as soon as they use their materials or devices in medical applications such as therapy of brain diseases they have to be aware of and deal with them. This paper is intended to raise sensitivity for the ethical, legal and social aspects (ELSA) involved in applying nanotechnology in brain implants or other devices by highlighting the short term problems of testing and clinical trials within the existing regulatory frameworks (A), the short and medium-term questions of risks in the application of the devices (B) and the long-term perspectives related to problems of enhancement (C). To identify and address such issues properly nanotechnolo- gists should involve ethical, legal and social experts and regulatory bodies in their research as early as possible. This will help to remove pressure from regulatory bodies, to settle public concern and to prevent non-acceptable developments for the benefit of the patients. Keywords Brain . ELSA . Implants . Nano2Life . Nanobio . Neuro Introduction An especially sensitive research area from an ethical, social and legal point of view is the development of brain implants, which constitute a major opportunity to treat neurological illness. The therapy of brain diseases is difficult because of the low accessibility of the brain as well as the high functionality of most of its parts. Systemic therapy using drugs has many Nanoethics (2008) 2:241249 DOI 10.1007/s11569-008-0044-9 DO00044; No of Pages F. Berger INSERM, Grenoble, France e-mail: [email protected] S. Gevers Department of Social Medicine, Academic Medical Center, Amsterdam, The Netherlands e-mail: [email protected] L. Siep Philosophisches Seminar, Westfälische Wilhelms-Universität, Münster, Germany e-mail: [email protected] K.-M. Weltring (*) Gesellschaft für Bioanalytik Münster e.V., Mendelstr. 11, 48149 Münster, Germany e-mail: [email protected]

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Page 1: Ethical, Legal and Social Aspects of Brain-Implants Using Nano-Scale Materials and Techniques

ORIGINAL PAPER

Ethical, Legal and Social Aspects of Brain-Implants UsingNano-Scale Materials and Techniques

Francois Berger & Sjef Gevers & Ludwig Siep &

Klaus-Michael Weltring

Received: 29 January 2008 /Accepted: 18 September 2008 / Published online: 11 October 2008# Springer Science + Business Media B.V. 2008

Abstract Nanotechnology is an important platformtechnology which will add new features like improvedbiocompatibility, smaller size, and more sophisticatedelectronics to neuro-implants improving their therapeuticpotential. Especially in view of possible advantages forpatients, research and development of nanotechnologi-cally improved neuro implants is a moral obligation.However, the development of brain implants by itselftouches many ethical, social and legal issues, which alsoapply in a specific way to devices enabled or improved bynanotechnology. For researchers developing nanotech-nology such issues are rather distant from their daily work

in the lab, but as soon as they use their materials ordevices in medical applications such as therapy of braindiseases they have to be aware of and deal with them.This paper is intended to raise sensitivity for the ethical,legal and social aspects (ELSA) involved in applyingnanotechnology in brain implants or other devices byhighlighting the short term problems of testing andclinical trials within the existing regulatory frameworks(A), the short and medium-term questions of risks in theapplication of the devices (B) and the long-termperspectives related to problems of enhancement (C). Toidentify and address such issues properly nanotechnolo-gists should involve ethical, legal and social experts andregulatory bodies in their research as early as possible.This will help to remove pressure from regulatory bodies,to settle public concern and to prevent non-acceptabledevelopments for the benefit of the patients.

Keywords Brain . ELSA . Implants . Nano2Life .

Nanobio . Neuro

Introduction

An especially sensitive research area from an ethical,social and legal point of view is the development ofbrain implants, which constitute a major opportunityto treat neurological illness. The therapy of braindiseases is difficult because of the low accessibility ofthe brain as well as the high functionality of most ofits parts. Systemic therapy using drugs has many

Nanoethics (2008) 2:241–249DOI 10.1007/s11569-008-0044-9

DO00044; No of Pages

F. BergerINSERM,Grenoble, Francee-mail: [email protected]

S. GeversDepartment of Social Medicine, Academic Medical Center,Amsterdam, The Netherlandse-mail: [email protected]

L. SiepPhilosophisches Seminar,Westfälische Wilhelms-Universität,Münster, Germanye-mail: [email protected]

K.-M. Weltring (*)Gesellschaft für Bioanalytik Münster e.V.,Mendelstr. 11,48149 Münster, Germanye-mail: [email protected]

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negative side effects due to the absence of local andfunctional targeting. Brain dysfunction is often locat-ed in a specific neuronal network and therefore verydifficult to target from the periphery. Compared tosystemic therapy local targeting provided by brainimplants promises a better efficacy. Moreover, braindevices can deliver a functional and reversible effect,which dramatically increases their safety.

Since the work of Alim Louis Benabid in 1987, ithas been demonstrated that high frequency electrostimulation is able to do the same as an irreversiblelesion by reversibly inhibiting brain functions in thespecific location targeted by the electrodes. Thisconcept proved highly efficient in the treatment ofthe Parkinson’s disease tremor and was extended toother targets providing a major cure for previouslyincurable neurological illnesses such as dystonia orepilepsy. Long-term effects and safety were clearlydemonstrated, with a follow-up of 20 years for olderpatients. More recently, therapeutic efficacy was alsoobserved in major depression and obsessive compul-sive disorders resistant to chemical therapy. 40,000patients all around the world were treated with thenew technology [18, 28]

In what sense are implants and stimulationschanged by nanotechnology? In medical applicationsthe implementation of nano-modifications on micro-devices will promise major progress, because itpositively influences resistance, biocompatibility,physiological integration in the tissue and implemen-tation of multifunctionality from diagnosis to therapy.Research will tend to decrease the size and to addnano-materials to the micro-devices.

Miniaturization is a prerequisite for the secondgeneration of devices mandatory for improved targetingof a specific area in the brain or for a complexstimulation associating several locations at the sametime to treat more complex diseases using multi-targettri-dimensional brain stimulation [6]. The neuropros-thetic field is another application of brain implantswhich supports nano-modifications [25]. First applica-tions, which have been carried out recently in animaland humans, demonstrated that patient thoughts can berecorded in paraplegic patients to guide an externaldevice. To do that, silicon microelectrode arrays havebeen developed for in vivo recording of neural activity,but this has been hampered by scar tissue formation atthe site of implantation. Therefore, increasing biocom-patibility and improving the interfaces between technical

devices and the biological environment is a crucialresearch direction [26]. The unique properties ofsingle-wall carbon nanotubes (SWNTs) [13] or othernano-scale coatings for example may have a tremendousimpact in the future developments of micro-systems forneural prosthetics [24]. Several publications havedemonstrated that such well-controlled nano-scalecoatings have the potential to significantly improvethe compatibility and performance of these implants[15]. Another example are nano-beads which havebeen demonstrated to be able to reach the brain afterintravenous injection. We can imagine that thesebeads could be used to target a specific brain areausing, for example, magnetic targeting and local-isation. Magnetic stimulation can be deliveredoutside the brain; the result of magnetic stimulationis a local current. This concept could provide adirection for the next “nano-electrodes”.

The introduction of nano-modifications on theclassical and validated devices used in patients for brainneuro-stimulation should support the development ofmethodology for in vivo to in vitro anticipation of thetoxicity of nano-modifications in humans [12]. A majorissue will be to validate specific tests addressing thisissue as well as the indispensable methods to controlthe systemic diffusion of the nano-material in the body.

To sum up, nanotechnology can lead to majorprogress in neuro-stimulation of the brain, becausenano-tools will help to improve the targeting andavoid lesions. Effects may be recorded immediatelyand application is tightly controlled. Thus patients areprotected from unwanted or negative side effects in abetter way due to the miniaturization process and tothe ability to modify neuronal pathology in afunctional non-lesional way. In addition, brainimplants are applied to a growing number ofpathologies from neurodegenerative diseases such asParkinson disease, movement disorders such asdystonia or tremor, psychiatric disorders such asdepression and obsessive disorders or pain. Further-more, the new field of prosthetic device therapy wasrecently introduced in human (neuro-surgery), with afirst patient suffering from paraplegia treated in 2007.These are all major pathologies in European countrieswith a growing number of cases especially due to theaging population. Nanotechnology promises to bringconsiderable benefits to the growing number ofpatients suffering from brain diseases and degenerativeprocesses, if the location in the brain is known.

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Since help for suffering patients is an inherentduty in all moral codes1 and theories [1], there areobviously many good ethical reasons to proceed withthese technologies. However, brain surgery isalready an ethically controversial form of therapy.It is, of course, highly invasive and touches a verycomplex and sensitive organic system, which formsthe basis for the most important mental states andactivities of the human being. Public concernregarding the development and application of suchtherapies and techniques is quite natural. Theseconcerns are likely to increase in the case of neuro-stimulation, the more so, if it takes place by meansof nano-containing implants. Every researchershould be aware of this and consider the impact ofhis research on some serious ethical and legal andsocial aspects (ELSA).

The modern use of the term “Ethics”, especially ina European context, reflects the plurality of legal,moral and religious norms and convictions within acommunity of pluralistic democratic societies. Itincludes not only norms of what is legally or morallyforbidden—especially moral permissions are, ofcourse, in many cases controversial—but also theduty not to risk the advantages which may beachieved by technological progress. However, thedevelopment of safe techniques to achieve theseadvantages often has to pass experimental phaseswhere individuals or groups bear risks or even sufferdamage which are not outbalanced by the benefits forthem. In these situations not only the legal order butalso the principles of “common morality”, especiallyautonomy, welfare, and justice come into play.[1]Moreover, in the long term these techniques maychange our way of life, our body and our environmentin a way, which few people really want. Publicconcern is quite understandable although “slipperyslope” arguments are often speculative. Thereforeforesight and the assessment of consequences tocommon morality and public acceptance is a task forethical considerations in projects dealing with thenanotechnological improvements of neuro-implants.

There are many issues that can be raised in thiscontext, both with a view to the immediate future and

in a more extended time perspective. In this paper, wefocus on the following questions, the first and secondrelating to short and medium-term, the third rather tolong-term developments.

A. Are there special issues regarding the testing ofmicro-nano-devices in clinical trials?

B. What are the individual risks for safety, autonomyand self-understanding involved in the implantationof micro devices with nano- components intohuman brains?

C. Do micro-nano-implants constitute a new step onthe way to enhancement beyond other forms ofbrain therapy (pharmaceutical or technical)?

The following sections will describe the issues relatedto the above questions to sensitize nanotechnologists tothe ethical, social and legal frameworks they have toknow and deal with once they want to apply theirtechnologies to brain implants.

Issues Concerning the Testing of Nano-enabled BrainDevices

Before a new medical product or procedure is offeredto patients on a regular basis clinical research isrequired to evaluate its safety and effectiveness. Fornano-enhanced brain implants the following threeissues are important to consider:

a) Which regulatory framework applies to nano-brain devices and to what extent?

b) What does this imply and what does it mean forthe so-called phase-1 studies of humans inparticular?

c) Patients who need brain implants may not becompetent and able to give informed consent;does this exclude them from clinical research withnano-enabled devices?

To answer these questions, it is necessary to takeinto account the relevant national and internationalregulations and standards on drugs, medical devicesand clinical research. Here, we will focus oninternational and in particular European standards.

(a) In general, ‘nanomedicine’ does not stand for anew category of health care products; it is rather anew enabling technology used in the design andproduction of medical devices and pharmaceuticals.[7] The problem is that the regulatory framework isquite different, depending on whether the product is a

1 Compare for instance the European Convention on HumanRights and Biomedicine, Preamble and Art.3 [4].

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pharmaceutical (i.e. drug; medicinal product) or adevice.2

Basically, on the basis of the relevant EU direc-tives, pharmaceuticals need preliminary marketauthorisation (Directive 2001/83); this authorisationwill be given only, if the manufacturer can demon-strate that the medicinal product has been investigatedin a clinical trial. Devices, however, can be introducedwithout previous authorisation (Directive 1993/42).The manufacturers themselves are responsible for theperformance and related safety of their devices on thebasis of an appropriately conducted and systematicrisk management procedure, taking into account allthe relevant information they can gather. For devicesfalling in a higher risk class, like implantable devices,their conclusions must be examined and confirmed byan independent third party (‘Notified Body’). Usually,implantable devices will need some kind of clinicalevaluation, which may include a clinical trial, beforethe declaration can be issued that it meets the officialrequirements. It is up to the Notified Body that isresponsible for that declaration to decide whether theclinical evaluation carried out by the manufacturercan be considered sufficient.

So, to some extent, the regulations of pharmaceut-icals are of a different nature compared to theregulations of medical devices. While in the first theprotection of the patient/consumer/research subject ispredominant, in the latter the functioning of themarket and the process of innovation have been takeninto account to a greater extent, leading to a lessrestrictive regime. The result of the co-existence ofthese two regimes is a certain tension between thelevel of protection required on the one hand, and theformal requirements that are based on a presupposeddichotomy between drugs and devices on the other(whereas in reality there is a grey area between thetwo). The European Technology Platform documenton Nanomedicine rightly points out that this situationcalls for improved collaboration between regulatorsresponsible for medical devices and medicinal prod-

ucts, as integration of competences might be requiredfor complex nanotechnology based products.[8] (Anexample of this is a drug eluting stent.)

Since, from a legal point of view, it matters whethera product should be considered a medicinal product ora device, the relevant EU directives on pharmaceuticalsand on medical devices contain definitions for thatpurpose. The definition of a pharmaceutical is verywide, and furthermore in case of doubt (when aproduct has both the characteristics of a device and apharmaceutical) the rules on pharmaceuticals takeprecedence. So, unless a micro-implant with nano-material is obviously ‘only’ a device, it will beconsidered a pharmaceutical; the latter applies anyway,if it is presented as a pharmaceutical.

Although the relevant regulations deal in a differentway with ‘drugs’ and ‘devices’ as to whether clinicalresearch is essential, in practice that difference may notexist when nano brain implants are used. It is hard tosee that such implants would be introduced intoclinical practice without prior research on humans.Even if the Notified Body did not require suchresearch, hospitals and other health care institutionswould not be likely to proceed to such new and riskyprocedures without previous systematic testing in aclinical situation.

(b) Basically, if a clinical trial takes place, theinternational standards for human subject researchwill apply, e.g. Declaration of Helsinki, AdditionalProtocol to the Biomedicine Convention on Biomed-ical Research. On the whole, these standards are quitesubstantive (for example, they require approval by anethics committee of the research protocol, on the basisof a complete description of the study, including detailedinformation on the risks and burdens that it may entailfor research participants and on the ways participantswill be selected and requested to participate). However,in the case of a drug trial the applicable regulations aremuch more extensive and elaborate, since clinical trialsmust meet all the requirements laid down under the EUclinical trial directive (2001/20) and the EU goodclinical practice directive (EU 2005/28); for instance,the research protocol must also be submitted to acompetent national authority which may object to thestudy, even if the ethics committee will approve it.

What does this mean for so-called phase-1 studies?The wording ‘phase 1’ has its origin in clinical trialswith medicinal products/drugs, but is also often usedin other research settings where a new procedure or

2 We are discussing here the regulations on the marketing ofboth kind of products; when a drug or a device has beenintroduced on the market and it turns out to be unsafe, themanufacturer is in both cases liable for physical injury causedby the product; this product liability is stricter than liabilitybased on negligence.

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device is applied for the first time to human beings. Ingeneral, phase-1 studies are intended primarily toassess the safety of the new product or procedure. Inaddition, they are expected to yield the first data aboutits potential effectiveness in humans. In principle,phase-1 studies should be done with healthy volunteers,unless this raises substantive problems.

It seems obvious that brain implants cannot betested on healthy volunteers (because the burdens andrisks would be disproportional), and that therefore theresearch subjects are likely to be patients with somekind of brain disease. As a consequence, the safety ofthe implant has to be tested as much as possiblebefore by appropriate in vitro or animal testing.

If the product to be implanted is to be considered apharmaceutical/medicinal product, the EU regulationsand the documents referred to therein will requireanimal testing before the product is used in a clinicaltrial (the Investigators Brochure to be submitted to theEthical Review Committee must contain informationon pharmacokinetics and product metabolism inanimals). If the product is rather a medical deviceaccording to the meaning of the relevant EU directive(1993/42), then it would seem to depend on the‘Notified Body’ (see above) whether appropriateclinical evaluation has to include previous animaltesting. Since nano-materials have new chemicalproperties one can expect that nano-devices will alsorequire toxicology and safety test including animalmodels.

(c) Patients in brain implant trials might or mightnot be incompetent (for instance most Parkinsonpatients can still make decisions).

In the latter case, the general rule is that if theresearch intervention is ‘therapeutic’ (i.e. one mayexpect that it will directly benefit the patient), it canbe carried out, provided that the legal representativeof the incompetent person gives their consent. See forinstance the most authoritative document on humansubject research in Europe, viz. the AdditionalProtocol to the Convention on Biomedicine andHuman Rights on Biomedical Research [5]. Thisprotocol further stipulates that ‘research of compara-ble effectiveness cannot be carried out on individualscapable of giving consent.’

It is very likely that a research project on a brainimplant will be ‘therapeutic’, at least if the product isimplanted in a person who needs it on a medicalbasis, even if the study is a so called phase-1 study. If,

for some reason, the intervention cannot be consid-ered ‘therapeutic’, then strict requirements apply.First, incompetent patients can only be included ifthe study cannot be done with competent individuals.Second, as to the level of burden/risk to be allowed, if‘the research has not the potential to produce resultsof direct benefit to the health of the person concerned’it should entail only ‘minimal risk and minimalburden’.[5] The EU clinical trial directive (2001/20)is even stricter, since if there are no benefits for theresearch subject, there should be no risk at all; thisprovision only applies however, when the product thatis tested must be considered a pharmaceutical ormedicinal product, rather than a device.

The regulations and ethical considerations describedabove have to be taken into account when estimating theethical and regulatory problems of using nano-materialsin brain therapy.

Risks and Possible Damage(s) Involved in UsingNano-Devices in the Brain

There are two main aspects regarding this question:

a) Problems of safety, data protection and controlover one’s own body.

b) Conflicts between a possible change of personal-ity and the patient’s autonomy and informedconsent

(a) The brain functions like a “holist” network andthe change of specific functions may have conse-quences, which are hard to foresee, to control and toreverse. With reference to the techniques used so far,the problems of side effects like depression (suicide),apathy, hypomania, gambling etc. have been reportedwith deep brain stimulation (less than 1% of patients),mainly caused by the bad position of the devices, forexample implanted outside the motor area. Beside afunction in motor regulation, the subthalamic nucleus,which is the target for Parkinson disease, is also involvedin mood regulation explaining some psychiatric effects.[19, 27]

In addition, technical devices may malfunction orbecome overused. It has to be discussed whethernano-tools used to improve implants or instrumentsfor neuro-stimulation can diminish these risks. On theone hand, it is easier to target and survey them. Onthe other hand, nano-devices may get out of controlmore easily than other technical devices due to their

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size and complexity. These problems should be takeninto account in any further technical development.

Particular problems may arise for the patient’sautonomy and self-determination. Risks may behigher if they transmit data and receive signals beyondthe control of the “owner” (questions also discussedregarding telemedicine, [21] theranostics etc.). Therehas been a good deal of discussion regarding the rightto “informational self-determination” especially in thefield of genetic diagnostics. If therapeutic devices andmicro-transmitters using nano-particles were moredifficult to control by patients and therapists, the self-determination of the patient could be endangered, notonly concerning information and data processing etc.but also with regard to the control over his or her ownbody.[9]

(b) Like other brain-implants, implants with nano-elements may pose difficult problems regardingpossible personality changes in the person.3 Forinstance a psychiatric patient may undergo a changefrom being a deeply depressed person to a extremelycheerful one. To begin with, such a change wouldonly seem legitimate, if behaviour and personalitywere abnormal, and if this abnormality was beyondthe threshold.

Specifying these conditions and identifying realimprovements is not an easy task. It requires, forinstance, the specification of a “normal” degree ofcheerfulness. In addition, normality is a standard oraverage concept whereas personality is characterizedby uniqueness. There are scales and thresholds of“abnormality” regarding rigidity, tremor, anxiety,compulsion, mania, aggression, sadness, hope, indif-ference, creativity, and mood. But can there be ageneralization when it comes to very differentcharacters? From the point of view of modern ethics,these questions should not be decided according togeneral quantitative standards but by a preciseanalysis of the singular case and the particular person.On the other hand, standards drawn from a broadrange of cases may function as a guideline forindividual cases.

Regarding the patient’s autonomy the question willarise, whether the cured person is the same as beforethe treatment. Is she ever capable of consenting to her

treatment with hindsight? This question is not limitedto cases of incompetent patients. Even competentones may not be able to decide about their future as a“different person”. Which degree of paternalism isallowed in curing a person with a nano-enhancedmicro-implant? Are there means of identifying inadvance which degree of suffering a patient wouldaccept to maintain his/her unique personality? Howshould the value of “remaining the same” be weighedagainst “getting rid of pains and disablement”? Is thewish to reverse a procedure a proof of autonomy if theperson has changed? On the other hand, one mayrefer to similar cases where such a change ofpersonality seems to be accepted, for instance casesof voluntary change of gender.

While it is not clear whether nano-tools posespecial problems with regard to these questions, everyresearcher and therapist dealing with far-reachingchanges of psychical traits in their patients shouldconsider them seriously. Although nano-researchersmay not, at first sight, relate directly to such issues,nonetheless their work may have considerable con-sequences in this context for instance concerning thelifetime of implants or the accessibility of brain areas.“Making aware” is an important task of ethics andethics boards or committees. Of course, such a list ofethical questions for nano-researchers may includeissues, which are relevant in other fields of medicaltechnology as well.4

Micro-Implants in the Brain and the Questionof Therapy vs. Enhancement

The discussion about the permissibility or “desirabil-ity” of enhancing human faculties by drugs orimplants has a special emphasis on brain-enhance-ment.5 Since the brain is the bodily “center ofcontrol” and the basic condition for cognitive per-formances, its enhancement has far-reaching conse-quences for human interaction. Most of theseperformances, e.g. the faculties of memory andattention, are already within the reach of psycho-

3 Similar questions of personality changes have been discussedregarding brain-tissue transplantation. Quante [16] cf. alsoGharabaghi, and Tatagiba [11].

4 Another, long-term issue concerns the question whether theself-understanding and self-feeling within a partly mechanisedand robotised body leads to an estrangement of the traditionalhuman self understanding. See Bruce [3] and Siep [20].5 For general problems of enhancement cf. E. Parens [14] Fuchs[10] Siep [23].

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pharmaceuticals. But the use of implants with nano-elements might improve the “fine-tuning” of theseinfluences, not all of which might be desirable. [2, 17]

Some of these consequences are of a socialcharacter. If somebody’s faculties are enhancedbeyond the normal level, equal opportunity and otherprinciples of “justice as fairness” are endangered,especially if medical techniques are expensive and notpaid for by the public insurance system. Although wecertainly do not live in a perfectly fair society,increasing the distance between the “improved” andthe normal human beings collides certainly withaccepted criteria of equality and solidarity. It may beless likely that healthy persons will use brain implantsfor enhancement purposes than drugs. However, if the“transhumanist” arguments6 are increasingly accept-ed, we may see more interests and pressure in thisdirection which would have serious implications. Ifhumans with radically improved brain capacities everbecame a social fact rather than merely a futurespeculation, humanity might split up in different “sub-species” which could even have difficulties understand-ing each other. Such consequences would challengewidely accepted basic principles of equality, autonomyand even non-violence. This, of course, is a long-termperspective.

Another part of the enhancement problem has beentouched on already. If a depressed person becomes acheerful one, is the person cured or enhanced? If aperson with a hearing defect is turned into anextraordinarily good hearer, is this the best outcomeof the therapy? If defects can be cured, why not aimfor the best possible quality of the function, which isdamaged? But will the “cured” person be able to copewith her new capability? This may raise problemseven for the tuning of devices: which degree ofperformance should be tuned in or programmed?

The outcome of a technical perfectionism of thissort may be problematic at least in three aspects:

(a) The person may feel estranged in her own body.She may not “recognize” herself any more andmay lose her familiar sensations and behaviour.

(b) She may develop problems with her environ-ment. Already the questions of autonomy andconsent may be part of this problem. But there

may be other difficulties with family and socialenvironment.

(c) The problems of social equality mentioned abovemay emerge. A “run for the best brain” may betriggered off.

There are other social aspects, in particularconcerning the change of acceptance and expect-ations. For instance, the expectations regarding thehearing qualities of elderly persons have certainlychanged. This may have social consequences espe-cially if the age of retirement is increasingly post-poned. With new possibilities to improve the facultiesof the aging brain, new forms of competition andresulting stress may arise. Sometimes, however,reasonable social practices are developed regardingproblems which may seem impossible to solve fromthe present ethical perspective.

Final Comments

Neuro-stimulation by brain implants has been workedon for decades and it provides an alternative therapyto drug treatment of neurological diseases. Thedemand for such treatment will increase in the futuredue to the aging population, which will cause anincrease in Parkinson’s and Alzheimer’s disease, forexample. Nanotechnology is an important platformtechnology to assist in meeting this demand because itwill add new features like improved biocompatibility,smaller size, and more sophisticated electronics toneuro-implants improving their therapeutic potential.Therefore, it would be unethical simply to stop or slowdown Research and Development of nanotechnologicalimproved neuro implants.

However, development of brain implants by itselftouches many ethical, social and legal issues, whichapply in a specific way to devices enabled orimproved by nanotechnology. Therefore we havediscussed in this paper the short term problems oftesting and clinical trials (A), the short and medium-term questions of risks in the application of thedevices (B) and the long-term perspectives related toproblems of enhancement (C).

Researchers working with these new technologieshave the obligation to thoroughly consider such issuesand consequences before they start and while theycarry out their projects. To discuss possible ethical

6 For a discussion of the transhumanist arguments see Siep[22].

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implications with ELSA experts early on in a projectmay relieve the pressure for regulatory bodies to beproactive in response to the high speed of thedevelopment, because normally regulations are basedon long term learning and experience. The consequenceof an open and early communication process betweenresearcher, regulatory bodies and ELSA committees willbe a mutual learning process, which can serve to identifyand handle ELSA issues as they arise and therebyaccommodate the fast development. This will help toprevent ethically, socially and legally non-acceptabledevelopments for the benefit of patients—and also thesuccess of the European health economy.

Regulations are not the only answer, and too muchregulation can even be ethically unacceptable, be-cause it might make research too expensive. Thiswould result in a growing dependency on bigpharmaceutical companies. Therefore a social debateinvolving health insurance companies and patientinterest groups is needed. It must tackle the problemsof who finances the development and enables thecompanies to develop a new nano-enhanced implant,even if it is more expensive than a less effective drug.

Due to the speed of development in nanotechnologynew possibilities open up fast. This raises the questionof how to test the safety and efficacy of emerging newdevices and therapies with the traditionally low numberof patients in clinical trials for brain therapy. Improvedbiocompatibility will enable more applications, but it isdifficult to test the risk of long-term effects. Nano-coatings or particles as such might bear a risk oftoxicity. A possible solution could be the developmentof new in vitro test systems not only for toxicologystudies of new materials but also for neuronal functionsin cell cultures. More research is needed to test thevalue of nano-structured 2D and 3D scaffolds forneuronal cells in this regard. This would reduce thenumber and risk of clinical and even of animal trialswhich are ethically problematic as well.

Nanotechnology will almost certainly lead to moresophisticated devices which provide better targetingwith fewer side effects on the one hand but also thepossibility of more external control, data transmissionand misuse on the other. They might also lower thebarrier to enhancement, because the devices are morebiocompatible and therefore seem less risky. To avoidthese effects, the involvement of ELSA experts inforesight exercises and a close monitoring of the fieldis needed to identify such developments and to initiate

a social debate concerning them. This will require theset-up of competent ELSA boards at the Europeanlevel, with enough competence in the different fieldsrequired for achieving their tasks. The benefit wouldbe a transparent, ethically and socially acceptabledevelopment of nano-enhanced brain therapies.

Acknowledgements This paper is in large parts the result ofintensive discussions between members of the ELSA Board andScientists of the European Network of Excellence Nano2Life.

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