European debate on human enhancement technologies

Nanotechnology plays, or rather: will play, a major role in technical and biological human enhancement. We have written about this at length in previous Spotlights such as "Nanotechnology, transhumanism and the bionic man" or in the debate about converging technologies.

The term human enhancement refers to a wide range of existing, emerging and visionary technologies, including pharmaceutical products: neuroimplants that provide replacement sight or other artificial senses, drugs that boost brain power, human germline engineering and existing reproductive technologies, nutritional supplements, new brain stimulation technologies to alleviate suffering and control mood, gene doping in sports, cosmetic surgery, growth hormones for children of short stature, anti-ageing medication, and highly sophisticated prosthetic applications that may provide specialized sensory input or mechanical output. All these technologies signal the blurring of boundaries between restorative therapy and interventions that aim to bring about improvements extending beyond such therapy. As most of them stem from the medical realm, they can boost societal tendencies of medicalization when increasingly used to treat non-pathological conditions.

A recently released study commissioned by the European Parliament attempts to bridge the gap between visions on human enhancement (HE) and the relevant technoscientific developments. It outlines possible strategies of how to deal with HE in a European context, identifying a reasoned pro-enhancement approach, a reasoned restrictive approach and a case-by-case approach as viable options for the EU. The authors propose setting up a European body (temporary committee or working group) for the development of a normative framework that guides the formulation of EU policies on HE. Here are excerpts from the report.

Defining human enhancement

The authors of the study do not rely on the still widespread conceptual distinction between “therapy” and “enhancement”, but instead, in line with recent political statements on the issue, adopt a notion of human enhancement that includes non-therapeutic as well as some therapeutic measures.

Defining human enhancement as any “modification aimed at improving individual human performance and brought about by science-based or technology-based interventions in the human body”, they distinguish between

1) restorative or preventive, non-enhancing interventions,
2) therapeutic enhancements, and
3) non-therapeutic enhancements.

Faced with the often highly visionary and strongly ideological character of the debate on human enhancement, one must strive for a balance between advancing a rational discussion through critical analysis of the relevant visions and normative stances, and taking a close look at the diversity of HE technology and their actual social, technological and political significance.

Bridging the gap between vision and scientific development

The STOA study is a systematic attempt to bridge the gap between, on the one hand, the visions and their cultural and ideological aspects, and, on the other hand, the scientific developments in question and their social aspects and implications. The tension between these two faces of the human enhancement topic is maintained throughout the study. It neither relies on views that discard the issue (and with it many of the technologies in question) on account of its speculative features, nor does it intermingle fantasies and vision with real or emerging developments in a way that hinders rational discussion and misleads policy-makers and the public.

Accordingly, instances of the use of existing or emerging technologies for non-therapeutic human enhancement are presented and discussed in some detail, with the goal of separating the hype and far-flung visions from the actual state of the art and realistic expectations. In general, one can say that the great majority of HE technology discussed in the debate on human enhancement are still therapeutic, and do not offer their users significant advantages over “non-enhanced” humans; indeed, the level of improvement is often well below the level of normal function.

However, there are also strong indications that more and more effective means of non-therapeutic enhancement will be developed in the near future, and that some existing lines of research and development already have the potential to significantly alter human corporeality and cognition. Visions of human enhancement that are, for example, based on neurotechnologies which might allow for super-human performance or species-untypical abilities still have no real basis in research development, but the technologies in question show the potential to fundamentally change man-machine interrelations in the foreseeable future.

If one takes a closer look at certain segments of the discourse on human enhancement (e.g. gene doping, designer babies, use of drugs for cognitive enhancement, and mood enhancement by means of brain implants) and the involved technologies, it becomes obvious that these diverse cases all share certain characteristics.

They all relate, for example, to ideas that push back the boundaries of medical and scientific research. All the research on which these technologies are based stretches the known limitations of the scientific disciplines.

Furthermore, novel applications for new technologies can be developed for derivative purposes other than those for which the technology was originally designed. Moreover, many HE technologies have the potential to increase the incidence of currently illegal practices, and all raise questions of distributive justice now or in the future. They often throw up questions about fundamental cultural values and tend to challenge our view of what it means to be human.

More pressing are concerns regarding the costs of the technologies in question, the unintended (side-) effects, the desirability of the social changes they will precede, and the acceptability of medical tourism benefiting from highly specialized medical or enhancement tourism.

Strategies to deal with human enhancement technologies

The study outlines and discusses possible general strategies of how to deal with the topic of human enhancement and HE technologies in a European context, rejecting a total ban and a laissez-faire approach as inappropriate, and identifying a reasoned pro-enhancement approach, a reasoned restrictive approach, and a systematic case-by-case approach as viable options for the EU.

However, like all the experts they consulted, the study's authors hold that a strategic positioning of the EU with regard to the topic of human enhancement needs in any case to be based on a normative framework which does not yet exist. The development of such a framework should take into account those dimensions – not of “human nature” (a contested subject) but of the human condition – that we tend to consider fundamental to our self-respect and mutual cooperation.

As demonstrated in this study, human enhancement issues are not just academic: the technologies and trends involved can have both beneficial and adverse effects on several kinds of political domain, provide opportunities for individuals and for society, present new risks, create new needs and social demands, and challenge crucial cultural notions, social concepts and views of the human condition.

Currently however, the EU has no platform for monitoring and discussing human enhancement issues. Arenas are lacking where the normative issues can be politically deliberated and the gap between the needs and the concerns of the broader public and the practitioners and experts bridged. The study's authors believe that such a platform should be created on the basis of a critical vision of the phenomenon of human enhancement. They propose to set up a European body for the development of a normative framework for human enhancement that guides the formulation of EU policies in this field.

Guiding EU policies with a normative framework

For the establishment of such a body, they see two institutional options, both of which have been chosen in the past for human genetics and genetic testing. The European Parliament could decide to set up a temporary committee. Alternatively the European Commission could decide to install a working group in which members of the European Parliament participate. In any case, the involvement of the European Parliament in such a body would be highly desirable in order to strengthen the body’s intermediate and public role.

The primary task of the body would be to develop a normative framework for human enhancement. This framework would help to:

• Evaluate the effectiveness and risks of the technologies in question;
• Organize a comprehensive impact assessment of human enhancement technologies (taking into account political, ethical, legal, societal, cultural, political, safety, security, and health aspects);
• Assess whether the EU should fund technologies that are potentially disruptive to the social fabric, or European cultural value systems;
• Identify further research needs on the topic of human enhancement and single human enhancement technologies;
• Define the limits within which each country can regulate human enhancement within its own boundaries;
• Prevent undesirable (side) effects of human enhancement technologies within member states and the EU as a whole;
• Prevent inequalities arising in healthcare between member states;
• Prepare the ground for a policy on the funding of human enhancement research;
• Prepare and stimulate a social dialogue on the topic of human enhancement at large.

In order to achieve these objectives, the body would have to properly monitor the current and emerging developments in HE technologies. By doing this, it would have to establish a solid ground for discussions on normative and regulatory aspects by carefully defining the subject of its activities. It must be ensured that the work of the body is not overloaded by highly visionary or ideological thoughts and aspirations currently triggered by the term “enhancement”.

It should, however, monitor relevant activities, in Europe or elsewhere, in which more radical visions of human enhancement are promoted. Without neglecting possible future societal changes, one of the most prominent tasks of the body would be to focus the debate on human enhancement on emerging technologies and observable societal trends that might lead to an increased use of enhancement technologies in everyday life.

Nanotechnology listening device for neuronal talks

Nanotechnology listening device for neuronal talks

Carbon nanotubes, like the nervous cells of our brain, are excellent electrical signal conductors and can form intimate mechanical contacts with cellular membranes, thereby establishing a functional link to neuronal structures. There is a growing body of research on using nanomaterials in neural engineering ("Nanotechnology to repair the brain"). Most studies simply grow carbon nanotubes (CNTs) over microelectrodes to interface with neurons extracellularly (outside the neural membrane). Such an extracellular interface is non-invasive, but it only allows the action potential of neurons to be recorded. In contrast, an intracellular interface allows all of the sophisticated neural activity to be probed, but it is an invasive approach that usually destroys the neuron.

Now, new research by scientists in Taiwan is the first to explore the feasibility of using CNTs to probe neural activity intracellularly (inside the neural membrane), opening the way for intracellular neural probes that minimize damage to the neuron.

Scientists experimenting with CNT-based neural probes are still challenged by fully understanding the mechanisms underlying the electrical coupling at the CNT-electrolyte interface. Most studies indicated that CNT electrodes were like metal electrodes, relying on capacitive coupling to record and to stimulate neural activity.

The new study by the Taiwanese team brings two important findings for future nanotechnology work with CNT-based neural probes. Firstly, the electrical conduction at the CNT-electrolyte interface involves not only capacitive coupling but also resistive conduction to a comparable extent. Secondly, both the resistive and capacitive conductivity improves (increases) towards favoring neural recording after the CNTs conduct direct currents for a long time.

Single-walled carbon nanotubes grown on an AFM tip. CNT length: 2µm; CNT diameter: <10nm.

"An intracellular interface not only improves the signal-to-noise ratio by several tens of times but also makes it possible to record action potentials and postsynaptic potentials with better selectivity," Hsin Chen explains to Nanowerk. "By placing CNT bundles in a glass pipette and using the pipette tip to penetrate the neuronal membrane, we demonstrated that the CNTs are capable of recording and stimulating neurons intracellularly, with a performance comparable to the conventional silver/silver chloride electrodes used in physiological experiments."

Chen, an assistant professor in the Department of Electrical Engineering at National Tsing Hua University (NTHU), also points out that, interestingly, the recording capability of the CNTs was found to improve – instead of degrading – after delivering direct-current stimuli for a long period of time. "The long-term endurance of CNTs makes CNT probes particularly suitable for long-term usage, superior to the silver/silver chloride (Ag/AgCl) electrodes which normally wear out after the silver chloride is reduced into silver."

Chen's team, which included scientists from NTHU's Institute of Molecular Medicine, Institute of Electronics Engineering, Department of Materials Science and Engineering, and Institute of Nano Engineering and Micro System, as well as the Microsystem Technology Center, ITRI, further investigated the mechanisms supporting the intriguing properties of CNTs with impedance measurement, cyclic voltammetry, and high-resolution imaging.

"We found that the CNT-electrolyte interface has non-negligible resistive conductivity, which allowed the CNTs to record the equilibrium potentials of neurons intracellularly, or to deliver direct-current stimuli" says Chen. "We were able to determine that the resistive conduction relied mainly on the abundant functional groups on the CNTs' surface. More interestingly, we found that the impedance of the CNT-electrolyte interface improved with the delivery of current stimuli, apparently because it induces hydrolysis reactions and polishing effects at the CNT surface."

For their study, Chen's team made two types of CNT probes – in both cases bundles of multi-walled CNTs connected to a silver wire; one coated with insulating epoxy, one inserted into a sharp glass pipette – to measure neural activity not only extracellularly but also intracellularly. But unlike other CNT-coated microelectrodes, these probes had only carbon nanotubes at the probe tips involved in interfacing neurons, facilitating the characterization of the CNT-electrolyte interface.

The researchers compared the performance of their CNT probes with that of conventional Ag/AgCl electrodes with the well-characterized escape neural circuit of the crayfish, Procambarus clarkia. These tests showed that the CNT probes have comparable performance to the currently used Ag/AgCl electrodes, as well as a superior long-term endurance, making them a new tool for general neural physiological experiments as well as therapeutic devices such as brain-machine interfaces.

Having demonstrated CNTs' capability to interface with neurons intracellularly, the main goal of the Taiwanese team now is to develop fully functional nanoscale neural probes based on the CNTs.

"Our main challenge is that the interface impedance will increase significantly if the probe consists of only one or a few CNTs" says Chen. "Therefore, techniques for growing CNTs longer than 10µm are important to us. In addition, as the nanoscale probe penetrates the neuronal membrane, one segment of the CNTs will always remain outside the membrane. This segment needs to be insulated from extracellular fluids to ensure that the CNTs record only the potentials of the intracellular fluid. Therefore, we also need to develop a technique for coating an insulating nanoscale layer over CNT probes."

NanoMedical-Towards electronic-based single-molecule DNA sequencing

NanoMedical-Towards electronic-based single-molecule DNA sequencing

It its more than 25 years of existence, Scanning Tunneling Microscopy has predominantly brought us extremely detailed images of matter at the molecular and atomic level. The Scanning Tunneling Microscope (STM) is a non-optical microscope that scans an electrical probe over a surface to be imaged to detect a weak electric current flowing between the tip and the surface. It allows scientists to visualize regions of high electron density and hence infer the position of individual atoms and molecules on the surface of a lattice.

In nanoelectronics, using single molecules as electronic components is the ultimate goal for future electronic nanotechnology devices and scientists have already made important progress by contacting a single molecule using a STM in a liquid environment at room temperature (read: The long road towards single molecule nanotechnology electronics).

In chemistry, STMs have already been used for real-time single-molecule imaging of an entire chemical reaction. Now, researchers in Japan have managed to partially sequence a single DNA molecule with a STM. Reporting their findings in Nature Nanotechnology ("Partial sequencing of a single DNA molecule with a scanning tunnelling microscope") they show that it is possible to sequence individual guanine bases in real long-chain DNA molecules with high-resolution scanning tunneling microscope imaging and spectroscopy.

Tomoji Kawai, a professor at the Institute of Scientific and Industrial Research at Osaka University, and research assistant Hiroyuki Tanaka have developed a method for extending and fixing DNA strands – a significant step towards the realization of electronic-based single-molecule DNA sequencing.

"Of the four bases, we were able to precisely identify guanine because the STM is able to pick up on the characteristics of its electronic state, which is largely independent of the adsorption structure," says Kawai. "If vibrational spectroscopy is performed using inelastic electron tunneling spectroscopy, it should be possible to identify all of the base molecules. Furthermore, because STM can select a specific position of interest along a DNA strand, the technique could have a unique advantage in analyzing, for example, single nucleotide polymorphisms."

In the past, when scientists tried to sequence single long-chain DNA molecules with the STM some of the difficulties they encountered were due to the unsuitability of the sample preparation methods. Very few studies have been able to make use of the full resolving power of the STM to achieve clear and reproducible observation of individual nucleotides.

Whereas detailed STM imaging, spectroscopy and manipulation studies of molecules are almost always restricted to molecules that can be deposited onto a surface from the gas phase, Kawai and Tanaka have developed a method (for which they have applied for and received a Japanese patent: Kokoku 2005-46665) for stretching out and fixing single-stranded M13mp18 DNA molecules (the double-stranded, covalently closed, circular form of DNA derived from bacteriophage M13, which contains 7,249 bases) by using the flow effects resulting from the oblique injection of a DNA solution onto a substrate using a pulse-injection technique. "Using this extended DNA, and to check whether or not it is possible to assign the individual guanine units, we measured topography images and dI/dV map images over a 100-nm-wide region" says Kawai. "In the resulting topography image, the individual nucleotides are shown as bright points, which are exceptionally bright in some places."

Deposition and STM analysis of single-stranded M13mp18 DNA molecules on a Cu(111) surface. a) Schematic illustration of the oblique injection method. DNA strands tend to align more perpendicular than horizontal to the flow (injection) direction. The Cu(111) substrate is inclined at ∼45° to the aqueous solution of DNA, which is introduced from a pulse valve. b) Typical wide-area image of M13mp18. Atomic steps in the Cu(111) substrate form a staircase surface structure. In this image, sections of M13mp18 are visualized as linear adsorbed material running from the top left to bottom right. c) An enlarged view of the rectangular region enclosed by the white dashed line in b. d) A dI/dV map of the same region as in c. To maximize the detection of the density of states of guanine, the measurements were made under slightly lower bias conditions than in c. e) Part of the base sequence of M13mp18 obtained from a databank (the sequence of bases at positions 5322 through 5461). To facilitate comparison with the STM data, the guanine sites are indicated by red characters and are also connected by red arrows to the corresponding parts of the image

Currently, there are two main problems with this STM technique: One, to become viable as a practical tool it must be able to clearly recognize all four types of base molecule of DNA, not just guanine. Two, and a killer as far as commercial or large-scale applications are concerned, is the time it takes to perform the sequencing. It took almost an hour to obtain the dI/dV map of image d in the above figure. The researchers point out that, in general, lock-in detection sacrifices temporal resolution for the sake of improved signal-to-noise ratio. "In our measurement system, to obtain the dI/dV spectrum, it was necessary to stop the scanning and feedback of the STM probe and then measure the I–V characteristic, so that a time ranging from 1 second to 1 minute was needed for each point

Kawai and Tanaka explain that if STM software and control mechanisms capable of finding chain-shaped polymers such as DNA can be developed, then the time taken to scan parts where the sample is not present can be greatly reduced. "Savings in cost and time can also be made if sequencing is performed from the topographic image alone without using a lock-in amplifier, but it would still be necessary to use a method for identifying contamination."

Nanomedical-DNA-encasing increases carbon nanotubes' tumor killing power

DNA-encasing increases carbon nanotubes' tumor killing power

Various forms of hyperthermia – a form of cancer treatment with elevated temperature in the range of 41-45°C – have been intensively developed for the past few decades to provide cancer clinics with more effective and advanced cancer therapy techniques. The recent use of nanomaterials has shown promising for developing more effective hyperthermia agents (read more: Self-heating nanoparticles as tumor-destroying hyperthermia agents).

While most nanomedical hyperthermia research is conducted with various nanoparticles, carbon nanotubes are also of interest in these thermal ablation applications. So far, however, the utility of carbon nanotubes for in vivo use has been limited by self-association – i.e. they stick to each other. A new study has now demonstrated that DNA-encasement of multi-walled carbon nanotubes (MWCNTs) results in well-dispersed, single MWCNTs that are soluble in water and that display enhanced heat production efficiency relative to non-DNA-encased MWCNTs.

"We showed that single-stranded DNA efficiently solubilizes multi-walled carbon nanotubes," William H. Gmeiner, a professor in the Department of Cancer Biology at Wake Forest University, tells Nanowerk. "Further, the DNA-encasement of the MWCNTs actually increased the amount of heat produced upon irradiation of the nanotubes with near-infrared light. Importantly, we were able to show that the heat produced by the DNA-encased MWCNTs was sufficient to selectively and completely eradicate a tumor mass without causing any significant toxicity to surrounding tissue."

SEM images for (left) non-DNA-encased MWCNTs and (right) DNA-encased MWCNTs. Upon DNA-encasement, the MWCNTs are well-dispersed with few aggregates observed

Gmeiner explains that DNA-encasement has been used previously with single-walled nanotubes (see: "Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction") and that it was shown that they may be excited upon irradiation with near-infrared light (nIR) to release heat sufficient to kill cancer cells in tissue culture. MWCNTs, though, have a larger diameter than SWCNTs and it was not known how well this strategy would work for them. It was also not known if DNA-encasement would inhibit the thermal ablative properties of MWCNTs.

The Wake Forest team has now shown that it is possible to prepare DNA-encased MWCNTs and quantify the production of heat upon nIR irradiation. Their findings also indicate that control of these parameters – power and time – can be exercised to provide the desired selectivity of cell kill without damaging surrounding normal tissue.

Reporting their findings in the August 5, 2009 online edition of ACS Nano ("Increased Heating Efficiency and Selective Thermal Ablation of Malignant Tissue with DNA-Encased Multiwalled Carbon Nanotubes"), Gmeiner and his team also demonstrate that the conversion of nIR irradiation to heat by DNA-encased MWCNTs is linear with respect to both power and time.

Gmeiner explains that modest temperature increases of 3-5°C are sufficient to cause protein denaturation and subsequently cell death. "Our present study demonstrates that DNA-encasement of multi-walled carbon nanotubes increases heat production 2- to 3-fold relative to non-DNA-encased MWCNTs" he says. "This increased efficiency in heat production occurs over a wide range of MWCNT concentrations and irradiation times and a moderate range of power levels. Importantly, the time-dependent increase in temperature for both DNA- encased MWCNTs and non-DNA-encased MWCNTs was linear under all conditions that we evaluated."

Since their SEM and AFM images clearly show that the DNA-encased MWCNTs are well-dispersed – in contrast to the non-encased nanotubes that tend to lump together – the researchers assume that decreased aggregation is the likely origin of the increased heating from DNA-encased MWCNTs relative to non-DNA-encased MWCNTs.

This increased heating efficiency means that effective hyperthermia treatments could be developed using a lower concentration of carbon nanotubes – a positive development given the toxicity concerns surrounding the medical use of carbon nanotubes. Control of the power/time parameters also mean that, for a given MWCNT concentration, the required laser power could be decreased by increasing the irradiation time producing the same amount of heat while reducing damage to normal surrounding tissue in vivo.