Introduction
Humans have constantly attempted to improve themselves through technology. Whether it is increased physical attractiveness through cosmetic surgery or decreased likelihood of hereditary disorders in embryos using pre-implantation genetic testing, human enhancement in one form or another is not a foreign concept.
In the context of engineering, human enhancement can be defined as the application of technology to overcome physical or mental limitations of the body, resulting in the temporary or permanent augmentation of a person’s abilities and features. By this definition, human enhancement entails both the treatment of disease and disability, as well as the upgrading of human aptitude (1). Furthermore, human enhancement is dichotomous in nature: while it heavily implements theoretical ideas by raising important questions about the human application of a diverse array of emerging technology, it also uses applied science and current technology, often borrowing from interdisciplinary scientific fields and methods.
Enhancing Substances
Several technologies exist today that can be properly classified as human enhancement technology. In addition to cosmetic techniques such as plastic surgery and orthodontics, there are drugs known as lean mass builders that directly improve physical performance by increasing muscle growth and density. These substances include membrane-permeable anabolic-androgenic steroids and the water-soluble growth hormone (GH). Although the two drugs differ in their pharmacodynamics and rates of induced muscle growth, both result in increased anabolism, the activity of pathways that promote protein biosynthesis (2). GH spurs lean muscle growth by increasing both lipolysis (breakdown of lipids) and protein synthesis, and producing insulin-like growth factor 1 (IGF-1) which stimulates overall tissue growth (3). Similarly, anabolic steroids stimulate the formation of new muscle fibers by increasing protein synthesis and causing hypertrophy (enlargement) of skeletal muscle even in the absence of strength training (4). Steroids increase both the cross-sectional area of the muscle and the length of the muscle, by raising the myofibril count and the number of sarcomeres per myofibril, respectively (5). Furthermore, research has shown anabolic steroids increase the activity of mitochondrial enzyme carnitine palmitoyltransferase in fast-twitch (Type II) muscle mitochondria, suggesting that androgens (including anabolic steroids) may have an important physiological role in the regulation of fatty acid oxidation by way of speeding up ATP synthesis (6). With the advent of reverse-engineered biochemicals such as recombinant human growth hormone (rhGH) for the treatment of growth disorders, these drugs have been employed as physical enhancers both legally and otherwise, especially in competitive sports (7).
In addition to drugs that allow heightened physical abilities, nootropic pharmaceuticals can enhance certain mental abilities of an individual. There are several classes of drugs that have been shown to improve cognitive processes such as memory and attention (8). One such class is cholinergic drugs, which affect the neurotransmitter acetylcholine (a facilitator of memory retention and formation) and are usually prescribed to moderate the effects of a variety of memory disorders including Alzheimer’s disease (9,10). Acetylcholine may augment the encoding of new memories by not only stimulating long-term potentiation, but also strengthening feed-forward input to the cortex while decreasing excitatory feedback activity (11). Evidence suggests that drugs like acetylcholinesterase inhibitors, which increase the amount and longevity of acetylcholine in the brain, could be effectively implemented in healthy individuals for the purpose of improving memory functions in the absence of genuine medical needs (10).
Additionally, several pharmaceutical companies have been attempting to create a new class of mechanism-based, memory-enhancing drugs using information about the induction and consolidation of the memory encoding process (12). The most recent results of these efforts are known as ampakines, stimulants that improve short-term and long-term memory, as well as attention span and alertness. These compounds have a strong affinity for the glutaminergic AMPA receptor, which is important for encoding memory (10). Ampakines have been investigated by DARPA as a potential means of increasing military efficiency, namely by reducing performance degradation due to sleep deprivation (13,14). Another type of stimulant, prescribed clinically to treat attention-deficit hyperactivity disorder (ADHD), is the mixed salts of amphetamine and is often sold under the brand name Adderall. Amphetamine’s mechanism of action involves the release of dopamine and norepinephrine, important neurotransmitters involved in the regulation of attention (15). Amphetamine facilitates dopamine neurotransmission in striatal brain regions, which is thought to play a critical role in the therapeutic effects and stimulates the release of vesicular dopamine stores in presynaptic terminals, increasing extracellular dopamine levels (16).
The use of pharmaceuticals by the healthy to enhance mental faculties like memory and attention is a controversial neuroethical issue, as there are both positive and negative implications. In a non-clinical study involving the testing of amphetamine and related stimulants on healthy individuals without ADHD, the drugs were found to have a positive effect on cognition, improving performance on tasks that required sustained attention (16). The use of stimulants as cognitive enhancers is hardly a new idea; the United States Department of Defense distributed amphetamine tablets to troops as recently as the Gulf War (17). However, along with the positive effects of increased focus and productivity, these substances often have negative effects (10).
The negative consequences of using enhancing drugs include unexpected side effects and degenerative societal impacts. Although modern pharmaceuticals go through exhaustive laboratory trials before they are ever implemented clinically, there is still a risk of side effects in certain individuals. Furthermore, even when taking drugs medically prescribed to treat disorders, people can form addictive habits. Allowing the proliferation of enhancing substances could lead to increased drug abuse.
Genetic Engineering
The human enhancement methods discussed hitherto have been pharmaceutical drugs with a mostly temporary duration of effect that are currently regulated and administered for restricted medical use in the United States. In addition to ongoing pharmaceutical engineering efforts, there are many nascent and visionary technologies that could have extensive biological, social, political, and economic impacts if applied to humans for the purpose of enhancement. A number of these techniques are banned, some are not sufficiently developed to be implemented in an enhancing manner, and others are purely theoretical at present due to limits of technology.
With the emergence of biotechnology and recombinant DNA methods, the opportunity for true, permanent enhancement of humans exists on a profound level. Currently, human genetic engineering is legally limited to somatic gene therapy, a technique that involves the injection of a transgene (artificially introduced genetic material) into a somatic (body) cell of an individual to prevent a genetic defect (18,19). Any genetic effect or modification will be restricted to the individual treated and is not inherited by the progeny (18). Somatic gene therapy can be divided into two distinct approaches: in vivo and ex vivo. In vivo gene therapy comprises the introduction of a gene (in the form of a DNA liposome complex, recombinant virus, or DNA plasmid) into an individual to reduce or eliminate a defect (18). Ex vivo gene therapy involves removal of target cells from an individual, the subsequent modification of their genetic constitution by inserting a transgenic virus, the reintroduction of altered cells via transfusion, and finally the production of the desired protein or hormone (18). Germ line gene therapy, currently banned for use in humans, refers to the injection of a functional gene into the germ cells of an individual, allowing any genetic modifications made to be passed on to the offspring via gametes (18). Theoretically, this method should be quite effective in counteracting genetic disorders and hereditary diseases, but cannot be used in humans due to the risk of severe side effects and developmental problems because of limitations in current technology (18,20).
These types of gene therapy not only represent the means to cure genetic defects and hereditary disorders, but are also ways in which human genetic enhancement could eventually be performed through related processes. Echoing something encountered in the futuristic world of the video game BioShock, genetic enhancement is a form of positive eugenics that theoretically adds favorable genetic traits, such as disease resistance, strength, physical attractiveness, and even intelligence (18). Although somatic and germ line gene therapy methods can be an effective treatment for a genetic disorder where one mutant gene is the problem, they limit prospects for genetic enhancement because most human traits involve the interactions of many genes and their products. Efficient, directed genetic change to enhance human traits will probably require a technique able to introduce multiple human genes at the same time (21). However, genetic engineering for the purpose of enhancement is still in its infancy, and there are major scientific hurdles to overcome before this technology could be used in humans (22). Genetic enhancement is controversial in that it is no longer therapy for a disorder, but is instead the insertion of additional normal genes to produce a desired change in a characteristic (22). Even more controversial is eugenic genetic engineering, where a ‘designer baby’ would be created by manipulating any physical or behavioral trait that is controlled by genes using a perfected form of pre-implantation genetic diagnosis (23). However, this is not realistic at present: potentially hundreds of unknown genes that interact in unknown ways likely contribute to each trait and environmental influencers are poorly understood (22). Nonetheless, gene replacement, an emerging technique not yet perfected in humans, allows for excision of an abnormal gene from its chromosome and replacement with a normal gene. It has the potential for use in genetic enhancement, as genes for unfavorable attributes could be replaced with pre-engineered genes for more desirable traits (24).
Just as human genetic engineering techniques produced effective treatments for hereditary disorders, the development of genetic enhancement technology in humans is certainly possible, albeit much more difficult. With the potential to be an incredibly powerful scientific tool, human genetic enhancement would likely have both positive and negative effects. Due to the artificial augmentation of innate physical and mental qualities, genetic enhancement might have an effect on evolution (especially in a germ line enhancement). However, direct control over evolution is unlikely as the evolution of the human species is a nonrandom change in allelic frequencies resulting from selective pressure (25). Furthermore, genetic enhancement in humans would bring into question issues of genetic inequality and create potential for discrimination on a genetic basis. Possibly stemming from the fact that it is a quite nascent technology, there also exist stigma and fear surrounding this biotechnology in modern society. This is a factor that, while protecting humans from the possible dangers of experimental ideas, may concurrently obstruct innovation, scientific progress, and sociocultural evolution.
Enhancing Devices
In addition to drugs and genetic engineering techniques, there are a number of actual and visionary devices that could be used in the near future for the purpose of human enhancement. Many of these apparatuses are being proposed through emerging interdisciplinary scientific fields and have important applications to human enhancement. However, much of this technology is speculative or in its infancy. Nanomedicine has potential for use in human enhancement. Molecular nanotechnology is relevant to human enhancement because of molecular assemblers, theoretical machines that could re-order matter on the molecular or atomic scale to build biocompatible medical nanorobots, by way of positionally-controlled mechanosynthesis guided by molecular machine systems (26). The ability to design, construct, and deploy large numbers of medical nanorobots would facilitate the rapid elimination of disease and the reliable and relatively painless recovery from physical trauma via cell repair (26). Medical nanorobotics could also allow for the convenient correction of genetic defects, thus increasing lifespan (26). Furthermore, it has been hypothesized that diamondoid–based medical nanorobotics would be able to augment the natural capabilities of human biological systems: respirocytes are hypothetical artificial red blood cells composed of a spherical diamondoid pressure tank operated at up to 1000 atm of pressure – able to carry 236 times more oxygen to tissues than an equal volume of natural red blood cells, supplementing or replacing the function of the human body’s normal respiratory system (27).
Emerging enhancement technologies could provide functional augmentation for various parts of the human body. The powered exoskeleton is a recently developed technology used to increase the wearer’s strength, endurance, and agility (28). Reminiscent of the metal-clad character in the movie Iron Man, the exoskeleton includes an outer framework and employs electromechanical technology, featuring sensors that follow the wearer’s movements. Microcontrollers then translate the movements into signals fed to a series of hydraulic actuators, emulating and amplifying the force of the movements (28). A common problem with mobile robotic suits like the powered exoskeleton is the extremely limited battery life, although more innovative technologies like lithium–sulfur batteries will be implemented in the future (28). Researchers are investigating the possibility of neural-controlled exoskeletons and integration of humans and robotic machines, as a human-machine interface was established at the neuromuscular level by using the neuromuscular signal (EMG) as the primary command signal for the exoskeleton system (29). As prosthetic technology advances, some scientists are considering the use of advanced prosthetic enhancements (which apply principles of biomorphic robotics), replacing healthy body parts with artificial mechanisms and systems to improve function (30). With the advent of 3D organ printing and improved tissue engineering techniques, it could be possible to print fully functional replacement organs in the near future (31,32). These 3D printed organs could eventually be genetically modified to have enhanced functions.
Neural Enhancement
Because it directly and invasively interacts with the human brain, neural engineering would have the highest potential for negative effects if it was used for enhancement purposes. Clinical neurostimulation techniques such as deep brain stimulation (DBS) with micro-electrodes are already used to treat Parkinson’s disease, dystonia, and tremors (33). Also, neural prosthetics include integrated circuits, used to restore cognitive function to individuals with brain tissue loss, and cochlear implants that restore hearing (34). The increased use of these therapeutic methods could lead to the destigmatization of brain implants. Although neural engineering is a nascent science, implants in the prefrontal cortex of monkeys demonstrated a 10% increase in decision-making abilities (35). There would likely be similar neuroenhancement in humans if artificial neurotechnological devices were developed and implanted, possibly allowing humans to acquire superior perception, cognition, motor control, and positive moods (36). Additionally, there are direct communication pathways between an external device and the human brain, known as brain-computer interfaces (BCI), which can allow the brain to directly control a computer when a BCI is linked to the outer layers of the neocortex (37). Given the plasticity of the brain and the increased clinical use of neurostimulation devices and BCIs, it is possible that cybernetic organisms might exist in the future. These ‘cyborgs’ are humans who have synthetic elements infused in their body – they would be examples of human enhancement taken to the extreme. As early as 2007, a paper questioning the ethics of brain implants stated that “…there can be ethical problems inherent in the proper human uses of technologies and because brain chips are a very likely future technology, it is prudent to formulate policies and regulations that will mitigate their ill effects before the technologies are widespread” (38). Improvements to devices such as neurochips, neurocybernetics (integration of machines into living organisms), and neurobionics (substitution of failed and damaged brain areas with artificial, implantable information processing systems) could make the use of brain-enhancing implants more appealing and practical. There is a possibility that retinal implants and bionic eyes could become so advanced that upgrades to our natural hardware may be advantageous. Bioelectronics and biomechatronics could also be used in human enhancement for the purpose of creating cyborgs. Currently, biocompatible nanoscale wires have been successfully embedded into engineered human tissues in a laboratory (39). Biorobots, with a biological brain and mechanical limbs, would be the ultimate form of cyborg technology, presently only created artificially. Mind uploading (whole brain emulation) and the exocortex are two purely theoretical enhancement technologies. Mind uploading would involve the copying of a conscious mind from a brain to a non-biological form, while an exocortex would involve an artificial external information processer that would augment the cognitive function of the brain.
Conclusion
Human enhancement refers to the use of technology designed and implemented not for medical reasons but for enhancing the human body. However, as the enhancing technology becomes more abstract and far-influencing, ethical concerns arise. In addition to possibly affecting the identity of an individual, there are social implications of biological enhancement through science: the wealthy may be the only ones with access, those who choose not to enhance themselves may be ostracized, or the enhancement technology could start an arms race between nations. Also, human ingenuity has given us a means of enhancing our brains through inventions such as written language, printing, and the Internet. Yesterday’s science fiction is today’s technology, and in a sense, human enhancement is the most extreme form of protective science. Thus, although the level of biological enhancement is limited by current technology and legal barriers, it is likely that human enhancement will become a controversial socio-scientific issue in the future. Humans must decide if increased physical and mental acuity from human enhancement technologies would be worth the potential side effects and costs to society and personal identity. Although enhancement has drawbacks, it does have the potential to be extremely beneficial and protective to humans, fostering innovation and possibly improving our species.
Contact John Steward at
john.a.steward.15@dartmouth.edu
References
1. C. Elliott, “What’s wrong with enhancement technologies?” (1998). CHIPS public lecture, Center for Bioethics at the University of Minnesota, 26 February, 1998.
2. A. T. Kicman, Pharmacology of anabolic steroids. Brit. J. Pharmacol. 154, 502-521 (June 2008).
3. Actions of anterior pituitary hormones: physiologic actions of GH. Medical College of Georgia (2007).
4. D.C. Taylor, D.E. Brooks, J.B. Ryan, Anabolic-androgenic steroid administration causes hypertrophy of immobilized and nonimmobilized skeletal muscle in a sedentary rabbit model. Am. J. Sport. Med. 27, 718-727 (1999).
5. B. Braun, “Muscle hypertrophy and anabolic agents” (November 2007). Lectures 20 and 21 for Kinesiology 380: Diet, Supplements and Athletic Performance, University of Massachusetts Amherst. Available at http://courses.umass.edu/kin380 (14 August 2013).
6. M. Guzmán et al., Treatment with anabolic steroids increases the activity of the mitochondrial outer carnitine palmitoyltransferase in rat liver and fast-twitch muscle. Biochem. Pharmacol. 41, 833-835 (1991).
7. A. Takeda et al., Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation. Health Technol. Asses. 14, 1-209 (2010).
8. C. Lanni et al., Cognition enhancers between treating and doping the mind. Pharmacol. Res. 57, 196-213 (2008).
9. M. Eidi et al., Effects of histamine and cholinergic systems on memory retention of passive avoidance learning in rats. Eur. J. Pharmacol. 465, 91-96 (2003).
10. W. Dekkers, M. O. Rikkert, Memory enhancing drugs and Alzheimer’s disease: enhancing the self or preventing the loss of it? Med. Health Care Philos. 10, 141-151 (2007).
11. M. E. Hasselmo, The role of acetylcholine in learning and memory. Curr. Opin. Neurobiol. 16, 710-715 (2006).
12. G. Lynch, Memory enhancement: the search for mechanism-based drugs. Nat. Rev. Neurosci. 5, 1035-1038 (2002).
13. W. Saletan, Night of the Living Meds: The U.S. military’s sleep-reduction program (2008). Available at http://www.slate.com/articles/health_and_science/human_nature/2008/07/night_of_the_living_meds.html (15 August 2013).
14. E. Williams et al., “Human performance” (Tech. Rep. JSR-07-625, Office of Defense Research and Engineering, Washington, DC, 2008).
15. F. P. Bymaster et al., Atomoxetine increases extracellular levels of norepinephrine and dopamine in prefrontal cortex of rat: a potential mechanism for efficacy in attention deficit/hyperactivity disorder. Neuropsychopharmacol. 27, 699-711 (2002).
16. L. C. Bidwell, F. J. McClernon, S. H. Kollins, Cognitive enhancers for the treatment of ADHD. Pharmacol. Biochem. Be. 99, 262-274 (2011).
17. E. Borin, The U.S. Military Needs Its Speed (2003). Available at http://www.wired.com/medtech/health/news/2003/02/57434 (15 August 2013).
18. E. M. Berger, “Recombinant DNA III: human biology” (2013). Lecture delivered at Dartmouth College, 25 July 2013.
19. P.J. Russell, iGenetics: A Molecular Approach (Benjamin Cummings, San Francisco, CA, ed. 3, 2010), pp. 280.
20. T. O. Nielsen, Human germline gene therapy. McGill J. Med. 3, 126-132 (1997).
21. The President’s Council on Bioethics, Human Genetic Enhancement (2002). Available at http://bioethics.georgetown.edu/pcbe/background/humangenetic.html (15 August 2013).
22. W. F. Anderson, Human gene therapy: scientific and ethical considerations. J. Med. Philos. 10, 275-291 (1985).
23. D. Simmons, Genetic Inequality: Human Genetic Engineering (2008). Nature Education. Available at http://www.nature.com/scitable/topicpage/genetic-inequality-human-genetic-engineering-768 (15 August 2013).
24. R. M. Sade, G. Khushf, Gene therapy: ethical and social issues. J. S. C. Med. Assoc. 94, 406-410 (1998).
25. K. E. Hanna, Genetic Enhancement (2006). National Human Genome Research Institute. Available at http://www.genome.gov/10004767 (15 August 2013).
26. R. A. Freitas, Jr., Current status of nanomedicine and medical nanorobotics. J. Comput. Theor. Nanos. 2, 1-25 (2005).
27. R. A. Freitas, Jr., A Mechanical Artificial Red Cell: Exploratory Design in Medical Nanotechnology (1999). Foresight Institute. Available at http://www.foresight.org/Nanomedicine/Respirocytes.html (15 August 2013).
28. R. Bogue, Exoskeletons and robotic prosthetics: a review of recent developments. Ind. Robot. 36, 421-427 (2009).
29. J. Rosen, M. Brand, M. B. Fuchs, M. Arcan, A myosignal-based powered exoskeleton system. IEEE T. Syst. Man Cy. A. 31, 210-222 (2001).
30. F. Tenore, R. Etienne-Cummings, Biomorphic circuits and systems: control of robotic and prosthetic limbs. IEEE BioCAS, 241-244 (2008). Available at http://ieeexplore.ieee.org/stamp/stamp.jsp?tp=&arnumber=4696919 (15 August 2013)
31. M. S. Mannoor et al., 3D printed bionic ears. Nano Lett. 13, 2634-2639 (2013).
32. I. T. Ozbolat, Y. Yu, Bioprinting toward organ fabrication: challenges and future trends. IEEE T. Biomed. Eng. 60, 691-699 (2013).
33. J. S. Perlmutter, J. W. Mink, Deep brain stimulation. Annu. Rev. Neurosci. 29, 229-257 (2006).
34. T. W. Berger et al., Restoring lost cognitive function. IEEE Eng. Med. Biol. 24, 30-44 (2005).
35. The futuristic brain implant that makes monkeys smarter (2012). Available at http://theweek.com/article/index/233419/the-futuristic-brain-implant-that-makes-monkeys-smarter (15 August 2013)
36. J. K. Berg-Olson, S. A. Pedersen, V. F. Hendricks, Eds., A Companion to the Philosophy of Technology (Wiley-Blackwell, Hoboken, NJ, 2009), pp. 392-396.
37. P. R. Kennedy, R. A. E. Bakay, M. M. Moore, K. Adams, Direct control of a computer from the human central nervous system. IEEE T. Rehabil. Eng. 8, 198-202 (2000).
38. E. M. McGee, G. Q. Maguire, Jr., Becoming borg to become immortal: regulating brain implant technologies. Camb. Q. Heathc. Ethic. 16, 291-302 (2007).
39. P. Reuell, Merging the biological, electronic (2012). Available at http://news.harvard.edu/gazette/story/2012/08/merging-the-biological-electronic (15 August 2013).