Brain Archive

21^st Century Medicine

It is always somewhat presumptuous to attempt to predict the future, but in this case we are on solid ground because most of the prerequisite historical processes are already in motion and all of them appear to be clearly pointing in the same direction.

Medical historian Roy Porter notes that the 19^th century saw the establishment of what we think of as scientific medicine. From about the middle of that century the textbooks and the attitudes they reveal are recognizable as not being very different from modern ones. Before that, medical books were clearly written to address a different mindset.

But human health is fundamentally biological, and biology is fundamentally molecular. As a result, throughout the 20^th century scientific medicine began its transformation from a merely rational basis to a fully molecular basis. First, antibiotics that interfered with pathogens at the molecular level were introduced. Next, the ongoing revolutions in genomics, proteomics and bioinformatics²³²¹ provided detailed and precise knowledge of the workings of the human body at the molecular level. Our understanding of life advanced from organs, to tissues, to cells, and finally to molecules, in the 20^th century. By the early 21^st century, the entire human genome will be mapped. This map will inferentially incorporate a complete catalog of all human proteins, lipids, carbohydrates, nucleoproteins and other molecules, including full sequence, structure, and much functional information. Only some systemic functional knowledge, particularly neurological, may still be lacking by that time.

This deep molecular familiarity with the human body, along with simultaneous nanotechnological engineering advances (Chapter 2), will set the stage for a shift from today's molecular scientific medicine in which fundamental new discoveries are constantly being made, to a molecular technologic medicine in which the molecular basis of life, by then well-known, is manipulated to produce specific desired results. The comprehensive knowledge of human molecular structure so painstakingly acquired during the 20^th and early 21^st centuries will be used in the 21^st century to design medically-active microscopic machines. These machines, rather than being tasked primarily with voyages of pure discovery, will instead most often be sent on missions of cellular inspection, repair, and reconstruction. In the coming century, the principal focus will shift from medical science to medical engineering. Nanomedicine will involve designing and building a vast proliferation of incredibly efficacious molecular devices, and then deploying these devices in patients to establish and maintain a continuous state of human healthiness.

The very earliest nanotechnology-based biomedical systems may be used to help resolve many difficult scientific questions that remain. They may also be employed to assist in the brute-force analysis of the most difficult three-dimensional structures among the 100,000-odd proteins of which the human body is comprised, or to help ascertain the precise function of each such protein. But much of this effort should be complete within the next 20-30 years because the reference human body has a finite parts list, and these parts are already being sequenced, geometered and archived at an ever-increasing pace. Once these parts are known, then the reference human being as a biological system is at least physically specified to completeness at the molecular level. Thereafter, nanotechnology-based discovery will consist principally of examining a particular sick or injured patient to determine how he or she deviates from molecular reference structures, with the physician then interpreting these deviations in light of their possible contribution to, or detraction from, the general health and the explicit preferences of the patient.

In brief, nanomedicine will employ molecular machine systems to address medical problems, and will use molecular knowledge to maintain human health at the molecular scale.

Volitional Normative Model of Disease

What, exactly, is "medicine"? Dictionaries give several definitions, ranging from the very restrictive to the most general, as follows: "a drug or remedy";²²²³,²²²⁴ "any substance used for treating disease";²²²⁰ "any drug or other substance used in treating disease, healing, or relieving pain";²²²¹ "in a restricted sense, that branch of the healing art dealing with internal diseases";²²²⁰ "treatment of disease by medical, as distinguished from surgical, treatment";²²²³ "the branch of this science and art that makes use of drugs, diet, etc., as distinguished especially from surgery and obstetrics";²²²¹ "the study and treatment of general diseases or those affecting the internal parts of the body";²²²⁴ "the science of treating disease, the healing art";²²²⁰ "the art and science of preventing or curing disease";²²²⁴ "the act of maintenance of health, and prevention and treatment of disease and illness";²²²³ "the department of knowledge and practice dealing with disease and its treatment";²²²² or, most generally, "the science and art of diagnosing, treating, curing, and preventing disease, relieving pain, and improving and preserving health".²²²¹ In this book, we shall adopt the latter, maximally-inclusive, definition of "medicine"(Figure 1.3).

Reviewing Figure 1.3, the contemporary physician might at first be inclined to relegate molecular approaches to some minor subfield, perhaps "nanoanalytics," "nanogenomics," or "nanotherapeutics." This would be a serious mistake, because the application of molecular approaches to health care will significantly impact virtually every category of laboratory and clinical practice across the board. Thus we are led to the broadest possible conception of nanomedicine as "the science and technology of diagnosing, treating, and preventing disease and traumatic injury, of relieving pain, and of preserving and improving human health, using molecular tools and molecular knowledge of the human body."

This brings us to the question of "disease," a complex term whose meaning is still hotly debated among medical academics.^2225-2230 Figure 1.4 shows the results of a survey of four different groups of people who were read a list of common diagnostic terms and then asked if they would rate the condition as a disease. Illnesses due to microorganisms, or conditions in which the doctor's contribution to the diagnosis was important, were most likely to be called a disease, but if the cause was a known physical or chemical agent the condition was less likely to be regarded as disease; general practitioners also had the broadest definition of disease.

No less than eight different types of disease concepts are held by at least some people currently engaging in clinical reasoning and practice, including:²²²⁶,²²²⁷

1. Disease Nominalism&#8212A disease is whatever physicians say is a disease. This approach avoids understanding and forestalls inquiry, rather than furthering it.

2. Disease Relativism&#8212A disease is identified or labeled in accordance with explicit or implicit social norms and values at a particular time. In 19^th century Japan, for example, armpit odor was considered a disease and its treatment constituted a medical specialty. Similarly, 19^th-century Western culture regarded masturbation as a disease, and in the 18^th century, some conveniently identified a disease called drapetomania, the"abnormally strong and irrational desire of a slave to be free."²²⁰⁵ Various nonwestern cultures having widespread parasitic infection may consider the lack of infection to be abnormal, thus not regarding those who are infected as suffering from disease.

3. Sociocultural Disease—Societies may possess a concept of disease that differs from the concepts of other societies, but the concept may also differ from that held by medical practitioners within the society itself. For instance, hypercholesterolemia is regarded as a disease condition by doctors but not by the lay public; medical treatment may be justified, but persons with hypercholesterolemia may not seek treatment, even when told of the condition. Conversely, there may be sociocultural pressure to recognize a particular condition as a disease requiring treatment, such as alcoholism and gambling.

4. Statistical Disease&#8212A condition is a disease when it is abnormal, where abnormal is defined as a specific deviation from a statistically-defined norm. This approach has many flaws. For example, a statistical concept makes it impossible to regard an entire population as having a disease. Thus tooth decay, which is virtually universal in humans, is not abnormal; those lacking it are abnormal, thus are "diseased" by this definition. More reasonably, a future highly-aseptic society might regard bacterium-infested 20^th century humans (who contain in their bodies more foreign microbes than native cells; Section 8.5.1) as massively infected. Another flaw is that many statistical measurables such as body temperature and blood pressure are continuous variables with bell-shaped distributions, so cutoff thresholds between "normal" and "abnormal" seem highly arbitrary.

5. Infectious Agency&#8212Disease is caused by a microbial infectious agent. Besides excluding systemic failures of bodily systems, this view is unsatisfactory because the same agent can produce very different illnesses. For instance, infection with hemolytic Streptococcus can produce diseases as different as erysipelas and puerperal fever, and Epstein-Barr virus is implicated in diseases as varied as Burkitt's lymphoma, glandular fever, and naso-pharyngeal carcinoma.²²²⁷

6. Disease Realism&#8212Diseases have a real, substantial existence regardless of social norms and values, and exist independent of whether they are discovered, named, recognized, classified, or diagnosed. Diseases are not inventions and may be identified with the operations of biological systems, providing a reductionistic account of diseases in terms of system components and subprocesses, even down to the molecular level. One major problem with this view is that theories may change over time — almost every 19^th century scientific theory was either rejected or highly modified in the 20^th century. If the identification of disease is connected with theories, then a change in theories may alter what is viewed as a disease. For example, the 19^th century obsession with constipation was reflected in the disease labeled "autointoxication," in which the contents of the large bowel were believed to poison the body. Consequently much unnecessary attention was paid to laxatives and purgatives and, when surgery of the abdomen became possible toward the end of the century, operations to remove the colon became fashionable in both England and America.²²⁰⁵

7. Disease Idealism&#8212Disease is the lack of health, where health is characterized as the optimum functioning of biological systems. Every real system inevitably falls short of the optimum in its actual functioning. But by comparing large numbers of systems, we can formulate standards that a particular system ought to satisfy, in order to be the best of its kind. Thus "health" becomes a kind of Platonic ideal that real organisms approximate, and everyone is a less than perfect physical specimen. Since we are all flawed to some extent, disease is a matter of degree, a more or less extreme variation from the normative ideal of perfect functioning. This could be combined with the statistical approach, thus characterizing disease as a statistical variation from the ideal. But this view, like the statistical, suffers from arbitrary thresholds that must be drawn to qualify a measurable function as representing a diseased condition.

8. Functional Failure—Organisms and the cells that constitute them are complex organized systems that display phenomena (e.g. homeostasis) resulting from acting upon a program of information. Programs acquired and developed during evolution, encoded in DNA, control the processes of the system. Through biomedical research, we write out the program of a process as an explicit set (or network) of instructions. There are completely self-contained "closed" genetic programs, and there are "open" genetic programs that require an interaction between the programmed system and the environment, e.g. learning or conditioning. Normal functioning is thus the operation of biologically programmed processes, e.g. natural functioning, and disease may be characterized as the failure of normal functioning. One difficulty with this view is that it enshrines the natural (Section 1.3.4) as the benchmark of health, but it is difficult to regard as diseased a natural brunette who has dyed her hair blonde in contravention of the natural program, and it is quite reasonable to regard the mere possession of an appendix as a disease condition, even though the natural program operates so as to perpetuate this troublesome organ.*

* The vermiform appendix may have some minor immune function, but it is clearly nonessential and can kill when infected. Yet natural selection has not eliminated it. Indeed, there is evidence for positive selection due to the following accident of physiological evolution. Appendicitis results when inflammation causes swelling, compressing the artery supplying blood to the appendix. High bloodflow protects against bacterial growth, so any reduction aids infection, creating more swelling; if flow is completely cut off, bacteria multiply rapidly until the organ bursts. A slender appendix is especially susceptible, so untreated appendicitis applies positive selective pressure to maintain a larger appendix.²¹⁸⁵

A second weakness of this view is that disease is still defined against population norms of functionality, ignoring individual differences. As a perhaps overly simplistic example, 65% of all patients employ a cisterna chyli in their lower thoracic lymph duct, while 35% have no cisterna chyli (Figure 8.10)—which group has a healthy natural program, and which group is "diseased"?

The author proposes a ninth view of disease, a new alternative which seems most suitable for the nanomedical paradigm, called the "volitional normative" model of disease. As in the "disease idealism" view, the volitional normative model accepts the premise that health is the optimal functioning of biological systems. Like the "functional failure" view, the volitional normative model assumes that optimal functioning involves the operation of biologically programmed processes.

However, two important distinctions from these previous views must be made. First, in the volitional normative model, normal functioning is defined as the optimal operation of biologically programmed processes as reflected in the patient's own individual genetic instructions, rather than of those processes which might be reflected in a generalized population average or "Platonic ideal" of such instructions; the relative function of other members of the human population is no longer determinative. Second, physical condition is regarded as a volitional state, in which the patient's desires are a crucial element in the definition of health. This is a continuation of the current trend in which patients frequently see themselves as active partners in their own care.

In the volitional normative model, disease is characterized not just as the failure of "optimal" functioning, but rather as the failure of either (a) "optimal" functioning or (b) "desired" functioning. Thus disease may result from:

1. a failure to correctly specify desired bodily function (specification error by the patient),

2. a flawed biological program design that doesn't meet the specifications (programming design error),

3. flawed execution of the biological program (execution error),

4. external interference by disease agents with the design or execution of the biological program (exogenous error), or

5. traumatic injury or accident (structural failure).

In the early years of nanomedicine, volitional physical states will customarily reflect "default" values which may differ only insignificantly from the patient's original or natural biological programming. With a more mature nanomedicine, the patient may gain the ability to substitute alternative natural programs for many of his original natural programs. For example, the genes responsible for appendix morphology or for sickle cell expression might be replaced with genes that encode other phenotypes, such as the phenotype of an appendix-free cecum or a phenotype for statistically typical human erythrocytes.*

* It is often pointed out that sickle cell is advantageous in malaria-infested countries because the trait confers resistance to malaria. This flaw-tolerant view makes a virtue of necessity&#8212a direct cure for malaria will undoubtedly be more efficient. Sickle cell is disadvantageous in hypoxic conditions, which is why no one with this trait can hold a civil airline pilot's license.²²²⁷

Many persons will go further, electing an artificial genetic structure which, say, eliminates age-related diminution of the secretion of human growth hormone and other essential endocrines. (The graduated secretion of powerful proteolytic enzymes, perhaps targeted for gene-expression in appropriate organs, may reverse and control the accumulation of highly crosslinked collagenaceous debris; by 1998, many members of the mainstream medical community were already starting to regard aging as a treatable condition.)^{2310,2976-2981} On the other hand, a congenitally blind patient might desire, for whatever personal reasons, to retain his blindness. Hence his genetic programs that result in the blindness phenotype would not, for him, constitute "disease" as long as he fully understands the options and outcomes that are available to him. (Retaining his blindness while lacking such understanding might constitute a specification error, and such a patient might then be considered "diseased.") Whether the broad pool of volitional human phenotypes will tend to converge or diverge is unknown, although the most likely outcome is probably a population distribution (of human biological programs) with a tall, narrow central peak (e.g., a smaller standard deviation) but with longer tails (e.g., exhibiting a small number of more extreme outliers).

One minor flaw in the volitional normative model of disease is that it relies upon the ability of patients to make fully informed decisions concerning their own physical state. The model crucially involves desires and beliefs, which can be irrational, especially during mental illness, and people normally vary in their ability to acquire and digest information. Patients also may be unconscious or too young, whereupon default standards might be substituted in some cases.

Nevertheless, the volitional normative view of disease appears most appropriate for nanomedicine because it recognizes that the era of molecular control of biology could bring considerable molecular diversity among the human population. Conditions representing a diseased state must of necessity become more idiosyncratic, and may progressively vary as personal preferences evolve over time. Some patients will be more venturesome than others—"to each his own." As an imperfect analogy, consider a group of individuals who each take their automobile to a mechanic. One driver insists on having the carburetion and timing adjusted for maximum performance (the "racer"); another driver prefers optimum gas mileage (the "cheapskate"); still another prefers minimizing tailpipe emissions (the "environmentalist"); and yet another requires only that the engine be painted blue (the "aesthete"). In like manner, different people will choose different personal specifications (Section 1.2.5). One can only hope that the physician will never become a mere mechanic even in an era of near-perfect human structural and functional information; an automobile conveys a body, but the human body conveys the soul. Agrees theorist Guttentag:²²³⁴ "The physician-patient relationship is ontologically different from that of a maintenance engineer to a machine or a veterinarian to an animal."

Naturophilia

As already noted (Section 1.3.1), living things in general and the human body in particular are awesome examples of a powerful and intricately woven natural molecular technology to which human engineers, in 1998, still aspire. But embracing Nature is not the same as finding her perfect. Today, the word "natural" has acquired a strong connotation of rightness, even of sanctity. For most of human history, notes biologist Steven Vogel,²⁰²² "the natural and human worlds stood opposed. Nature was something to be tamed and utilized; we had the ordinary attitude of organisms toward other species. Nowadays the natural world intrudes far less but gets venerated far more. And why not? When one's meat is bought in a store, when locusts don't threaten one's corn crop, when central heating and plumbing are the norm, the aesthetics of nature hold greater appeal." And so we embrace the natural rectitude or moral superiority of nature's ways, a kind of pantheism which may be called ethical naturalism,²²⁹⁹ biophilia,²²⁹⁶ or naturophilia.

Many great minds have fallen prey to naturophilia. In the 4^th century BC, Aristotle wrote²²⁹⁷ that "if one way be better than another, that you may be sure is Nature's way." In the 15^th century, we have from Leonardo da Vinci:²²⁹⁸ "Human ingenuity may make various inventions, but it will never devise any inventions more beautiful, nor more simple, nor more to the purpose than Nature does; because in her inventions nothing is wanting and nothing is superfluous."

However, as Virginia Postrel notes in The Future and Its Enemies:²²⁹⁹ "If nature is itself a dynamic process rather than a static end, then there is no single form of `the natural.' An evolving, open-ended nature may impose practical constraints, but it cannot dictate eternal standards. It cannot determine what is good. The distinction between the artificial and the natural must lie not in their source—human or not&#8212but in their characteristics, in the way they relate to the world around them."

According to the dictionary, "artificial" usually means "made by man, rather than occurring in nature." More usefully, Herbert Simon²³⁰¹ defines the artificial as that which is designed, expresses goals, and possesses external purposes. The artificial is controlled and serves its creators' purposes, subject to the universal laws of physics. Kevin Kelly³⁸¹ defines the natural as "out of control." Nature is evolved, not designed, and serves no goal or external purpose save its own survival. Nature, lacking intent, is amoral—it simply is.²²⁹⁹ By building the artificial, observes Postrel, "we do not overthrow nature, but cooperate with it, using nature's own art to create new natural forms. Our artifice alters the path of nature, but it does not end it, for nature has no stopping point, no final shape. It is a process, not an end."

Some naturophilist writers have decried the increasing "medicalization of society" in which formerly natural functions have come to be regarded as medical conditions requiring intervention or treatment.^{2204,2302-2308} However, history suggests that naturophilia is usually undermined by any new medical technology that offers clear, safe, and immediate benefits to patients. For example, prior to 1842, intense pain was viewed as the natural outcome of being cut with a scalpel during surgery. It had always been so—how could it ever be otherwise? The invention of anesthesia in 1842 (Section 1.2.1.9.2) suddenly altered this natural outcome and replaced it with a less painful artificial outcome, despite anguished cries from naturophiles within the medical community that eliminating pain might somehow diminish the human character.

Another example of a widely-accepted medicalization of normal function is childbirth, a quite natural activity that can nevertheless be very dangerous to the mother's health. Precise prehistoric death rates are unknown, although archeological evidence shows that Neanderthal females tended to die before the age of 30 due to hazards of childbirth.^2339,2340 In the worst 19^th century maternity hospitals the natural death rate from childbirth was 9-10%, falling to a very artificial 0.4% rate in England by 1930 and to less than 0.01% in the U.S. during the 1990s. As a result, it now seems "natural" for a woman always to survive childbirth, even though the reverse may have been true for most of human history. Warns historian Roy Porter:²²⁰⁴ "We should certainly not hanker after some mythic golden age when women gave birth naturally, painlessly, and safely; the most appalling Western maternal death rate today is among the Faith Assembly religious sect in Indiana, who reject orthodox medicine and practice home births; their perinatal mortality is 92 times greater than in Indiana as a whole."

A disease seems "natural" to those who suffer from it when no treatment exists. But once a treatment is discovered and is widely employed, the disease becomes rare and its absence now becomes "natural." To those in the past, writes K.E. Drexler,⁹ "the idea of cutting people open with knives painlessly would have seemed miraculous, but surgical anesthesia is now routine. Likewise with bacterial infections and antibiotics, with the eradication of smallpox, and the vaccine for polio: each tamed a deadly terror, and each is now half-forgotten history. What amazes one generation seems obvious and even boring to the next. The first baby born after each breakthrough grows up wondering what all the excitement was about." In the next century, says Charles Sheffield,³⁴³ "our descendants will look on angiograms, upper and lower GIs, and biopsies the way we regard the prospect of surgery without anesthetics."

Future generations who take for granted an all-pervasive nanomedicine in their lives may look aghast upon the 20^th century, wondering among other things how we managed to retain productive focus given the constant annoyance of our numerous undiagnosed minor disease states. Most of these diseases are not yet recognized as such, and many are still regarded as "natural" and not worthy of treatment. In a few decades, this may change. Some examples:

1. Addictions—In 1998, many people laugh off seemingly harmless addictions to chocolate (chocoholics), fats or sugar (sweet tooth), food (gluttony), nicotine (smokers), caffeine (coffee and cola drinkers), work (workaholics), exercise (runner's high), telling falsehoods (pathological liars), gambling (wagerphilia), stealing (kleptomania), medical treatments (hypochondria), marriage (polygamy), power-seeking (domination), skydiving or bungee-jumping (thrillseeking), superstition (astrology), shopping (spendoholics), driving cars that kill 40,000 Americans per year (mobilophilia), unusual sexual preferences (bestiality), sexual activity (nymphomania, satyriasis), or pregnancy (gravidophilia). Without making any value judgements, it is highly likely that most or all of these addictions have genetic or physiological components which, once properly modified, can greatly reduce or eliminate the addiction if so desired. Many on the list are already suspected to have genetic components, much like schizophrenia, drug abuse, bulimia, and alcoholism (dipsomania).

2. Allergies and Intolerances&#8212A food allergy²⁹⁹⁷ is an allergic reaction to a particular food, although true food allergies are much rarer than is generally believed.¹⁶⁰⁴ In the cases of milk, eggs, shellfish, nuts, wheat, soybeans, and chocolate, sufferers may lack an enzyme necessary for digesting the substance. In other cases, dust particles, plant pollens, pet danders, drugs, or foods may be allergens for natural IgE-mediated immunosensitivity. Intolerance, a much more common condition, is any undesirable effect of eating a particular food, including gastrointestinal distress, gas, nausea, diarrhea, or other problems. Urticaria (hives), angioedema and even mild anaphylaxis are common reactions to various drugs, insect stings or bites, allergy shots, or certain foods, particularly eggs, shellfish, nuts and fruits. Physical allergies to ordinary stimuli such as cold, sunlight, heat, pollen, pet dander, or minor injury can produce itching, skin blotches, pimples, and hives.

3. Minor Physical Annoyances—In a world where most major medical maladies are readily treated, numerous minor medical conditions which today escape our notice will rise up from obscurity and present themselves annoyingly to our conscious minds, demanding attention. These conditions may be of several kinds. First is cosmetics, including small moles, freckles and blemishes on the skin; broken fingernails or unevenly-growing cuticles; minor skin reddenings or pimples; old childhood scars, wrinkled skin, birthmarks or stretch marks; unwanted hair growth in unusual places, or differential hair color or texture growing in patches; fingerprint patterns that are aesthetically unappealing; and mismatched leg lengths, hands with different left/right ring sizes, an asymmetrical face, or lopsided breasts. Second is minor aches and pains, which may include headaches; eyebrow hairs trapped in the eyeball conjunctiva; bent-hair pain (folliculalgia); dyspepsia; creaking limb joints and stomach growling; ingrown nails and hairs; earwax plugs and temporary tinnitis; chapped lips, canker sores and heat rashes; stuffy nose or gritty eyes upon rising in the morning; dermal chafing marks from elastic bands in clothing; minor flatulence; PMS (premenstrual syndrome); a leg or arm "falling asleep" in certain postures; nervous tics, itches, and twitches; uncracked knuckles, stiff neck, or backache; blocked middle ear following descent from high altitude; restless leg syndrome (akathisia); rotationally-induced dizziness, as on an amusement park ride; or rock-and-roll neck, wherein active musical performers or listeners bob their heads violently, rupturing small blood vessels in the neck. Third is minor physical or functional flaws, such as poor stream during male urination, female papillary leakage, colorblindness, snoring, unpleasant body odors, nosebleeds, declining visual or aural acuity, handedness (currently ~90% dextromanual, ~10% sinistromanual,^3136,3137 mild strabismus (eyeball misalignment), bad moods (neurotransmitter imbalances), or post-intoxication hangover.

4. Undiscovered Infectious Agents—Peptic ulcers once were thought to result from a stressful life, a purely natural response to a lifestyle choice. Then it was found that the major cause of ulcers is the presence of Helicobacter pylori bacteria in the stomach. Bacteria have been implicated in some cases of atherosclerosis²⁹⁷⁰ and Alzheimer's disease,²⁹⁷¹ and nanobacteria have been proposed as possible nucleation sites for kidney stones.²¹⁴⁹ Other seemingly natural but undesirable conditions may also be due to undiscovered microbial agents,³²³⁷ especially since bacteria outnumber tissue cells in our highly infested 20^th century bodies by more than 10:1 (Section 8.5.1).

5. Unwanted Syndromes—Syndromes are groups of related symptoms and signs of disordered function that define a disease whose cause remains unknown, that is, idiopathic. A good example is irritable bowel syndrome (IBS), which affects up to 20% of the adult U.S. population and includes symptoms of abdominal distention and pain, with more frequent and looser stools. Many are unaware they are afflicted. In 1998 there was no known cause or simple complete treatment for this still "natural" disease.^3713-3717 Even more mysterious than IBS is our general activity level—some people seem to have high-energy personalities, while others have more phlegmatic low-energy personalities. Either may be regarded as "natural," but nanomedicine can probably bring this ill-defined neurophysiological variable under human control. The need to sleep is another imperfectly understood syndrome. It is experienced by everyone and thus was universally regarded as "natural" in the 20^th century. Physiological short sleepers²¹²² were unusual, insomnia or asomnia³²⁷³ was thought of as an abnormal state, and there were a few anecdotal but medically undocumented instances of total nonsomnia, such as the celebrated case of Al Herpin.²³¹²

6. Psychological Traits—Psychological traits which, if identified by a patient as undesirable, might be subject to genetic or physiological modification could include: sexual preference (6-10% of the adult population is homosexual);¹⁶⁰⁴ shyness or boldness;²³³² acquisitive or altruistic propensity; misanthropy or philanthropy; theistic or atheistic orientation; loquacity or dourness; childhood imprinting; criminal propensity (up to 1-5% of the population); various recognized personality disorders that affect ~10% of the population²¹²² such as antisocial, paranoid, schizotypal, histrionic, narcissistic, avoidant, dependent, obsessive-compulsive, and passive-aggressive disorders; panic attacks (experienced at least once by ~33% of all adults each year);¹⁶⁰⁴ and phobic disorders such as social phobias (~13% of the population), specific phobias including fear of large animals (zoophobia), snakes (ophidiophobia), spiders (arachnophobia), needles (belonephobia,³²⁷² ~10%), the dark (noctiphobia or scotophobia), or strangers (xenophobia) (total ~5.7%), the fear of blood or hemophobia (~5%), agoraphobia (~2.8%),¹⁶⁰⁴ and other unusual phobias²²²³ such as the fears of certain colors (chromophobia), daylight (phengophobia), girls (parthenophobia), men (androphobia), stars in the sky (siderophobia), the number thirteen (triskaidekaphobia), and even the fear of developing a phobia (phobophobia).

The above sampling of minor afflictions, almost all considered "natural" in 1998, may come to be regarded as commonplace correctable medical conditions in the nanomedical era. By the time such petty annoyances are deemed worthy of immediate treatment, biotechnology and nanomedicine already will have defeated the most fearsome illnesses of the late 20^th century²³¹⁰ and will have moved on to other challenges.^{2311,2864,2973} Naturophiles may dissent, but the emerging trend from medical biotechnology is to characterize health, not as a static standard, but rather as a condition defined by the lives that people want to lead. Affirming the volitional normative model of disease (Section 1.2.2), Virginia Postrel concludes:²²⁹⁹

"Different goals will produce different choices about tradeoffs and standards. What makes a condition unhealthy is not that it is unnatural but that it interferes with human purposes. Revering nature [would mean] sacrificing the purposes of individuals to preserve the world as given. It [would require] that we force people to live with biological conditions that trouble them, whether diseases such as cystic fibrosis or schizophrenia, disabilities such as myopia or crooked teeth, or simply less beauty, intelligence, happiness, or grace than could be achieved through artifice. In a world where it's no big deal to take hormone therapy, Viagra, or Prozac, to have a face lift, or to know a child's sex before birth, a world in which even such radical interventions as sex-change operations and heart transplants have failed to turn society upside down, it is extremely difficult to argue that medical innovations are dangerous simply because they fool Mother Nature."

Changing View of the Human Body

How does a patient regard his or her own body, and how might this most intimate of all relationships change in the nanomedical era? The so-called dualist theory of the human compound, as originally developed by Descartes and widely accepted today by the ordinary person, holds that the human being consists of two separate kinds of thing: the body and the mind or soul. The body acts as a host or receptacle for the mind. The mind, often called "the ghost in the machine," is manifested by the brain, which it uses (via the bodily senses) to acquire and store information about the world and to integrate this with its genetically-driven imperative to live, thus resolving internal conflicts among action-choices and expressing these in what we (in our consciousness) experience as decisive action.

Scientific medicine has concentrated primarily on the body. The ancient Roman physician Galen first dissected and vivisected a variety of animals to increase his knowledge of anatomy and physiology, and dissection became increasingly important in the training of physicians and surgeons, and in painting and sculpture, during the Renaissance. By the late 20^th century, dissection had reached the molecular level, with the insides of the human cell and nucleus being taken apart and examined by molecular biologists, literally receptor by receptor. Dissection and the mechanistic understanding it provides have led some to decry what they regard as the modern "soulless" view of the human body as a mere machine.

In the nanomedical era, even the most diehard reductionist must come to see the human body not merely as a heap of parts but rather as a finely tuned vehicle that is owned and piloted by a single human mind. As with automobiles, some body-owners will be more diligent about maintenance, regular tuneups, and paint jobs than other body-owners. Some will crave the latest upgrades, while others may prefer a more conservative model that reliably gets them around town. At either extreme, all human vices and virtues will be on full display, though one may perhaps anticipate an increasing pride of corporeal ownership if for no other reason than because maintenance and repair will become quick, convenient, and inexpensive.

From this simple analogy of body-and-mind to car-and-driver, it might at first appear that the advent of nanomedical technology will confirm and strengthen the traditional dualist conception of the body. But closer inspection reveals that the analogy is at best incomplete, and at worst deeply flawed. This is because mind, first being necessarily embedded in physical structure and relying upon that structure for its faithful execution, and second, this physical structure now being manipulable at the molecular level, enters also into the purview of our mechanic. Both car and driver may be modified in the shop. Speaking allegorically, it is as if the driver, after getting his car a tuneup, emerges from the shop no longer favoring chocolate but enjoying vanilla instead, or now preferring jazz over classical, the opposite of before. Such psychological changes may be either volitional or emergent.

Until the late 20^th century, human progress was measured almost exclusively in terms of externalities. Food was gathered, then sown, then manufactured. Shelters had no running water, then gained outhouses, then indoor plumbing. Natural lighting and campfires gave way to candles, then oil lamps, then electric illumination. Finger-counting yielded first to the abacus, then the mechanical adding machine, and finally to the digital computer. But throughout all of history, the human body itself has remained largely untouched by progress. We have always regarded our bodies, evolved by natural selection, as fundamentally inviolate and immutable—subject perhaps to various natural or traumatic degradations, but rarely to any significant intrinsic improvement on the timescale of human civilization.

Now we are set to embark upon an era in which our natural physiological equipment may for the first time in history become capable of being altered, improved, augmented, or rendered more comfortable or convenient, due to advances in medical technology. The physical human body may be one of the last bastions of "naturalness" (Section 1.3.4). It will also be one of the last elements in our common worldview to be modernized.

Our subjective experience of reality will shift by subtle degrees. For instance, all objective information about our physical surroundings has traditionally arrived in the conscious mind via the various natural senses such as hearing, sight, and smell. In the nanomedical era, machine-mediated sensory modalities may permit direct perception of physical phenomena well removed from our bodies in both time and space, or which are qualitatively or quantitatively inaccessible to our original natural senses. Perception will gradually expand to incorporate nonphysical phenomena including abstract models of mental software, purely artificial constructs of simulated or enhanced realities,²⁹⁹¹ and even the mental states of others. Such new perceptions will inevitably alter the way our minds process information.

But the winds of change will sweep deeper still, into our very souls. Like ants oblivious to the collective purpose of their colony, the billions of neurons in the human brain are all busily buzzing, wholly ignorant of the emergent plan. This is the physical, mechanical world of our electrochemical hardware. People also have thoughts, feelings, emotions, and volitions, a higher level in the data processing hierarchy which in turn is equally oblivious of the brain cells. We can happily think while being totally unaware of any help from our neurons. But nanomedicine will give us unprecedented systemic multilevel access to our internal physical and mental states, including real-time operating parameters of our own organs, tissues, and cells, and, if desired, the activities of small groups of (or even individual) neurons. Diverse parts of our selves previously closed to our attention may slowly conjoin and enter our conscious awareness.

Will this access promote an integrated identity or lead to hopeless confusion, or worse? Marvin Minsky, in his collection of essays The Society of Mind,²⁹⁸² persuasively argues that our selves or identities are in fact networks of semiautonomous neurological "agencies" which sometimes cooperate and sometimes compete with one another. We think of ourselves as singular "persons," but we also experience "conflicting desires" and "differing viewpoints" within our minds that are, in Minsky's view, a direct experience of the multiplicity of our brain's neurostructures. Other models of the human mind^{2988-2990,3728} suggest that our internal mental states, prospectively transparent via nanomedical augmentation,^2992,2993 are diverse and intricate; Julian Jaynes²⁹⁸³ is one of many writers who have drawn attention to profound dichotomies between the two cerebral hemispheres. The component-oriented personality models of Freud (e.g. ego/id/superego),²⁹⁸⁴ Jung (e.g. archetypes),²⁹⁸⁵ and Rank (e.g. will/counterwill),²⁹⁸⁶ and the identification of 4541 distinct personality traits by Allport and Odbert²⁹⁸⁷ warn us that full access to our brain's architecture could be perilous.

More seriously, most of us suppose that we are endowed with free will. But if choices by free will are simply the resolution of conflicts of neurological subsystems, and we become consciously aware of those subsystems and are able to intervene in their processes, do we run the risk of runaway instabilities at the deepest levels of what we presently call our "minds"? Will we find that these instabilities are profound counterparts to the maladies we currently designate as epilepsy, or psychosomatic illnesses? In any redesigns of our brains which would involve opening doors to, quite literally, the ultrastructure of our thoughts, we could become "naked to ourselves" in ways that we can only vaguely speculate about at present. Along with any other dangers we might encounter, this will raise entirely new issues of the proper role of psychotherapy and the sanctity of personal privacy.²⁹⁹⁶

Repairs to the brain may be carefully monitored to ensure quality control and to verify intended results, as already proposed in another context.³⁰⁰⁰ Major modifications might be strictly regulated, both to prevent abuse by unscrupulous third parties and also to forestall accidental or volitional alterations that could render the patient a significant threat to society. Nanomedical alterations to the brain and other physical systems may give us vastly expanded freedom to be who we choose to be (Section 1.3.4), along with increased responsibility to make wise and informed choices. The ethical and legal aspects of these questions, as well as the scientific and psychological ones, are extremely important and should be thoroughly debated in the years and decades that lie ahead.

Additional related links:

www.foresight.org/Nanomedicine

www.foresight.org/Nanomedicine/Gallery/index.html

' 1996-2003 Robert A. Freitas, Jr. Reprinted with permission.