Nanomedicine, Volume I: Basic Capabilities

© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999


1.2.2 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 -- A disease is whatever physicians say is a disease. This approach avoids understanding and forestalls inquiry, rather than furthering it.

2. Disease Relativism -- A disease is identified or labeled in accordance with explicit or implicit social norms and values at a particular time. In 19th century Japan, for example, armpit odor was considered a disease and its treatment constituted a medical specialty. Similarly, 19th-century Western culture regarded masturbation as a disease, and in the 18th century, some conveniently identified a disease called drapetomania, the"abnormally strong and irrational desire of a slave to be free."2205 Various non-Western 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 ofdisease 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 -- A 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 20th 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 -- Disease 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 -- Diseases 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 19th century scientific theory was either rejected or highly modified in the 20th 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 19th century obsession with constipation was reflected in the disease labelled "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 -- Disease 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.* 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 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

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.* 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).

* 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 -- a 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

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."


Last updated on 5 February 2003