Ideas of health, its pathogenesis, and disease have radically evolved  throughout the history of medicine right up to the emergence of modern  evidence-based medicine. Yet, in each period of medical culture, the  consultation of those in pain with those offering a cure was the  prototypical medical encounter. The hope for a cure, a renewed absence  of disease, is still one of the central legitimizing forces in the  project of medicine. The promise of a cure inspires hope in patients and  motivates doctors and researchers. But is it really a useful concept  for guiding medical research and assessing the success of medical  treatment?

The idea of a cure is simple enough to be useful irrespective of  different concepts of health and disease. Whether disease is understood  as divine punishment, an imbalance of internal processes in the form of  humours, an external entity, a germ, or an aberrant internal process,  the cure is the promise of resolution. Its apparent ahistorical character and indifference to other conceptual frameworks within which  it operates, seems to empty the idea of much concrete content. But the  cure cannot be understood as a vacuous placeholder for what is deemed  medical success at a given time. It is surprisingly a deeply problematic  concept within the framework of modern medicine.

Precision

The precision of modern medicine in localizing or mapping disease  processes in the body presents a serious challenge to our common sense  idea of the cure. In a popular understanding, modern medicine arose from  increasing knowledge of the spatial constitution of the body (anatomy),  the many systems encapsulated within this for maintaining homeostasis  (physiology), and the role disease plays in disturbing them (pathology).  Elucidations of the chemical interactions explaining many of these  features (biochemistry and molecular biology) and the information coding  for the molecular constituents of the body (genomics) have arisen much  more recently. By fracturing the body into ever smaller constituent  parts, the physical substrate of a person can increasingly be described  with precise numbers and measures, and denoted on a minute scale.

Whether it is the voxels of the MRI machine, the specific folding  pattern of a crucial protein, the base pair composition of our DNA or  its methylation pattern, the number of parts the body can be divided  into is ever increasing. At each level, the medical sciences ask two  questions: “Does this explain the pathology of the disease experienced  by a person” and “If we were to inhibit, replace or enhance this  process, would it cure the disease?” A causal link is established  between the person sitting before me in a hospital gown, in pain,  discomfort or mortifying anxiety, and an object unimaginably small. Most  diseases in this light are not unified entities anymore, but radically  dispersed through the body.

Dispersal and heterogeneity

Dispersal itself is not a new problem in describing disease entities.  For a long time we have understood that colonies of microorganisms—e.g.  bacteria living in tissues that cannot tolerate their presence—cause  pathology. However, their susceptibility to strong therapeutic agents  such as antibiotics made them appear to be a single entity. If we can  find their weak spot, target something specific to them and not present  in us, their dispersal would not pose a problem in combating them. This  magic bullet theory of pharmacological treatments still captures the  public imagination. If we think of a future cure, we hope it will be  like the antibiotics: taken for a brief time and followed by a swift  return to health with no lasting impairment.

The importance we placed on antibiotics as the prototypical drug  stands in stark contrast to the huge crises antibiotics face today. The  last major class of antibiotics was discovered three decades ago[i]  and many pharmaceutical companies have shut down research into new  antibiotic agents. This is partially due to the hope for more profitable  drugs for other diseases, but also to our understanding that bacterial  colonies cannot only disperse through the body but display radical  heterogeneity. Bacteria possess a plethora of methods to exchange  genetic information, both intragenerational and intergenerational,  allowing them to quickly propagate effective methods to combat  antibiotics throughout a colony.[ii]  Heterogeneity, or greater genetic flexibility, led to the eventual  emergence of antibiotic resistance. This inevitability is the true  crisis in antibiotic research. But is this only a problem with this  specific type of cure? Or does it point to a more fundamental problem  with the idea itself?

The problem

Dispersal and heterogeneity of the disease entity are compounded by  the precision of our body maps. As we dig deeper into the undergrowth of  molecular biology, we can map out the normal and pathological in ever  greater detail. But this precision entails an increase in entities that  can be identified as normal or pathological. If to be cured means an  absence of the disease-causing entity—in contrast with remission, a  temporary diminution in severity—we are increasingly faced with a  situation in which the number of points to be sampled exceeds practical  means. Establishing an absence is statistically difficult if we deal  with a complex object like the body, divided into many different  compartments, with many different tissues made up of even more  specialized cells. Furthermore, the heterogeneity of the pathological  entity makes it incredibly difficult to map it in its entirety.   Paradoxically, increasing precision, or a higher resolution of our body  maps, makes the ascertainment of a cure ever more difficult as it  increases the number of entities to be sampled.

This heterogeneity also plays a role in the identification of  infectious agents and the effectiveness of our drugs against them. It is  a greater problem for ascertaining the cure of many non-infectious  diseases. Cancer, for example, is now understood to be a principally  genetic disease, which commonly develops over a lifetime through the  gradual accumulation of mutations.[iii]  As there are many innate safeguards against carcinogenesis a large  number of genetic “hurdles” need to be overcome before a tumor becomes  pathological. (Strongly hereditary cancers occurring early in life  represent a relatively rare exception to this model.) A tumor is not  necessarily a genetically homogenous mass of cells, but is likely to  include a larger number of cells with different mutations and  properties. As mutagenesis is one of the hallmarks of cancer,[iv]  a clear identification of what is normal and pathological may not be  easily achieved, especially if genetic changes have no simple phenotypic  expression. Although the genome is constantly being repaired, we now  understand that it is not a static blueprint that is simply read out.  Many levels of control modifiable by environmental factors play an  important role determining the constituents of the body.[v]  Hence, the normal is itself in flux, even if we were to assume that  change occurs only at the epigenetic and regulatory level.  This  heterogeneity and our inability to clearly delimit the boundaries of the  normal and pathological within this, represent an additional level of  complexity when trying to diagnose a cure.

An additional problem for the cure is that scientific tests have  error bars and varying sensitivity to what they are meant to establish.   Absence must always be described as falling below the lowest detectable  level. As a result we can only ever estimate the presence of absence  rather than ascertain it with any precision. The precision with which  the body is mapped in the life sciences and the more limited techniques  of clinical practice, may mask this to a certain extent. It is the  absolute nature of the cure that makes the concept extremely difficult  to delineate precisely in scientific medicine.

Some may want to argue that the modern notion of a cure already  incorporates these epistemological problems of scientific medicine. In  HIV research[vi],  for example, a distinction exists between the development of a  functional and a sterilizing cure. A functional cure describes the  ability of a patient to discontinue antiretroviral therapy without  suffering any adverse consequences. A sterilizing cure describes the  complete eradication of the HIV virus from the body. The idea of a  functional cure allows us to declare someone cured without knowledge  about the exact localization of the virus. Does it matter that we are  unable to ascertain an absence of the virus, if we can describe someone  as functionally cured?

A functional cure

HIV infection is a peculiar disease insofar as most patients  experience a long period following initial infection during which they  display no symptoms. The virus is present in their blood, they are  infectious to others, but it is only when a sufficient number of CD4+  lymphocytes have been depleted, that AIDS manifests itself as a  drastically diminished ability to fight common infections. Being cured  of HIV therefore would mean to be certain not to be infectious to others  and assurance that AIDS will not develop. The cure is essential not for  relieving acute symptoms, but for quelling the potential to develop the  disease.

HIV infection is diagnosed by the number of infectious HIV copies or,  more commonly, by the presence of specific antibodies to the virus. [vii]  The HAART drug regimen, a cocktail of potent antiretrovirals, is highly  effective in reducing the number of HIV copies to a level where they  are practically undetectable.  However, these patients are not  considered to be functionally cured, since a cessation of the drug  regimen results in a rapid rebound of the HIV copies in the blood. This  is believed to be due to the presence of latently infected cells that  are capable of producing new HIV copies. Latent infection means that  HIV, as a retrovirus, inserts its own genome into the host cell’s  genome, where it may or may not be expressed to produce the functional  virus particle. Cells that do not express the virus are not easily  identifiable by the immune system and present a reservoir from which new  viral particles can be generated when reactivated. This is complicated  by the fact that the mechanism HIV uses to insert itself into the host  genome is highly error-prone, accounting for the heterogeneity of the  virus. A complete cure, then, necessitates the eradication of the virus  particles from the blood stream and, critically, the destruction of all  HIV genome sequences capable of producing new virus particles. The  dispersal of the infection and the heterogeneity of the target may serve  as theoretical explanations for why a HIV cure has remained elusive.

A number of functional cures have now been reported, where patients  have ceased to take drugs and have not experienced a rebound in the  number of HIV copies in their blood. In the famous case of the  “Mississippi baby”[viii],  a neonate was infected during birth, but a high dose of antiretroviral  drugs was administered within 30 hours. Antiretroviral medication was  continued until the 18th month, when therapy was interrupted by the  mother for unknown reasons. Five months later, the mother returned with  the child, but HIV was no longer detectable in the girl’s blood. After  several tests and continued observation the patient was declared to be  functionally cured. Unfortunately, during more recent tests the virus  was again detected in the blood, overturning the belief that the girl  was effectively cured by the high dose of antiretroviral drugs following  birth.

The idea of a functional cure does not capture our expectations of  what it really means to be ‘cured’. If being HIV positive is about the  potential to infect others and the development of AIDS in the future, a  functional cure cannot provide certainty without ascertaining an  inability of HIV to replenish itself in the future. As there are no  symptoms to relieve, a functional cure is unlikely to alleviate anxiety  about the potential to develop the disease and infect others.

Susan Sontag said that “everyone who is born holds dual citizenship in the kingdom of the well and in the kingdom of the sick.”[ix]  The cure is the implicit promise of returning to a previous life to  join the perpetually healthy. However, these cultural connotations rely  on the ability to give a certain diagnosis with the precise tools of  modern medicine. If the conceptual problems the cure faces cannot be  resolved, the cultural promise cannot be fulfilled. What does this mean  for the idea and possibility of medicine without the promise of a cure  at its center?

New norms

“In any case no cure is a return to biological  innocence. To be cured is to be given new norms of life, sometimes  superior to the old ones.”

— Georges Canguilhem, The Normal and  Pathological, [x]

The promise of a cure inspires hope in patients and motivates doctors  and researchers. Should we dismiss the idea because of an  epistemological technicality in spite of its apparent social utility? At  this point it is important to note that I have not tried to make  predictions about the future. It is likely that more cures will be  developed and I make no attempt to dismiss the great achievement this  represents. The question posed here is whether the cure represents a  useful concept in guiding medical research and assessing the success of  medical treatment. The focus on the cure, given that it has become a  concept with a very fuzzy operational definition, has many negative  consequences.

The promise of the cure divides patients into those with curable and  incurable diseases, or more conventionally into those with acute and  chronic conditions. For those deemed incurable, the chronically ill,  there is only the promise that further medical research, by developing a  cure, will let them break out of their condition. The number of the  chronically ill is increasing, whether from high blood pressure,  diabetes, psychiatric conditions or incurable cancer. The increasing  number of elderly patients suffering from a number of co-morbidities is  likely to increase even more, with little hope that medicine will return  them to perfect health.[xi]  It is not possible to generalize the experience of chronic illness, the  different expectations and anxieties a patient may develop.  Nevertheless, how we conceptualize disease and, conversely, the  possibility of a resolution, impacts the way treatment is administered.  Many doctors may resign to the fact that most treatment is not curative  and may be reluctant to declare a patient cured. Yet ‘the cure’ remains  at the center of medical culture and may distort priorities for patients  and doctors alike in trying to find a solution. How many patients seek  out or receive excessive and unnecessary treatment for the abstract  promise of being cured?

If the cure is a problematic concept within modern medicine, other  ways for patients to conceptualize their own situation may arise. For  medicine as a whole, the withering away of the promise of the cure could  open up new avenues to organize the encounter between patient and  doctor. Rather than seeing the inability to treat a patient as a failure  and nuisance to be rectified by medical progress, we may be able to  redefine medical progress by returning the cure to its etymological  root.

cure |kjʊə, kjɔː|

verb [ with obj. ]

ORIGIN Middle English (as a noun): from Old French curer (verb), cure  (noun), both from Latin curare ‘take care of’, from cura ‘care’. The  original noun senses were ‘care, concern, responsibility’, in particular  spiritual care […]. In late Middle English the senses ‘medical care’  and ‘successful medical treatment’ arose, and hence ‘remedy’.[xii]