List of unsolved problems in medicine

Short description: Notable unsolved problems in Medicine

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This article discusses notable unsolved problems in medicine. Many of the problems relate to how drugs work (the so-called mechanism of action), and to diseases with an unknown cause, the so-called Idiopathic diseases.

## Contents

* 1 Definition of "disease"
* 2 Evidence-based medicine
* 3 Psychiatry and psychology
* 4 Diseases with unknown cause
* 5 Mechanisms of action
* 6 Gates Foundation Grand Challenges
* 7 References

## Definition of "disease"

There is no overarching, clear definition of what a disease is. On one hand, there is a scientific definition which is tied to a physiological process, and on the other hand, there is the subjective suffering of a patient and the loss of his or her life quality. Both approaches do not need to match, and they can even be contradictory.

For example, when a patient seeks medical help because of a severe flu, the doctor will not care about the specific virological and immunological process behind the clearly visible suffering. This is contrasted by many hemochromatosis patients who will neither see suffering nor a change in his life quality, while the disease-causing process is severe and often deadly if left untreated. Similarly, many cancers in their very early stages are asymptomatic (e.g. pancreatic cancer) and the patient still feels healthy, which delays seeking treatment.

Sometimes, cultural factors also play a role in defining "disease". Erectile dysfunction was long seen as a negative but non-pathological state. The introduction of effective treatments has led to its acceptance as a disease.[1]

Even more difficulties arise when it comes to mental disorders. Depressions and anxiety disorders cause significant subjective suffering in the patient, but do not harm third persons. On the contrary, a narcissistic disorder or an impulse-control disorder does not cause any suffering in the patient, though the maintenance of healthy interpersonal relationships will be affected, and third persons can be harmed. There is also debate on whether non-normal behavior like paraphilias should be classified as a disease if they neither cause subjective suffering in the patient, nor endanger third persons.

## Evidence-based medicine

Evidence-based medicine (EBM) has become the central paradigm in medical practice and research. However, debate continues around EBM and about how results obtained from large samples of patients can be applied to the individual.[2][3][4][5]

## Psychiatry and psychology

Lack of reliable diagnoses in some disorders

Though manuals like the DSM have covered a lot of ground when it comes to defining mental illnesses, in some disorders the reliability of diagnosis is still very poor. For example, inter-rater reliability in cases of dementia is very high, with a kappa value of 0.78, while major depressive disorder is often diagnosed differently by independent experts who see the same patient, with a kappa value of just 0.28.[6]

Cultural issues in defining mental disorders

Some mental illnesses like paraphilias are still defined by societal and cultural norms, rather than putting the individual's well-being in focus. For example, DSM defined homosexuality as a mental illness, until the American Psychiatric Association decided otherwise in 1973. As Richard Green pointed out in a review on pedophilia, psychiatry should identify unhealthy mental processes and treat them, and not focus on cultural norms, moral questions or legal issues.[7]

As textbooks and handbooks like DSM are usually written by Western authors, a culturally neutral definition of mental diseases is an unsolved problem. Though newer editions of the DSM “respect” non-Western cultures by mentioning culture-specific symptom presentations (e.g. a very long time of mourning is regarded as a sign of depression in some cultures, but not in others), the inclusion of cultural factors into diagnostic criteria is seen as a political decision, but not a scientifically founded one. The Western viewpoint when defining mental illnesses also creates a cultural blind spot: Manuals rarely discuss how our own Western lifestyle and culture modifies or hides symptoms of mental illnesses.[8]

Still no causal classification of mental disorders

A patient with a paralysis is referred to an oncologist if the condition is caused by a cancer metastasis in the spinal cord; a treatment by a neurologist is a secondary consideration. Likewise, renal insufficiency is sometimes caused by heart problems, and the treatment is thus led by a cardiologist. In psychiatry, however, grouping mental disorders by their cause is still an unsolved problem. Psychiatric textbooks and manuals cluster disorders by symptoms, which is thought to impede the search for effective treatments. This has been compared to an ornithologist's field guide: It allows you to identify birds, but it does not tell you why a species exists in biotope A but not B.[9]

## Diseases with unknown cause

Idiopathic is a descriptive term used in medicine to denote diseases with an unknown cause or mechanism of apparent spontaneous origin.[10] Examples of idiopathic diseases include: Idiopathic pulmonary fibrosis, Idiopathic intracranial hypertension, and Idiopathic pulmonary haemosiderosis. Another example is that the cause of aggressive periodontitis – resulting in rapid bone loss and teeth in need of extraction – is still unknown.[11]

## Mechanisms of action

It is sometimes unknown how drugs work. Often it is possible to study gene expression in a model organism, and determine the genes that are inhibited by a certain substance, and make further inferences from this data. A classical example of an unknown mechanism of action is the mechanism of general anesthesia. Other examples are paracetamol, antidepressants and lithium.

## Gates Foundation Grand Challenges

Main article: Organization:Grand Challenges In Global Health

On 26 January 2003, Bill & Melinda Gates Foundation made available $200 million for a medical research initiative on "Grand Challenges in Global Health". The initial list were:[12]

> To improve childhood vaccines:

>   * GC 1: Create effective single-dose vaccines that can be used soon after birth;
>   * GC 2: Prepare vaccines that do not require refrigeration;
>   * GC 3: Develop needle-free delivery systems for vaccines.

> To create new vaccines:

>   * GC 4: Devise reliable tests in model systems to evaluate live attenuated vaccines;
>   * GC 5: Solve how to design antigens for effective, protective immunity;
>   * GC 6: Learn which immunological responses provide protective immunity.

> To control insects that transmit agents of disease:

>   * GC 7: Develop a genetic strategy to deplete or incapacitate a disease-transmitting insect population;
>   * GC 8: Develop a chemical strategy to deplete or incapacitate a disease-transmitting insect population.

> To improve nutrition to promote health:

>   * GC 9: Create a full range of optimal bioavailable nutrients in a single staple plant species.

> To improve drug treatment of infectious diseases:

>   * GC 10: Discover drugs and delivery systems that minimize the likelihood of drug-resistant microorganisms.

> To cure latent and chronic infections:

>   * GC 11: Create therapies that can cure latent infections;
>   * GC 12: Create immunological methods that can cure chronic infections.

> To measure disease and health status accurately and economically in poor countries:

>   * GC 13: Develop technologies that permit quantitative assessment of population health status;
>   * GC 14: Develop technologies that allow assessment of individuals for multiple conditions or pathogens at point-of-care.

## References

1. ↑ Chiong, Winston (2001). "Diagnosing and defining disease". JAMA. doi:10.1001/jama.285.1.89-JMS0103-2-1.
2. ↑ Kulkarni, Abhaya V. (2005). "The challenges of evidence-based medicine: A philosophical perspective". Medicine, Health Care and Philosophy 8 (2): 255–260. doi:10.1007/s11019-004-7345-8. PMID 16215804.
3. ↑ Greenhalgh, Trisha (2012). "Why do we always end up here? Evidence-based medicine's conceptual cul-de-sacs and some off-road alternative routes". Journal of Primary Health Care 4 (2): 92–7. doi:10.1071/HC12092. PMID 22675691. https://www.researchgate.net/publication/225276822.
4. ↑ Wieringa, Sietse; Engebretsen, Eivind; Heggen, Kristin; Greenhalgh, Trish (2017). "Has evidence-based medicine ever been modern? A Latour-inspired understanding of a changing EBM". Journal of Evaluation in Clinical Practice 23 (5): 964–970. doi:10.1111/jep.12752. PMID 28508440.
5. ↑ Loughlin, Michael; Lewith, George; Falkenberg, Torkel (2013). "Science, Practice and Mythology: A Definition and Examination of the Implications of Scientism in Medicine". Health Care Analysis 21 (2): 130–145. doi:10.1007/s10728-012-0211-6. PMID 22622355.
6. ↑ Freedman, Lewis (2013). "The Initial Field Trials of DSM-5: New Blooms and Old Thorns". American Journal of Psychiatry. doi:10.1176/appi.ajp.2012.12091189.
7. ↑ Green, Richard (2002). "Is pedophilia a mental disorder?". Archives of Sexual Behavior. doi:10.1023/a:1020699013309. PMID 12462476.
8. ↑ Widiger, T. (2000). "Adult Psychopathology: Issues and Controversies". Annual Review of Psychology. doi:10.1146/annurev.psych.51.1.377.
9. ↑ "Striving for Coherence: Psychiatry's Efforts over classification". JAMA. 2005. doi:10.1001/jama.293.20.2526. PMID 15914753.
10. ↑ Martin, Elizabeth A. (2010). "Idiopathic". Concise Medical Dictionary (8th ed.). doi:10.1093/acref/9780199557141.001.0001. ISBN 9780199557141. http://www.oxfordreference.com/abstract/10.1093/acref/9780199557141.001.0001/acref-9780199557141-e-4863?rskey=FABEbD&result=5295. Retrieved 2019-01-04.
11. ↑ Clark, Danielle. "Aggressive periodontitis: The unsolved mystery". Quintessence International. doi:10.3290/j.qi.a37387. http://www.quintpub.com/userhome/qi/qi_48_2_clark_p103.pdf.
12. ↑ Varmus, H.; Klausner, R.; Zerhouni, E.; Acharya, T.; Daar, A. S.; Singer, P. A. (2003). "PUBLIC HEALTH: Enhanced: Grand Challenges in Global Health". Science 302 (5644): 398–399. doi:10.1126/science.1091769. PMID 14563993.

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