This article talks about important problems in medicine that scientists have not yet solved. Many of these problems involve understanding how drugs work and diseases that have no known cause, which are called idiopathic diseases.

Definition of "disease"

There is no single, clear definition of what a disease is. One approach focuses on scientific details, such as how the body works during illness. Another approach considers how a person feels physically or emotionally and how their daily life is affected. These two views do not always agree and may even conflict.

For example, when a person visits a doctor with a severe flu, the doctor focuses on the symptoms, such as fever and cough, rather than the specific virus causing the illness. In contrast, some people with hemochromatosis (a condition where the body stores too much iron) may not feel sick or notice changes in their daily life, even though the disease can be serious and deadly if not treated. Similarly, early stages of some cancers, like pancreatic cancer, may not cause symptoms, making it harder for patients to seek help in time.

Cultural beliefs can also influence how diseases are defined. For example, erectile dysfunction was once not considered a disease, even though it caused problems for some people. However, after treatments became available, it was reclassified as a medical condition.

Mental health conditions add more complexity. Depression and anxiety cause strong emotional pain for the person affected but do not harm others. In contrast, conditions like narcissistic personality disorder or impulse-control disorder may not cause the person to feel pain, but they can harm relationships and affect others around them.

There is also discussion about whether certain uncommon or socially sensitive behaviors should be considered diseases. These behaviors may not cause pain to the person or harm others, such as some traits of autism spectrum disorder (like repetitive actions or unusual sensory preferences) or behaviors considered "inappropriate" by society.

A "wastebasket diagnosis" is a term used for conditions where the cause is not clearly understood. These diagnoses are sometimes used to help insurance companies cover treatments that may help a person feel better or manage symptoms. Whether such conditions are officially classified as diseases is still debated. An example is fibromyalgia, a condition diagnosed based on widespread muscle pain with no clear cause.

Evidence-based medicine

Evidence-based medicine (EBM) is now the main approach used in medical care and research. However, some people still discuss how findings from studies with many patients can be used for individual patients.

Psychiatry and psychology

Manuals like the Diagnostic and Statistical Manual of Mental Disorders (DSM) help define mental illnesses, but some disorders still have unreliable diagnoses. For example, when diagnosing dementia, experts often agree, with a reliability score of 0.78. However, for major depressive disorder, experts may disagree more, with a reliability score of only 0.28.

Some mental illnesses, such as paraphilias, compulsive sexual behavior, and personality disorders, are still partially defined by cultural or societal norms, rather than by harm to an individual’s health. For example, the DSM once classified homosexuality as a mental illness, but the American Psychiatric Association changed this in 1973. Richard Green, in a review about pedophilia, stated that psychiatry should focus on treating unhealthy mental processes, not on cultural, moral, or legal issues.

Textbooks like the DSM are often written by Western authors, which makes it difficult to create definitions of mental illnesses that are neutral across all cultures. Newer editions of the DSM mention how cultural differences can affect symptoms, such as long periods of mourning being linked to depression in some cultures but not others. However, including cultural factors in diagnosis is seen as a political choice, not a scientific one. The Western focus in defining mental illnesses also creates a blind spot: manuals rarely explain how Western lifestyles or cultures might influence or hide mental illness symptoms.

In other areas of medicine, patients with certain conditions are referred to specialists based on the cause of their illness. For example, a patient with paralysis caused by cancer in the spinal cord is treated by an oncologist, while a neurologist might be a secondary option. Similarly, kidney problems caused by heart issues are treated by a cardiologist. In psychiatry, however, grouping mental disorders by their cause remains a challenge. Textbooks and manuals instead group disorders by symptoms, which may make it harder to find effective treatments. This approach is sometimes compared to a birdwatcher’s guide: it helps identify birds but does not explain why certain species live in specific areas.

It is also debated how medications help patients. Some believe they fix chemical imbalances in the brain, while others think they improve quality of life or manage symptoms without addressing the root cause. For example, using drugs that reduce sexual desire to treat unwanted paraphilias may suppress the behavior entirely, rather than changing it to something more acceptable.

Diseases with unknown cause

There are many diseases for which the causes are not known. Some diseases have causes that are completely or partly understood, but treatments that work well are not yet available.

The term "idiopathic" is used in medicine to describe diseases whose causes are not known or seem to appear without a clear reason. Examples of idiopathic diseases include idiopathic pulmonary fibrosis, idiopathic intracranial hypertension, and idiopathic pulmonary haemosiderosis. Another example is aggressive periodontitis, a condition that causes quick bone loss around teeth and may require tooth removal. The cause of this condition is still unknown.

Mechanisms of action

Sometimes, scientists do not know exactly how drugs work. They can study how genes are active in a model organism, such as a mouse or fruit fly, to find out which genes are blocked by a drug. This information helps them learn more about the drug's effects. One example of a drug with an unknown mechanism is general anesthesia. Other examples include paracetamol, antidepressants, and lithium. Even if a drug is known to affect a specific process, like how serotonin is moved back into a nerve cell, it may still be unclear how this process helps improve symptoms that people experience.