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Every disease is a rare disease: How to make personalized medicine work (in theory).

Tags personalized medicine
By: Rafael Najmanovich  
October 17 2012


A comment on the formidable BMJ blog entry by Richard Smith: Stratified, personalised, or precision medicine

There is no such thing as a disease, what exists is a person that is unhealthy (leaving the definition of healthy for the reader to decide). Luckily, many such states of unhealthiness in different people present varying levels of similarities at all scales, from general physiological similarities (coughing is common to unhealthy conditions caused by many different sources) to specific molecular causes (sickle cell anemia, one specific SNP in the beta-Globin gene). At some level of specificity and selectivity of similarities, a 'disease' can be defined. Just like we understand that there are differences in the causative agent of a disease (for example multiple variants of the flu virus) and these differences can affect treatment options, there are also multiple differences among the people afflicted by a condition. Well, it takes two to tango, isn't it?

By definition, the more complex a disease is, the more it is affected by multiple factors and therefore, the more it will depend on individual differences among the people afflicted. As our technology improves with personal genomes and in the future hopefully personal transcriptomes and proteomes, it shall be possible to recognize that every disease is personal, not just from a sociological and psicological point of view, but from a causative point of view. As expected, commonalities between people and diseases mean that different conditions can be understood using model systems, others can only be understood and treated in a unique way in humans, others still may harbour crucial differences between ages or genders or particular human populations. There is a continuum of different levels at which particular conditions can and should be understood and then treated. In many cases we don't yet know that we are grouping together people that shouldn't be treated the same. As our knowledge of their differences vis-a-vis disease states increases, we shall be able to split these common groups and treatment forms.

The economic difficulties facing personal medicine have been very well described in the blog post above. What I want to suggest here is that as we better understand the differences above, the bottleneck will be regulatory and ethical issues regarding human trials.

As an extreme case, imagine some disease today recognized as rare afflicting one single patient in the world. Lets say that some research group has the will and the means to develop a new therapy for that. Well, if I was the patient, and if my condition meant that my quality of life would be worst without intervention as it could be taking in consideration the potential risk of undergoing treatment, well, I would do it. The same is already true in other areas of medicine, patients often weight the risks vs benefits of complicated, dangerous and often unproven/little-useful surgical procedures. So why not do that with the development of novel therapeutic procedures that are a little more sophisticated than a knife?

It turns out that we already do that for terminal diseases based on compassionate grounds with FDA's nod of approval. But why not extend that to other non-terminal conditions?

In an imaginable future we will have access to the full extent of all the 'omic' (genomic, transcriptomic, epigenetic, proteomic, etc) particularities of an individual, and with time we will learn more and more how these relate and affect the entire system with the integration of structural and systems biology methods. It may sound far fetched but it is not, the technology exists and every human is a finite, although perhaps ever changing, machine.

As the number of biological molecules is finite, the number of interactions between biological molecules is also finite. Can we envision a situation in which we are capable of intervening in a safe way on a single molecular interaction at a time?

As we approach this imaginable future and we learn more and more that each disease is unique to its bearer, we will need to test novel therapeutics in smaller samples, that will unlikely be applicable to other groups of people in the future. How can we test these therapies? Clinical trials will not give clear answers any longer due to the lack of proper controls and small samples. What will be necessary is first and foremost, ensure that toxicity is acceptable for any proposed therapy. After that, well, its a clinical trial with one patient at a time. Like in the old, old, old times...

Comment added on Oct 23: This link shows how we can move on to more personalized medicine with extra investments. There is a wealth of data waiting to be discovered in previous unsuccessful clinical trials.



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