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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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February 12, 2013

Do We Really Know the Cause for Over 4500 Diseases?

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Posted by Derek

Since I mentioned the NIH in the context of the Molecular Libraries business, I wanted to bring up something else that a reader sent along to me. There's a persistent figure that's floated whenever the agency talks about translational medicine: 4500 diseases. Here's an example:

Therapeutic development is a costly, complex and time-consuming process. In recent years, researchers have succeeded in identifying the causes of more than 4,500 diseases. But it has proven difficult to turn such knowledge into new therapies; effective treatments exist for only about 250 of these conditions.

It shows up again in this paper, just out, and elsewhere. But is it true?

Do we really know the causes of 4,500 diseases? Outside of different cancer cellular types and various infectious agents, are there even 4,500 diseases, total? And if not, how many are there, anyway, then? I ask because that figure seems rather high. There are a lot of single-point-mutation genetic disorders to which we can pretty confidently assign a cause, but some of them (cystic fibrosis, for example) are considered one disease even though they can be arrived at through a variety of mutations. Beyond that, do we really know the absolute molecular-level cause of, say, type II diabetes? (We know a lot of very strong candidates, but the interplay between them, now, there's the rub). Alzheimer's? Arthritis? Osteoporosis? Even in the cases where we have a good knowledge of what the proximate cause of the trouble is (thyroid insufficiency, say, or Type I diabetes), do we really know what brought on that state, or how to prevent it? Sometimes, but not very often, is my impression. So where does this figure come from?

The best guess is here, GeneMap. But read the fine print: "Phenotypes include single-gene mendelian disorders, traits, some susceptibilities to complex disease . . . and some somatic cell genetic disease. . ." My guess is that a lot of what's under that banner does not rise to "knowing the cause", but I'd welcome being corrected on that point.

Comments (22) + TrackBacks (0) | Category: Biological News


1. barry on February 12, 2013 1:28 PM writes...

although "cancer cellular types" are still defined by the FDA as different disease, even Richard Pazdur (head of oncology, FDA) acknowledges that that's an historical accident and that they need to move to defining cancers by the driving biology.

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2. Glue on February 12, 2013 1:53 PM writes...

What constitutes knowing the cause of a disease?

I do not think that breaking everything down to molecular interactions is a reasonable goal but, as a chemist, I have a hard time looking elsewhere.

Even if we had Star Trek tech and could trace the onset of a patients cancer to a single DNA LMDS from wayward stream of radiation, that's not fantastically useful for treatment or satisfactory explanation of the cause.

I am having a hard time imagining the answer being anything other than "That depends..."

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3. johnnyboy on February 12, 2013 2:27 PM writes...

As you have surmised, this is a pretty useless number - but simple minds like simple arguments, hence the proliferation of useless statistics. The first step would be to define what exactly do you consider a disease. Is a sprained ankle a disease ? If not, why ? If so, should you count as a different disease every tendon and ligament injury that may or may not be implicated in the sprain ? A cold is certainly a disease, but it can be caused by numerous different viruses, each which potentially slightly different cell target and tropism and mechanism of cell damage - so how many diseases do you count as part of the common cold ? etc etc...

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4. Helical_Investor on February 12, 2013 3:20 PM writes...

For a broad term like 'cause', I'm not sure why you expect a narrowly classified definition. The 'cause' of Alzheimer's disease is pretty easily stated as the loss of functional connectivity in the brain. Diabetes is the loss of the ability to effectively regulate blood sugar levels. But no, these broadly noted 'causes' don't much help progress toward a therapeutic or mechanical treatment/solution, (or even narrow to just Alzheimer's). Diseases after all aren't named for their underlying mechanisms, but often by and for those who connect symptoms to some broad 'cause'. I wouldn't call cause any more than the association of some underlying biology with a symptomatic set that allows for classification of a disease. The disease can be sub-categorized as we learn more (such as a 'flu' caused by an identified virus).

But anyway, as to NIH and the first link. Making libraries available for researchers will be nice for expanding academic learning, sure. But to drive this to translational progress toward new therapeutics, the barrier is more the 'inadequacy of only 5 years of data exclusivity' than lack of innovative approaches.


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5. Anonymous on February 12, 2013 5:11 PM writes...

If you start digging down below the surface of any 'disease' it always starts to split into sub-diseases ad infinitem. It is not just cancer that is unique to every individual - I have come to believe all diseases are unique at the level of the individual. Understanding diseases at that level is just a dream for the foreseeable future. And even if you did, why would the cure be obvious or achievable??

So we need to stop thinking about understanding every disease at the molecular level (you would need to study every individual for that) and start just honestly dealing with symptom 'relief' (for most diseases excepting oncology/infections). That is the level we are at even if we wish we had a greater knowledge and capability.

This is not a bad place. Most current therapies work via this approach and there is plenty of scope to do a lot more to improve health in this way in a realistic timeframe.

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6. anon on February 12, 2013 6:34 PM writes...

Frankly it all smacks of a little of PR hype. But possibly a naive question, how many people are just ref'ing in an intro rather than talking about it specifically? hopefully questioning such authoritative statements can become more common. As has already been said what you mean by "cause" and "disease" suddenly becomes very important when you get down to brass tacks.

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7. Biff on February 12, 2013 7:43 PM writes...

This sounds suspiciously like the product of one of those senior management driven, back-of-the-envelope, hand-waving exercises we undertook a decade or so ago when we were asked for the number of "druggable" targets, knowing full well that whatever number we came up with would influence people's annual performance reviews for years to come.

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8. dlib on February 12, 2013 9:24 PM writes...

They have a ton listed here:

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9. Insilicoconsulting on February 12, 2013 10:12 PM writes...

Well most of these "diseases" are not characterized by a BIG recognizable physical/physiological effect. They are really abnormal phenotypic endpoints .

Then there are syndromes . Are they "Diseases" ? And how do we find their causes! :-)

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10. HFM on February 12, 2013 10:28 PM writes...

I'd believe that there are ~4K catastrophic-but-rare Mendelian-ish genetic diseases that have been documented by someone, somewhere, and traced to the genetic defect responsible. Not clear that most of these will ever be treatable, short of brute force (see: enzyme replacement, Gaucher's disease et al) or genetic engineering (see: science fiction). This is not the same thing as a valid drug target.

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11. JRnonchemist on February 12, 2013 10:50 PM writes...

Well, you use the method of pedantically sorting, say, stupidities into different categories based on trivial differences. Do this until you have padded your real numbers enough.

Then one can say that the root cause of these is a deficiency in being killed. Dress this up in fancy language.

Then one can talk about how the real problem is that medicinal chemists have a blind spot; they aren't willing to consider things cures that are explicitly intended to kill the people in question.

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12. Sisyphus on February 12, 2013 11:32 PM writes...

Salt, sugar and fat.

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13. Shane on February 13, 2013 12:42 AM writes...

Will you be covering this rather interesting article?

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14. ScientistSailor on February 13, 2013 1:18 AM writes...

Despite billions of dollars in funding and thousands of hours of laboratory research, Death is still the leading killer in America...

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15. RKN on February 13, 2013 1:45 AM writes...

[...]are there even 4,500 diseases, total?

I don't know how credible the World Health Organization is, but according to their web site:

"Monogenic diseases result from modifications in a single gene occurring in all cells of the body. Though relatively rare, they affect millions of people worldwide. Scientists currently estimate that over 10,000 of human diseases are known to be monogenic. Pure genetic diseases are caused by a single error in a single gene in the human DNA. The nature of disease depends on the functions performed by the modified gene."

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16. anonymous on February 13, 2013 7:44 AM writes...

For a plethora of "genetic disorders", check out the OMIM website from NCBI - there are a hell of a lot of them !

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17. simpl on February 13, 2013 10:32 AM writes...

diseases are more than genetic malfunction see a section in e.g.
The classification idea is flexible, as you can go as deep into disease subtypes as you like, giving a partial answer to how many diseases exist: as many as doctors can distinguish between. The ATC classification is similar, adressing the question how many drug classes and drugs exist for treatable conditions.

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18. darwinsdog on February 13, 2013 11:00 AM writes...

In addition to these points, suspect a lot of questionable "syndromes" "disorders" and "affects"(restless legs, chronic fatigue, inappropriate laughter, snoring etc) in this tally - a lot of which are characterized only by having a drug, lets say a serotonin or dopamine modulating one, that to some extent alleviates symptoms.

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19. David R Bachinsky on February 13, 2013 1:25 PM writes...

OMIM has some data:

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20. Dr. Manhattan on February 13, 2013 1:33 PM writes...

I agree that it is hard to put a firm number as well as decide what really constitutes a "disease" (darwinsdog makes a good point above in that regard).

But, hey, we are always pushing back the frontiers of science! 25 years ago we were totally ignorant of ED, now we solve that with a simple pill and a couple of bathtubs out in the wild (I saw that on TV, so it must be true). Of course, if you experience an erection that last longer than....etc.

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21. Tom C on July 3, 2013 10:14 AM writes...

Ive lost my taste back in March 2013, but its not that I lost my taste,everything I eat tastes horrible and bitter and I have a salty taste in my mouth. Ive been tested for tons of blood work and a MRI on the brain with and without contrast. Every thing was negative. But they did fine that Ive have Sjogrens but with no systoms, The numbers was only 1pt on the Sjogrens. The doctors are confuse and Im going crazy. Can anybody help me with this? Thank you

Permalink to Comment

22. Tom C on July 3, 2013 10:15 AM writes...

Ive lost my taste back in March 2013, but its not that I lost my taste,everything I eat tastes horrible and bitter and I have a salty taste in my mouth. Ive been tested for tons of blood work and a MRI on the brain with and without contrast. Every thing was negative. But they did fine that Ive have Sjogrens but with no systoms, The numbers was only 1pt on the Sjogrens. The doctors are confuse and Im going crazy. Can anybody help me with this? Thank you

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