Thursday, February 17, 2011

Why Study Rare Diseases?

The times they are a-changin’!  When I began my career as a scientist, NIH funded 25% of the applications they received.   That number is now down to less than 10%, and if there really are radical cuts in the discretionary federal budget, that number could fall even further.  Many of my colleagues (including myself) are concerned that this would lead to an emphasis on funding projects directly related to common problems (heart disease, breast cancer, emphysema) at the expense of less common diseases (like childhood cancer).

An article published on my birthday by Science:  Translational Medicine demonstrates the danger in cutting off funding for rare disorders.

In this study, Dr. Jaime Guevara-Aguirre and his colleagues published the results of their 22 year study of an isolated population of individuals living in a remote village in Ecuador.  The 99 subjects all have Growth Hormone Receptor Deficiency, or Laron Syndrome.  This is not a public health menace, even in Ecuador.  This article states that there are only 250 known people with Laron Syndrome worldwide.

So why study such a rare disorder?  Well, interestingly, people with Laron Syndrome don’t get cancer (they also don’t get diabetes, but this is a blog about cancer, so we’ll focus on that).  This interesting observation raises a really obvious question:  Why not?

At first blush, there could be a very simplistic answer:  IGF-1 makes your body grow.  For you to grow from the size of an infant to the size of an adult, your cells have to divide many, many times.  Each time a cell divides, it risks developing a mutation, and the accumulation of mutations leads to cancer.  If you don’t grow any larger than a 7-year old, there are fewer cell divisions.  Fewer cell divisions means fewer mutations.

But if that were the answer, people with Laron Syndrome would have a lower than average rate of cancer.  That is not what was observed, however.  What was observed was an almost complete lack of cancer.  This must tell us something profound about how cancer develops.

It turns out that Growth Hormone Receptor Deficiency results in low circulating levels of insulin-like growth factor-1 (IGF-1; also called somatomedin C because it mediates the effects of growth hormone, or somatotrophin).  IGF-1 has been in the news a lot recently because its receptor appears to be important for the growth and survival of a wide variety of tumors, making it a darling of drug developers.   The fact that people with Laron Syndrome don’t get cancer suggests that IGF-1 signaling through its receptor probably plays a role in cancer development, not just the survival of cancer cells once the tumor develops.  More importantly, this must be a general property of cancers, because it’s not the case that people with Laron Syndrome are protected from just one or a few types of cancer.  They don’t develop cancer at all.

This sort of insight could never have come about from a focused study of a particular tumor type, nor could it have been derived from studying cells in a lab.  Only because someone was interested in the biology of a rare disorder was this discovery made.  I can only hope that the people in charge of the federal government’s medical research budget consider this when deciding how much research we can afford, and whether to focus on the common disorders, or whether we can let scientists study what is interesting… because we never know where the next important discovery will come from.

Related Posts:
A Smarter War on Cancer
Is Cancer Contagious?
What Rufus Can Teach Us About Pain


Obsessedwithlife said...

Fascinating! Thanks for sharing.

Aayushi Mehta said...

Very interesting article.

kathleen said...


Good Day to you, i have been trying to find good topic on google for my blog
and i found yours, i found it very interesting i ve learn alot



jennifer haejung said...

thank you for sharing this, Dr. David! I am a 1st year medical student, and we just happened to go over Growth Hormone today in lecture. Your blogs are eye-opening, fun, and interesting to read. thanks for sharing.

Erica J. Thiel said...

As an adult with an extremely rare disorder (1:500,000) - MPS I or mucopolysaccharidoses type I) I truely hope the NIH does not further get cut but knowing the way out Govt works I am sure it will. :/ Thanks for this fascinating article!


Stephanie Hunt -- Mrs.Michigan America 2010 said...

Thank you!

siggy said...

cant we just then cure cancer by erradicating IGF1R in adults?

siggy stud MD said...

You should have seen the first comment i wrote.. lol

Amy-Beth said...

Interesting blog Dr. David! Try visiting

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Erica J. Thiel said...

As an individual with an extremely rare disorder thank you for this blog and for what you are doing trying to bring about some form of awareness of the various issues going on in many platforms.
Thank you~


Cliff merchant MD said...

Hello, I am Cliff merchant and I read a report on Rare Diseases and according to this report "A rare disease is one that affects fewer than 200,000 Americans, and NIH estimates there are about 6,800 of these conditions, ranging from multiple symmetric lipomatosis or Madelung's disease, characterized by large fat deposits around the neck and nervous system abnormalities, to pseudomyxoma peritonei, in which tumor cells swell up the abdomen." Thats why I think we should study this.We should take some serious steps towards Rare Diseases..

Medical Jobs Australia said...

Thank you for sharing.