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.

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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.

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