Tuesday, November 22, 2011

"The Shape of It All" or "Dr. Licorice Explains Why Bisphenol-A is Scary"

I recently made a chemical that smelled extremely familiar, but after numerous wafts, I couldn't quite tell what it reminded me of.

Me wafting the chemical I made.  The chemical is the tiny bit of brown oil in that small clear jar in my left hand.

This puzzle went unsolved for days until my labmate Michelle used some of the chemical and was like, "Lee, have you noticed how that chemical you made smells just like licorice?"

I was like, "OMG, you solved it!!!!"

Victory Licorice!!!

Of course, the next thing I did was find out what chemical gives licorice its smell.  That is when I became super psyched.  The chemical in licorice is called anethole, which is shaped super-similarly to the chemical I made!

Even though they are made of different atoms, the similar shape of these two chemicals is almost certainly why they smell the same.  DISCLAIMER: I have done no experiments to prove this, so this is just my hypothesis.  However, the validity of my hypothesis is supported by one of the pillars of modern biology, often described as form follows function.  Namely, the way things act in biological systems is directly related to their shape.  This is of course an oversimplification, but a powerful one nonetheless.  To make matters a bit more complicated (but more amazing!!), many scientists think our sense of smell not only senses chemicals' shapes but also how they vibrate!  See comments section below for more details.

How does this "form follows function" thing actually work though??  One of the primary ways is when tiny molecules (like those drawn above) fit snugly into tiny pockets of big proteins (like the smell receptors in your nose).  When this molecule-protein match is made all sorts of crazy things can happen.  In addition to smell, this is how adrenaline makes peoples' hearts go crazy and viagra makes dudes' penises go crazy.

Adrenaline or viagra?  You be the judge.

Pharmaceutical companies spend much of their time making differently shaped molecules until they find one that fits just right into the desired protein.  Below is an image of that happening.  In this case, the molecule squeezing into a pocket of the protein causes cancer cells to age and die--all because of the relative shapes of the molecule and protein.  Amazing!

Image of a drug called nutlin (the small green stick-looking thing) fitting into a pocket of a protein called MDM2 (the big blobby-looking thing).  via

Sometimes companies make new molecules and they just accidentally happen to be the right shape to fit into certain proteins.  This is the case with the chemical Bisphenol-A, or BPA.  BPA is similar in shape to estrogen molecules, so it fits into proteins in your body into which estrogens also fit.  Here is BPA side by side with the estrogen known as estradiol.

They may not look too similar, but 3D models make the similarities more clear.  Also it turns out the portions highlighted in blue are the ones that interact most strongly with estrogen-related proteins in the body, and those blue portions are pretty much exactly alike.  This is why BPA is known as an estrogen mimic, because its shape allows it to act very similarly to estrogen in the body.

Estradiol and other estrogen molecules are known as hormones, because they interact with our bodies' endocrine system.  Our endocrine system is super-duper fundamental to our existence and is responsible for a wide variety of extremely important bodily functions.  When something is wrong with our endocrine system it can cause crazy things to happen like the development of diabetes, obesity, buttloads of cancers, and tons of sexually-related changes, just to name a few.

Endocrine system organs.
Also, first nudity on Science Minus Details ever!  You are witnessing it!

Our endocrine system is exquisitely sensitive to tiny amounts of hormones.  This is one reason why BPA acting like a hormone is so scary, because you don't have to be exposed to much of it for it to have an effect.  This is especially so during early development (fetuses, babies, children).  One team of researchers found that pregnant women with higher levels of BPA in their urine during pregnancy were more likely to have children that were hyperactive and aggressive (ref).  BPA can potentially change the way your children act for life!!!!*  Call me alarmist, but come on, that is super intense!  Adults are not immune either, as male workers in a factory producing BPA were found to have reduced sexual desire, reduced satisfaction with their sex life, and increased risk of erectile and ejaculation difficulty, relative to a  non-BPA-exposed control group (ref).  Erectile dysfunction!  Mega bummer!

But you don't have to be a factory worker to be exposed to BPA.  Aside from being found in those polycarbonate bottles from which everyone has (hopefully) stopped drinking, BPA can also be found in canned foods and even cash-register receipts! (ref, ref, ref)  This chemical is everywhere, including in your body!  Studies have shown that up to 95% of people in the united states have BPA in their body (ref).

"Would you like paper, plastic, or a messed up endocrine system?"

I could go on and on about this, but I'll stop by saying that BPA is just one in a class of chemicals known as endocrine disruptors.  These are in all sorts of consumer products, from rubber duckies (!!!) to couches and other furniture.  Wowza!

Instead of ending on a down-note, let's talk about how crazy, confusing, and amazing the universe is.  THC (the chemical in weed, duh) fits snugly into proteins in your body known as cannabinoid receptors, and this results in the sensation of being "high."

mmmmmmmm, activated cannabinoid receptors...

Your body makes its own chemical that fits snugly  into your cannabinoid receptors too.  Based on what I've told you so far, you would predict that this chemical would be shaped kind of like THC.  However, in 1992 researchers discovered that it looks waaaaaay different (ref).  So, sometimes things of different shape can end up acting in a similar way in your body.  Biology is pretty complicated!!!  Here are the two molecules side-by-side.

The "anand" in anandamide is the sanskrit word for bliss.  Scientists are cool!

In summary, the shape of molecules is super-duper important to how they behave in your body.  However, just when you think you have things figured out, life throws you a weed-laced curve ball to remind you how how awesome the universe is.  That's all folks!

Further reading on endocrine disruptors:

Awesome book, great for non-scientists and scientists alike:
Our Stolen Future: Are We Threatening our Fertility, Intelligence, and Survival?--A Scientific Detective Story

Awesome technical literature reviews:
The Steroid Hormone Biosynthesis Pathway as a Target for Endocrine-Disrupting Chemicals

*This study is still ongoing.  Data only exists for the children at two years of age.  Also, this study only shows a correlation, but data exists in lab mice that shows causation.  So come on.


  1. I love this! A great explanation of how drugs work, and how some compounds inadvertently act like drugs in the body. I wish we'd take the time to consider how certain chemicals can harm and others can help our bodies, instead of the simplistic notion that all chemicals are bad for us.

  2. Thanks for your kind words. I 100% agree with your comment. The interface of chemistry and biology is super-complex, and not well-suited to simple notions like "bad chemicals".

  3. so am I right that recently every Chemist is doing click chemistry?

  4. "click" chemistry has certainly become quite popular for people who are trying to form chemical bonds in unusual and challenging settings, such as on surfaces or in various types of materials like polymers. There is still plenty of chemistry being done involving making complex molecules or developing new ways of making chemicals. In the latter case, some of these new ways of making molecules may eventually become "click" chemistry, but only time will tell

  5. Thanks for the post Lee. Have you run into the awesome controversy over the biology of smell? Many scientist think that shape may be less important than vibrational states of a molecule for our sense of smell. Smell is awesome because it functions over something like 6 orders of magnitude in concentration. We can sense some sulfur compounds in ppb concentrations! Also look at theses two similarly smelling compounds: 1) Muscone
    2) Nitro-Musks

    The later were discovered by scientists making new explosives and are now found in perfume!

  6. Smell blows my mind, especially the sensitivity. ppb!
    Thanks for pointing out that controversy! I had heard about that but totally forgotten. Here are some links to recent articles about this. It seems it might be a combined (shape & vibration) sense.

    Also that musk stuff blows my mind! Thanks for bringing that to my attention. I found this awesome review article of musk scent stuff:

    I will change the post above to refer to these comments, just so people know it is not as simple as just shape.

    Thanks again!!!!

  7. Here is another early article about this:

  8. Lee, I love your captions and photographs -- in addition to your engaging explanations, of course! Thanks so much for sharing your excitement about science with the rest of us!

  9. Thank you! & Thanks 4 reading!

  10. There was a good TED talk about scent...

  11. Angela, that TED talk ruled, thank you! I loved his explanation of why all thiols smell so horrible, because of the SH vibrations being different from almost any other chemical. Still a mystery to me why it smells awful to us... there must have been something deadly in our evolutionary history to make this happen. The video certainly lends more credence to the hypothesis that vibration (not shape) is everything when it comes to smell. From the papers I read, not all scientists in the field seemed fully convinced of this. I guess we'll let them battle it out and check back in a few years. Thanks again!

  12. This is an excellent description! Thank you.

    1. No problem. Glad you liked it. Thanks for visiting!! :-)