Bone Love

Until recently, I didn’t give much thought to my forearm. And I’m guessing that you haven’t either. Consider it with me for a moment. Take a minute to appreciate the engineering marvel that is your arm.

Roll up your sleeve and extend your right arm out straight in front of you, with the palm of your hand facing in, your elbow  tucked to your side. Now run your left forefinger up the length of your forearm from wrist to your elbow. That is the radius bone –flared at the thumb-end and  shaped like the head of a nail at the elbow end. That’s one bone, but there are actually two in there.

Radius is on the thumb-side.

Ulna is on the pinky-side.

Now, keeping your arm out in the same position, run your left fingers along the bottom side of your arm from the wrist to the elbow. That is the ulna – bone #2.  Your ability to grasp, rotate, pronate, turn, deliver all comes from the intricate interactions between these two slender osteo companions living in your forearm. Encircle your right wrist, with the fingers of your left hand and then turn your right arm to the left and right and you’ll see what I mean. The ulna is actually a fixed bone but the radius capers over and around it, twirling, like Ginger Rogers around a steadfast Fred Astaire, working together in a well-choreographed tango that allows you to do everything from turning a screwdriver, to opening a jar, to picking up an infant.

Yes, that arm of yours is an engineering marvel. Except when it’s not. When broken, your bones must be held perfectly still in order for bone-building cells to do their work and lay down new bone. Spongey, like tofu (I was told), at first then gradually, over weeks, to something harder and more stable. Like wet cement, it must be allowed to stiffen overtime, undisturbed. That’s where the cast comes in. It is only when you have a harder-than-steel fiberglass cast on your forearm that you fully realize how magical the movements of your ulna and radius are. Without their intricate gliding and swooning, your arm and hand become a robotic cudgel, capable of only the most primitive moves. Pushing, blocking, and just laying there. You have no grasping power. You can’t squeeze, pinch, or turn.  Not only that, but your two hands can’t work in concert together.

You’d be amazed by the number of quotidian tasks that require the sophisticated enterprise of two functional arms working, ahem, hand-in-hand. Zipping your pants, tying your shoes, driving, buttoning, cutting vegetables, and basically any form of multitasking – period

I have growing superstitions over the pending removal of this cast. Once they cut this sheath off my arm, what will happen? Will the quivering lump of bone, sinew, and skin be able to return to all of those crazy functions? Will my ulna and radius resume they’re well-rehearsed choreography and glide over each other in rhythm? Will the reconstituted bone hold up to the rigors of my daily life? Will I be able to lift boxes, type, carry grocery bags, turn the steering wheel hand-over-hand, support a downward-facing dog?

And what if I fall again? Will that delicate patch of bone hold my weight? Has the word gone out to the other 205 bones  – she’s breakable!

 

 

A Closer Look at a Caffeine Story

Coffea canephora. Bali – Indonesia – July 2007 – Guy Sabattier

Like many people around the world, I begin my every morning with a rather large cup of coffee. Caffeine – found in coffee, tea, mate, and chocolate – is the most widely consumed psychoactive substance in the world. So it was with great interest that I greeted the news, published in Science on Thursday last week, that an international team of scientists has sequenced the genome of the coffee plant, Coffea canephora.

Molecular structure of caffeine.

Getting inside the coffee plant’s genome provides a biochemical view into the mechanism for creating caffeine (start with xanthosine, shave a bit off here, add a bit there and – voila – caffeine).  But here’s the really interesting part – the coffee plant and the cacao plant produce caffeine in different ways. In other words, the biochemical pathway for producing this important molecule evolved more than once. Different evolutionary paths to the same end point. Biologists call this phenomenon convergent evolution. The independent evolution of similar features in different lineages (think wings in birds and bats, the camera eye in vertebrates and octopuses, the ability to glide in flying squirrels and sugar gliders). When this happens, it’s a good indication that the evolved adaptation is pretty useful. And, indeed, caffeine is a very useful molecule for these plants – it helps to ward off enemies, to attract pollinators (and keep them coming back for more), makes the soil immediately surrounding the plant inhospitable to competing plants, and it deters leaf-eating pests. For the rest of us, it provides that much-needed kick-in-the-pants each morning.

As excited as I was about this story, I was quite taken with the way different news groups elected to cover it:

Here’s the New York Times article:

Here’s the Washington Post article:

Washington Post.

And here is Fox News coverage:

Fox News.

The thrust of the WaPo and Fox coverage is on the “mutation”, the possibilities for manipulation, and the slightly shadow-ey (the “quirk”) scariness of what might come next – genetically modified coffee??

It’s startling to see how few of the primary news channels covered what was most interesting about this finding. Namely, the intensely interesting evolution story and the way genomic tools help scientists solve problems and understand the mechanisms of life.  Only Carl Zimmer, that noteworthy NYT Science journalist, included a clear and helpful description of the evolution element in his story. Sidebar: note the illustration choices in the three articles – the cup of coffee, the barista’s product. The New York Times at least shows the coffee beans but not a one of them show the actual plant, let alone the plant in its environment.  How we report the news – the headline, the image, the story – these are all vital ingredients that help shape public perception and our attitudes toward science.

 

 

Tiny Conspiracies

The Bassler Lab

Bonnie Bassler

We’ve just concluded the ninth annual Biology Leadership Conference (BLC) in South Carolina and what a weekend it was! Our keynote speaker,  Dr. Bonnie Bassler , gave the meeting a rip-roaring start with a research talk about her lab’s work with bacteria, figuring out how they talk to each other, and, as an outgrowth of that work, gaining insight into the evolution of  multicellularity.

Bacteria, Earth’s earliest lifeforms, are single-celled organisms, covered with a membrane, and filled with cytoplasm that includes only one piece of DNA.  Compared with humans and other mammals, they have very little genetic information (only a couple of thousand genes) with which to work.  Their lives appear to be fairly mundane – they grow, divide and replicate.

As humans, our relationship, with bacteria is pretty interesting.  Humans, like all organisms, are made up of cells – roughly a trillion cells that make up one human body.  It turns out that you have 10 times more bacteria cells than human cells on and inside of you (there are roughly 40,000 species of bacteria in the gut alone!).  In other words, you are really 90% bacteria.  And if you look at the gene pool, those proportions become even more astounding. We know that there are 20k genes in the human being.  Well, if you tally up all of that bacterial genetic material, you have 100x more bacterial genes, than human genes, in and on you.  So, doing the math – you are only 1% human.

Bacteria R Us, illustration by Bryan Christie

But all of those bacteria are not just passive riders in and on your human form, they are very busy creatures.  They provide an amazing repertoire of functions that you can’t do on your own – food digestion, educating your immune system, and vitamin production.  They also cover you in an invisible film – a sort of body armor.

But we don’t hear much about all of those positive contributions. When we hear news about bacteria, it’s mostly bad news  – lyme disease, toxic shock, or food poisoning – the myriad ways that bacteria make us sick.

Hawaiian Bobtail Squid

Dr. Bassler started as a postdoctoral fellow in the lab of Dr. Mike Silverman (from the Agoroun Institute, now retired), who had been working on a special kind of bacteria, Vibrio fischeri, that live in a mutally beneficial relatonship with a marine organism – the Hawaiian bobtail squid (pictured at left).  This squid has a pristine, one-to-one symbiotic relationship with the bacterium Vibrio fischeri.  The squid provides a safe and comfortable home, the bacteria provide light.

Here’s the story from the squid’s point of view:  during the day, the squid buries itself in sand to avoid being eaten by predators. Good strategy. In this video you can see the squid’s camoflauge behavior. It comes out at night to hunt, but of course, it’s difficult to hunt in the dark.  Fortunately, the bobtail squid has a specialized light organ, two glowing lobes, located on the underside of its body, loaded with (10 to the 12th cells per ml) bioluminescent bacteria.   The squid’s ink sac works like a shutter, controlling the amount of light shining down, into the dark water below.  The light organ and ink sac are controlled by  a light organ on the squid’s topside, so that the bacterial light precisely matches the light coming from the stars and moon above. In effect, the squid counter-illuminates itself to avoid predation, while hunting.  Together, the squid and its bacteria are the stealth bomber of the ocean.

Vibrio fisheri

From the bacteria’s point of view, the light organ is a safe haven,  loaded with nutrients.  The bacteria and the squid, as a pair, manage to avoid wasting valuable resources by only turning on the light when appropriate – that is, only at night, and only when there are enough bacteria around to make it worthwhile.  The light is turned on by a sort of chemostat – the bacteria make and release a small pheromone (called an autoinducer).  As they grow and divide, they sense the level of the autoinducer.  A particular autoinducer level is the cue to turn on the light.  In the morning, the squid pumps out most of the bacteria from its light organ – and the process resets itself.

The biochemical key to this beautiful process is this autoinducer.  As the bacteria grow and divide, the molecule builds up precisely in proportion to the number of bacteria present.  The bacteria use the autoinducer as a communication proxy – initiating a response (turning on the light), based on the detection of that chemical’s level. In effect, the bacteria are using the level of the autoinducer as a method for counting their number – or quorum sensing.  It’s as if the bacteria vote chemically –  and then turn on the group behavior.

The enzyme that makes the autoinducer freely moves in and out of the bacterial cell.  The receptor that detects the molecule’s presence sits on the cell surface (like a hormone receptor). When the molecule reaches a certain concentration, it binds to the receptor on many bacterial cells, in the typical lock and key manner, and that binding action turns on the bioluminescence. Like a light switch.

Endosymbiosis

And here’s the interesting connection to the evolution of multicellularity.  According to the endosymbiotic theory, early ancestors of eukaryotic cells engulfed and incorporated other prokaryotic cells.  Eventually, the engulfed cell formed a relationship with its engulfer and became a cell living within another cell – an endosymbiont.  In the same way, we can look at quorum sensing as an early version of development in complex, multicellular organisms.  Turning on the light among hundreds of bioluminescent bacteria is similar to turning on hundreds of genes in a multicellular organism at a particular time.  These luminescing bacteria perform their action in synchrony – behaving just like multicellular organisms when they do.

So what all are these bacteria doing with quorum sensing? Turns out, there’s a wide range of these autoinducer chemicals that participate in various bacterial group functions. To mention just two examples: such a chemical in  P. aeruginosa is involved with production of virulence factors and biofilms and such a chemical in E. carotovora is involved with  antibiotic production.

Quorum sensing helps bacteria to strategically time their invasions. When you think about it, it makes no sense from the bacterium’s point of view to kill the organism it has invaded. The better idea is to dribble out molecules and give the host a chance to mount an immune response so that the host and the bacteria can continue their relationship.  For the bacteria, it is much better to wait, count itself, and then, when the numbers are right, mount a group assault and infect the host in such a way that both the host and the bacteria survive.

Bacterial community: biofilm on your teeth.

But it’s not as simple as one species of bacteria living in or on one host. Like all other organisms, bacteria live in complex communities, surrounded by many other bacterial species.  Take for example, that thick film you feel on your teeth in the morning?  There are roughly  600 species of bacteria at work, creating that lovely film for you each day. Imagine the “noise” with 600 bacterial species, sending out their biochemical signals. So, if bacteria live in these complex communities, surrounded with all of that biochemical noise, how do they take a census?

To answer that question, the Bassler lab went looking for genes.  In the process, they found that there were really two signals.  Two chemical signals (autoinducers 1 and 2) tell the Vibrio fisheri bacteria to produce light.  But why two?  Why is it useful to have two circuits to provide one line of information?  To get to the bottom of that question, the Bassler lab made bacterial mutants with only one system, then collected their bacterial chemical output and applied it to bacteria with both systems. Using this method, they figured out that the second system was turned on by every species’ autoinducer chemical.  In other words, one system allows bacteria to detect “self” and talk with their kin while the second system detects “other” and allows for interspecies communication.

The gene involved in interspecies communication  is luxS and all of bacteria studied by Bassler’s lab have this gene.  When the researchers collected the molecule produced by the luxS gene, purified it, and determined its structure, they found that every bacterial species made the exact same molecule.  In effect, the chemical encoded by the luxS gene provides a common chemical  “language”. The bacteria are, in a sense, “bilingual”.  They can talk to each other, within their species, and they can talk across species. “Am I alone?”  “Am I in a group?”  “Am I winning or am I losing?”

The film on your teeth, mentioned earlier, is a complex, architected community.  Bonnie speculates that there is most likely a vast chemical lexicon among bacteria yet to be discovered. Imagine the possibilities if we could devise methods to interfere with these bacterial conversations! Take antibiotic-resistant bacterial pathogens, for example. Rather than search for newer and stronger antibiotics to kill these resistant bacteria, perhaps we could modify their behavior and limit their virulence by interrupting their conversations?  And by interrupting the signal, perhaps we could buy time for the host’s immune system to get rid of the bacteria on its own.  Chemical interference could be aimed at  the autoinducer 1 signal, for a targeted approach, or the autoinducer 2 signal for a broad spectrum approach.

What method might be taken to interfere with the bacteria’s signal?  One approach would be to search for an antagonist to block signal reception – a way to interfere with the shape of the lock/key fit of the signal chemical and its membrane-bound receptor.  Turns out, there are libraries of thousands of molecules, created by chemists, that can be screened in search of molecules for this purpose.  And here’s the really sweet part about the bioluminescent bacteria: They give a no-nonsense indication of each chemical candidate’s success – does the light go on or not?  Robots in the Bassler lab screen scads of these chemicals – up to a million molecules in ten days –  testing them with their bacterial communities. Of course, they devise methods to make certain that the tested molecules aren’t acting like bleach and just killing the bacteria.  As a result of this work, they’ve now narrowed it down to 12 molecule candidates that interfere with the receptor.  Initial experiments with these candidates and a virulent bacterium that kills mice looks very encouraging. The chemicals interfere with the bacterial conversation sufficiently to prevent the mouse from succumbing to the bacterial infection.  Of course, there are many miles yet to go before these methods might be available to apply to human bacterial diseases – the molecules must be tested, refined, made deliverable in human systems, etc.  But the important thing is – it works.

If you’d like to hear more from Bonnie, you can view her 2009 TED talk or this wonderful video of Bonnie, in her lab, talking about the nature of science and the work in her lab.  Thank you, Bonnie, for such an inspirational talk!

Watson and Crick Model

During our recent family trip to London, I managed a stealth visit to the Science Museum, located just behind the Natural History Museum in South Kensington.  I had heard that the Science Museum housed the original model that molecular biologists, James Watson and Francis Crick, created in 1953 to depict the structure of DNA.  The.  Original.

So while the rest of my family explored the Natural History Museum, I dashed over (both museums are free admission – what a concept).  I spotted a helpful looking museum guide and breathlessly asked him where I might find the Watson/Crick model.  He broke into a big smile and delightedly offered to walk me to it (he must not get the request very often).  Sure enough – there it was – in a glass case. Humbly displayed with other 19th and 20th century innovations.

I was struck by two things when looking at this remarkable piece of science history.  First, how BIG it was.  This was no small-scale, desk-top model – they were really trying to make a statement with this thing.  Second, that it was made up of odd sorts of materials – clamps and wire and shapes cut of of sheet metal.  It was as if they just looked around the lab to see what they had on hand and said, “right!  let’s use this!”  I loved it.  Have a look:

and another...

Watson and Crick DNA Model

And another view...

Now that’s taking extinction seriously!

Mole cricket tattoo

Most of us worry about the growing list of endangered species, many of us donate time or money to groups who work to protect them, but how many of us have taken steps to promote the cause by tattooing images of extinct organisms on our bodies?  I mean, really.  I ask you?

Well, 100 dedicated folks in Great Britain have.  That’s how seriously they’re taking it.  It started with a group called ExtInk and a November, 2009 exhibit of drawings, illustrating 100 of the most endangered species in the British Isles. Creatures like the water vole, the tundra swan, and narrow-leaved hellaborine.  It concluded with the live tattooing of the drawings on 100 willing volunteers. Apparently, you had to apply for the priveledge of having one of these tatoos (would love to read a few of those letters!).  Here’s the full list of all the participants, along with which tatoo they received.

I love the idea of these 100 people, walking around as bold biodiversity ambassadors.  Can’t you imagine the conversation?  “What’s that on your arm?”  …”Oh, that?  Well, that’s a red-backed shrike.  Let me tell you about it…”

Personal Genomics

Personal Genomics

I’ve been reading more about some of these web-based personal genomics
services. Firms like 23andMe and Navigenics that are offering personal genome services. Using their home testing kit, you send in a salvia sample and get back “the secrets of your own DNA”.

For $999.00, 23andMe (which, by the way, is funded by Google and
Genentech) promises to provide information in your personalized “Gene
Journal” on a long list of diseases/conditions such as lupus, MS,
obesity, cancer, diabetes, chrohn’s disease, macular degeneration, and
earwax type (!).

They offer a suite of “ancestry tools” on their web site that “let you
find out where and how your ancestors lived”. Apparently, you can
compare your genome to thousands of others around the world and find
out which people are more similar to you. They also lay claim to
“helping you discover how your genes may affect such things as your
athletic ability.”

Navigenics takes a slightly different approach (and charges more),
giving you only some of the genetic information (that which they
determine to be “medically relevant”) and then they set you up with a
paid membership arrangement where they continue to test your genome
against new research and offer you future opportunities to meet with
their genetic counselors to interpret it.

To my ear, it sounds like these services are playing into some pretty
grave misconceptions about genetics and inheritance. There are so
many factors involved between a print out of your genomic data and the
onset of disease – couldn’t this sort of testing lead to black and
white thinking about our health? And I wonder if the FDA or an
appropriate federal regulating body is examining these firms and what
they’re promising? I’m curious to hear what you all think about these
companies and the products they are selling? Do your students ask you
about this?