Punching Your Way to a Healthier You

artwork by Molly Fischer

The sketches at the top of this post belong to my talented former student, Molly Fischer.  She has a knack for pulling beauty from subjects that may at first seem clinical or even macabre.  But I agree with her that bones tell a beautiful story.   Sort of like Stonehenge: a mystery structure leaving clues to what was.

Much of our natural history is told through skeletons – from the dinosaurs to early Homo sapiens.  But bones can tell us more than just the size and shape of something long gone.  Bones are alive (at least while we’re alive) so they hold clues to how that life was lived.  They are an amazing material that grows and adjusts in response to external forces.  And the protein responsible for bone’s adaptability is made by this week’s gene of interest: sclerostin or SOST

Bones are in a constant state of flux – broken down and rebuilt over and over [1].  Breakdown is done by cells called osteoclasts; rebuilding, by osteoblasts.  All things being equal, bone will be rebuilt in the same way, never changing structure.  That makes this sound like a useless process, but when there’s a change, constant rebuilding allows the bone to adapt to new forces in the environment.

For example, in space, bone density drops because there are almost no external forces.  Astronauts lose about 1% of their bone mass for each month spent in zero gravity, so bone loss will be a huge obstacle for long-term space travel [2].  But bone density can increase too.  Many martial arts, including the style that I train (Goju-ryu), regularly condition their bodies to strengthen their bones.  Sensei Morio Higaonna, a 10th degree black belt in Goju-ryu, regularly strengthens his hands by pounding his fists on a boulder [3].  With each hit, he strengthens the bones in his hands, effectively transforming his fists into boulders.  See below for a video of this sophisticated training technique.  And please, talk to your sensei before trying this at home.

So how can bone feel force?  Bone is embedded with cells called osteocytes.  They’re woven through bone like little spider webs [1].  These cells constantly make a protein called sclerostin (from the SOST gene).  Osteocytes function as microscopic strain gauges.  When they feel force, they stop making sclerostin.  This tells the osteoblasts and osteoclasts on the surface to build stronger bone on their next cycle.

Osteoclasts and osteoblasts constantly breakdown and rebuild bone, while osteocytes make sclerostin. (1) When a force is applied, (2) the osteocytes stop producing sclerostin, (3) which signals to the osteoblasts to make stronger bone. (4) After the bone is remodeled, osteocytes start making sclerostin again.

So sclerostin functions as an “everything’s OK” alarm.  No force: plenty of sclerostin.  Sensei Higaonna pounds his fist into a boulder: sclerostin turns off; the body builds denser bone until the force is no longer felt.

If small bits of force, from running, lifting weight, punching boulders, create strong bones then it should come as no surprise that modern bones are weaker than those of our ancestors [4].  After the introduction of farming about 7,000 years ago, people became more sedentary and their bones reflected that change.   Bones steadily lost density, especially in regions on the legs associated with running and walking long distances.  So bones record our history, activity level, maybe even changes in our diet.  What story will your bones tell?

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References
[1] Bonewald, L. (2011). “The Amazing Osteocyte”. J Bone Miner Res. 26(2): 229–238. PMC 3179345.
[2] “Bone Remodeling”. Wheeless’ Textbook of Orthopaedics. 13 September 2011.
[3] “Morio Higaonna’s 3 Ultimate Lessons of Karate Wisdom”. Karate by Jesse.
[4] “Researchers Discover Why Our Ancestors Had Stronger Bones”. Newsmax. 18 May 2015.

You Are What You Bleed

What’s your blood type?  In Japan you’re more likely to hear this question than “What’s your sign?”  That’s because it’s a popular belief in Japan that your biology and genetics determine your temperament (which honestly makes more sense than the night sky dictating personality) [1].  My blood type is A+.  That means I’m outwardly calm and patient, but I also have a tendency to be a perfectionist.  I guess that’s not too far off.  I do find it oddly satisfying that my blood type has the highest possible grade.

But if it’s true that blood type determines your personality, that means there’s only four types of people in the world, type A, B, O, and AB.  People seem more complicated than that, but maybe I’ve missed something. Let’s take a closer look at the gene that determines blood type, this week’s gene of interest: ABO.

People have always held strange beliefs about blood.  Physicians used to believe that balancing blood volumes controlled health.  Bloodletting, or controlled bleeding, was a common treatment for almost any illness [2].  It was even used to treat stab wounds.  In 1824, after a French general was stabbed through the chest, his physicians treated him with regular bloodletting for a month “to prevent inflammation”.  He lived, but his “treatment” cost him 4.8 liters of blood, not including extra blood loss from the medicinal leeches (probably another liter) [3].  For reference, average blood volume is about 5 liters.  His blood loss was spread over a month, but still, that guy had to replenish his entire blood supply – and survive a stab wound.

“Already healing nicely.  Just in case, I’ll prescribe some medicinal leeches.”

Unlike leeches, blood transfusions were avoided because they generally resulted in death.  It wasn’t until 1901 that we discovered why.

When Karl Landsteiner mixed his blood with that of his lab members, he noticed that while many of the samples would clump when mixed, some did not [4].  The clumps were caused by antibodies attacking blood cells.  The body makes thousands of antibodies against foreign proteins called antigens.  Generally antigens can be found on the outside of bacteria and viruses, but cells can have antigens too.  The ABO gene makes a kind of antigen.  Each blood type refers to the type of antigen that’s present on the outside of red blood cells.  Type A has the A antigen; type B, the B antigen; type AB, both A and B antigens; and type O, neither.

Arrows indicate blood type compatibility.  Type O can donate to all blood types, type A to itself and type AB, type B to itself and type AB.

The immune system makes antibodies for everything except the body’s own antigens.  For someone like me with type A blood, the immune system makes antibodies against the B antigen, but not the A antigen.  So, as long as I don’t receive a transfusion that contains the type B antigen (type B or type AB), I should be fine.

In reality, blood types are a little more complicated than the ABO system.  The ‘+’ after my A+ means my body also makes the Rh factor, another antigen controlled by another gene: RHD.  But it gets even more complicated.  There are actually hundreds of different blood antigens [5].  With new antigens discovered every few years, it’s actually safer to repeat Landsteiner’s test before each transfusion than rely on a simple blood type system.  Mix a sample of the patient’s blood with a possible donor’s.  If it clumps, try the next one.

The ABO +/- system helps narrow down compatible donors, but in reality a true blood type would look more like this: O, r”r”, K:–1, Jk(b-).  This means that blood type personality system might need a revision to account for the millions of possible blood types.  Or maybe it’d be easier to just get to know people instead of sorting them into little boxes.

“Ironically, the killer wrote this in B+.”

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References
[1] “Japan and blood types: Does it determine personality?”. BBC News. 5 November 2012.
[2] “Bloodletting”. British Science Museum. 2009.
[3] “Case of a Wound of the Right Carotid Artery”. Lancet 6 (73): 210–213.
[4] Dean L. (2005). Blood Groups and Red Cell Antigens. National Center for Biotechnology Information. Bookshelf ID NBK2267.
[5] “Your Blood Type is a Lot More Complicated Than You Think”. Smithsonian.com. 5 June 2014.

Déjà Food: Would You Eat Cloned Beef?

Less than two decades after the birth of Dolly the cloned sheep, the Chinese company Boyalife plans to construct a cattle cloning factory by mid-2016.  Read all about it in my article at LadyFreethinker.org

Can a Virus Regrow Your Arm?

Did you know salamanders can regenerate their limbs? They can regrow their tails, hearts, and eyes too. And their potential to repair tissue is almost limitless [1]. As they grow older, their ability to regenerate slows down, but it never goes away completely. Why can’t people do that? No more organ donor wait-lists or prosthetic limbs. Just regrow what you’ve lost. Scientists are studying salamanders to find the key to regrowing body parts. Imagine how the world would change if this could work in people.

We’re still not sure how salamanders do this, but stem cells may be the key. When salamanders lose a limb, cells at the site of amputation reprogram themselves into adult stem cells [1]. These cells have the potential to turn into many different cell types, a property called multipotency. Cells at the amputation site rapidly divide and form muscle, bone, and skin to replace the lost limb. Humans also have adult stem cell populations that replenish red and white blood cells and participate in limited healing, but regrowing a human limb remains just out of reach (Amputation puns are disarming).

Adult stem cells might not be able to do the job, but human embryonic stem cells (ESCs) could. ESCs can turn into any type of cell, a property known as pluripotency. As an embryo matures and develops into a fetus, embryonic stem cells select one of three lineages that will later form tissues found in the outer (ectoderm), middle (mesoderm), and inner (endoderm) parts of the body [2]. As embryonic stem cells mature, they lose the ability to turn into other types of cells, or lose pluripotency.

Recently, scientists have discovered genes that can reactivate pluripotency in any cell. And one of those genes is today’s gene of interest: octomer-binding transcription factor 4 or Oct4.

Oct4 was one of four pluripotency genes identified by the Yamanaka Lab in Tokyo, Japan (the other three were Sox2, c-Myc, and Klf4) [3]. When mature cells are forced to express these four genes, they regained their pluripotency and became induced pluripotent stem cells or iPSCs (Actually which genes are required to induce pluripotency is still being debated, and there’s one article that claims it can be achieved using only Oct4) [4]. The first human iPSCs were made from fibroblasts (wound healing cells found in skin and connective tissue). After Oct4 and its buddies were introduced into these cells they reverted to stem cells capable of turning into any cell type.

It’s not easy to get cells to express a new gene. To do this, scientists used retroviruses. A quick background on retroviruses (because I think they’re cool): normally in a cell, a protein is made by copying the DNA for a gene into RNA (another nucleic acid very similar to DNA). The RNA copy is read by the cell and used as instructions to build a protein [5]. Retroviruses hijack this process. They inject their viral RNA into the cell and, using an enzyme called reverse transcriptase, insert their viral genes into the host cell’s genome. Once it’s in the genome, it’s stuck forever. The host cell reads the gene and builds more viruses that leave the host cell to infect cells in other parts of the body [6].

Retroviruses hijack the host cell to create copies of itself.  1) The virus enters the cell. 2) Reverse transcriptase converts viral RNA into viral DNA. 3) The viral DNA integrates into the host genome. 4) The host cell creates copies of the viral RNA. 5) The host cell assembles new viruses.  6) The newly assembled viruses exit the cell to infect other cells.

To induce pluripotency, we’ve stolen the retrovirus’s tricks. Using tamed versions of the virus, scientists can insert genes like Oct4 into an adult cell. Instead of producing more viruses, the cell produces Oct4 which reverts it to a pluripotent state [6].

In fact, scientists are finding these induced genes work so well that cells will stubbornly remain pluripotent despite attempts to turn them into a particular cell type [7]. So the only thing stopping us from growing new limbs is convincing these iPSCs to just grow up.

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References
[1] “Salamanders may hold the key to regrowing human limbs, study finds”. Fox News Health. 19 June 2014.
[2] “What are embryonic stem cells?”. National Institutes of Health.
[3] Takahashi, K.; Yamanaka, S. (2006). “Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors”. Cell 126 (4): 663–76. PMID 16904174.
[4] Kim, JB.; Sebastiano, V.; Wu, G.; Araúzo-Bravo, MJ.; Sasse, P.; Gentile, L.; Ko, K.; Ruau, D.; Ehrich, M.; van den Boom, D.; Meyer, J.; Hübner, K.; Bernemann, C.; Ortmeier, C.; Zenke, M.; Fleischmann, BK.; Zaehres, H.; Schöler, HR. (2009) “Oct4-induced pluripotency in adult neural stem cells”. Cell  136 (3): 411-9. PMID 19203577.
[5] “From genes to proteins”. Genetic Home Reference. 30 November 2015.
[6] Kurth, Reinhard; Bannert, Norbert, eds. (2010). Retroviruses: Molecular Biology, Genomics and Pathogenesis. Horizon Scientific. ISBN 978-1-904455-55-4.
[7] “Researchers pinpoint roadblocks to lab-grown stem cells’ maturation”. Phys.org. 12 November 2015.