Hollywood Communications

Are you reading this article on a cell phone? Maybe you’re on the wifi at a local coffee shop. Well, this article, and anything else you browse while waiting for your frappuccino, is delivered to your mobile device thanks to a 1940’s Hollywood starlet. Digital communications wouldn’t exist without the elegant brilliance of Hedy Lamarr, another prominent woman in science.

Austrian born, Hedy Lamarr debuted in America opposite Charles Boyer in the 1938 film Algiers [1]. She became a sensation thanks in large part to her beauty, working with Hollywood headliners like Clark Gable, Jimmy Stewart, and Judy Garland. Her biggest success was her titlular role in Samson and Delilah, the highest grossing film of 1949 [2]. But Hollywood started to typecast Hedy as the seductress—roles that required very little beyond looking pretty. Bored with her acting career, Hedy switched to inventing [3].

Her first few inventions were flops, including a tablet to automatically carbonate water (which Hedy admitted made the drink taste like alka seltzer) [3]. Then she focused on military inventions to help the Allies in WWII. At a dinner party, Hedy met composer George Anthiel, and chatted about radio communications used to control torpedoes [1]. These signals could easily be intercepted or jammed by the enemy, but Hedy realized that randomly changing the frequency of the transmission might make radio communications harder to decipher.  The two started working on a “frequency-hopping” procedure they later patented [4].

Source: Krzysztof S pl / Wikimedia Commons

Hedy and George’s ‘frequency-hopping’ system was inspired by paper piano rolls, where up to 88 perforations in a roll of paper control which keys are played on self-playing pianos. But instead of playing a song, the paper rolls would control the frequency of the radio message. Transmitting and receiving stations would synchronize identical paper rolls, allowing communications to hop between frequencies seemingly at random [4]. With the transmitter and receiver hopping frequencies to the tune of Camptown Races, the Nazis wouldn’t be able to lock in on a signal to intercept communications or jam the frequency.

Hedy and George’s invention was never used in WWII, but it was adopted for military communications during the Cuban Missile Crisis. Later, Hedy and George’s invention would form the basis of secure digital communications via satellite, wifi, and cellular phones [5].

Each of these mobile devices trades something akin to an electronic piano roll, to sync their communications and prevent interference between signals.

This technology wasn’t widely adopted until after their patent expired, so Hedy didn’t strike it rich in the digital age. But she was recognized for her invention in 1997 with an Electronic Frontier Foundation (EFF) Pioneer Award and was the first female recipient of a BULBIE Gnass Spirit of Achievement Award [5].

Hedy once said “Any girl can be glamorous; all you have to do is stand around and look stupid” [1]. Lucky for the internet, it was all an act.

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References
[1] “Hedy Lamarr Biography“. Biography.com. Retrieved 22 May 2016.
[2] Barton, Ruth (2010). Hedy Lamarr: The Most Beautiful Woman in Film. University Press of Kentucky. ISBN 9780813126104.
[3] “‘Most Beautiful Woman’ By Day, Inventor By Night”. NPR. 22 November 2011.
[4] “Patent 2,292,387“. United States Patent and Trademark Office. Filed 10 June 1941. Retrieved 22 May 2016.
[5] “Hedy Lamarr – Invention of Spread Specturm Technology“. Famous Women Inventors. Retrieved 22 May 2016.

Tongue-in-Cheek

Source: Hmwith / Wikimedia Commons

Can you roll your tongue? I can. Most people can. It’s often presented as an example of a genetic trait, but don’t be fooled. It’s possible for maternal twins to differ in their tongue rolling abilities, even though maternal twins are supposed to be genetically identical [1]. Myth busted.

Sorry to disappoint. This post isn’t about the tongue rolling gene (rolled oral factor lingua, or ROFL). Maybe a few genes combine to give us the power to make the tongue tube, possibly genes that offer better muscle control or flexibility. The tongue is a weird muscle too—wiggling around in there, fiddling with that rough spot on your tooth—and it achieves that wiggling and fiddling thanks to this week’s gene of interest: myosin or MYH1.

Muscles can only pull, never push [2]. Think about that for a second. We can achieve so many artful and dexterous movements (fencing, the tango, punching someone in the face) and manage it entirely by a timely contraction of a series of tissues to achieve the desired effect. To me, that’s mind blowing. Even pushing achieved through pulling.

Muscles pull by way of two proteins, actin and myosin, that work together in a chemical tug-of-war [3]. Actin is the rope and myosin is the hand that pulls on that rope.  Myosin attaches to actin and (using energy from ATP) pulls on actin sliding it forward.

Muscle is organized into groups of parallel actin and myosin fibers called sarcomeres [3].  Each muscle has millions of sarcomeres—millions upon millions of molecules pulling against one another to create force.

Pitting muscles against each other, antagonistic pairs, gives us movement. For example, the bicep and the tricep (Did you get your tickets to the gun show? flexes bicep). In the tongue, several antagonistic pairs are woven together, both parallel and perpendicular to the surface. They pull against each other in a soft mass, with anchor points in the jaw, mandible, and the front and back of the throat [4]. And a few of those pairs combine to pull off the tongue roll. What a weird thing to have inside our mouths.  Enjoy being aware your tongue for the next hour!

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References
[1] “Debunking the Biggest Genetic Myth of the Human Tongue“. PBS. 5 August 2015.
[2] “Why Do Muscles Only Pull And Not Push“. ezinearticles.com. 13 August 2012.
[3] “How Muscle Works“. How Stuff Works. 11 April 2001.
[4] “Anatomy Angel: The Tongue and Balance“. Dr. Dooley Noted. 30 October 2014.

Doo-W0p DNA

Sorry for my absence this past month.  A new teaching gig has been eating up all my time.  But work is slowing down, so I should have a new post soon.

In the meantime, I thought I’d share this video from SciShow, a vlog that’s a favorite around the Allen household.  Their videos combine science with a sense of humor (a style I awkwardly try to replicate at G of I).  Their video below describes “musical genes”, genes that control your musical aptitude.  Check out the rest of their videos at this link: https://www.youtube.com/user/scishow.

Women in Science

My latest article for LadyFreethinker.org focuses on stereotypes against female scientists. While researching for this article, I stumbled upon a study that found most people can only name one prominent female scientist (Quick! Who can you name?). I quizzed myself and Marie Curie popped into my head, along with Rosalind Franklin and a few others from UCSF and Berkeley where I did my graduate and postdoctoral studies. But I have to admit, the names of women were harder to think of than those of famous male scientists. I couldn’t even remember Rosalind Franklin’s full name without a quick google. I’m so ashamed.

As penance, I’ve decided to do a recurring set of posts on female scientist for Gene of Interest. These women were trail blazers in a field that did not welcome them-some would argue still doesn’t.

Marie Curie

Though most people already know of her, I’ll start with Marie Curie. Born Maria Sklodowska, in Russian-occupied Poland in 1867, both of her parents were teachers. She studied at Warsaw’s “Flying University,” an underground university that accepted women at the time, but longing for a real degree she eventually moved to France to pursue her masters at the Sorbonne University in Paris [1].

In France, she changed her name to Marie, the French version of Maria. She met Pierre Curie at the Sorbonne and the pair bonded over their mutual love of science. They pushed each other to pursue PhDs, working in Pierre’s modest lab. At first the pair worked on separate projects: Pierre on crystals and magnetism; Marie on a new type of ray emitted by uranium discovered by Henri Becquerel. Marie found that uranium caused the surrounding air to conduct electricity. This property depended only on the amount of uranium, regardless of its form or the surrounding chemical composition. From this, she hypothesized that radiation came from the atom itself, a landmark discovery [2].

Marie and Pierre Curie

Even though she regularly asked Pierre for advice, Marie made it a point to establish ownership of her ideas. Research into the properties of uranium was entirely her idea, and she knew that no one would believe a woman had developed this work on her own [3]. As her work developed, Pierre found her research more interesting and eventually abandoned his own work to help her full time.

In the summer of 1898, Marie and Pierre published a paper on their discovery of a new element they named ‘polonium’ after Marie’s native Poland. Just months later, they published another paper on a second element they named ‘radium’. They also coined the term ‘radioactivity’ [4]. Their work won them a Nobel Prize in Physics, an award that almost didn’t include Marie. Pierre had to convince the committee to add Marie’s name to an award for work that was almost entirely hers [5].

Marie Curie was the first woman awarded a Nobel Prize. A few years later, for her discovery of ‘polonium’ and ‘radium’, she was awarded a second Nobel Prize in Chemistry, and became the first person in history to win two Nobel Prizes [6].

Sadly, little was known about the dangers of radiation at the time. Marie Curie would often walk around with samples of radium in her pockets. Her laboratory notes emit radiation to this day [7]. After years of exposure to radioactive material, Marie died of aplastic anemia.  In 1995, both Pierre and Marie’s remains were moved to the Pantheon in Paris, in honor of their great scientific achievements [8].

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References
[1] “Marie Curie – Biography“. Nobelprize.org. 4 July 1934.  Retrieved 6 April 2016.
[2] “Research Breakthroughs (1897 – 1904)“. American Institute of Physics. 2000.
[3] Robert William Reid (1974). Marie Curie. New American Library. ISBN 0-00-211539-5.
[4] “The Discovery of Radioactivity“. Berkeley Lab. 9 August 2000.
[5] “Recognition and Disappointment (1903 – 1905)“. American Institute of Physics. 2000.
[6] “Marie Curie – Facts“. Nobelprize.org. 4 July 1934. Retrieved 6 April 2016.
[7] “Marie Curie’s Research Papers are Still Radioactive 100+ Years Later“. Open Culture.com. 8 July 2015.
[8] “The Radium Institute (1919 – 1934)“. American Institute of Physics. 2000.

Mammals Go Viral

So far on Gene of Interest, we’ve explored what can go wrong: how genes are lost; terrible diseases caused by small mutations; tiny errors that have massive consequences.  But that’s only half the picture. With all this chaos, how did humanity end up with a working genome in the first place? Where do genes come from? The likely answer: many many happy accidents, but I’d like to examine one – without it none of us would have been born – this week’s gene of interest: syncytin (ERVW-1).

Humans are mammals – we’re hairy, warm-blooded, and the ladies have boobs – and we’re part of the largest subset of mammals, placentals. All placentals have the unique ability to carry their developing young inside a womb until fully developed. A baby needs nutrients to develop, so an unborn placental has to collects nutrients from its mother’s bloodstream, but it has to do so carefully. Not only can mother and child have different blood types (so direct connection of blood vessels would be a huge no-no), to the mother’s immune system, the developing baby is a foreign invader. The mother’s white blood cells are adapted to slip themselves between other cells to reach any part of the body, so baby has to create a barrier to protect itself from mommy [1].

Studies of Embryos by Leonardo da Vinci

The solution is a placenta – a vast network of intertwined capillaries from both mother and child. To keep out the mother’s immune system, the cells lining the fetal side of the placenta merge into one giant cell, leaving no gaps for white blood cells to squeeze through. This single cell layer is called a syncytiotropoblast, created by the production of syncytin [2].

But syncytin is an odd gene. It’s produced nowhere else in the body, only a particular type of cell in the placenta and then never again after birth. And it’s related to a protein found in retroviruses – a protein that helps viruses invade our cells [3].

We’ve discussed retroviruses before. A retrovirus inserts its viral RNA into the host cell’s genome using an enzyme called reverse transcriptase [4].  The host cell then reads these genes like an instruction manual to build more viruses. A gene similar to syncytin allows the virus to incorporate it’s membrane with that of the cell – sort of like a smaller soap bubble merging with a larger one.

Millions of years ago, an early mammal was infected with a virus that had this syncytin gene. After the infection had subsided, the syncytin gene was left in the mammals genome and it somehow found a way to put it to work, merging one cell with another cell to create a better barrier for the placenta [5].

Retroviral infection with syncytin. 1) Virus invades the cell using syncytin to merge with the cell membrane. 2) Reverse transcriptase converts viral RNA into DNA. 3) The syncytin gene integrates into the cells genome. 4) The cell copies the syncytin gene. 5) The cell produces its own syncytin and uses it to merge with surrounding cells to form a syncytiotrophoblast.

According to DNA analysis, this adoption of viral DNA happened more than once. The human syncytin gene is similar to that of other primates, but completely unique from the syncytin genes found cats, mice, and rabbits. So far, scientists have found six different versions of the syncytin gene in related species of placentals, suggesting multiple ‘infection’ events and a huge selective advantage to retaining this gene [6]. So even though the placenta developed first without viral DNA, the addition of syncytin was so beneficial that everyone starting doing it.

An estimated 8 percent of our genome came from viruses – the spoils of war after an infection. Most of our viral DNA is in pieces and sits dormant, but a few are functional and even essential to our survival [7]. Odd to think that pregnancy functions thanks to an ancient viral infection. Definitely a happy accident.

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References
[1] “Placenta ‘Fools Body’s Defences’“. BBC. 10 November 2007.
[2] Musicki B, Pepe G, Albrecht E. (1997). “Functional differentiation of placental syncytiotrophoblasts during baboon pregnancy: developmental expression of chorionic somatomammotropin messenger ribonucleic acid and protein levels.” J Clin Endocrinol Metab 82 (12): 4105–10, PMID 9398722
[3] “Virus Gene Syncytin Insinuated Itself in Mammalian DNA Millions of Years Ago“. SciTechDaily.com. 18 February 2012.
[4] Kurth, Reinhard; Bannert, Norbert, eds. (2010). Retroviruses: Molecular Biology, Genomics and Pathogenesis. Horizon Scientific. ISBN 978-1-904455-55-4.
[5] “The Syncytin Gene: Viruses Responsible for Human Life“. IScienceMag. 10 June 2015
[6] “Mammals Made by Viruses“. Discover Magazine. 14 February 2012.
[7] “Our Inner Viruses: Forty Million Years in the Making“. National Geographic. 1 February 2015.

 

Cyanide and the Cell

In Ian Fleming’s novels, all 00 agents are issued cyanide capsules in case of enemy capture, but James Bond threw his away. What a dummy. Sure, Bond always escapes, but why risk it? The rest of his peers understood their orders and were ready to die to keep their country’s secrets. Cyanide pills aren’t mere tropes either, but a real spy tool – a gruesome last resort to keep information out of enemy hands [1]. A lethal dose of cyanide kills in minutes – so effective because it blocks the body’s ability to make energy, via this week’s gene of interest: ATP synthase gamma subunit (ATP5C1).

There are few molecules so important that they’re found in all cellular life. DNA for one (obviously), but also the common fuel source for all cells: adenosine triphosphate or ATP [2]. Related to DNA, ATP is an adenine nucleotide with three phosphate groups attached. Think of each ATP molecule like a tiny rechargeable battery. The bonds connecting each phosphate group store the energy that drives the majority of biochemical reactions in the body – from charging neurons to powering muscle movement [3,4].

The charging stations for these molecular batteries are the mitochondria. Metabolites like glucose are broken down inside the mitochondria, one chemical bond at a time, to release energy [5]. ATP synthase, an enzyme embedded in the mitochondria, uses this released energy to make ATP. The gamma subunit (ATP5C1) sits in the center of ATP synthase and rotates to change the shape of the enzyme.  For each rotation, ATP synthase adds a phosphate group to ADP (adenosine diphosphate) to make ATP [6].  The cell then distributes these newly minted ATP molecules to power nearly all of its biochemical reactions.

ATP synthase in action.  ADP and a phosphate group (pink) attach to one of three sections of ATP synthase.  As the gamma subunit (black) rotates, ATP synthase changes shape, combining ADP and the phosphate group into ATP.  ATP synthase then ejects the ATP molecule (red) and the cycle repeats [6].

ATP synthase works constantly to keep up with the cell’s energy demands. Each molecule of ATP is created and consumed at a rate of approximately 3 times per minute [7]. In all its cells, the human body contains only 250 grams of ATP, but each day it turns over an equivalent of its own body weight in ATP. At any moment, one cell can have up to one billion ATP molecules, but that’s only enough energy to keep the cell running for a few minutes [2].

Cyanide pills take advantage of the cell’s lack of energy storage. By binding to another enzyme found in mitochondria, it blocks the cell’s ability to transfer energy from glucose to ATP synthase.  No energy means no rotation of the gamma subunit inside ATP synthase, which means no new ATP. Unable to recycle spent molecules, the body burns through its ATP reserves in minutes.  It’s effectively like an off-switch for a spy – not a pretty way to go, but effective at keeping state secrets out of the hands of villains like Goldfinger.

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References
[1] “Last hero of Telemark: The man who helped stop Hitler’s A-bomb“. BBC. 25 April 2013.
[2] “Nature’s batteries’ may have helped power early lifeforms“. Science Daily. 25 May 2010.
[3] “ATP and Muscle Contraction“. Boundless.com. 7 January 2016.
[4] “Nerve Impulse Transmission within a Neuron: Resting Potential “. Boundless.com. 8 January 2016.
[5] “How Cells Obtain Energy from Food“. (2002) Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York: Garland Science.
[6] Nakamoto RK, Scanlon JAB, Al-Shawi MK. (2008).”The Rotary Mechanism of the ATP Synthase” Arch. Biochem. Biophys. 476 (1): 43–80.  PMID 18515057
[7] Kornberg, A. (1989) “For the love of enzymes.”Harvard University Press. Cambridge, MA.Humphery, N. ISBN-13: 978-0674307766.
[8] “How cyanide affects the electron transport chain“. The Biochem Synapse. 13 April 2013.

 

Do-It-Yourself Vitamin C

People can’t live without vitamin C, but everyone’s heard a story about that one college student who tried to live off of nothing but chips and ramen [1]. And were it not for a mutation a few millions of years ago, the story wouldn’t end in the clinic with a diagnosis of scurvy.  We could synthesize all the vitamin C we need with a few repairs to this week’s gene of interest: L-gulono-γ-lactone oxidase or GLO.

Vitamin C has a several important jobs. It’s an antioxidant – neutralizing nasty free-radicals [2].  It stimulates the immune system, possibly by acting as an oxidizer to destroy bacteria and viruses during infection [3].  And it’s required to make collagen, a protein found in nearly every tissue in the body [4].

Vitamin C deficiency leads to scurvy, a disease forever linked to pirates and sailors. On lengthy sea voyages, fresh fruits and vegetables didn’t last long. Without any vitamin C, sailors became sluggish, their gums would bleed, old wounds would ache, then jaundice, fever, convulsions, and finally death [5]. A horrible way to go and easily remedied by an orange or two. Multiple times in history citrus was identified and dismissed as a cure for scurvy.  Many were confused why sucking on a lime might cure scurvy, but the juice was less effective and preserved fruit even less so. Vitamin C degrades in light and heat, so processing and preservation would make the food useless. It wasn’t until the 1930’s that vitamin C was isolated and identified as the cure to scurvy.

Raw meat can even cure scurvy, because most animals (like plants) make their own vitamin C.  Humans are among a minority of animals – along with guinea pigs, bats, and other primates – that can’t synthesize their own vitamin C.  Most animals convert glucose into vitamin C using several specialized enzymes [6].  We lost the ability due to mutations in the gene for GLO, the enzyme responsible for the last step in vitamin C synthesis [7].

We still have the GLO gene, it just doesn’t work anymore.  Ever since that first mutation knocked out GLO gene function 61 million years ago, more mutations have eaten away at the gene.  Every gene is made up of several sections of coding DNA (called exons) separated by sections of non-coding DNA. Only the exons are used to build a protein. Of the 12 exons in the GLO gene, humans have lost 7 [7].

Human GLO pseudogene compared to the functional GLO gene from a rat [7].

GLO is an example of a pseudogene – a gene that’s lost its function.  It differs from other mutated genes we’ve discussed because it’s harmless, as long as we eat enough vitamin C to compensate. Early primates may have lost the GLO gene because their diet was rich in vitamin C. Gorging on fruits and veggies, there was no real disadvantage to loosing natural vitamin C production [6].

Our genome is likely full of psuedogenes. Each one sits dormant in our genome, a relic of our evolution. For example, scientists have identified 390 different olfactory genes, responsible for our sense of smell, but there are another 468 olfactory pseudogenes [8]. Compared to what we’ve lost, our nose is basically worthless. Think of all the smells we’re missing.

So that’s why you should eat your fruits and veggies – because evolution has failed you. But considering the American diet, it’s probably a good thing we can’t make our own vitamin C. If not for a horrifying death by scurvy, too many people would opt to avoid anything green for tasty, tasty junk food.

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References
[1] “Scurvy Is a Serious Public Health Problem”. Slate. 20 November 2015.
[2] Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee JH, Chen S, Corpe C, Dutta A, Dutta SK, Levine M. (2003). “Vitamin C as an antioxidant: evaluation of its role in disease prevention”. J Am Coll Nutr 22 (1): 18–35. PMID 12569111
[3] Wintergerst ES, Maggini S, Hornig DH.(2006) “Immune-enhancing role of vitamin C and zinc and effect on clinical conditions”. Ann Nutr Metab 50(2):85-94. PMID 16373990
[4] Peterkofsky B (1991). “Ascorbate requirement for hydroxylation and secretion of procollagen: relationship to inhibition of collagen synthesis in scurvy”. Am. J. Clin. Nutr. 54 (6): 1135S–1140S. PMID 1720597
[5] “Scott and Scurvy”. Idlewords.com. 6 March 2010.
[6] “Plagiarized Errors and Molecular Genetics”. Talkorigins.org. 5 May 2003.
[7] Drouin G, Godin JR, Pagé B. (2011). “The Genetics of Vitamin C Loss in Vertebrates”. Curr Genomics. 12 (5): 371–378. PMCID PMC3145266
[8] “The Smell of Evolution”.  National Geographic. 11 December 2013.

Royal Disorder

Rare genetic disorders are hard to study because they’re rare.  With public awareness almost nil, funding doesn’t come easy so treatments develop slowly.  But a few ‘lucky’ disorders present in notable patients, boosting awareness and jump-starting research.  Hemophilia is one of the lucky few, and it’s caused by a mutation in this week’s gene of interest: coagulation factor IX or F9.

Prince Leopold, Duke of Albany

‘Royal’ hemophilia first appeared in Prince Leopold, the son of Britain’s Queen Victoria.  A delicate boy, Leopold  bruised and hemorrhaged at the slightest bump or scratch, and these wounds would take longer than normal to heal – a result of poor coagulation [1].  Little was known about hemophilia at the time, but physicians tried everything to treat the disease.  While some treatments made sense – like applying ice and compressing the wound to slow bleeding – others were a little more creative – like treating the wound with lime, hydrogen peroxide, or diluted snake venom.  If bleeding was severe, they would also transfuse hemophiliacs with the blood of a relative – a potential disaster if their blood was incompatible [2].  Ultimately, hemophiliacs like Leopold were destined to live short, sheltered lives as they could bleed to death from nearly any injury.

Queen Victoria tried to cover up Leopold’s condition, likely swearing his physicians to secrecy to protect the dignity of the bloodline [3].  While understanding of the disease was still limited, researchers had noticed it was hereditary.  If word of Leopold’s hemophilia got out, Victoria’s other children might have trouble marrying into other royal families.  She kept it a secret as best she could and hoped the disease was isolated to Leopold.  She was wrong.

Historians now believe Queen Victoria was the source of the hemophilia mutation that spread through European royalty [3].  We now know that two of her daughters were carriers and passed the mutation on to other royal families in Spain, Germany, and Russia [1].

Carriers can have the mutation, but never suffer from hemophilia.  Normally, you need two bad copies of a gene (one on each set of chromosomes) for a genetic disorder to present.  A single bad copy makes you a carrier –  you stay healthy because of your one working copy, but you might pass on the bad copy to your children.  But hemophilia is X-linked – F9 is located on the ‘X’ chromosome.  Girls have two ‘X’ chromosomes.  Boys have only one ‘X’ and one ‘Y’.  Therefore, a girl can inherit a single bad copy of F9 and have no issue, but if a boy inherits a single bad copy, he’ll develop hemophilia [4].

Queen Victoria’s family tree: A light gray band indicates a normal copy of the F9 gene. A red band indicates a mutated copy of F9. Alice and Beatrice were both carriers of the mutated F9 gene while Leopold, with his single faulty copy of F9, developed hemophilia [1].

Technically female hemophiliacs are possible but rare, because she would have to inherit the mutation from both parents.  In Leopold’s time, it was especially rare, as hemophiliacs usually died young.  Though his condition was a secret in life, after his death, his former physicians (forgetting their word to the Queen) published several articles detailing his life and the circumstances of his death [3].  The notoriety of Leopold’s death sparked more research into this rare disease.  Soon the missing coagulation factors were identified.  Today hemophiliacs lead relatively normal lives with prophylactic treatment (regular injections of coagulation factor IX), thanks in part to high profile victims of the disease.

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References
[1] “Hemophilia: ‘The Royal Disease'”. National for Case Study Teaching in Science. 20 September 2003.
[2] “History of Bleeding Disorders”. National Hemophilia Foundation.
[3] “A Royal Shame: Prince Leopold’s Hemophilia and Its Effect on Medical Research”. Dartmouth Undergraduate Journal of Science. 22 May 2009.
[4] Rogaev, E.I.; Grigorenko, A.P.; Faskhutdinova, G.; Kittler, E.L.; Moliaka, Y.K. (2009). “Genotype analysis identifies the cause of the ‘royal disease'”. Science. 326 (5954): 817. PMID 19815722

Error Prone

Damaged chromosomes (blue arrows).  Source: Square87~commonswiki / Wikimedia Commons

The world is rough, especially on our genome.  Our DNA is regularly bombarded by sunlight, radiation, smoke and soot in the air [1].  Even our own natural metabolism creates chemical by-products that can damage DNA [2].  This damage occurs anywhere from 10,000 to 1,000,000 times per cell per day – a rate that should leave us squishy, mutated blobs.

Luckily, we have repair genes regularly fixing every nick in our genome.  One such repair gene is this week’s gene of interest: xeroderma pigmentosum, complementation group A or XPA.

Antioxidants have worked their way into every fiber of the health food market.  Anti-aging, cancer-fighting superfruit supplements.  Ads claim these products protect against free-radicals – villains robbing us of our health and youth [3].  But when put to the test, few antioxidant-rich foods can live up to marketing claims.  Basically, a healthy diet has all the antioxidants we need [4].

But there’s a bit of truth to the hype.  Free-radicals are destructive.  They’re natural by-products of our metabolism that regularly damage DNA through harmful chemical reactions.  For example, one by-product, reactive oxygen species (ROS), can react to convert the DNA nucleotide guanine into 8-oxoguanine [5].

The extra oxygen on the 8-oxoguanine isn’t a huge problem on its own, but when the cell copies its DNA, 8-oxoguanine can accidentally pair with adenine.  The code in DNA works under a very simple premise: A is paired with T, and C with G.  Therefore, if 8-oxoguanine is mispaired with adenine (G with A), that chemical reaction has effectively rewritten a small part of the genome [6].

This problem is as old as DNA – these types of chemical reactions have always eroded the code.  Nearly all life on earth has a way of fixing these errors quickly before they get out of hand.  One method is nucleotide excision repair (NER), and it requires XPA.

Nucleotide Excision Repair (NER)

First, DNA is scanned for errors.  When an 8-oxoguanine base is detected, several proteins, including XPA, form a complex at the site of the error.  The protein complex unwinds the double helix and cuts the DNA several base pairs away from the 8-oxoguanine base.  Once the chunk with the error is removed, a new protein complex rewrites the missing piece of DNA [7].

Good as new!  For about 9 seconds until another error forms somewhere else.

XPA is named after xeroderma pigmentosum (XP), a disorder caused by mutations in NER genes.  Cells have other repair mechanisms besides NER, but losing a gene like XPA means no NER and errors pile up quickly, especially in the sun.  In an earlier post, I mentioned sunburns are actually skin cells killing themselves in the face of overwhelming DNA errors.  People with XP sunburn in minutes – errors build up that quickly without NER.  They are also 10,000 times more vulnerable to skin cancer [8].  It’s the loss of NER in this disorder that reveals the daily attack on our DNA.   Without it, people with XP have to live their lives in the dark, protecting their genome from the harsh rays of the sun.

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References
[1] Lodish, H.; Berk, A.; Matsudaira, P.; Kaiser, CA.; Krieger, M.; Scott, M.P.; Zipursky, S.L.; Darnell, J. (2004). Molecular Biology of the Cell. New York, NY: WH Freeman. pp. 963. ISBN-10: 0-7167-3136-3.
[2] De Bont, R.; van Larebeke, N. (2004) “Endogenous DNA damage in humans: a review of quantitative data”. Mutagenesis 19 (3): 169-185. Review. PMID 15123782
[3] “POM-boozled: Do health drinks live up to their labels?”. CNN Health. 27 October 2010.
[4] “The Truth about Antioxidants”. Time. 6 August 2013.
[5] Kanvah, S.; et al. (2010). “Oxidation of DNA: Damage to Nucleobases”. Acc. Chem. Res. 43 (2): 280–287. PMID 19938827
[6] Cheng, K.C.; Cahill, D.S.; Kasai, H.; Nishimura, S.; Loeb, L.A. (1992). “8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G→T and C→A substitutions”. J Biol Chem. 267 (1): 166–72. PMID 1730583
[7] Le May, N.; Egly, J.M.; Coin, F. (2010). “True lies: the double life of the nucleotide excision repair factors in transcription and DNA repair”. J Nucleic Acids. 616342 PMID 20725631.
[8] “For Children with XP Gene, Sunlight Can Kill”. Everyday Health. 17 October 2012.

 

Weaponized Genetics

Genome editing a potential WMD?  According to the recent worldwide threat assessment, genetic engineering is as concerning as North Korea’s nuclear program.  Sounds silly, but the implications of recent advances, particularly CRISPR-Cas9, are pretty scary.  Follow the link below to my newest article on LadyFreethinker.org to read more.

Genome Editing Now Listed as a Weapon of Mass Destruction

CRISPR-Cas9 acts like a word processor for the human genome.  The potential advances in medicine, agriculture, even human evolution are staggering.  I’ve attached a great video by Youreka Science and iBiology that explains how CRISPR-Cas9 works using only a white board.  I mean the video uses a white board, not CRISPR… Check it out below.