EFTA00805732

NAUTILUS education • Text Sets Science Connected EFTA00805732 NAUTIL.US I TEXTSETS Introducing Nautilus Education The modern world has placed an unprecedented emphasis on science literacy. But most existing science texts do not emphasize literacy, and most literary texts don't have science. This Nautilus Education text set pamphlet is a beta product intended to fill this gap. It contains three groups of articles from the award-winning science magazine, Nautilus, each accompanied by lesson plans and guides for teachers. Key science concepts like genetics and astronomy are explored through narrative story telling and tailor-made artwork, letting science spill over its usual borders, and waking the imagination and interest of the student. This kind of literary science classroom material was designed to helps teachers satisfy the new U.S. common core and next gen standards but have global application. The relevant standards are listed in each lesson plan. Nautilus is looking for partners interested in using and further developing this kind of content. For more information, please write to education@nautil.us. —Michael Segal Editor-in-Chief About Nautilus Magazine Nautilus is a new kind of science magazine. Each monthly issue tackles a single topic in contemporary science using multiple vantage points, from biology and physics to culture and philosophy. We are science, connected. 2 EFTA00805733 NAUTILUS I TEXT SETS Contents Physics Biology 4 Astronomy & Space Travel 28 Genetics & Human Health 6 Roadmap to Alpha Centauri 30 Their Giant Steps to a Cure Pick yourfavorite travel mode— Battlingarareform ofmuseulardystrophy, big,smakdark, oriwisted afamilyfindsanactivist leader, andhope BY GEORGE MUSSER BYJUDE ISABELLA 36 An Unlikely Cure Signals 12 Chemistry & Fuels Hope for Cancer How "areeptionalresponders" areremlutionizing treatmentfor the deadly disease 16 You are Made of Waste BY KAT MCGOWAN Searchingfor the ultimate example ofreeyeling? Look in the mirror BY CURT STAGER 22 Frack'er Up Naturalgasisshakingupthesearchfor green gasoline. BY DAVID BIELLO 0 O 3 EFTA00805734 NAUTILUS EDUCATION I BETA PRODUCT Astronomy&SpaceTravel How would we travel nearly five light years? This article explores different engineering solutions to the puzzle of taking a very, very, long trip, intertwining science-fiction goals with real world solutions. Students will explore fanciful applications of Newton's second law, and concepts of momentum, ions, and nuclear fusion. Lesson Plan Review vocabulary words in class. Have students read the article and answer the reading comprehension ques- tions for homework, as well as generate a discussion question of their own. In class, address any conceptual questions that the class might have. Have students write discussion questions on the board, along with the ones suggested in this document. Have students break up into small groups, each of which should address one of the discussionquestions. IS MIN Dedicate the remaining class time to completing one of the activities. 30-45 MIN Teacher's Notes: Roadmap to Alpha Centauri VOCAB WORDS Magneticfield: produced by a magnetic material or a Nuclearfusion: when two or more clusters ofneu- current, a magnetic field will push or pull a moving trons and protons collide, forming a new nucleus and charge or magnet that comes in contact with it. releasing energy. Ion: an atom in which the number of electrons and protons is unequal—thus, the atom is positive or READING COMPREHENSION negative. I. What does AU stand for? Momentum: the product of the mass and velocity of an object. 2. How fast is Voyager I moving in miles per hour? Recoil: the backward momentum from a fired gun. 3. "The engine first strips propellant atoms [typi- cally xenon] of their outermost electrons." What Plasma: one of the four fundamental states of matter, is the charge of a stripped xenon atom? composed of ions and electrons. 4 EFTA00805735 NAUTIL.US I TEXT SETS 4. What concept is at work in the ion drive? (Hint: WHERE THIS FITS IN THE CURRICULUM what is conserved?) Structure and Properties ofMatier (HS-PSI-8)Develop S. What other travel options work on this principle? models to illustrate the changes in the composition of the nucleus of the atom and the energy released 6. How much momentum does an electron fired during the processes of fission, fusion, and radioac- from a gun have? tivedecay. Forces and Interactions (HS-PS2-I) Analyze data to sup- DISCUSSION QUESTIONS port the claim that Newton's second law of motion describes the mathematical relationship among the I. Why not take a traditional rocket to Alpha net force on a macroscopic object, its mass, and its Centauri? acceleration. 2. Which of the propulsion meturds listed is most Forces and Interactions (HS-PS2-2) Use mathematical likely to succeed? Would any be used together? representations to support the claim that the total 3. Would it be worth going if it took generations? momentum of a system of objects is conserved when there is no net force on the system. 4. How far away is the next-nearest star? Engineering Design (11S-E7S1-3) Evaluate a solution to a complex real-world problem based on priori- ACTIVITIES tized criteria and trade-offs that account for a range of constraints, including cost, safety, reliability, and I. Research and create a brochure or ad enticing aesthetics, as well as possible social, cultural, and astronauts to make the nip. What would they eat? environmental impacts. What psychological qualities would they need? If robots were sent, how would they be fixed? What kind of data could they expect to collect? 2. Propose another method of traveling to Alpha Centauri. ADDITIONAL MULTIMEDIA I. Voyager I Leaves the Solar System (The Guardian) I MIN 45 SEC A quick explanation of where Voyager I is, and how scientists know its location: httplAvww. voyager-I -leaves-solar-system-video 2. New Mars Rover Powered by Plutonium i)2 MIN 30 SEC An introduction to the nuclear battery on board the Mars Curiosity Rover, and the advantages of not using solar power (as with past missions): watch?v= I JOPWSztAcgEt EFTA00805736 t7 • • e O EFTA00805737 MATTER I TECHNOLOGY Roadmap to Alpha Centauri Pickyourfavorite travelmode—big small, light, dark, or twisted BY GEORGE MUSSER VER SINCE THE DAWN of the space age, a and magnetic fields of the sun give way to those of quixotic subculture of physicists, engineers, interstellar space—finding, among other things, what and science-fiction writers have devoted their Ralph McNutt, a Voyager team member and planetary lunch hours and weekends to drawing up plans scientist, describes as "weird plasma structures" beg- for starships, propelled by the imperative for humans ging to be explored. The mysteries encountered by to crawl out of our Earthly cradle. For most of that the Voyagers compel scientists to embark on follow- time, they focused on the physics. Can we really fly to up missions that venture even deeper into the cosmic the stars? Many initially didn't think so, but now we woods—out to 200 AU and beyond. But what kind of know it's possible. Today, the question is: Will we? spacecraft can get us there? Truth is, we already are flying to the stars, with- out really meaning to. The twin Voyager space probes Going Small: Ion Drives launched in 1977 have endured long past their original NASA's Dawn probe to the asteroid belt has demon- goal of touring the outer planets and have reached strated one leading propulsion system: the ion drive. the boundaries of the sun's realm. Voyager 1 is 124 An ion drive is like a gun that fires atoms rather than astronomical units (AU) away from the sun—that bullets; the ship moves forward on the recoil. The sys- is, 124 times farther out than Earth—and clocking tem includes a tank of propellant, typically xenon, and 16 AU per year. Whether it has already exited the a power source, such as solar panels or plutonium bat- solar system depends on your definition of "solar sys- teries. The engine first strips propellant atoms of their tem," but it is certainly way beyond the planets. Its outermost electrons, giving them a positive electric instruments have witnessed the energetic particles charge. Then, on the principle that opposites attract, ILLUSTRATION BY CHAD HAGEN 7 EFTA00805738 NAUTILUS EDUCATION I BETA PRODUCT momentum and push- es on whatever surface it strikes. The force is feeble, but becomes noticeable if you have a large enough surface, a low mass, and a lot of time. Sunlight can accelerate a large sheet of lightweight material, such as Kapton, to an impressive speed. To reach the velocity need- ed to escape the solar system, the craft would first swoop toward the sun, as close as it dared—inside the orbit of Mercury—to fill its sails with lusty sunlight. Such sail craft could a negatively charged grid draws the atoms toward the conceivably make the back of the ship. They overshoot the grid and stream crossing to Alpha Centauri in a thousand years. Sails off into space at speeds 10 times faster than chemical are limited in speed by how close they can get to the rocket exhaust (and 100 times faster than a bullet). sun, which, in turn, is limited by the sail material's For a post-Voyager probe, ion engines would fire for 15 durability. Gregory Matloff, a City University of New years or so and hurl the craft to several times the Voy- York professor and longtime interstellar travel propo- agers' speed, so that it could reach a couple of hundred nent, says the most promising potential material is gra- AU before the people who built it died. phene—ultrathin layers of carbon graphite. Star flight enthusiasts are also pondering ion drives A laser or microwave beam could provide an even for a truly interstellar mission, aiming for Alpha Cen- more muscular push. In the mid-1980s, the doyen of tauri, the nearest star system some 300,000 AU away. interstellar travel, Robert Forward, suggested piggy- Icarus Interstellar, a nonprofit foundation with a mis- backing on an idea popular at the time: solar-power sion to achieve interstellar travel by the end of the cen- satellites, which would collect solar energy in orbit tury, has dreamed up Project Tin Tin—a tiny probe and beam it down to Earth by means of microwaves. weighing less than 10 kilograms, equipped with a min- Before commencing operation, an orbital power sta- iaturized high-performance ion drive. The trip would tion could pivot and beam its power up rather than still take tens of thousands of years, but the group sees down. A 10-gigawatt station could accelerate an ultra- Tin Tin less as a realistic science mission than as a light sail—a mere 16 grams—to one-fifth the speed of technology demonstration. light within a week. Two decades later, start see- ing live video from Alpha Centauri. Going Light: Solar Sails This "Starwisp" scheme has its dubious features—it A solar sail, such as the one used by the Japanese would require an enormous lens, and the sail is so frag- IKAROS probe to Venus, does away with propel- ile that the beam would be as likely to fry it as to push lant and engines altogether. It exploits the physics of it—but it showed that we could reach the stars within light. Like anything else in motion, a light wave has a human lifetime. 8 EFTA00805739 NAUTIL.US I TEXTSETS Going Big: Nuclear Rockets it. "Today the closest technology we have would be Sails may be able to whisk tiny probes to the stars, nuclear pulse," Matloff says. If anything, most people but they can't handle a human mission; need would be happy to load up all our nukes on a ship and a microwave beam consuming thousands of times be rid of them. more power than the entire world currently generates. Ideally, the bomb blasts would be replaced with con- The best-developed scheme for human space travel is trolled nuclear fusion reactions. That was the approach nuclear pulse propulsion, which the government-fund- suggested by Project Daedalus, a '70s-era effort to ed Project Orion worked on during the 1950s and '60s. design a fully equipped robotic interstellar vessel. The When you first hear about it, the scheme sounds biggest problem was that for every ton of payload, unhinged. Load your starship with 300,000 nucle- the ship would have to carry 100 tons of fuel. Such a ar bombs, detonate behemoth would be the one every three sec- size ofa battleship, with a onds, and ride the blast length of 200 meters and waves. Though extreme, a mass of 50,000 tons. it works on the same "It was just a huge, basic principle as any monstrous machine," other rocket—namely, says Kelvin Long,an Eng- recoil. Instead of shoot- lish aerospace engineer ing atoms out the back and co-founder of Project of the rocket, the nucle- Icarus, a modern effort ar-pulse system shoots to update the design. blobs of plasma, such as "But what's happened fireballs of tungsten. since then, of course, is You pack a plug of microelectronics, minia- tungsten along with a turization of technology, nuclear weapon into a nanotechnology. All these metal capsule, fire the developments have led capsule out the back of to a rethinking. Do you the ship, and set it off really need these mas- a short distance away. sive structures?" He says In the vacuum of space. Project Icarus planned to the explosion does less unveil the new design in damage than you might London in October 2013. expect. Vaporized tung- Interstellar design- sten hurtles toward the ship, rebounds off a thick ers have come up with all sorts of ways to shrink the metal plate at the ship's rear, and shoots into space, fuel tank. For instance, the ship could use electric or while the ship recoils, thereby moving forward. Giant magnetic fields to scoop up hydrogen gas from inter- shock absorbers lessen the jolt on the crew quarters. stellar space. The hydrogen would then be fed into a Passengers playing 3-D chess, or doing whatever else fusion reactor. The faster the ship were to go, the faster interstellar passengers do, would feel rhythmic thuds it would scoop—a virtuous cycle that, if maintained, like kids jumping rope in the apartment upstairs. would propel the ship to nearly the speed of light. The ship might reach a tenth the speed of light. Unfortunately, the scooping system would also pro- If for some reason—solar explosion, alien invasion— duce drag forces, slowing the ship, and the headwind we really had to get off the planet fast and we didn't of particles would cook the crew with radiation. Also, care about nuking the launch pad, this would be the pure-hydrogen fusion is inefficient. A fusion-powered way to go. We already have everything we need for ship probably couldn't avoid hauling some fuel from 9 EFTA00805740 NAUTILUS EDUCATION I BETA PRODUCT Going Dark: Scavenging Exotic Matter Contrary to popular belief, Einstein's theory of rela- Instead of scavenging hydrogen gas, Jia Liu, a physics tivity does not rule that out completely. According to graduate student at New York University, has pro- the theory, space and time are elastic; what we perceive posed foraging for dark matter, the invisible exotic as the force of gravity is in fact the warping of space and material that astronomers think makes up the bulk time. In principle, you could warp space so severely that of the galaxy. Particle physicists hypothesize that shorten the distance you want to cross, like fold- dark matter consists of a type of particle called the ing a rug to bring the two sides closer together. If so, you neutralino, which has a useful property: When two could cross any distance instantaneously. You wouldn't neutralinos collide, they annihilate each other in a even notice the acceleration, because the field would blaze of gamma rays. Such reactions could drive a zero out g-forces inside the ship. The view from the ship ship forward. Like the hydrogen scooper, a dark-mat- windows would be stunning. Stars would change in col- ter ship could approach the speed of light. The prob- or and shift toward the axis of motion. lem, though, is that dark matter is dark—meaning it It seems almost mean-spirited to point out how far doesn't respond to electromagnetic forces. Physicists beyond our current technology this idea is. Warp drive know of no way to collect it, let alone channel it to would require a type of material that exerts a gravita- produce rocket thrust. tional push rather than a gravitational pull. Such mate- If engineers somehow overcame these problems rial contains a negative amount of energy—literally less and built a near-light-speed ship, not just Alpha Cen- than nothing, as if you had a mass of —50 kilograms. tauri but the entire galaxy would come within range. Physicists, inventive types that they are, have imagined In the 1960s astronomer Carl Sagan calculated that, if ways to create such energy, but even they throw up their you could attain a modest rate of acceleration—about hands at the amount of negative energy a starship would the same rate a sports car uses—and maintain it long need: a few stare worth. What is more, the ship would enough, get so close to the speed of light that be impossible to steer, since control signals, which are cross the galaxy in just a couple of decades of restricted to the speed of light, wouldn't be fast enough shipboard time. As a bonus, that rate would provide a to get from the ship's bridge to the propulsion system comfortable level ofartificial gravity. located on the vessel's perimeter. (Equipment within On the downside, hundreds of thousands of years the ship, however, would function just fi would pass on Earth in the meantime. By the time you When it comes to starships, it's best not to get hung up got back, your entire civilization might have gone ape. on details. By the time humanity gets to the point it might From one perspective, though, this is a good thing. The actually build one, our very notions of travel may well tricks relativity plays with time would solve the eter- have changed. "Do we need to send full human?' asks nal problem of too-slow computers. If you want to do Long. "Maybe we just need to send embryos, or maybe in some eons-long calculation, go off and explore some the future, you could completely download yourself into distant star system and the result will be ready for you a computer, and you can remanufacture yourself at the when you return. The starship crews of the future may other end through something similar to 3-D printing." not be voyaging for survival, glory, or conquest. They Today, a starship seems like the height of futuristic think- may be solving puzzles. ing. Future generations might fi it quaint. ,€) Going Warp: Bending Time and Space With a ship moving at a tenth the speed of light, george musser is a writer on physics and cosmology and humans could migrate to the nearest stars within a authorofTheComplereIdiot:.Guide ToString Theory(Alpha, lifetime, but crossing the galaxy would remain a jour- 2008). He was a senior editor at Scientific American for 14 years and has won honors such as the American Institute of Physics ney of a million years, and each star system would still ScienceWritingAward. be mostly isolated. To create a galactic version of the global village, bound together by planes and phones, need to travel faster than light. 10 EFTA00805741 NAUTILUS EDUCATION I BETA PRODUCT Chemistry & Fuels The matter in our world is recycled. The pair of articles here explores how elements and atoms wend their way through space and time. Students will explore how chemical reactions usher ele- ments through their journeys. You Are Made of Waste illustrates, in five short vignettes, the lives of the elements that make up our teeth, fi breath, hair,andblood. Frac* ger Up isan in-depth look at the botched promise of biofuel—energy from cars made from renewable plant growth. In the "curriculum" section of the teacher's notes, you will find information on how these pieces can help fulfill requirements of the Next Generation Science Standards. Specifically, they make for entry points to—or a means of reinforcing—lessons on photosynthesis, chemical reactions, valence electrons, and energy. But more than that, these lessons will connect to the students' daily lives, and spark discussion. Lesson Plan: Ask students to read one or both of the articles for homework. Briefly introduce or review the vocabulary words in class. Assign all or a selection of the reading comprehension questions for the students to complete along with the reading, and ask them to come up with one question for further discussion. (Note that a couple of the questions for each article are redundant.) Start class with students raising any technical questions they might have about the readings. Ask them to contribute their discussion questions, and write these on the board, along with the questions provided in the teacher's notes. Ask the students to break into small groups; assign each group to address a question, and briefly present to the class for further discussion. 30-45 MIN In the following class time (or another class) have the students complete one or more of the activities in the teacher's notes in small groups. 30 MIN Teacher's Notes: You Are MadeofWaste VOCAB WORDS Mass: a physical property that describes an object's Radioactive decay: the process by which a nucleus resistance to force. The mass of an object can be used ejects alpha particles, particles ofionizing radiation. to calculate its weight: (mass) x (gravitational force) A nucleus that does this is considered "unstable;" a = weight. substance that contains unstable nuclei is consid- ered "radioactive." This process usually only occurs in Carbon: an element found in stars, planets, comets, atoms heavier than iron. as well as in all known living things. 12 EFTA00805742 NAUTIL.US I TEXT SETS Fusion: when two or more nuclei collide, fusing to 2. How does the story change the way you see your- make a new nucleus and releasing energy. This pro- self? Others? cess usually only occurs in atoms lighter than iron. ACTIVITIES Chemical bond: an attraction between two or more I. Pick an element not discussed in this article. atoms that allows them to form a substance of defi- Where else is it found? Where did it come from? nite chemical composition. Breaking these bonds requires energy. 2. Draw a map or annotated illustration of all the places carbon goes in this article. Use outside Petroleum: a "fossil fuel" that forms when organisms research to complete a full picture of the carbon are crushed under rock and subjected to lots of pres- cycle. sure, and lots of time. Like the organisms it's made of, petroleum consists largely of carbon. ADDITIONAL MULTIMEDIA READING COMPREHENSION I. Whose air do you share? (It's OK To Be Smart, PBS) 3 m IN 30 SEC I. "Each ofthose waste molecules is a carbon atom A video that explains how we breathe recycled borne on two atomic wings of oxygen." Write out air—including molecules of air exhaled by Ein- the chemical equation for the molecule described stein himself: here. 2. "Organic" is used in two different ways in this 2. We Are Star Stuffsegment piece. What are the two different definitions? (Carl Sagan's Cosmos) 8 MIN 3. What does it mean for a chemical to be "highly Carl Sagan explains how the elements of life reactive?" Identify oxygen's location on the peri- were born in stars, evolved into simple organ- odic table, the group of atoms that it belongs to, isms, then into us: intelligent creatures, capable and why they are considered "highly reactive." of exploring the stars we came from: 4. Which elements on the periodic table are the least reactive? 3. The Microbes We're Made Of 5. "Fossil-based carbon dioxide molecules that a MIN 30 SEC We're not just made of waste. We're made of are not soaked up by oceans or stranded in the trillions of other organisms. This video provides upper atmosphere are eventually captured by a quick exploration of the microbiome crucial plants, shorn of their oxygen wings, and woven to keeping our bodies working, and what we're into botanical sugars and starches." What is the doing to kill them: process described here? (Hint: it is mentioned http:f/www.smithsonianmag. by name later in the piece.) Write down the equa- com/videos/category/3play_1/ tion for this reaction. the-microbes-were-made-of7?no-ist DISCUSSION QUESTIONS WHERE THIS FITS IN THE CURRICULUM I. "Chemophobia" is the fear of chemicals. What are ChemicalReactions (HS-PSI-2)Construct and revise some chemophobic practices or products that we an explanation for the outcome of a simple chemical engage with? Are there good reasons to be afraid reaction based on the outermost electron states of of chemicals? atoms, trends in the periodic table, and knowledge of chemical properties. I3 EFTA00805743 NAUTILUS EDUCATION I BETA PRODUCT Matter andits interactions (HS-PSI-I) Use the peri- 2. A polymer is a chainofmolecules.Identify a kind odic table as a model to predict the relative properties ofpolymer in the story, and the monomer that of elements based on the patterns of electrons in the composes it. outermost energy level of atoms. 3. Plants need carbon dioxide for photosynthesis. From molecules to organisms: structureandpro- What are some of the sources for this carbon cases (HS-LSI-6) Construct and revise an explana- dioxide? tion based on evidence for how carbon, hydrogen, and oxygen from sugar molecules may combine with other elements to form amino acids and/or other large DISCUSSION QUESTIONS carbon-based molecules. I. Why is it advantageous for companies to be Ecosystems:Interactions, energy anddynamics (HS- green? LS-3) Construct and revise an explanation based on 2. Would you pay more for gas—or any other prod- evidence for the cycling ofmatter and flow ofenergy uct, say a shirt—from a "green" company? What in aerobic and anaerobic conditions. if some of that company's practices were just as questionable as those of "dark" companies? 3. How would the world change if gasoline could be made cheaply from natural gas? Should we Teacher's Notes: Frack 'er Up consider this technology to be progress given VOCAB WORDS that natural gas has it's own environmental consequences. Ethanol: also found in beer and wine, it is a kind of biofuel that is sometimes added to gasoline for use in automobiles. Ethanol can be made from corn, ACTIVITIES potatoes, or green plants. Its chemical formula is CHICH2OH. Have students construct a timeline of fuel. Ask them to include dates mentioned from the story, Biofuel: a fuel made from plants or other organisms, and to research and add other relevant informa- in recent time. tion: like the moment in history when organisms Biomass: material from recently livingorganisms. die, the life cycle of a tree that contributed the author's container ofPrimus fuel. Organic compound: a molecule containingcarbon. 2. Draw a map or annotated illustration ofall the plac- Hydrocarbon: Made ofjust hydrogen and carbon, es carbon goes in this article. Use outside research these are the simplest kind of organic compound. to complete a full picture ofthe carbon cycle. Octane: a highly flammable hydrocarbon,and compo- 3. Write a 30-second ad convincing car drivers to nent ofgasoline. Its chemical formula is Cla n. pay a premium for green gasoline like Primus'. Catalyst: a component of a chemical reaction that Include "fine print"—side effects, or caveats—as helps facilitate the reaction, but is not used up. you see nerproiry. READING COMPREHENSION ADDITIONAL MULTIMEDIA I. "Plant biomass absorbs carbon dioxide as it grows." 1. Algae (The Guardian) What is the name of the process by which plants do An interactive slide show that illustrates how this? Look up and write down the chemical reaction. biofuels are made out ofalgae: 14 EFTA00805744 NAUTIL.US I TEXT SETS active/2008/jun/26/algae 2. Bioprospecting (TED-Ed) 4 MIN An animated video introducing the concept of biofuels, and how they could help reduce reliance on our planet's limited supply of fossil fuels: prospecting-for-beginners-craig-a-kohn 3. The Microbes We're Made Of 2 MIN 30 SEC We're not just made of waste. We're made of trillions of other organisms. This video provides a quick exploration of the microbiome crucial to keeping our bodies working, and what we're doing to kill them: http://www.smithsonianmag. com/videos/category/3play_1/ the-microbes-were-made-of/?no-ist WHERE THIS FITS IN THE CURRICULUM Matter and energy in organisms and ecosystems (HS-LSI-5) Use a model to illustrate how photosyn- thesis transforms light energy into stored chemical energy. HistoryoftheEarth (HS-ESSI -6) Applyscientific reasoning and evidence from ancient Earth materials, meteorites, and other planetary surfaces to construct an account of Earth's formation and early history. Chemical reactions (HS-PSI-2)Construct and revise an explanation for the outcomes of simple chemical reactions based on the outermost electron state of atoms, trends in the periodic table, and knowledge of the patterns of chemical properties. Ecosystems: Interactions, energy and dynamics (HS- LS-3) Construct and revise an explanation based on evidence for the cycling of matter and flow of energy in aerobic and anaerobic conditions. IS EFTA00805745 MATTER I ENVIRONMENT You Are Made of Waste Searchingfor the ultimate example ofrecycling? Look in the mirror BY CURT STAGER YOU MAY THINK OF YOURSELF as a highly refined and sophisticated creature—and you are. But you are also full of discarded, rejected, and recycled atomic elements. Don't worry, though—so is almost everyone and everything else. Carbon: Your inky nails Look at one of your fingernails. Carbon makes up carbon-rich animal tissues, finding their way into half of its mass, and roughly I in 8 of those carbon meat and dairy products. Historically, atmospheric atoms recently emerged from a chimney or a tail- carbon dioxide was mainly replenished by volcanoes, pipe. Coal-fired power plants, petroleum-guzzling forest fires, and biotic respiration. Today, one quarter of cars, and kitchen gas stoves release carbon dioxide atmospheric CO2 is the result of fossil fuel combustion, into the atmosphere. Each of those waste molecules whether it rose from smokestacks or was displaced is a carbon atom borne on two atomic wings of oxy- from the oceans. (When fossil-fuel CO2 dissolves into gen. Fossil-based carbon dioxide molecules that are ocean water, it displaces already-dissolved carbon not soaked up by the oceans or stranded in the upper dioxide derived from natural sources.) And because atmosphere are eventually captured by plants, shorn all of the carbon in your body derives from ingested of their oxygen wings, and woven into botanical sug- organic matter, which in turn obtains it from the atmo- ars and starches. Eventually, some of them end up in sphere, your fingernails and the rest of the organic bread, sweets, and vegetables, while others help form matter in your body are built, in part, from emissions. ILLUSTRATIONS BY YUKOSHIMIZU 16 EFTA00805746 NAUTILUS I TEXT SE TS 17 EFTA00805747 NAUTILUS EDUCATION I BETA PRODUCT Radioactive Carbon-14: Your pearly whites When you smile, the gleam of your teeth obscures a way into our water supply and meals. If they happen to slight glow from radioactive waste. During the late disintegrate within your DNA, they can damage your 1950s and early 1960s, atmospheric testing of thermo- genes. And many of them are bound up in your teeth. nuclear weapons scattered so much radioactive car- Unlike most of the atoms in your body, those embed- bon-14 into the atmosphere that it contaminated vir- ded in your strong, stable tooth enamel have been with tually every ecosystem and human. Several thousand you ever since you ingested them through your umbili- unstable radiocarbon atoms explode within and among cal cord and your infant feeding. If you were born dur- your cells every second as their unstable nuclei under- ing the early 1960s, you have more nuclear waste in go spontaneous radioactive decay. Some are the natu- your teeth than if you were born later, when soils and ral products of cosmic rays that can turn atmospheric oceans had had time to bury radioactive atoms. In fact, nitrogen into carbon-I4, while others result from the forensic scientists use the proportion of bomb carbon decay of unstable mineral elements that are found in in tooth enamel to determine the age of unidentified soil. But many of them represent the echoes of ther- human remains. monuclear airbursts from the Cold War, finding their IS EFTA00805748 NAUTIL.US I TEXT SETS Oxygen: Your leafy breath The oxygen in your lungs and bloodstream is a highly Oxygen absorbs electrons released by broken food reactive waste product generated by vegetation and molecules, which attract hydrogen ions, resulting in microbes. Trees, herbs, algae, and blue-green bacte- a molecular waste of your own making: metabolic ria split oxygen atoms out of water molecules during water, which comprises one tenth of your body fluids. photosynthesis. They use most of the resultant gas for An average adult carries between 8 and 10 pounds of their own purposes, but thankfully some leaks out to homemade wastewater within them, and 1 in 10 ofyour sustain you. In fact it makes up about a fifth of the tears are the metabolic by-products of your breathing air you breathe. Your cells harness oxygen to release and eating. energy from chemical bonds in the food you consume. EFTA00805749 NAUTILUS EDUCATION I BETA PRODUCT Nitrogen: Your natural curls The next time you brush your hair, think of the nitrog- Every flash of lightning and every automotive spark enous waste that helped create it. All of your proteins, plug emits a puff ofnitrogen oxide, which can dissolve including hair keratin, contain formerly airborne into raindrops and fall to earth as a form of fertilizer, nitrogen atoms. But the nitrogen in air is biologically again finding its way into food webs through plants. inert. For nitrogen to become a component of your But most of the nitrogen in modem foods comes from hair, it has to be converted into a more accessible form. urea and ammonium nitrate fertilizers artificially fixed Nitrogen-fixing bacteria is one way that can happen. by industrial processes. In ages past, the nitrogen in They live among the roots of beans, peas, and other human hair came mainly from bacterial waste and legumes, consuming atmospheric nitrogen and releas- lightning. But today, unless you eat a strictly organ- ing it as ammonia, a kind of microbial manure that ic diet, you run your hairbrush through nitrogenous fertilizes soil in which plants grow. When you eat a frameworks that are mostly ofhuman origin. plant, you consume formerly atmospheric nitrogen. EFTA00805750 NAUTIL.US I TEXT SETS Iron: Your ancient blood When you cut yourself, the wreckage of stars spills iron at supersonic speeds, filling great swathes of space out. Every atom of iron in your blood, which helps with debris that can form new solar systems. The iron your heart shuttle oxygen from your lungs to your in your frying pan, house keys, and blood is essentially cells, once helped destroy a massive star. The fierce cosmic shrapnel from the tremendous explosions that nuclear fusion reactions that set stars ablaze create ripped through our galaxy billions of years ago. The the atomic elements of life. As the star ages, it fin- same blasts also released carbon, nitrogen, oxygen, and es progressively larger elements, such as silicon, sul- other elements of life, which later produced the sun, fur, and calcium. Eventually, iron atoms are fused. the Earth, and eventually—you. ® The problem is that iron fusion consumes as much energy as it produces, so it weakens the star. If the star is big enough, it will collapse in on itself, its outer curt stager is an ecologist and climate scientist at Paul layers rebounding against the dense inner core, and a Smith's College. He is the author ofDeepFuture: TheNext i00,000 Years ofLife On Earth, and alsoco-hosts a weekly science program supernova explosion will result. The blast sprays out on North Country Public Radio. 21 EFTA00805751 EFTA00805752 NIAT TER :SI( t. Frack 'er Up Naturalgas is shaking up the searchfor green gasoline BY DAVID BIELLO AM SPEEDING DOWN New Jersey's highways, has been called the "olive economy"—companies that I - propelled by gasoline with a dash of ethanol, an alcoholic biofuel brewed from stewed corn ker- nels. As I drive through the outskirts of the town- are neither bright green nor darkest black, but com- bine environmentally-friendlier technologies with old- er and dirtier ones in order to compete. In fact, Primus ship of Hillsborough, in the center of the state, I see may become a leader in advancing this kind of technol- that spring has brought with it a bounty of similar "bio- ogy. "We can be as dark as you want or as green as you mass," as the fuel industry likes to call plants. Trees want," says geologist, serial entrepreneur, and Primus line the road and fresh-cut grass covers the sidewalks salesman George Boyajian. as I pull into the business park that is home to Pri- In July, President Barack Obama gave a major mus Green Energy—a company that has been touting speech on climate change that described natural gas a technology to transform such biomass into a green as a "transition fuel" towards the "even cleaner energy and renewable form ofgasoline. economy of the future." But Primus's trajectory raises But there's a hitch. The boom in hydraulic fracturing, the question of whether natural gas is a boost on the or "fracking," a technique in which horizontal drilling road to a genuinely green fuel, or if it is prolonging our and high-pressure jets of water are deployed to release addiction to dirty modes of transport, and taking us on gas trapped in sedimentary shale rock, has made natu- a detour from a low-carbon path. ral gas cheap and plentiful. That's not bad for Primus, At the Primus headquarters, I first meet Primus's whose technology can make gasoline from natural gas, chief chemist Howard Fang in front of a prototype of biomass, or even low-grade coal, such as lignite or peat. a Primus conversion machine. Fang, who joined the This versatility makes Primus a potential part of what company for what he calls his "semi-retirement," is ILLUSTRATION BY PETER &MARIA HOEY 23 EFTA00805753 NAUTILUS EDUCATION I BETA PRODUCT avuncular and black-haired. His interests are broad: River each summer as a result of fertilizer washing off He spends his spare time writing and reading history, the endless cornfields of the Midwest. But ethanol is and has authored books on conflict in the Middle East unlikely to ever fully replace conventional fossil fuels, and the role of Christian missionaries in China. since it is more difficult to transport, produces a frac- A lifetime in fuels chemistry left Fang with one tion of the energy of oil, and would require engines to burning question: "What is the real solution to the be refitted or replaced on a massive scale. energy crisis?" His career at oil companies BP and Hence the interest in "drop-in" biofuels as a sub- ExxonMobil, and engine manufacturer Cummins, stitute for conventional fuels in existing cars, planes, spanned not just one but two major energy upheav- and trucks. The problem is not one of infrastructure, als—the oil crisis of the 1970s and then its sequel in but chemistry: Companies must find a way to eco- the first decade of the 2Ist century, which is arguably nomically imitate and fast-track a process for which still ongoing. These experiences impressed on Fang time and geology have done most of the work in con- the importance of securing the fuel supply in such ventional fossil fuels. The energy in these fuels is the a way as to avoid despoiling the environment. The pent-up power of ancient sunlight, which billions of solution, says the bespectacled chemist, is "nature- photosynthetic microorganisms soaked up before sourced biomass or natural gas converted effectively dying, fossilizing, and turning into the hydrocarbon- to gas or diesel." rich stew we know as petroleum, and from which we Primus's original idea was simple: take scrap wood refine gas, diesel, and jet fuel, among other products. or other biomass, turn it into pellets, and apply pres- In theory, then, it should be possible to turn the car- sure and heat (700 degrees Celsius or more) to break bohydrates and other chemicals that store energy for it down into hydrogen and carbon monoxide. Then today's living things into the hydrocarbons we rely on build this composite "syngas," shorthand for "synthet- for transportation. ic gas," back up into whatever hydrocarbon product is Potential routes to such "green crude" include desired—the molecules of eight carbon and 18 hydro- algae, other photosynthetic organisms, and specialty gen atoms known as iso-octane that are a measure microbes engineered to spit out hydrocarbons. Biofuel of the quality of conventional gasoline, or the longer company Solazyme has a contract to supply United chains of similar hydrocarbons that comprise diesel or Airlines with 20 million gallons of algal jet fuel, and jet fuel. Because plant biomass absorbs carbon dioxide teamed up with a green fuel-station network to offer as it grows, the emissions produced by burning the biodiesel in a test run in San Francisco's Bay Area. But biofuel should balance out overall—every molecule of it takes a lot of water—and a lot ofenergy to move that CO2 emitted when the fuel is burned was previously water around—in order to grow algae in large quan- absorbed by the plant that made the fuel. tities, and tailor-making microbes is expensive at its The story of the search for such green fuel is lit- current scale. As a result, companies are diversifying. tered with disappointments, however. Major compa- Algal fuel producer Sapphire Energy is now focusing nies brew ethanol in large quantities in the United on isolating the genetic traits in the ancestors of all States. It is routinely added to gasoline (at levels of plants that might be usefully incorporated into other around 10 percent, on its way to 15 percent) as a way crops. Solazyme is making oils and specialty fats to sell to improve combustion, reduce pollution, and support at high margins to cosmetics and food companies, as industrial corn farmers. But most ethanol is still made is would-be microbial fuel-maker Amyris. The industry from the edible kernels of corn plants, instead of the for "advanced biofuels is literally in its infancy," con- inedible cellulose that was promised in the heady days cedes Jonathan Wolfson,Solazyme CEO. of the mid-2000s, when Congress passed a spate of The allure of Primus's technology is its promise to laws promoting biofuel production. Since 1978, the harness waste wood and other inedible biomass that ethanol industry has enjoyed subsidies and tax credits would otherwise be thrown into landfills, and turn to the order of 40 cents per gallon, and now produces it into a renewable source of gasoline. Its "syngas to an annual dead zone at the mouth of the Mississippi gasoline plus" process consists, essentially, of four 24 EFTA00805754 NA UTIL.US I TEXT SETS "We can be as dark as you want or as green auotovant," says Boyajian. chemical reactors. One turns the syngas into methanol. more than happy to reveal all those dark arts—a pros- The next makes methanol into a molecule known as pect that makes the affable Boyajian nervous and tight- dimethyl ether, or DME in chemist-speak. In the third lipped. For now, the fledgling company buys the neces- reactor, catalysts known as zeolites knit DME into gas- sary catalysts off the shelf and must sign agreements oline, in the most expensive and energy-intensive part not to examine these zeolites too closely. of the process. The fourth reactor eliminates some of Using different catalysts in the reactors, Fang notes, the unwanted byproducts that cause the resulting fuel the company could spit out diesel or jet fuel instead to congeal at low temperatures. of gasoline. And for every 100 kilograms of syngas, The key is the zeolites, porous minerals made up of he says, Primus can make 30 kilograms of gasoline or aluminum, silicon, and oxygen that allow the desired more, using a continuous looping system within the chemical reactions to take place. Both Primus and a machine that eliminates the need for wasting energy conventional oil refinery employ zeolites to manipu- to convert gases to liquids along the way. Little red late hydrocarbons. At an oil refinery, these catalysts containers of Fang-made gasoline record its charac- help crack and sort hydrocarbons broken down from teristics, scrawled on masking tape affixed to the sides: crude oil. At Primus, heat and pressure allow zeolites low vapor pressure, a higher-than-average octane con- to build gasoline hydrocarbons from the smaller mol- tent of around 93, and a favorable absence of sulfur ecules of syngas. Such "catalysts are a bit ofa dark art," or benzene. Oil prices have been rising over the last says Boyajian. He spars with Fang over whether or not month, and are currently at more than $100 per barrel; the company will one day make their own. Fang does the company estimates that its gasoline costs as little not accept Boyajian's need for secrecy, and would be as that derived from oil at $65 per barrel—and could 25 EFTA00805755 NAUTILUS EDUCATION I BETA PRODUCT cost as little as $2 per gallon, or about half the price gas currently goes for at local pumps, to produce at a nth-sized facility, even though such an industrial plant would require a lot of capital to build. However, the machine Fang shows me is not run- ning on the biomass that Fang originally tested: wood chips, switchgrass, canary grass, miscanthus. Instead, it chums through natural gas, turning methane into syngas. Making long hydrocarbons from the single car- bon in methane molecules is "very easy," he assures me. But "natural gas is not true green," he concedes. "There is no benefit in [the reduction of] greenhouse gases. Biomass is still true green." Natural gas from the fracking boom has revolution- ized the global energy landscape—particularly in the United States, the world's biggest producer of shale gas. But it is also controversial. Gas burns cleaner, but it still produces around half the greenhouse emissions of its dirtier cousins like coal, not including the excess methane that leaks from fracking sites and the pipe- lines that transport the gas. Fracked gas can also con- taminate groundwater supplies. And while in 2012 it brought America's carbon footprint down to its low- est level in 20 years, relying on it in the long-term will make it hard to eliminate greenhouse gas emissions, as is required to combat climate change. As the price of natural gas slid in response to the glut of shale gas, Primus changed gears in mid-2012 to move away from biomass and to focus on making syngas from natural gas. This is not a new idea: Exx- onMobil built a plant in New Zealand in 1986 to turn natural gas into methanol and then gasoline, but aban- doned its efforts when the price of petroleum dropped dramatically in the mid I990s. Now, though, natural gas is cheap and attractive. Boyajian has a map of all the shale formations in North America tacked to the wall ofhis office. "The world is full of shale," he notes. An earlier version ofPrimus' machine, tuned to pro- cess biomass, sits swathed in silvery insulating tape The energy in thesefuels in a locked and darkened lab. "Right now it is aban- is thepent-uppower of doned," Fang says. The company insists that the state- ment doesn't apply to Primus's biomass efforts more ancient sunlight, which generally. "This is the way to get to biofuels," says Pri- billions ofphotosynthetic mus CEO Robert Johnsen, of the gas to gasoline pro- cess, through a tight smile. "Will we be the ones to get microorganisms soaked up there? Maybe." before dying. 26 EFTA00805756 NAUTIL.US I TEXT SETS Will natural gas be a bridge for Primus to green cleaner fuel for standard, dirty combustion engines fuel, or will it be too cheap and attractive to resist as may reinforce drivers' loyalty to today's technology. a permanent substitute for biomass? For the moment, Such lock-in makes a true revolution difficult until the company seems keen to squeeze what it can out of some alternative energy source—whether battery- the shale gale. With the help of more than $50 million driven electric cars or engines modified to burn car- in Israeli money, Primus is building a demonstration bon-neutral, as-yet-unmade biofuels—offers the kind plant the size of a house near its headquarters in New ofconvenience and low cost that justifies replacement. Jersey, due to open this year. The location is off the At present, Primus appears set to become part of a map—even Google won't guide you there, as if it were sprawling infrastructure that reinforces the incentives some secretive skunk works facility, which is how the to use greenhouse gas-producing, gasoline-like fuels. company likes to think of it. The plant will take natural And for all those concentrated octanes in my tank, I gas from the local utility, run it through its proprietary still have to pull into a Shell station to fill up on con- set of chemical reactions and, on the far end, out of a ventional gasoline, blended with corn ethanol, in order spigot, will come gasoline— 12.7 gallons per hour at full to drive home. e capacity. The company's first commercial plant, due to start construction next year, will likely be located near a source ofnatural gas. david biello is the Environment and Energy Editor for Scaling up the technology this way will reduce the ScientificAtnerican. He iseurrently working on a book about the overhead costs per unit of gasoline—that is, the cost Anthropocene. of fabricating the reactors and buying the zeolites and feedstocks. Plus, Primus' technology may prove eco- nomical enough at a scale small to allow its plants to be distributed close to remote natural gas wells or even sources of biomass. It is no coincidence that the com- pany based itself in verdant New Jersey, "the Garden State"; proximity to biomass is crucial for producers, because transporting heavy and unwieldy wood or corn stalks across large distances tends makes the end product too costly and undercuts the greenhouse-gas savings that are a large part ofits appeal. As I prepare to drive off, Fang carts out one of his collection of red plastic gas cans and dumps a liter or so of Primus-made, natural gas-to-gasoline fuel into my tank. A test car tooled around on it last summer, with no problems. The hope is to be able to charge a premium for the higher-octane premium product. "People pay twice as much for organic food," Boyajian says. "So why not pay more for green gasoline?" My fuel sensor can tell the difference: it registers an anom- alously high miles-per-gallon number. Fang gives me two thumbs up as I pull away, watch- ing me drive off on his preferred solution to the ener- gy crisis. It's unclear whether Primus will ever find the occasion to turn back towards biogasoline—and whether that's a long-term fix for the world's ener- gy and environmental conundrum. Striving to make 27 EFTA00805757 NAUTILUS EDUCATION I BETA PRODUCT Genetics & Human Health Since DNA is often heralded as the "code of life," what clues can mutations—changes to the DNA sequence—tell us about human health and disease? The pair of articles in the Genetics and Human Health module will explore the consequences of mutations in the context of cancer treatment and rare diseases such as muscular dystrophy. Their Giant Steps to a Cure discusses the challenges associated with treating a rare form of muscular dystrophy. An Unlikely Cure Signals Hopefor Cancer explores how specific mutations in a patient's cancer can be used to a patient's advantage. Lesson Plan Ask students to read both of the articles for homework. Briefly introduce or review the vocabulary words in class. Assign the questions listed under "Reading Comprehension" for them to complete along with the reading and ask them to come up with one question for further discussion. Stan class by asking students if they have any questions about the readings. Ask them to contribute their discus- sion questions (in addition to the ones provided under Deep Thinking / Discussion questions). Have the class brainstorm and answer both discussion questions. Is MIN. Next, break the class up into four groups for the Suggested Activity. Assign each group to one protein that is listed in the interactive. 15 MIN . Have each group present their thoughts to the class for further discussion. is MIN. Teacher's Notes: Their Giant Steps to a Cure, and An Unlikely Cure Signals Hope for Cancer VOCAB WORDS Muscular dystrophy: a genetic disease marked by of proximal (limb-girdle) muscles. progressive weakening of the muscles. Some forms of Cancer: A term used to describe disease in which muscular dystrophy are seen in infancy or childhood. abnormal cells divide without control and are able to Orphan diseases: diseases that have yet to be "adopt- invade into other tissues. Cancers are often catego- ed" by the pharmaceutical industry because there are rized based on the organ or cell type they originate in. very few incentives to develop new medications to Oncologist: A doctor who specializes in treating treat or prevent them. Orphan diseases can be rare patients with cancer. or they are common diseases that have been ignored (e.g.: tuberculosis, cholera, typhoid, malaria). Outlier: An observation that deviates from a major- ity and can be seen to be a rare event. In the context Calpainopathy: a rare type of muscular dystrophy of this piece, the outliers are patients who respond characterized by symmetric and progressive weakness 28 EFTA00805758 NAUTIL.US I TEXT SETS to therapy when the same therapy has failed other ACTIVITIES patients. Some genes are not specific to humans, but rather, Remission: a decline or disappearance of signs and are common to myriad species. In a smaller group, symptoms of cancer. you will be assigned to read about one of the pro- teins listed here: http://nautil.us/issue/5/fame/ genes-that-won-the-fame-game READING COMPREHENSION Pleaseanswerthefollowingquestions whenit isyour turn I. Why are orphan diseases underfunded? topresent to theclass: 2. How does the mutation in calpain 3 cause muscle I. What organisms is the gene present in? Were you to fail to grow? surprised by the presence of the gene in any of the organisms listed? If so, why? 3. What are some reasons pharmaceutical com- panies would want to develop drugs for orphan 2. If this protein was mutated, what could the con- diseases? What are some possible reasons they sequences look like? Could it cause a disease? would be against doing so? 3. Research and present one other case of an outlier 4. Statistically speaking, outliers are often ignored. being useful in science or medicine. In this story, why is patient number 45 such an interesting case? Why is it generally important to study the outliers of response? WHERE THIS FITS IN THE CURRICULUM S. Which protein's activity is blocked by evero- Structure andFunction (HS-LSI-VA cell contains limus? What is the function of this particular genetic information in the form of DNA molecules. protein? Genes are regions in the DNA that contain the instructions that code for the formation of proteins, which carry out most of the work of cells. DISCUSSION QUESTIONS Variation ofTraits (I-LS-LS3-2) Although DNA repli- I. In what contexts would it be desirable and unde- cation is tightly regulated and remarkably accurate, sirable to sequence your genome to see if you errors do occur and result in mutations, which are are at risk for a disease? What are the benefits also a source of genetic variation. Mutations can, in and downsides of knowing if you are at risk for a turn, cause disease and/or affect human health. The particular disease? pattern of mutations can also predict response to drugs. 2. In both pieces, mutations are responsible for causing disease. Compare and contrast the ways Inheritance and Variation of f-irs:tits -Environmental mutations can lead to muscular dystrophy and Factors (HS-LS3-3) Technological advances have cancer. Are the mutations in one case hereditary? influenced the progress of science and science has Are mutations leading to either disease caused influenced advances in technology. Technologies have by environmental factors? Are the mutations in evolved to sequence human genes, which can better either case preventable? If so, how could they be inform doctors of their patients' health. Likewise, prevented? pharmaceutical companies have also created many drugs for the treatment of human disease. 3. How should doctors and scientists decide whether to work on a rare condition? 29 EFTA00805759 EFTA00805760 BIOLOGY I MEDICINE Their Giant Steps to a Cure Battlingarareformofmusculardystrophy, afamilyfindsanactivistleader,andhope BYJUDE ISABELLA N 2007, AT HER high school graduation in Ques- about ramps everywhere they went, avoiding walking I nel, British Columbia, Ivana Topic stood at the top of the auditorium stairs, her long gown skimming — the floor, her dark brown hair spilling over her in snow and sleet. For years, Ivana and Antonia had been subjected to endless medical tests. In 2010, they learned they had a rare form of muscular dystrophy, shoulders. She had on ridiculously high heels. As she calpainopathy, which affects about 1 in 200,000 peo- eased down the stairs, very slowly, she hung on to her ple. The diagnosis meant both would likely be bound to date. She was afraid her knees would collapse, as her wheelchairs while they were still young women. muscles were weak for her age. Today, Ivana is 24. In May, she graduated from col- From the audience, Ivana's mother, Marijana, lege with a bachelor's degree in finance and general watched her daughter's every step, silently panicking business. She still walks up stairs in her house; her and breaking into a sweat. She knew Ivana could eas- bedroom is upstairs. "M definitely a fighter, and will ily tumble down the stairs and break a limb. The year try and walk for as long as I can," she says. "When I before, lvana had been diagnosed with muscular dys- notice El falling a lot, when I need help a lot, I will trophy, an incurable genetic disease characterized by go in a chair." progressive weakening of the muscles. Antonia, lvana's Muscular dystrophy treatment is limited to only pal- younger sister by five years, was later diagnosed with liative medications and therapies. Ivana herself prac- the same disease. tices yoga. While researchers worldwide are working Around the time of Ivana's graduation, the Top- on lasting cures for muscular dystrophy (funded in part ics, an unassuming family originally from Croatia, had by the famous Jerry Lewis Telethons), rare forms like begun adjusting their lives as best they could, inquiring calpainopathy are "orphans," with only a fraction of ILLUSTRATIONS BY ELLEN WEINSTEIN 31 EFTA00805761 NAUTILUS EDUCATION I BETA PRODUCT "Edefinitelyafighter, andwill try and walkfor as longasIcan." researchers and funds devoted to them. With quiet National Institute of Health allocated $3.5 billion to stoicism, the Topics have accepted that modem medi- research orphan diseases. Yet some diseases are so rare cine may not have a solution for their daughters' dis- that they remain stepchildren even among orphans. ease. Still, says Marijana, "Without hope, there's no As a result, they receive little research attention and life." funding. Neither do they fit the list of billable insur- Following a current grassroots trend in medicine, ance procedures. There's no standard healthcare path many individuals with orphan diseases do not wait for to diagnosis, let alone treatment. Similar to the Topics, the medical industry to care about them. Facing long many patients go through an ordeal, which Marijana odds, they are forced to raise money to find a potential describes as "a blur," only to find out that medicine cure themselves. But the Topics live by modest means. can't help them. Marijana runs a daycare center and her husband and Orphan disease organizations, such as the National the childrens' father, Niko, works for a lumber com- Organization for Rare Disorders and the Rare Disease pany. They are in no position to mount a quest. Foundation, encourage patients to take matters into But then there's Michele Wrubel, 49, a stay-at-home their own hands. "Families have to advocate," says Isa- parent from Connecticut who has calpainopathy. For bel Jordan, chair of the Rare Disease Foundation. She years, Wrubel has been a passionate crusader for a encourages patients to form organizations, find new cure. Affluent and well connected, she doesn't varnish methods of funding, and push for research. the truth about what it has taken to make the medical "Push for research" could be Michele Wrubel's call- industry pay attention to her. "To make a difference in ing card. She was diagnosed with muscular dystrophy this disease, you need money and meetings," she says. in her mid-20s. But even though calpainopathy was "Researchers are not going to study a disease unless identified nearly 20 years ago—about the same time there's money behind it to fund the research." For the Wrubel got her initial diagnosis—it took almost the Topics, Wrubel may be their best hope. entire second half of her life to determine that she was afflicted with calpainopathy. There were no clinical THE GLOBAL GENES PROJECT, an advocacy group, procedures that would lead to a diagnosis. estimates 350 million people suffer from orphan dis- "It took a really long time and a very concerted eases worldwide. Most rare diseases are genetic and effort," says Wrubel, who walks with canes, submitting tend to appear early in life. About 30 percent of chil- to a wheelchair for long trips or when in crowded places. dren who have them die before reaching their fifth "If you don't know what you're looking for, they don't birthday. The rest battle their conditions throughout know what to tell you or how to help you," she says. life, as most orphan diseases have no cure. Out of the In 2008, gene sequencing came of age, which aided 7,000 orphan diseases identified to date, with about physicians in diagnosing muscular dystrophy subtypes. 250 new ones added annually, less than 400 can be That year, Wrubel's husband, Lee, who holds a medical treated therapeutically. degree and a master's in public health from Tufts, an This year the European Commission gave 144 MBA from Columbia University, and is a venture capi- million euros to develop 200 new therapies and the talist in the medical field, tracked down a neurologist 32 EFTA00805762 NAUTILUS I TEXT SETS EFTA00805763 NAUTILUS EDUCATION I BETA PRODUCT In the quest for a cure, she says, a matter otpatients taking charge of their diagnosis. to sequence his wife's genomes. He paid several thou- sand dollars from his own pocket to learn his wife had calpainopathy. The Topics had no such luxury. But they did have luck. Cornelius Boerkoel, a clinical geneticist at the University of British Columbia, enrolled the Topics in one of his studies, and so they didn't have to pay to have each of the family member's genomes sequenced. The genome tests gave Ivana and Antonia the bad news about calpainopathy. Their younger brother, Mario, is free of the disease. Scientists classify calpainopathy, or "calpain," as a limb-girdle muscular dystrophy Type 2a, caused by a mutation in the gene calpain 3, predominantly expressed in skeletal muscle. Those who suffer from Type 2a, such as Wrubel, Ivana, and Antonia, gener- ally exhibit weak hip flexors—muscles that lift up the thigh. The weak flexors give them an awkward gait; they swing their legs forward, landing on their toes, and then sometimes on the sides or soles of their feet. Some walk only on the balls of their feet. The upper body muscle weakness creates abnormally prominent shoulder blades. Melissa Spencer from the University of California, Los Angeles, who has studied calpainopathy for 14 years, explains that the disease contains many sub- types. The problem with Type 2a, she says, "was a 34 EFTA00805764 NAUTIL.US I TEXTSETS really strange gene mutation that was completely inex- about clinical trials," Spencer says—and then another plicable." She says it has been a hard disease to study, five years before the drugs can be commercially avail- partially because the implicated protein is unstable able, she estimates. and partially because it was a rarity among the orphan Wrubel's coalition intends to get pharmaceutical diseases. When it comes to funding, calpainopathy companies interested, too. "Many pharmaceutical com- has been overshadowed by other forms of muscular panies see treating orphan diseases as a way to increase dystrophy. "Muscle studies have been underfunded profits," Wrubel says. Her husband, Lee, adds, "The forever and certainly a rare disease like 2a especially whole model for big pharmaceutical companies going underfunded," Spencer says. forward is different. There is too little in the big phar- In 2010, Wrubel formed the nonprofit Coalition to maceutical pipeline, and they're looking to feed that Cure Calpain 3. In the quest for a cure, she says, "It's beast as much as possible." A 2012 Thomson Reuters a matter of patients taking charge of their diagnosis." study found that drug companies stand to profit from She reached out to other sufferers via Facebook, and orphan drugs because, compared to drugs for common some donated money. She partnered up with two other afflictions, they often have shorter and less expensive nonprofits that had raised funds on their own, both clinical trials, with more surrns. Spencer says a drug started by those afflicted with Type 2a. So far Wrubel's for calpainopathy, for instance, would also be useful efforts have gathered close to half a million dollars. for patients with Lou Gehrig's Disease and bed rest With that money, she has funded a project with Louis patients, as it would help arrest the loss of bone and Kunkel, professor of genetics and pediatrics at Boston muscle mass. Wrubel hopes to bring Cydan Develop- Children's Hospital, one of the nation's key muscular ment, a venture-capital backed orphan drug developer, dystrophy researchers. to their upcoming fall conference in the Netherlands. Her coalition also organized a conference to bring As for the Topics, they were excited to learn about calpainopathy researchers together, including Spen- Wrubel from Nautilus. Ivan recently connected with cer. Years earlier, in 2005, Spencer made a significant Wrubel through Facebook. "I only talked with her a lit- breakthrough. She discovered that calpainopathy, tle bit, but she seems ambitious and driven," Ivan says. unlike more common forms of muscular dystrophy, "Definitely not someone who is going to sit around and was not a weakening of the muscle but a growth prob- wait for something to happen. Definitely inspiring. And lem—muscle forms, but fails to grow because of a the possibility that something might help in any way is a missing protein. It is different from other muscular good thing to hear, for sure!" Ivana says she now wants dystrophies in which the lack of the protein complex, to get involved and advocate for her own disease. "I def- dystrophin, damages muscle membranes. "With cal- initely want to do something," she says, and Wrubel's painopathy, the muscles lack the growth signal," she coalition "would be a good place to start." says. "It's not transmitted properly." That difference makes a drug cure more possible. "I think this is going to be the easiest muscular dystrophy to curer she says. Jude isabella is a science writer based in Victoria, Brit- Encouraged by the promise, the Coalition to Cure ish Columbia. Her new book Salmon, A Scientific Memoir, will be Calpain 3 gave Spencer's lab a $260,000 grant to released next year. investigate how to circumvent the signaling problem and come up with a drug to fix it. But because the United States Food and Drug Administration already has a library of approved compounds that stimulate cell growth in muscle, Spencer's team may arrive at a solution sooner. With the help of the coalition's money, her lab is now plowing through the thousands of existing compounds, choosing those fit for testing. "I think it will be five years before we start thinking 35 EFTA00805765 BIOLOGY I MEDICINE An Unlikely Cure Signals New Hope for Cancer How "exceptional responders "are revolutionizingtreatment for the deadlydesease BY KAT MCGOWAN J UST LIKE EVERY NEW drug the oncologists at environmental inputs. So sometimes a patient will be Memorial Sloan-Kettering Cancer Center test- cured by a drug that is useless for everyone else. In ed against bladder cancer in the last 20 years, the past, these spectacular reactions were written off this one didn't seem to be doing any good. For- as outlier responses that defied explanation—medical ty-four people in the study were given everolimus in a mysteries. Doctors just shrugged their shoulders and last-ditch attempt to slow down or stop their advanced thanked their lucky stars that even though the study cancer. When the researchers analyzed the data, they tanked, they did manage to help one person. could see that the drug wasn't slowing or stopping But this time was different. Clinical oncologist tumor growth. Everolimus seemed to be another bust. David Solit, director of developmental therapeutics Then there was patient number 45. She joined the at Sloan-Kettering, saw a new opportunity to explain trial with advanced metastatic cancer. Tumors had what happened by sequencing the whole genome of invaded deep into her abdomen, clouding her CT scan the woman's cancer. Just five years ago, decoding and with solid grey blotches. She was 73 years old. None of analyzing all 3 billion bases of the DNA from a tumor the standard bladder cancer drugs were working for would've been absurdly time-consuming and expen- her anymore; she had "failed treatment," in the dismal sive. Now the sequencing takes as little as a few days. lingo of oncologists. She enrolled in the study only Poring over the outlier patient's genetic code, Solit because she happened to be a patient at Sloan-Ketter- pinpointed two mutations that made her tumor sensi- ing in January 2010.1n Apri120 I 0, her cancer was gone. five to this drug. He found that one of her mutations This sort of happy surprise is not unheard of shows up in about 8 to 10 percent of other bladder can- in drug studies. Bodies are fluky, each with its own cer patients, meaning that they too might be helped idiosyncratic combination of genetic blueprints and by everolimus. His success has inspired a whole set of ILLUSTRATION BY ELLEN WEINSTEIN 36 EFTA00805766 NAUTIL.US I TEXT SETS programs to study "exceptional responders": those rare of HIV in his body, and his case has inspired a study cancer patients who do well while nobody else does. to genetically engineer HIV-positive patients' cells to Cancer is a personal disease, Solit explains. Each resist the virus. tumor constitutes its own world ofdefective genes and In the past, cancer researchers weren't able to proteins. By studying the genetic quirks of exception- capitalize on their unexpected outlier successes. Not al responders, physicians can systematically identify enough was known about the biology of cancer, and weaknesses in cancer subtypes and blast them with the right tools hadn't been invented. "Even if someone drugs that target their unique vulnerabilities. "It's a had a complete remission, you had no way to figure out testament to how much has been learned about the why," says James Doroshow, director ofthe Division of genome in the past 30 years," Solit says. "We've always Cancer Treatment and Diagnosis of the National Can- wanted to find out why some individuals respond so cer Institute (NCI). That changed in the 2000s, when well. Now we have the capacity. It's going to really it became possible to analyze the genetics of cancer change the way we treat patients." tumors for clues. The first major success came with studies of the UNLIKELY CASES HAVE AN eminent history inmedi- drug gefitinib in non-small-cell lung cancer (the most cine. The modern science of the mind owes a lot to common kind). Gefitinib helped less than 20 percent the freakish accident suffered by Phineas Gage, a of the people who took it, but a few outliers had dra- 19th century railroad construction foreman whose matic, rapid recoveries. In 2004, two Harvard groups job involved packing down explosive powder with a found that the responders had mutations in the epi- three-and-a-half-foot-long iron tamping rod. On Sept. dermal growth factor receptor (EGFR) gene. EGFR is 13,1848, the powder exploded in his face, blasting the one of many genes that regulates how cells grow and rod up through his chin and out the back of his head. when they die, and the mutation basically forced it to Against all odds, he survived. But his personality was pump out two or three times as much growth signal as transformed. The formerly shrewd and patient Gage it should, fueling the cancer. Gefitinib dialed down the became obnoxious and unreliable. signal. A clinical trial later proved that the drug keeps An observant doctor named John Martyn Harlow tumors at bay for more than nine months in people who cared for Gage proposed that his personality with certain EGFR mutations. change was due to the destruction of the frontal lobe More insights gleaned from extraordinary respond- of the left side of the brain. Gage's unlikely transfor- ers soon followed. One melanoma patient in a study of mation revealed a universal truth about brains, that 22 people taking sorafenib saw his tumor shrink quick- particular parts—the frontal lobes—are required for ly, a response due to a mutation in the gene KIT, which self-control. The strange case of Phineas Gage is still regulates cell growth, division and survival. People mentioned in neuroscience textbooks. with certain kinds of melanoma, such as the type that Rare events can also lead to new cures. As the story grows on mucus membranes, now routinely get tested goes, English physician Edward Jenner's observations for this mutation. The drug helps about 40 percent of of an 18th century milkmaid who caught cowpox and those with the mutation—an impressive advance in a thereby became immune to smallpox paved the way for cancer that once had no effective treatment. the fi vaccines. New ideas for curingHIV are emerg- In these studies, investigators had to make educat- ing from the famously unlucky lucky case ofthe"Berlin ed guesses about where in the genome to look for the patient." Timothy Ray Brown, who was HIV positive, culprit mutations. It was the keys-under-the-lamppost developed blood cancer leukemia in 2006. His chemo- phenomenon: They could only examine genes they therapy and radiation treatments wiped out the cells already suspected were involved in the cancer. But as of his immune system, where the virus is believed to the speed and efficiency ofDNA sequencing skyrocket- hide. He then got a bone marrow transplant from one ed, and its price plummeted, it started to look reason- of those rare people with a gene mutation that makes able to sequence the whole tumor genome to cast the them resistant to HIV. Today, Brown still has no sign widest possible net. By 2010, when the bladder cancer 37 EFTA00805767 NAUTILUS EDUCATION I BETA PRODUCT patient (who doesn't want her name made public) DOROSHOW OF THE National Cancer Institute says had such a wonderful response to everolimus, the tech- Solit's work "turned on the lightbulb." It showed how nology was ripe to analyze her entire tumor. the analysis of exceptional responders could be made The outlier patient had already gone through sev- systematic. Inspired by his example, the NCI is now eral rounds of treatment, including surgery at Memo- trawling through its own archives, revisiting outlier rial Sloan-Kettering. That was another stroke of luck responses among the roughly 10,000 patients who because it allowed Solit's group to acquire samples of enrolled in NCI-sponsored clinical trials during the her tissue to be sequenced. Cancers typically start with last decade. Picture the long rows of crates in the gov- mutations that cause cells to divide too much, ignoring emment warehouse at theendofRaidersoftheLostArk: normal stop signals and evading quality controls that There's treasure in there somewhere, if only someone repair or prevent errors in DNA reproduction. "Cancer would look. "We ought to study these people more, is a disease ofmutations," says Solit. since we have the means now," says Barbara Conley, The outlier patient's cancer had accumulated 17,136 the associate director of the cancer diagnosis program mutations, of which 140 seemed most suspect, because at NCI, who leads the project. they appeared in "coding" regions of the genome, the In the few months since the project began, Con- segments that include instructions on how to build the ley's team have already found about 100 exception- proteins that do the work in a cell. Out of those 140, al responders. The next steps are to find out if their two looked particularly menacing to Solit. In a gene tumors were biopsied, if that tissue sample is still sit- called TSCI, just two ofits 8,600 DNA base-pairs were ting in a freezer somewhere, and whether it's in good missing, but the error would cause the gene to make a enough shape to be sequenced. Starting next year, the defective version of the protein it was supposed to cre- group will start inviting any scientist who is doing a ate. In the gene NF2, an error meant a protein would clinical trial to submit new cases. be built only halfway, unable to do its job. The NCI project will include whole-genome Solit could now see how these mutations were sequencing (provided they have adequate tissue sam- affected by everolimus, a drug typically used to sup- ples) and repeated reads of the whole "exome—the press the immune system after organ transplants, and 1 percent of human DNA that is translated into exons, to combat advanced kidney cancer. Everolimus shuts the sequences that are used as templates for protein down one crucial link in a chain ofinteracting proteins construction. The reason to do both, explains Conley, is called the mTOR pathway that fuels cell growth, divi- that cancer cells, even within a single tumor,often have sion, and survival. The drug inhibits the cells of the a hodgepodge of mutations. Re-doing whole exome immune system from dividing, which they must do in sequencing dozens of times captures most of the sig- order to attack foreign tissue, and protects transplant- nificant genetic variation in one tumor, and it's more ed organs. Likewise, it slows down the uncontrolled practical than trying to sequence the whole genome cell division that happens in cancer. The kicker was over and over. Finally, RNA expression will also be ana- that both of the woman's mutations, NF2 and TSCI, lyzed. EvaluatingRNA, an intermediary betweenDNA affect the mTOR system. "It's not surprising, in ret- and proteins, provides a measure of which genes are rospect, that our patient responded really well to this switched on and how much protein they're producing. specific drug," Solit says. "She had the mutation that Other elite cancer research centers and genome- activated the pathway the drug targets." sequencing centers have similar in-house projects. Solit's team analyzed 13 more people from the tri- Much like the NCI project, the unusual responder pro- al and found different TSC1 mutations in three other gram at the University of Texas, MD Anderson Cancer people, including two whose tumor shrank a little in Center, is beginning by combing through the archives response to the drug. (Nobody else had NF2 mutations, to hunt for outliers of the past. A patient at the clinic which is probably why she alone responded dramati- who has an unusual response—good or bad—will also cally.) Meanwhile, eight of nine people whose tumors be referred for genome sequencing and other kinds of grew during the study did not have the mutation. genetic analysis. DR EFTA00805768 NAUTIL.US I TEXT SETS Even if each outlier case only applies to 3 or 7 per- kidney cancer, sent his cancer into remission. Wash- cent of one type of cancer, as more cases are solved, ington University now has a special genetic test for the benefits quickly add up. "We're talking about patients with his type of leukemia. small subsets of patients that together make a radi- Just recently, Solit's group solved another excep- cal change," says Funda Meric-Bemstam, chair of the tional responder mystery—a case of ureteral cancer Department ofInvestigational Cancer Therapeutics at eliminated with a combination of old and new drugs. MD Anderson, who leads the unusual responders pro- The old drug is a standard chemotherapy treatment gram. In some cases, existing cancer drugs can simply that prevents DNA from unwinding, which it must do be repurposed, such as discover- in order to duplicate itself dur- ing that an immunosuppressant ing cell division. The new one drug works for certain bladder sensitizes cells to the effects of cancers. Or it might mean find- radiation. This patient turned ing new life for an experimental out to have a mutation in RADSO, drug that had been abandoned. involved in repairing broken If Conley and Doroshow can DNA strands (badly repaired pinpoint who might be helped DNA can lead to uncontrolled by an abandoned drug, a phar- cancerous growth). Here, too, maceutical company might the outlier finding may lead to have to do just one or two fur- a new treatment, since about ther studies to get that drug 4 percent of the other tumors approved for routine use. Solit has looked at have muta- The future might look some- tions that affect part of the thing like what's been going on RADSO complex. "To look at for several years at the Genome these individuals' cancers can Institute of Washington Univer- tell us a lot more than just a sity, where genome sequenc- random case of cancer," says ing is being used to help people Solit. "There's a phenotype—a with relapsed cancers and who response—that gives you infor- have run out of options. The mation about the genes." project puts insights from stud- Solit is now making a quick, ies like Solit's into practice, analyzing a patient's tumor reliable test for the TSCI mutation to single out people to determine whether currently available drugs might with bladder cancer who might be helped by everoli- target the troublemaker mutations. Combining whole mus, and is planning a new study to test the drug in genome sequencing, exome sequencing, and RNA them. And the original outlier, the woman with blad- expression analysis—what Washington University pro- der cancer? Three years later, she's still on everolimus fessor of genetics and Genome Institute co-director and still havinga "complete response," Solit says. She's Elaine Mardis calls the "Maserati approach"—the team doing fine. di) compares a comprehensive genetic profile against a database of drugs that target specific gene variants looking for a match. kat mcgowan is a contributing editor at Discover magazine If there is a match, the results can be impressive, andanindependentjoumalist basedinBcrkcley,Calif., as was the case with a young Washington University and New York City. doctor with leukemia, Lukas Wartman, who had suf- fered two relapses. In his case, analysis revealed that a gene called FLT3 was expressing more RNA than normal. A drug that inhibits this gene, usually used in 39 EFTA00805769 EDUCATIONgNAUTIL. US EFTA00805770