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BETA PRODUCT Science Connected NAUTIL. US
NAUTIL. US | TEXT SETS
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.
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Contents
Physics
Biology
4 Astronomy & Space Travel
6 Roadmap to Alpha Centauri
Pick your favorite travel mode—
big, small, dark, or twisted
BY GEORGE MUSSER
12 Chemistry & Fuels
16 You are Made of Waste
Searching for the ultimate example of recycling? Look
in the mirror
BY CURT STAGER
28 Genetics & Human Health
30 Their Giant Steps to a Cure
Battling a rare form of muscular dystrophy,
a family finds an activist leader, and hope
BY JUDE ISABELLA
36 An Unlikely Cure Signals
Hope for Cancer
How “exceptional responders” are revolutionizing
treatment for the deadly disease
BY KAT MCGOWAN
22 Frack’er Up
Natural gas is shaking up the search for
green gasoline.
BY DAVID BIELLO
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Astronomy & Space Travel
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 questions
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
discussion questions. 15 MIN
Dedicate the remaining class time to completing one of the activities. 30-45 MIN
Teacher’s Notes: Roadmap to Alpha Centauri
VOCAB WORDS
Magnetic field: produced by a magnetic material or a
current, a magnetic field will push or pull a moving
charge or magnet that comes in contact with it.
Ion: an atom in which the number of electrons and
protons is unequal—thus, the atom is positive or
negative.
Momentum: the product of the mass and velocity of
an object.
Recoil: the backward momentum from a fired gun.
Plasma: one of the four fundamental states of matter,
composed of ions and electrons.
Nuclear fusion: when two or more clusters of neutrons
and protons collide, forming a new nucleus and
releasing energy.
READING COMPREHENSION
1. What does AU stand for?
2. How fast is Voyager 1 moving in miles per hour?
3. “The engine first strips propellant atoms [typically
xenon] of their outermost electrons.” What
is the charge of a stripped xenon atom?
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4. What concept is at work in the ion drive? (Hint:
what is conserved?)
5. What other travel options work on this principle?
6. How much momentum does an electron fired
from a gun have?
DISCUSSION QUESTIONS
1. Why not take a traditional rocket to Alpha
Centauri?
2. Which of the propulsion meturds listed is most
likely to succeed? Would any be used together?
3. Would it be worth going if it took generations?
4. How far away is the next-nearest star?
ACTIVITIES
1. Research and create a brochure or ad enticing
astronauts to make the trip. What would they eat?
What psychological qualities would they need? If
robots were sent, how would they be fixed? What
kind of data could they expect to collect?
WHERE THIS FITS IN THE CURRICULUM
Structure and Properties of Matter (HS-PS1-8) Develop
models to illustrate the changes in the composition
of the nucleus of the atom and the energy released
during the processes of fission, fusion, and radioactive
decay.
Forces and Interactions (HS-PS2-1) Analyze data to support
the claim that Newton’s second law of motion
describes the mathematical relationship among the
net force on a macroscopic object, its mass, and its
acceleration.
Forces and Interactions (HS-PS2-2) Use mathematical
representations to support the claim that the total
momentum of a system of objects is conserved when
there is no net force on the system.
Engineering Design (HS-ETS1-3) Evaluate a solution
to a complex real-world problem based on prioritized
criteria and trade-offs that account for a range
of constraints, including cost, safety, reliability, and
aesthetics, as well as possible social, cultural, and
environmental impacts.
2. Propose another method of traveling to Alpha
Centauri.
ADDITIONAL MULTIMEDIA
1. Voyager 1 Leaves the Solar System
(The Guardian) 1 MIN 45 SEC
A quick explanation of where Voyager 1 is, and
how scientists know its location: http://www.
theguardian.com/science/video/2013/sep/13/
voyager-1-leaves-solar-system-video
2. New Mars Rover Powered by Plutonium
(Space.com) 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): https://www.youtube.com/
watch?v=1JOPW8aAcgEt
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MATTER | TECHNOLOGY
Roadmap to Alpha Centauri
Pick your favorite travel mode—big, small, light, dark, or twisted
BY GEORGE MUSSER
VER SINCE THE DAWN of the space age, a
quixotic subculture of physicists, engineers,
and science-fiction writers have devoted their
lunch hours and weekends to drawing up plans
for starships, propelled by the imperative for humans
to crawl out of our Earthly cradle. For most of that
time, they focused on the physics. Can we really fly to
the stars? Many initially didn’t think so, but now we
know it’s possible. Today, the question is: Will we?
Truth is, we already are flying to the stars, without
really meaning to. The twin Voyager space probes
launched in 1977 have endured long past their original
goal of touring the outer planets and have reached
the boundaries of the sun’s realm. Voyager 1 is 124
astronomical units (AU) away from the sun—that
is, 124 times farther out than Earth—and clocking
3.6 AU per year. Whether it has already exited the
solar system depends on your definition of “solar system,”
but it is certainly way beyond the planets. Its
instruments have witnessed the energetic particles
and magnetic fields of the sun give way to those of
interstellar space—finding, among other things, what
Ralph McNutt, a Voyager team member and planetary
scientist, describes as “weird plasma structures” begging
to be explored. The mysteries encountered by
the Voyagers compel scientists to embark on followup
missions that venture even deeper into the cosmic
woods—out to 200 AU and beyond. But what kind of
spacecraft can get us there?
Going Small: Ion Drives
NASA’s Dawn probe to the asteroid belt has demonstrated
one leading propulsion system: the ion drive.
An ion drive is like a gun that fires atoms rather than
bullets; the ship moves forward on the recoil. The system
includes a tank of propellant, typically xenon, and
a power source, such as solar panels or plutonium batteries.
The engine first strips propellant atoms of their
outermost electrons, giving them a positive electric
charge. Then, on the principle that opposites attract,
ILLUSTRATION BY CHAD HAGEN
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a negatively charged grid draws the atoms toward the
back of the ship. They overshoot the grid and stream
off into space at speeds 10 times faster than chemical
rocket exhaust (and 100 times faster than a bullet).
For a post-Voyager probe, ion engines would fire for 15
years or so and hurl the craft to several times the Voyagers’
speed, so that it could reach a couple of hundred
AU before the people who built it died.
Star flight enthusiasts are also pondering ion drives
for a truly interstellar mission, aiming for Alpha Centauri,
the nearest star system some 300,000 AU away.
Icarus Interstellar, a nonprofit foundation with a mission
to achieve interstellar travel by the end of the century,
has dreamed up Project Tin Tin—a tiny probe
weighing less than 10 kilograms, equipped with a miniaturized
high-performance ion drive. The trip would
still take tens of thousands of years, but the group sees
Tin Tin less as a realistic science mission than as a
technology demonstration.
Going Light: Solar Sails
A solar sail, such as the one used by the Japanese
IKAROS probe to Venus, does away with propellant
and engines altogether. It exploits the physics of
light. Like anything else in motion, a light wave has
momentum and pushes
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 needed
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
conceivably make the
crossing to Alpha Centauri in a thousand years. Sails
are limited in speed by how close they can get to the
sun, which, in turn, is limited by the sail material’s
durability. Gregory Matloff, a City University of New
York professor and longtime interstellar travel proponent,
says the most promising potential material is graphene—ultrathin
layers of carbon graphite.
A laser or microwave beam could provide an even
more muscular push. In the mid-1980s, the doyen of
interstellar travel, Robert Forward, suggested piggybacking
on an idea popular at the time: solar-power
satellites, which would collect solar energy in orbit
and beam it down to Earth by means of microwaves.
Before commencing operation, an orbital power station
could pivot and beam its power up rather than
down. A 10-gigawatt station could accelerate an ultralight
sail—a mere 16 grams—to one-fifth the speed of
light within a week. Two decades later, we’d start seeing
live video from Alpha Centauri.
This “Starwisp” scheme has its dubious features—it
would require an enormous lens, and the sail is so fragile
that the beam would be as likely to fry it as to push
it—but it showed that we could reach the stars within
a human lifetime.
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Going Big: Nuclear Rockets
Sails may be able to whisk tiny probes to the stars,
but they can’t handle a human mission; you’d need
a microwave beam consuming thousands of times
more power than the entire world currently generates.
The best-developed scheme for human space travel is
nuclear pulse propulsion, which the government-funded
Project Orion worked on during the 1950s and ’60s.
When you first hear about it, the scheme sounds
unhinged. Load your starship with 300,000 nuclear
bombs, detonate
one every three seconds,
and ride the blast
waves. Though extreme,
it works on the same
basic principle as any
other rocket—namely,
recoil. Instead of shooting
atoms out the back
of the rocket, the nuclear-pulse
system shoots
blobs of plasma, such as
fireballs of tungsten.
You pack a plug of
tungsten along with a
nuclear weapon into a
metal capsule, fire the
capsule out the back of
the ship, and set it off
a short distance away.
In the vacuum of space,
the explosion does less
damage than you might
expect. Vaporized tungsten
hurtles toward the ship, rebounds off a thick
metal plate at the ship’s rear, and shoots into space,
while the ship recoils, thereby moving forward. Giant
shock absorbers lessen the jolt on the crew quarters.
Passengers playing 3-D chess, or doing whatever else
interstellar passengers do, would feel rhythmic thuds
like kids jumping rope in the apartment upstairs.
The ship might reach a tenth the speed of light.
If for some reason—solar explosion, alien invasion—
we really had to get off the planet fast and we didn’t
care about nuking the launch pad, this would be the
way to go. We already have everything we need for
it. “Today the closest technology we have would be
nuclear pulse,” Matloff says. If anything, most people
would be happy to load up all our nukes on a ship and
be rid of them.
Ideally, the bomb blasts would be replaced with controlled
nuclear fusion reactions. That was the approach
suggested by Project Daedalus, a ’70s-era effort to
design a fully equipped robotic interstellar vessel. The
biggest problem was that for every ton of payload,
the ship would have to carry 100 tons of fuel. Such a
behemoth would be the
size of a battleship, with a
length of 200 meters and
a mass of 50,000 tons.
“It was just a huge,
monstrous machine,”
says Kelvin Long, an English
aerospace engineer
and co-founder of Project
Icarus, a modern effort
to update the design.
“But what’s happened
since then, of course, is
microelectronics, miniaturization
of technology,
nanotechnology. All these
developments have led
to a rethinking. Do you
really need these massive
structures?” He says
Project Icarus planned to
unveil the new design in
London in October 2013.
Interstellar designers
have come up with all sorts of ways to shrink the
fuel tank. For instance, the ship could use electric or
magnetic fields to scoop up hydrogen gas from interstellar
space. The hydrogen would then be fed into a
fusion reactor. The faster the ship were to go, the faster
it would scoop—a virtuous cycle that, if maintained,
would propel the ship to nearly the speed of light.
Unfortunately, the scooping system would also produce
drag forces, slowing the ship, and the headwind
of particles would cook the crew with radiation. Also,
pure-hydrogen fusion is inefficient. A fusion-powered
ship probably couldn’t avoid hauling some fuel from
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Going Dark: Scavenging Exotic Matter
Instead of scavenging hydrogen gas, Jia Liu, a physics
graduate student at New York University, has proposed
foraging for dark matter, the invisible exotic
material that astronomers think makes up the bulk
of the galaxy. Particle physicists hypothesize that
dark matter consists of a type of particle called the
neutralino, which has a useful property: When two
neutralinos collide, they annihilate each other in a
blaze of gamma rays. Such reactions could drive a
ship forward. Like the hydrogen scooper, a dark-matter
ship could approach the speed of light. The problem,
though, is that dark matter is dark—meaning it
doesn’t respond to electromagnetic forces. Physicists
know of no way to collect it, let alone channel it to
produce rocket thrust.
If engineers somehow overcame these problems
and built a near-light-speed ship, not just Alpha Centauri
but the entire galaxy would come within range.
In the 1960s astronomer Carl Sagan calculated that, if
you could attain a modest rate of acceleration—about
the same rate a sports car uses—and maintain it long
enough, you’d get so close to the speed of light that
you’d cross the galaxy in just a couple of decades of
shipboard time. As a bonus, that rate would provide a
comfortable level of artificial gravity.
On the downside, hundreds of thousands of years
would pass on Earth in the meantime. By the time you
got back, your entire civilization might have gone ape.
From one perspective, though, this is a good thing. The
tricks relativity plays with time would solve the eternal
problem of too-slow computers. If you want to do
some eons-long calculation, go off and explore some
distant star system and the result will be ready for you
when you return. The starship crews of the future may
not be voyaging for survival, glory, or conquest. They
may be solving puzzles.
Going Warp: Bending Time and Space
With a ship moving at a tenth the speed of light,
humans could migrate to the nearest stars within a
lifetime, but crossing the galaxy would remain a journey
of a million years, and each star system would still
be mostly isolated. To create a galactic version of the
global village, bound together by planes and phones,
you’d need to travel faster than light.
Contrary to popular belief, Einstein’s theory of relativity
does not rule that out completely. According to
the theory, space and time are elastic; what we perceive
as the force of gravity is in fact the warping of space and
time. In principle, you could warp space so severely that
you’d shorten the distance you want to cross, like folding
a rug to bring the two sides closer together. If so, you
could cross any distance instantaneously. You wouldn’t
even notice the acceleration, because the field would
zero out g-forces inside the ship. The view from the ship
windows would be stunning. Stars would change in color
and shift toward the axis of motion.
It seems almost mean-spirited to point out how far
beyond our current technology this idea is. Warp drive
would require a type of material that exerts a gravitational
push rather than a gravitational pull. Such material
contains a negative amount of energy—literally less
than nothing, as if you had a mass of –50 kilograms.
Physicists, inventive types that they are, have imagined
ways to create such energy, but even they throw up their
hands at the amount of negative energy a starship would
need: a few stars’ worth. What is more, the ship would
be impossible to steer, since control signals, which are
restricted to the speed of light, wouldn’t be fast enough
to get from the ship’s bridge to the propulsion system
located on the vessel’s perimeter. (Equipment within
the ship, however, would function just fi
When it comes to starships, it’s best not to get hung up
on details. By the time humanity gets to the point it might
actually build one, our very notions of travel may well
have changed. “Do we need to send full humans?” asks
Long. “Maybe we just need to send embryos, or maybe in
the future, you could completely download yourself into
a computer, and you can remanufacture yourself at the
other end through something similar to 3-D printing.”
Today, a starship seems like the height of futuristic thinking.
Future generations might fi it quaint.
george musser is a writer on physics and cosmology and
author of The Complete Idiot’s Guide To String Theory (Alpha,
2008). He was a senior editor at Scientific American for 14 years
and has won honors such as the American Institute of Physics
Science Writing Award.
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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 elements
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, and blood. Frack ‘er Up is an 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 Made of Waste
VOCAB WORDS
Mass: a physical property that describes an object’s
resistance to force. The mass of an object can be used
to calculate its weight: (mass) x (gravitational force)
= weight.
Carbon: an element found in stars, planets, comets,
as well as in all known living things.
Radioactive decay: the process by which a nucleus
ejects alpha particles, particles of ionizing radiation.
A nucleus that does this is considered “unstable;” a
substance that contains unstable nuclei is considered
“radioactive.” This process usually only occurs in
atoms heavier than iron.
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Fusion: when two or more nuclei collide, fusing to
make a new nucleus and releasing energy. This process
usually only occurs in atoms lighter than iron.
Chemical bond: an attraction between two or more
atoms that allows them to form a substance of definite
chemical composition. Breaking these bonds
requires energy.
Petroleum: a “fossil fuel” that forms when organisms
are crushed under rock and subjected to lots of pressure,
and lots of time. Like the organisms it’s made of,
petroleum consists largely of carbon.
2. How does the story change the way you see yourself?
Others?
ACTIVITIES
1. Pick an element not discussed in this article.
Where else is it found? Where did it come from?
2. Draw a map or annotated illustration of all the
places carbon goes in this article. Use outside
research to complete a full picture of the carbon
cycle.
ADDITIONAL MULTIMEDIA
READING COMPREHENSION
1. “Each of those waste molecules is a carbon atom
borne on two atomic wings of oxygen.” Write out
the chemical equation for the molecule described
here.
2. “Organic” is used in two different ways in this
piece. What are the two different definitions?
3. What does it mean for a chemical to be “highly
reactive?” Identify oxygen’s location on the periodic
table, the group of atoms that it belongs to,
and why they are considered “highly reactive.”
4. Which elements on the periodic table are the
least reactive?
5. “Fossil-based carbon dioxide molecules that
are not soaked up by oceans or stranded in the
upper atmosphere are eventually captured by
plants, shorn of their oxygen wings, and woven
into botanical sugars and starches.” What is the
process described here? (Hint: it is mentioned
by name later in the piece.) Write down the equation
for this reaction.
1. Whose air do you share?
(It’s OK To Be Smart, PBS) 3 MIN 30 SEC
A video that explains how we breathe recycled
air—including molecules of air exhaled by Einstein
himself:
https://www.youtube.com/watch?v=BybkIJysAKc
2. We Are Star Stuff segment
(Carl Sagan’s Cosmos) 8 MIN
Carl Sagan explains how the elements of life
were born in stars, evolved into simple organisms,
then into us: intelligent creatures, capable
of exploring the stars we came from:
https://www.youtube.com/watch?v=iE9dEAx5Sgw
3. The Microbes We’re Made Of
(Smithsonian.com) 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
DISCUSSION QUESTIONS
1. “Chemophobia” is the fear of chemicals. What are
some chemophobic practices or products that we
engage with? Are there good reasons to be afraid
of chemicals?
WHERE THIS FITS IN THE CURRICULUM
Chemical Reactions (HS-PS1-2) Construct and revise
an explanation for the outcome of a simple chemical
reaction based on the outermost electron states of
atoms, trends in the periodic table, and knowledge of
chemical properties.
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Matter and its interactions (HS-PS1-1) Use the periodic
table as a model to predict the relative properties
of elements based on the patterns of electrons in the
outermost energy level of atoms.
From molecules to organisms: structure and processes
(HS-LS1-6) Construct and revise an explanation
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
carbon-based molecules.
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.
Teacher’s Notes: Frack ’er Up
VOCAB WORDS
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,
potatoes, or green plants. Its chemical formula is
CH 3CH 2OH.
Biofuel: a fuel made from plants or other organisms,
in recent time.
Biomass: material from recently living organisms.
Organic compound: a molecule containing carbon.
Hydrocarbon: Made of just hydrogen and carbon,
these are the simplest kind of organic compound.
Octane: a highly flammable hydrocarbon, and component
of gasoline. Its chemical formula is C 8H 18.
Catalyst: a component of a chemical reaction that
helps facilitate the reaction, but is not used up.
2. A polymer is a chain of molecules. Identify a kind
of polymer in the story, and the monomer that
composes it.
3. Plants need carbon dioxide for photosynthesis.
What are some of the sources for this carbon
dioxide?
DISCUSSION QUESTIONS
1. Why is it advantageous for companies to be
green?
2. Would you pay more for gas—or any other product,
say a shirt—from a “green” company? What
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
consider this technology to be progress given
that natural gas has it’s own environmental
consequences.
ACTIVITIES
1. Have students construct a timeline of fuel. Ask
them to include dates mentioned from the story,
and to research and add other relevant information:
like the moment in history when organisms
die, the life cycle of a tree that contributed the
author’s container of Primus fuel.
2. Draw a map or annotated illustration of all the places
carbon goes in this article. Use outside research
to complete a full picture of the carbon cycle.
3. Write a 30-second ad convincing car drivers to
pay a premium for green gasoline like Primus’.
Include “fine print”—side effects, or caveats—as
you see necessary.
READING COMPREHENSION
1. “Plant biomass absorbs carbon dioxide as it grows.”
What is the name of the process by which plants do
this? Look up and write down the chemical reaction.
ADDITIONAL MULTIMEDIA
1. Algae (The Guardian)
An interactive slide show that illustrates how
biofuels are made out of algae:
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http://www.theguardian.com/environment/interactive/2008/jun/26/algae
https://www.youtube.com/watch?v=BybkIJysAKc
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:
http://ed.ted.com/lessons/biofuels-and-bioprospecting-for-beginners-craig-a-kohn
3. The Microbes We’re Made Of
(Smithsonian.com) 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-LS1-5) Use a model to illustrate how photosynthesis
transforms light energy into stored chemical
energy.
History of the Earth (HS-ESS1-6) Apply scientific
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-PS1-2) 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.
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MATTER | ENVIRONMENT
You Are Made of Waste
Searching for the ultimate example of recycling? 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
half of its mass, and roughly 1 in 8 of those carbon
atoms recently emerged from a chimney or a tailpipe.
Coal-fired power plants, petroleum-guzzling
cars, and kitchen gas stoves release carbon dioxide
into the atmosphere. Each of those waste molecules
is a carbon atom borne on two atomic wings of oxygen.
Fossil-based carbon dioxide molecules that are
not soaked up by the oceans or stranded in the upper
atmosphere are eventually captured by plants, shorn
of their oxygen wings, and woven into botanical sugars
and starches. Eventually, some of them end up in
bread, sweets, and vegetables, while others help form
carbon-rich animal tissues, finding their way into
meat and dairy products. Historically, atmospheric
carbon dioxide was mainly replenished by volcanoes,
forest fires, and biotic respiration. Today, one quarter of
atmospheric CO₂ is the result of fossil fuel combustion,
whether it rose from smokestacks or was displaced
from the oceans. (When fossil-fuel CO₂ dissolves into
ocean water, it displaces already-dissolved carbon
dioxide derived from natural sources.) And because
all of the carbon in your body derives from ingested
organic matter, which in turn obtains it from the atmosphere,
your fingernails and the rest of the organic
matter in your body are built, in part, from emissions.
ILLUSTRATIONS BY YUKO SHIMIZU
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Radioactive Carbon-14: Your pearly whites
When you smile, the gleam of your teeth obscures a
slight glow from radioactive waste. During the late
1950s and early 1960s, atmospheric testing of thermonuclear
weapons scattered so much radioactive carbon-14
into the atmosphere that it contaminated virtually
every ecosystem and human. Several thousand
unstable radiocarbon atoms explode within and among
your cells every second as their unstable nuclei undergo
spontaneous radioactive decay. Some are the natural
products of cosmic rays that can turn atmospheric
nitrogen into carbon-14, while others result from the
decay of unstable mineral elements that are found in
soil. But many of them represent the echoes of thermonuclear
airbursts from the Cold War, finding their
way into our water supply and meals. If they happen to
disintegrate within your DNA, they can damage your
genes. And many of them are bound up in your teeth.
Unlike most of the atoms in your body, those embedded
in your strong, stable tooth enamel have been with
you ever since you ingested them through your umbilical
cord and your infant feeding. If you were born during
the early 1960s, you have more nuclear waste in
your teeth than if you were born later, when soils and
oceans had had time to bury radioactive atoms. In fact,
forensic scientists use the proportion of bomb carbon
in tooth enamel to determine the age of unidentified
human remains.
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Oxygen: Your leafy breath
The oxygen in your lungs and bloodstream is a highly
reactive waste product generated by vegetation and
microbes. Trees, herbs, algae, and blue-green bacteria
split oxygen atoms out of water molecules during
photosynthesis. They use most of the resultant gas for
their own purposes, but thankfully some leaks out to
sustain you. In fact it makes up about a fifth of the
air you breathe. Your cells harness oxygen to release
energy from chemical bonds in the food you consume.
Oxygen absorbs electrons released by broken food
molecules, which attract hydrogen ions, resulting in
a molecular waste of your own making: metabolic
water, which comprises one tenth of your body fluids.
An average adult carries between 8 and 10 pounds of
homemade wastewater within them, and 1 in 10 of your
tears are the metabolic by-products of your breathing
and eating.
NAUTILUS EDUCATION | BETA PRODUCT
Nitrogen: Your natural curls
The next time you brush your hair, think of the nitrogenous
waste that helped create it. All of your proteins,
including hair keratin, contain formerly airborne
nitrogen atoms. But the nitrogen in air is biologically
inert. For nitrogen to become a component of your
hair, it has to be converted into a more accessible form.
Nitrogen-fixing bacteria is one way that can happen.
They live among the roots of beans, peas, and other
legumes, consuming atmospheric nitrogen and releasing
it as ammonia, a kind of microbial manure that
fertilizes soil in which plants grow. When you eat a
plant, you consume formerly atmospheric nitrogen.
Every flash of lightning and every automotive spark
plug emits a puff of nitrogen oxide, which can dissolve
into raindrops and fall to earth as a form of fertilizer,
again finding its way into food webs through plants.
But most of the nitrogen in modern foods comes from
urea and ammonium nitrate fertilizers artificially fixed
by industrial processes. In ages past, the nitrogen in
human hair came mainly from bacterial waste and
lightning. But today, unless you eat a strictly organic
diet, you run your hairbrush through nitrogenous
frameworks that are mostly of human origin.
NAUTIL. US | TEXT SETS
Iron: Your ancient blood
When you cut yourself, the wreckage of stars spills
out. Every atom of iron in your blood, which helps
your heart shuttle oxygen from your lungs to your
cells, once helped destroy a massive star. The fierce
nuclear fusion reactions that set stars ablaze create
the atomic elements of life. As the star ages, it fuses
progressively larger elements, such as silicon, sulfur,
and calcium. Eventually, iron atoms are fused.
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
layers rebounding against the dense inner core, and a
supernova explosion will result. The blast sprays out
iron at supersonic speeds, filling great swathes of space
with debris that can form new solar systems. The iron
in your frying pan, house keys, and blood is essentially
cosmic shrapnel from the tremendous explosions that
ripped through our galaxy billions of years ago. The
same blasts also released carbon, nitrogen, oxygen, and
other elements of life, which later produced the sun,
the Earth, and eventually—you.
curt stager is an ecologist and climate scientist at Paul
Smith’s College. He is the author of Deep Future: The Next 100,000
Years of Life On Earth, and also co-hosts a weekly science program
on North Country Public Radio.
21

MATTER | BIOFUEL
Frack ’er Up
Natural gas is shaking up the search for green gasoline
BY DAVID BIELLO
AM SPEEDING DOWN New Jersey’s highways,
propelled by gasoline with a dash of ethanol, an
alcoholic biofuel brewed from stewed corn kernels.
As I drive through the outskirts of the township
of Hillsborough, in the center of the state, I see
that spring has brought with it a bounty of similar “biomass,”
as the fuel industry likes to call plants. Trees
line the road and fresh-cut grass covers the sidewalks
as I pull into the business park that is home to Primus
Green Energy—a company that has been touting
a technology to transform such biomass into a green
and renewable form of gasoline.
But there’s a hitch. The boom in hydraulic fracturing,
or “fracking,” a technique in which horizontal drilling
and high-pressure jets of water are deployed to release
gas trapped in sedimentary shale rock, has made natural
gas cheap and plentiful. That’s not bad for Primus,
whose technology can make gasoline from natural gas,
biomass, or even low-grade coal, such as lignite or peat.
This versatility makes Primus a potential part of what
has been called the “olive economy”—companies that
are neither bright green nor darkest black, but combine
environmentally-friendlier technologies with older
and dirtier ones in order to compete. In fact, Primus
may become a leader in advancing this kind of technology.
“We can be as dark as you want or as green as you
want,” says geologist, serial entrepreneur, and Primus
salesman George Boyajian.
In July, President Barack Obama gave a major
speech on climate change that described natural gas
as a “transition fuel” towards the “even cleaner energy
economy of the future.” But Primus’s trajectory raises
the question of whether natural gas is a boost on the
road to a genuinely green fuel, or if it is prolonging our
addiction to dirty modes of transport, and taking us on
a detour from a low-carbon path.
At the Primus headquarters, I first meet Primus’s
chief chemist Howard Fang in front of a prototype of
a Primus conversion machine. Fang, who joined the
company for what he calls his “semi-retirement,” is
ILLUSTRATION BY PETER & MARIA HOEY
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avuncular and black-haired. His interests are broad:
He spends his spare time writing and reading history,
and has authored books on conflict in the Middle East
and the role of Christian missionaries in China.
A lifetime in fuels chemistry left Fang with one
burning question: “What is the real solution to the
energy crisis?” His career at oil companies BP and
ExxonMobil, and engine manufacturer Cummins,
spanned not just one but two major energy upheavals—the
oil crisis of the 1970s and then its sequel in
the first decade of the 21st century, which is arguably
still ongoing. These experiences impressed on Fang
the importance of securing the fuel supply in such
a way as to avoid despoiling the environment. The
solution, says the bespectacled chemist, is “naturesourced
biomass or natural gas converted effectively
to gas or diesel.”
Primus’s original idea was simple: take scrap wood
or other biomass, turn it into pellets, and apply pressure
and heat (700 degrees Celsius or more) to break
it down into hydrogen and carbon monoxide. Then
build this composite “syngas,” shorthand for “synthetic
gas,” back up into whatever hydrocarbon product is
desired—the molecules of eight carbon and 18 hydrogen
atoms known as iso-octane that are a measure
of the quality of conventional gasoline, or the longer
chains of similar hydrocarbons that comprise diesel or
jet fuel. Because plant biomass absorbs carbon dioxide
as it grows, the emissions produced by burning the
biofuel should balance out overall—every molecule of
CO2 emitted when the fuel is burned was previously
absorbed by the plant that made the fuel.
The story of the search for such green fuel is littered
with disappointments, however. Major companies
brew ethanol in large quantities in the United
States. It is routinely added to gasoline (at levels of
around 10 percent, on its way to 15 percent) as a way
to improve combustion, reduce pollution, and support
industrial corn farmers. But most ethanol is still made
from the edible kernels of corn plants, instead of the
inedible cellulose that was promised in the heady days
of the mid-2000s, when Congress passed a spate of
laws promoting biofuel production. Since 1978, the
ethanol industry has enjoyed subsidies and tax credits
to the order of 40 cents per gallon, and now produces
an annual dead zone at the mouth of the Mississippi
River each summer as a result of fertilizer washing off
the endless cornfields of the Midwest. But ethanol is
unlikely to ever fully replace conventional fossil fuels,
since it is more difficult to transport, produces a fraction
of the energy of oil, and would require engines to
be refitted or replaced on a massive scale.
Hence the interest in “drop-in” biofuels as a substitute
for conventional fuels in existing cars, planes,
and trucks. The problem is not one of infrastructure,
but chemistry: Companies must find a way to economically
imitate and fast-track a process for which
time and geology have done most of the work in conventional
fossil fuels. The energy in these fuels is the
pent-up power of ancient sunlight, which billions of
photosynthetic microorganisms soaked up before
dying, fossilizing, and turning into the hydrocarbonrich
stew we know as petroleum, and from which we
refine gas, diesel, and jet fuel, among other products.
In theory, then, it should be possible to turn the carbohydrates
and other chemicals that store energy for
today’s living things into the hydrocarbons we rely on
for transportation.
Potential routes to such “green crude” include
algae, other photosynthetic organisms, and specialty
microbes engineered to spit out hydrocarbons. Biofuel
company Solazyme has a contract to supply United
Airlines with 20 million gallons of algal jet fuel, and
teamed up with a green fuel-station network to offer
biodiesel in a test run in San Francisco’s Bay Area. But
it takes a lot of water—and a lot of energy to move that
water around—in order to grow algae in large quantities,
and tailor-making microbes is expensive at its
current scale. As a result, companies are diversifying.
Algal fuel producer Sapphire Energy is now focusing
on isolating the genetic traits in the ancestors of all
plants that might be usefully incorporated into other
crops. Solazyme is making oils and specialty fats to sell
at high margins to cosmetics and food companies, as
is would-be microbial fuel-maker Amyris. The industry
for “advanced biofuels is literally in its infancy,” concedes
Jonathan Wolfson, Solazyme CEO.
The allure of Primus’s technology is its promise to
harness waste wood and other inedible biomass that
would otherwise be thrown into landfills, and turn
it into a renewable source of gasoline. Its “syngas to
gasoline plus” process consists, essentially, of four
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“We can be as dark as
you want or as green
as you want,” says
Boyajian.
chemical reactors. One turns the syngas into methanol.
The next makes methanol into a molecule known as
dimethyl ether, or DME in chemist-speak. In the third
reactor, catalysts known as zeolites knit DME into gasoline,
in the most expensive and energy-intensive part
of the process. The fourth reactor eliminates some of
the unwanted byproducts that cause the resulting fuel
to congeal at low temperatures.
The key is the zeolites, porous minerals made up of
aluminum, silicon, and oxygen that allow the desired
chemical reactions to take place. Both Primus and a
conventional oil refinery employ zeolites to manipulate
hydrocarbons. At an oil refinery, these catalysts
help crack and sort hydrocarbons broken down from
crude oil. At Primus, heat and pressure allow zeolites
to build gasoline hydrocarbons from the smaller molecules
of syngas. Such “catalysts are a bit of a dark art,”
says Boyajian. He spars with Fang over whether or not
the company will one day make their own. Fang does
not accept Boyajian’s need for secrecy, and would be
more than happy to reveal all those dark arts—a prospect
that makes the affable Boyajian nervous and tightlipped.
For now, the fledgling company buys the necessary
catalysts off the shelf and must sign agreements
not to examine these zeolites too closely.
Using different catalysts in the reactors, Fang notes,
the company could spit out diesel or jet fuel instead
of gasoline. And for every 100 kilograms of syngas,
he says, Primus can make 30 kilograms of gasoline or
more, using a continuous looping system within the
machine that eliminates the need for wasting energy
to convert gases to liquids along the way. Little red
containers of Fang-made gasoline record its characteristics,
scrawled on masking tape affixed to the sides:
low vapor pressure, a higher-than-average octane content
of around 93, and a favorable absence of sulfur
or benzene. Oil prices have been rising over the last
month, and are currently at more than $100 per barrel;
the company estimates that its gasoline costs as little
as that derived from oil at $65 per barrel—and could
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cost as little as $2 per gallon, or about half the price
gas currently goes for at local pumps, to produce at a
full-sized facility, even though such an industrial plant
would require a lot of capital to build.
However, the machine Fang shows me is not running
on the biomass that Fang originally tested: wood
chips, switchgrass, canary grass, miscanthus. Instead,
it churns through natural gas, turning methane into
syngas. Making long hydrocarbons from the single carbon
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 revolutionized
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 pipelines
that transport the gas. Fracked gas can also contaminate
groundwater supplies. And while in 2012 it
brought America’s carbon footprint down to its lowest
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: ExxonMobil
built a plant in New Zealand in 1986 to turn
natural gas into methanol and then gasoline, but abandoned
its efforts when the price of petroleum dropped
dramatically in the mid 1990s. Now, though, natural
gas is cheap and attractive. Boyajian has a map of all
the shale formations in North America tacked to the
wall of his office. “The world is full of shale,” he notes.
An earlier version of Primus’ machine, tuned to process
biomass, sits swathed in silvery insulating tape
in a locked and darkened lab. “Right now it is abandoned,”
Fang says. The company insists that the statement
doesn’t apply to Primus’s biomass efforts more
generally. “This is the way to get to biofuels,” says Primus
CEO Robert Johnsen, of the gas to gasoline process,
through a tight smile. “Will we be the ones to get
there? Maybe.”
The energy in these fuels
is the pent-up power of
ancient sunlight, which
billions of photosynthetic
microorganisms soaked up
before dying.
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Will natural gas be a bridge for Primus to green
fuel, or will it be too cheap and attractive to resist as
a permanent substitute for biomass? For the moment,
the company seems keen to squeeze what it can out of
the shale gale. With the help of more than $50 million
in Israeli money, Primus is building a demonstration
plant the size of a house near its headquarters in New
Jersey, due to open this year. The location is off the
map—even Google won’t guide you there, as if it were
some secretive skunk works facility, which is how the
company likes to think of it. The plant will take natural
gas from the local utility, run it through its proprietary
set of chemical reactions and, on the far end, out of a
spigot, will come gasoline—12.7 gallons per hour at full
capacity. The company’s first commercial plant, due to
start construction next year, will likely be located near
a source of natural gas.
Scaling up the technology this way will reduce the
overhead costs per unit of gasoline—that is, the cost
of fabricating the reactors and buying the zeolites and
feedstocks. Plus, Primus’ technology may prove economical
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 company
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 of its 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 anomalously
high miles-per-gallon number.
Fang gives me two thumbs up as I pull away, watching
me drive off on his preferred solution to the energy
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 energy
and environmental conundrum. Striving to make
cleaner fuel for standard, dirty combustion engines
may reinforce drivers’ loyalty to today’s technology.
Such lock-in makes a true revolution difficult until
some alternative energy source—whether batterydriven
electric cars or engines modified to burn carbon-neutral,
as-yet-unmade biofuels—offers the kind
of convenience and low cost that justifies replacement.
At present, Primus appears set to become part of a
sprawling infrastructure that reinforces the incentives
to use greenhouse gas-producing, gasoline-like fuels.
And for all those concentrated octanes in my tank, I
still have to pull into a Shell station to fill up on conventional
gasoline, blended with corn ethanol, in order
to drive home.
david biello is the Environment and Energy Editor for
Scientific American. He is currently working on a book about the
Anthropocene.
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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 Hope for
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.
Start class by asking students if they have any questions about the readings. Ask them to contribute their discussion
questions (in addition to the ones provided under Deep Thinking / Discussion questions). Have the class
brainstorm and answer both discussion questions. 15 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. 15 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
progressive weakening of the muscles. Some forms of
muscular dystrophy are seen in infancy or childhood.
Orphan diseases: diseases that have yet to be “adopted”
by the pharmaceutical industry because there are
very few incentives to develop new medications to
treat or prevent them. Orphan diseases can be rare
or they are common diseases that have been ignored
(e.g.: tuberculosis, cholera, typhoid, malaria).
Calpainopathy: a rare type of muscular dystrophy
characterized by symmetric and progressive weakness
of proximal (limb-girdle) muscles.
Cancer: A term used to describe disease in which
abnormal cells divide without control and are able to
invade into other tissues. Cancers are often categorized
based on the organ or cell type they originate in.
Oncologist: A doctor who specializes in treating
patients with cancer.
Outlier: An observation that deviates from a majority
and can be seen to be a rare event. In the context
of this piece, the outliers are patients who respond
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to therapy when the same therapy has failed other
patients.
Remission: a decline or disappearance of signs and
symptoms of cancer.
READING COMPREHENSION
1. Why are orphan diseases underfunded?
2. How does the mutation in calpain 3 cause muscle
to fail to grow?
3. What are some reasons pharmaceutical companies
would want to develop drugs for orphan
diseases? What are some possible reasons they
would be against doing so?
4. Statistically speaking, outliers are often ignored.
In this story, why is patient number 45 such an
interesting case? Why is it generally important to
study the outliers of response?
5. Which protein’s activity is blocked by everolimus?
What is the function of this particular
protein?
DISCUSSION QUESTIONS
1. In what contexts would it be desirable and undesirable
to sequence your genome to see if you
are at risk for a disease? What are the benefits
and downsides of knowing if you are at risk for a
particular disease?
2. In both pieces, mutations are responsible for
causing disease. Compare and contrast the ways
mutations can lead to muscular dystrophy and
cancer. Are the mutations in one case hereditary?
Are mutations leading to either disease caused
by environmental factors? Are the mutations in
either case preventable? If so, how could they be
prevented?
3. How should doctors and scientists decide
whether to work on a rare condition?
ACTIVITIES
Some genes are not specific to humans, but rather,
are common to myriad species. In a smaller group,
you will be assigned to read about one of the proteins
listed here: http://nautil.us/issue/5/fame/
genes-that-won-the-fame-game
Please answer the following questions when it is your turn
to present to the class:
1. What organisms is the gene present in? Were you
surprised by the presence of the gene in any of
the organisms listed? If so, why?
2. If this protein was mutated, what could the consequences
look like? Could it cause a disease?
3. Research and present one other case of an outlier
being useful in science or medicine.
WHERE THIS FITS IN THE CURRICULUM
Structure and Function (HS-LS1-1) A cell contains
genetic information in the form of DNA molecules.
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.
Variation of Traits (HS-LS3-2) Although DNA replication
is tightly regulated and remarkably accurate,
errors do occur and result in mutations, which are
also a source of genetic variation. Mutations can, in
turn, cause disease and/or affect human health. The
pattern of mutations can also predict response to
drugs.
Inheritance and Variation of Traits - Environmental
Factors (HS-LS3-3) Technological advances have
influenced the progress of science and science has
influenced advances in technology. Technologies have
evolved to sequence human genes, which can better
inform doctors of their patients’ health. Likewise,
pharmaceutical companies have also created many
drugs for the treatment of human disease.
29

BIOLOGY | MEDICINE
Their Giant Steps to a Cure
Battling a rare form of muscular dystrophy,
a family finds an activist leader, and hope
BY JUDE ISABELLA
N 2007, AT HER high school graduation in Quesnel,
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
shoulders. She had on ridiculously high heels. As she
eased down the stairs, very slowly, she hung on to her
date. She was afraid her knees would collapse, as her
muscles were weak for her age.
From the audience, Ivana’s mother, Marijana,
watched her daughter’s every step, silently panicking
and breaking into a sweat. She knew Ivana could easily
tumble down the stairs and break a limb. The year
before, Ivana had been diagnosed with muscular dystrophy,
an incurable genetic disease characterized by
progressive weakening of the muscles. Antonia, Ivana’s
younger sister by five years, was later diagnosed with
the same disease.
Around the time of Ivana’s graduation, the Topics,
an unassuming family originally from Croatia, had
begun adjusting their lives as best they could, inquiring
about ramps everywhere they went, avoiding walking
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,
calpainopathy, which affects about 1 in 200,000 people.
The diagnosis meant both would likely be bound to
wheelchairs while they were still young women.
Today, Ivana is 24. In May, she graduated from college
with a bachelor’s degree in finance and general
business. She still walks up stairs in her house; her
bedroom is upstairs. “I’m definitely a fighter, and will
try and walk for as long as I can,” she says. “When I
notice I’m falling a lot, when I need help a lot, I will
go in a chair.”
Muscular dystrophy treatment is limited to only palliative
medications and therapies. Ivana herself practices
yoga. While researchers worldwide are working
on lasting cures for muscular dystrophy (funded in part
by the famous Jerry Lewis Telethons), rare forms like
calpainopathy are “orphans,” with only a fraction of
ILLUSTRATIONS BY ELLEN WEINSTEIN
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“I’m definitely a fighter, and will try and
walk for as long as I can.”
researchers and funds devoted to them. With quiet
stoicism, the Topics have accepted that modern medicine
may not have a solution for their daughters’ disease.
Still, says Marijana, “Without hope, there’s no
life.”
Following a current grassroots trend in medicine,
many individuals with orphan diseases do not wait for
the medical industry to care about them. Facing long
odds, they are forced to raise money to find a potential
cure themselves. But the Topics live by modest means.
Marijana runs a daycare center and her husband and
the childrens’ father, Niko, works for a lumber company.
They are in no position to mount a quest.
But then there’s Michele Wrubel, 49, a stay-at-home
parent from Connecticut who has calpainopathy. For
years, Wrubel has been a passionate crusader for a
cure. Affluent and well connected, she doesn’t varnish
the truth about what it has taken to make the medical
industry pay attention to her. “To make a difference in
this disease, you need money and meetings,” she says.
“Researchers are not going to study a disease unless
there’s money behind it to fund the research.” For the
Topics, Wrubel may be their best hope.
THE GLOBAL GENES PROJECT, an advocacy group,
estimates 350 million people suffer from orphan diseases
worldwide. Most rare diseases are genetic and
tend to appear early in life. About 30 percent of children
who have them die before reaching their fifth
birthday. The rest battle their conditions throughout
life, as most orphan diseases have no cure. Out of the
7,000 orphan diseases identified to date, with about
250 new ones added annually, less than 400 can be
treated therapeutically.
This year the European Commission gave 144
million euros to develop 200 new therapies and the
National Institute of Health allocated $3.5 billion to
research orphan diseases. Yet some diseases are so rare
that they remain stepchildren even among orphans.
As a result, they receive little research attention and
funding. Neither do they fit the list of billable insurance
procedures. There’s no standard healthcare path
to diagnosis, let alone treatment. Similar to the Topics,
many patients go through an ordeal, which Marijana
describes as “a blur,” only to find out that medicine
can’t help them.
Orphan disease organizations, such as the National
Organization for Rare Disorders and the Rare Disease
Foundation, encourage patients to take matters into
their own hands. “Families have to advocate,” says Isabel
Jordan, chair of the Rare Disease Foundation. She
encourages patients to form organizations, find new
methods of funding, and push for research.
“Push for research” could be Michele Wrubel’s calling
card. She was diagnosed with muscular dystrophy
in her mid-20s. But even though calpainopathy was
identified nearly 20 years ago—about the same time
Wrubel got her initial diagnosis—it took almost the
entire second half of her life to determine that she
was afflicted with calpainopathy. There were no clinical
procedures that would lead to a diagnosis.
“It took a really long time and a very concerted
effort,” says Wrubel, who walks with canes, submitting
to a wheelchair for long trips or when in crowded places.
“If you don’t know what you’re looking for, they don’t
know what to tell you or how to help you,” she says.
In 2008, gene sequencing came of age, which aided
physicians in diagnosing muscular dystrophy subtypes.
That year, Wrubel’s husband, Lee, who holds a medical
degree and a master’s in public health from Tufts, an
MBA from Columbia University, and is a venture capitalist
in the medical field, tracked down a neurologist
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In the quest for a
cure, she says, “It’s
a matter of patients
taking charge of their
diagnosis.”
to sequence his wife’s genomes. He paid several thousand
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, generally
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 subtypes.
The problem with Type 2a, she says, “was a
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really strange gene mutation that was completely inexplicable.”
She says it has been a hard disease to study,
partially because the implicated protein is unstable
and partially because it was a rarity among the orphan
diseases. When it comes to funding, calpainopathy
has been overshadowed by other forms of muscular
dystrophy. “Muscle studies have been underfunded
forever and certainly a rare disease like 2a especially
underfunded,” Spencer says.
In 2010, Wrubel formed the nonprofit Coalition to
Cure Calpain 3. In the quest for a cure, she says, “It’s
a matter of patients taking charge of their diagnosis.”
She reached out to other sufferers via Facebook, and
some donated money. She partnered up with two other
nonprofits that had raised funds on their own, both
started by those afflicted with Type 2a. So far Wrubel’s
efforts have gathered close to half a million dollars.
With that money, she has funded a project with Louis
Kunkel, professor of genetics and pediatrics at Boston
Children’s Hospital, one of the nation’s key muscular
dystrophy researchers.
Her coalition also organized a conference to bring
calpainopathy researchers together, including Spencer.
Years earlier, in 2005, Spencer made a significant
breakthrough. She discovered that calpainopathy,
unlike more common forms of muscular dystrophy,
was not a weakening of the muscle but a growth problem—muscle
forms, but fails to grow because of a
missing protein. It is different from other muscular
dystrophies in which the lack of the protein complex,
dystrophin, damages muscle membranes. “With calpainopathy,
the muscles lack the growth signal,” she
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 cure,” she says.
Encouraged by the promise, the Coalition to Cure
Calpain 3 gave Spencer’s lab a $260,000 grant to
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
about clinical trials,” Spencer says—and then another
five years before the drugs can be commercially available,
she estimates.
Wrubel’s coalition intends to get pharmaceutical
companies interested, too. “Many pharmaceutical companies
see treating orphan diseases as a way to increase
profits,” Wrubel says. Her husband, Lee, adds, “The
whole model for big pharmaceutical companies going
forward is different. There is too little in the big pharmaceutical
pipeline, and they’re looking to feed that
beast as much as possible.” A 2012 Thomson Reuters
study found that drug companies stand to profit from
orphan drugs because, compared to drugs for common
afflictions, they often have shorter and less expensive
clinical trials, with more success. Spencer says a drug
for calpainopathy, for instance, would also be useful
for patients with Lou Gehrig’s Disease and bed rest
patients, as it would help arrest the loss of bone and
muscle mass. Wrubel hopes to bring Cydan Development,
a venture-capital backed orphan drug developer,
to their upcoming fall conference in the Netherlands.
As for the Topics, they were excited to learn about
Wrubel from Nautilus. Ivana recently connected with
Wrubel through Facebook. “I only talked with her a little
bit, but she seems ambitious and driven,” Ivana says.
“Definitely not someone who is going to sit around and
wait for something to happen. Definitely inspiring. And
the possibility that something might help in any way is a
good thing to hear, for sure.” Ivana says she now wants
to get involved and advocate for her own disease. “I definitely
want to do something,” she says, and Wrubel’s
coalition “would be a good place to start.”
jude isabella is a science writer based in Victoria, Brit-
ish Columbia. Her new book, Salmon, A Scientific Memoir, will be
released next year.
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BIOLOGY | MEDICINE
An Unlikely Cure Signals
New Hope for Cancer
How “exceptional responders” are revolutionizing treatment
for the deadly desease
BY KAT MCGOWAN
UST LIKE EVERY NEW drug the oncologists at
Memorial Sloan-Kettering Cancer Center tested
against bladder cancer in the last 20 years,
this one didn’t seem to be doing any good. Forty-four
people in the study were given everolimus in a
last-ditch attempt to slow down or stop their advanced
cancer. When the researchers analyzed the data, they
could see that the drug wasn’t slowing or stopping
tumor growth. Everolimus seemed to be another bust.
Then there was patient number 45. She joined the
trial with advanced metastatic cancer. Tumors had
invaded deep into her abdomen, clouding her CT scan
with solid grey blotches. She was 73 years old. None of
the standard bladder cancer drugs were working for
her anymore; she had “failed treatment,” in the dismal
lingo of oncologists. She enrolled in the study only
because she happened to be a patient at Sloan-Kettering
in January 2010. In April 2010, her cancer was gone.
This sort of happy surprise is not unheard of
in drug studies. Bodies are fluky, each with its own
idiosyncratic combination of genetic blueprints and
environmental inputs. So sometimes a patient will be
cured by a drug that is useless for everyone else. In
the past, these spectacular reactions were written off
as outlier responses that defied explanation—medical
mysteries. Doctors just shrugged their shoulders and
thanked their lucky stars that even though the study
tanked, they did manage to help one person.
But this time was different. Clinical oncologist
David Solit, director of developmental therapeutics
at Sloan-Kettering, saw a new opportunity to explain
what happened by sequencing the whole genome of
the woman’s cancer. Just five years ago, decoding and
analyzing all 3 billion bases of the DNA from a tumor
would’ve been absurdly time-consuming and expensive.
Now the sequencing takes as little as a few days.
Poring over the outlier patient’s genetic code, Solit
pinpointed two mutations that made her tumor sensitive
to this drug. He found that one of her mutations
shows up in about 8 to 10 percent of other bladder cancer
patients, meaning that they too might be helped
by everolimus. His success has inspired a whole set of
ILLUSTRATION BY ELLEN WEINSTEIN
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programs to study “exceptional responders”: those rare
cancer patients who do well while nobody else does.
Cancer is a personal disease, Solit explains. Each
tumor constitutes its own world of defective genes and
proteins. By studying the genetic quirks of exceptional
responders, physicians can systematically identify
weaknesses in cancer subtypes and blast them with
drugs that target their unique vulnerabilities. “It’s a
testament to how much has been learned about the
genome in the past 30 years,” Solit says. “We’ve always
wanted to find out why some individuals respond so
well. Now we have the capacity. It’s going to really
change the way we treat patients.”
UNLIKELY CASES HAVE AN eminent history in medicine.
The modern science of the mind owes a lot to
the freakish accident suffered by Phineas Gage, a
19th century railroad construction foreman whose
job involved packing down explosive powder with a
three-and-a-half-foot-long iron tamping rod. On Sept.
13, 1848, the powder exploded in his face, blasting the
rod up through his chin and out the back of his head.
Against all odds, he survived. But his personality was
transformed. The formerly shrewd and patient Gage
became obnoxious and unreliable.
An observant doctor named John Martyn Harlow
who cared for Gage proposed that his personality
change was due to the destruction of the frontal lobe
of the left side of the brain. Gage’s unlikely transformation
revealed a universal truth about brains, that
particular parts—the frontal lobes—are required for
self-control. The strange case of Phineas Gage is still
mentioned in neuroscience textbooks.
Rare events can also lead to new cures. As the story
goes, English physician Edward Jenner’s observations
of an 18th century milkmaid who caught cowpox and
thereby became immune to smallpox paved the way for
the fi vaccines. New ideas for curing HIV are emerging
from the famously unlucky lucky case of the “Berlin
patient.” Timothy Ray Brown, who was HIV positive,
developed blood cancer leukemia in 2006. His chemotherapy
and radiation treatments wiped out the cells
of his immune system, where the virus is believed to
hide. He then got a bone marrow transplant from one
of those rare people with a gene mutation that makes
them resistant to HIV. Today, Brown still has no sign
of HIV in his body, and his case has inspired a study
to genetically engineer HIV-positive patients’ cells to
resist the virus.
In the past, cancer researchers weren’t able to
capitalize on their unexpected outlier successes. Not
enough was known about the biology of cancer, and
the right tools hadn’t been invented. “Even if someone
had a complete remission, you had no way to figure out
why,” says James Doroshow, director of the Division of
Cancer Treatment and Diagnosis of the National Cancer
Institute (NCI). That changed in the 2000s, when
it became possible to analyze the genetics of cancer
tumors for clues.
The first major success came with studies of the
drug gefitinib in non-small-cell lung cancer (the most
common kind). Gefitinib helped less than 20 percent
of the people who took it, but a few outliers had dramatic,
rapid recoveries. In 2004, two Harvard groups
found that the responders had mutations in the epidermal
growth factor receptor (EGFR) gene. EGFR is
one of many genes that regulates how cells grow and
when they die, and the mutation basically forced it to
pump out two or three times as much growth signal as
it should, fueling the cancer. Gefitinib dialed down the
signal. A clinical trial later proved that the drug keeps
tumors at bay for more than nine months in people
with certain EGFR mutations.
More insights gleaned from extraordinary responders
soon followed. One melanoma patient in a study of
22 people taking sorafenib saw his tumor shrink quickly,
a response due to a mutation in the gene KIT, which
regulates cell growth, division and survival. People
with certain kinds of melanoma, such as the type that
grows on mucus membranes, now routinely get tested
for this mutation. The drug helps about 40 percent of
those with the mutation—an impressive advance in a
cancer that once had no effective treatment.
In these studies, investigators had to make educated
guesses about where in the genome to look for the
culprit mutations. It was the keys-under-the-lamppost
phenomenon: They could only examine genes they
already suspected were involved in the cancer. But as
the speed and efficiency of DNA sequencing skyrocketed,
and its price plummeted, it started to look reasonable
to sequence the whole tumor genome to cast the
widest possible net. By 2010, when the bladder cancer
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patient (who doesn’t want her name made public)
had such a wonderful response to everolimus, the technology
was ripe to analyze her entire tumor.
The outlier patient had already gone through several
rounds of treatment, including surgery at Memorial
Sloan-Kettering. That was another stroke of luck
because it allowed Solit’s group to acquire samples of
her tissue to be sequenced. Cancers typically start with
mutations that cause cells to divide too much, ignoring
normal stop signals and evading quality controls that
repair or prevent errors in DNA reproduction. “Cancer
is a disease of mutations,” says Solit.
The outlier patient’s cancer had accumulated 17,136
mutations, of which 140 seemed most suspect, because
they appeared in “coding” regions of the genome, the
segments that include instructions on how to build the
proteins that do the work in a cell. Out of those 140,
two looked particularly menacing to Solit. In a gene
called TSC1, just two of its 8,600 DNA base-pairs were
missing, but the error would cause the gene to make a
defective version of the protein it was supposed to create.
In the gene NF2, an error meant a protein would
be built only halfway, unable to do its job.
Solit could now see how these mutations were
affected by everolimus, a drug typically used to suppress
the immune system after organ transplants, and
to combat advanced kidney cancer. Everolimus shuts
down one crucial link in a chain of interacting proteins
called the mTOR pathway that fuels cell growth, division,
and survival. The drug inhibits the cells of the
immune system from dividing, which they must do in
order to attack foreign tissue, and protects transplanted
organs. Likewise, it slows down the uncontrolled
cell division that happens in cancer. The kicker was
that both of the woman’s mutations, NF2 and TSC1,
affect the mTOR system. “It’s not surprising, in retrospect,
that our patient responded really well to this
specific drug,” Solit says. “She had the mutation that
activated the pathway the drug targets.”
Solit’s team analyzed 13 more people from the trial
and found different TSC1 mutations in three other
people, including two whose tumor shrank a little in
response to the drug. (Nobody else had NF2 mutations,
which is probably why she alone responded dramatically.)
Meanwhile, eight of nine people whose tumors
grew during the study did not have the mutation.
DOROSHOW OF THE National Cancer Institute says
Solit’s work “turned on the lightbulb.” It showed how
the analysis of exceptional responders could be made
systematic. Inspired by his example, the NCI is now
trawling through its own archives, revisiting outlier
responses among the roughly 10,000 patients who
enrolled in NCI-sponsored clinical trials during the
last decade. Picture the long rows of crates in the government
warehouse at the end of Raiders of the Lost Ark:
There’s treasure in there somewhere, if only someone
would look. “We ought to study these people more,
since we have the means now,” says Barbara Conley,
the associate director of the cancer diagnosis program
at NCI, who leads the project.
In the few months since the project began, Conley’s
team have already found about 100 exceptional
responders. The next steps are to find out if their
tumors were biopsied, if that tissue sample is still sitting
in a freezer somewhere, and whether it’s in good
enough shape to be sequenced. Starting next year, the
group will start inviting any scientist who is doing a
clinical trial to submit new cases.
The NCI project will include whole-genome
sequencing (provided they have adequate tissue samples)
and repeated reads of the whole “exome”—the
1 percent of human DNA that is translated into exons,
the sequences that are used as templates for protein
construction. The reason to do both, explains Conley, is
that cancer cells, even within a single tumor, often have
a hodgepodge of mutations. Re-doing whole exome
sequencing dozens of times captures most of the significant
genetic variation in one tumor, and it’s more
practical than trying to sequence the whole genome
over and over. Finally, RNA expression will also be analyzed.
Evaluating RNA, an intermediary between DNA
and proteins, provides a measure of which genes are
switched on and how much protein they’re producing.
Other elite cancer research centers and genomesequencing
centers have similar in-house projects.
Much like the NCI project, the unusual responder program
at the University of Texas, MD Anderson Cancer
Center, is beginning by combing through the archives
to hunt for outliers of the past. A patient at the clinic
who has an unusual response—good or bad—will also
be referred for genome sequencing and other kinds of
genetic analysis.
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Even if each outlier case only applies to 3 or 7 percent
of one type of cancer, as more cases are solved,
the benefits quickly add up. “We’re talking about
small subsets of patients that together make a radical
change,” says Funda Meric-Bernstam, chair of the
Department of Investigational Cancer Therapeutics at
MD Anderson, who leads the unusual responders program.
In some cases, existing cancer drugs can simply
be repurposed, such as discovering
that an immunosuppressant
drug works for certain bladder
cancers. Or it might mean finding
new life for an experimental
drug that had been abandoned.
If Conley and Doroshow can
pinpoint who might be helped
by an abandoned drug, a pharmaceutical
company might
have to do just one or two further
studies to get that drug
approved for routine use.
The future might look something
like what’s been going on
for several years at the Genome
Institute of Washington University,
where genome sequencing
is being used to help people
with relapsed cancers and who
have run out of options. The
project puts insights from studies
like Solit’s into practice, analyzing a patient’s tumor
to determine whether currently available drugs might
target the troublemaker mutations. Combining whole
genome sequencing, exome sequencing, and RNA
expression analysis—what Washington University professor
of genetics and Genome Institute co-director
Elaine Mardis calls the “Maserati approach”—the team
compares a comprehensive genetic profile against a
database of drugs that target specific gene variants,
looking for a match.
If there is a match, the results can be impressive,
as was the case with a young Washington University
doctor with leukemia, Lukas Wartman, who had suffered
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
kidney cancer, sent his cancer into remission. Washington
University now has a special genetic test for
patients with his type of leukemia.
Just recently, Solit’s group solved another exceptional
responder mystery—a case of ureteral cancer
eliminated with a combination of old and new drugs.
The old drug is a standard chemotherapy treatment
that prevents DNA from unwinding, which it must do
in order to duplicate itself during
cell division. The new one
sensitizes cells to the effects of
radiation. This patient turned
out to have a mutation in RAD50,
involved in repairing broken
DNA strands (badly repaired
DNA can lead to uncontrolled
cancerous growth). Here, too,
the outlier finding may lead to
a new treatment, since about
4 percent of the other tumors
Solit has looked at have mutations
that affect part of the
RAD50 complex. “To look at
these individuals’ cancers can
tell us a lot more than just a
random case of cancer,” says
Solit. “There’s a phenotype—a
response—that gives you information
about the genes.”
Solit is now making a quick,
reliable test for the TSC1 mutation to single out people
with bladder cancer who might be helped by everolimus,
and is planning a new study to test the drug in
them. And the original outlier, the woman with bladder
cancer? Three years later, she’s still on everolimus
and still having a “complete response,” Solit says. She’s
doing fine.
kat mcgowan is a contributing editor at Discover magazine
and an independent journalist based in Berkeley, Calif.,
and New York City.
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