Magazine's 125 Questions
What Is the Universe Made Of?
What is the Biological Basis of Consciousness?
Why Do Humans Have So Few Genes?
To What Extent Are Genetic Variation and Personal Health Linked?
Can the Laws of Physics Be Unified?
How Much Can Human Life Span Be Extended?
What Controls Organ Regeneration?
How Can a Skin Cell Become a Nerve Cell?
How Does a Single Somatic Cell Become a Whole Plant?
How Does Earth's Interior Work?
Are We Alone in the Universe?
How and Where Did Life on Earth Arise?
What Determines Species Diversity?
What Genetic Changes Made Us Uniquely Human?
How Are Memories Stored and Retrieved?
How Did Cooperative Behavior Evolve?
How Will Big Pictures Emerge from a Sea of Biological Data?
How Far Can We Push Chemical Self-Assembly?
What Are the Limits of Conventional Computing?
Can We Selectively Shut Off Immune Responses?
Do Deeper Principles Underlie Quantum Uncertainty and Nonlocality?
Is an Effective HIV Vaccine Feasible?
How Hot Will the Greenhouse World Be?
What Can Replace Cheap Oil -- and When?
Will Malthus Continue to Be Wrong?
Is ours the only universe?
A number of quantum theorists and cosmologists are trying to figure out
whether our universe is part of a bigger "multiverse." But others
suspect that this hard-to-test idea may be a question for philosophers.
What drove cosmic inflation?
In the first moments after the big bang, the universe blew up at an
incredible rate. But what did the blowing? Measurements of the cosmic
microwave background and other astrophysical observations are narrowing
When and how did the first stars and galaxies form?
The broad brush strokes are visible, but the fine details aren't. Data
from satellites and ground-based telescopes may soon help pinpoint,
among other particulars, when the first generation of stars burned off
the hydrogen "fog" that filled the universe.
Where do ultrahigh-energy cosmic rays come from?
Above a certain energy, cosmic rays don't travel very far before being
destroyed. So why are cosmic-ray hunters spotting such rays with no
obvious source within our galaxy?
What powers quasars?
The mightiest energy fountains in the universe probably get their power
from matter plunging into whirling supermassive black holes. But the
details of what drives their jets remain anybody's guess.
What is the nature of black holes?
Relativistic mass crammed into a quantum-sized object? It's a recipe
for disaster--and scientists are still trying to figure out the ingredients.
Why is there more matter than antimatter?
To a particle physicist, matter and antimatter are almost the same.
Some subtle difference must explain why matter is common and antimatter
Does the proton decay?
In a theory of everything, quarks (which make up protons) should somehow
be convertible to leptons (such as electrons)--so catching a proton
decaying into something else might reveal new laws of particle physics.
What is the nature of gravity?
It clashes with quantum theory. It doesn't fit in the Standard Model.
Nobody has spotted the particle that is responsible for it. Newton's
apple contain ned a whole can of worms.
Why is time different from other dimensions?
It took millennia for scientists to realize that time is a dimension,
like the three spatial dimensions, and that time and space are inextricably
linked. The equations make sense, but they don't satisfy those who ask
why we perceive a "now" or why time seems to flow the way
Are there smaller building blocks than quarks?
Atoms were "uncuttable." Then scientists discovered protons,
neutrons, and other subatomic particles--which were, in turn, shown
to be made up of quarks and gluons. Is there something more fundamental
Are neutrinos their own antiparticles?
Nobody knows this basic fact about neutrinos, although a number of underground
experiments are under way. Answering this question may be a crucial
step to understanding the origin of matter in the universe.
Is there a unified theory explaining all correlated electron systems?
High-temperature superconductors and materials with giant and colossal
magnetoresistance are all governed by the collective rather than individual
behavior of electrons. There is currently no common framework for understanding
What is the most powerful laser researchers can build?
Theorists say an intense enough laser field would rip photons into electron-positron
pairs, dousing the beam. But no one knows whether it's possible to reach
Can researchers make a perfect optical lens?
They've done it with microwaves but never with visible light.
Is it possible to create magnetic semiconductors that work at room
Such devices have been demonstrated at low temperatures but not yet
in a range warm enough for spintronics applications.
What is the pairing mechanism behind high-temperature superconductivity?
Electrons in superconductors surf together in pairs. After 2 decades
of intense study, no one knows what holds them together in the complex,
Can we develop a general theory of the dynamics of turbulent flows
and the motion of granular materials?
So far, such "nonequilibrium systems" defy the tool kit of
statistical mechanics, and the failure leaves a gaping hole in physics.
Are there stable high-atomic-number elements?
A superheavy element with 184 neutrons and 114 protons should be relatively
stable, if physicists can create it.
Is superfluidity possible in a solid? If so, how?
Despite hints in solid helium, nobody is sure whether a crystalline
material can flow without resistance. If new types of experiments show
that such outlandish behavior is possible, theorists would have to explain
What is the structure of water?
Researchers continue to tussle over how many bonds each H2O molecule
makes with its nearest neighbors.
What is the nature of the glassy state?
Molecules in a glass are arranged much like those in liquids but are
more tightly packed. Where and why does liquid end and glass begin?
Are there limits to rational chemical synthesis?
The larger synthetic molecules get, the harder it is to control their
shapes and make enough copies of them to be useful. Chemists will need
new tools to keep their creations growing.
What is the ultimate efficiency of photovoltaic cells?
Conventional solar cells top out at converting 32% of the energy in
sunlight to electricity. Can researchers break through the barrier?
Will fusion always be the energy source of the future?
It's been 35 years away for about 50 years, and unless the international
community gets its act together, it'll be 35 years away for many decades
What drives the solar magnetic cycle?
Scientists believe differing rates of rotation from place to place on
the sun underlie its 22-year sunspot cycle. They just can't make it
work in their simulations. Either a detail is askew, or it's back to
the drawing board.
How do planets form?
How bits of dust and ice and gobs of gas came together to form the planets
without the sun devouring them all is still unclear. Planetary systems
around other stars should provide clues.
What causes ice ages?
Something about the way the planet tilts, wobbles, and careens around
the sun presumably brings on ice ages every 100,000 years or so, but
reams of climate records haven't explained exactly how.
What causes reversals in Earth's magnetic field?
Computer models and laboratory experiments are generating new data on
how Earth's magnetic poles might flip-flop. The trick will be matching
simulations to enough aspects of the magnetic field beyond the inaccessible
core to build a convincing case.
Are there earthquake precursors that can lead to useful predictions?
Prospects for finding signs of an imminent quake have been waning since
the 1970s. Understanding faults will progress, but routine prediction
would require an as-yet-unimagined breakthrough.
Is there--or was there--life elsewhere in the solar system?
The search for life--past or present--on other planetary bodies now
drives NASA's planetary exploration program, which focuses on Mars,
where water abounded when life might have first arisen.
What is the origin of homochirality in nature?
Most biomolecules can be synthesized in mirror-image shapes. Yet in
organisms, amino acids are always left-handed, and sugars are always
right-handed. The origins of this preference remain a mystery.
Can we predict how proteins will fold?
Out of a near infinitude of possible ways to fold, a protein picks one
in just tens of microseconds. The same task takes 30 years of computer
How many proteins are there in humans?
It has been hard enough counting genes. Proteins can be spliced in different
ways and decorated with numerous functional groups, all of which makes
counting their numbers impossible for now.
How do proteins find their partners?
Protein-protein interactions are at the heart of life. To understand
how partners come together in precise orientations in seconds, researchers
need to know more about the cell's biochemistry and structural organization.
How many forms of cell death are there?
In the 1970s, apoptosis was finally recognized as distinct from necrosis.
Some biologists now argue that the cell death story is even more complicated.
Identifying new ways cells die could lead to better treatments for cancer
and degenerative diseases.
What keeps intracellular traffic running smoothly?
Membranes inside cells transport key nutrients around, and through,
various cell compartments without sticking to each other or losing their
way. Insights into how membranes stay on track could help conquer diseases,
such as cystic fibrosis.
What enables cellular components to copy themselves independent of
Centrosomes, which help pull apart paired chromosomes, and other organelles
replicate on their own time, without DNA's guidance. This independence
still defies explanation.
What roles do different forms of RNA play in genome function?
RNA is turning out to play a dizzying assortment of roles, from potentially
passing genetic information to offspring to muting gene expression.
Scientists are scrambling to decipher this versatile molecule.
What role do telomeres and centromeres play in genome function?
These chromosome features will remain mysteries until new technologies
can sequence them.
Why are some genomes really big and others quite compact?
The puffer fish genome is 400 million bases; one lungfish's is 133 billion
bases long. Repetitive and duplicated DNA don't explain why this and
other size differences exist.
What is all that "junk" doing in our genomes?
DNA between genes is proving important for genome function and the evolution
of new species. Comparative sequencing, microarray studies, and lab
work are helping genomicists find a multitude of genetic gems amid the
How much will new technologies lower the cost of sequencing?
New tools and conceptual breakthroughs are driving the cost of DNA sequencing
down by orders of magnitude. The reductions are enabling research from
personalized medicine to evolutionary biology to thrive.
How do organs and whole organisms know when to stop growing?
A person's right and left legs almost always end up the same length,
and the hearts of mice and elephants each fit the proper rib cage. How
genes set limits on cell size and number continues to mystify.
How can genome changes other than mutations be inherited?
Researchers are finding ever more examples of this process, called epigenetics,
but they can't explain what causes and preserves the changes.
How is asymmetry determined in the embryo?
Whirling cilia help an embryo tell its left from its right, but scientists
are still looking for the first factors that give a relatively uniform
ball of cells a head, tail, front, and back.
How do limbs, fins, and faces develop and evolve?
The genes that determine the length of a nose or the breadth of a wing
are subject to natural and sexual selection. Understanding how selection
works could lead to new ideas about the mechanics of evolution with
respect to development.
What triggers puberty?
Nutrition--including that received in utero--seems to help set this
mysterious biological clock, but no one knows exactly what forces childhood
Are stem cells at the heart of all cancers?
The most aggressive cancer cells look a lot like stem cells. If cancers
are caused by stem cells gone awry, studies of a cell's "stemness"
may lead to tools that could catch tumors sooner and destroy them more
Is cancer susceptible to immune control?
Although our immune responses can suppress tumor growth, tumor cells
can combat those responses with counter-measures. This defense can stymie
researchers hoping to develop immune therapies against cancer.
Can cancers be controlled rather than cured?
Drugs that cut off a tumor's fuel supplies--say, by stopping blood-vessel
growth--can safely check or even reverse tumor growth. But how long
the drugs remain effective is still unknown.
Is inflammation a major factor in all chronic diseases?
It's a driver of arthritis, but cancer and heart disease? More and more,
the answer seems to be yes, and the question remains why and how.
How do prion diseases work?
Even if one accepts that prions are just misfolded proteins, many mysteries
remain. How can they go from the gut to the brain, and how do they kill
cells once there, for example.
How much do vertebrates depend on the innate immune system to fight
This system predates the vertebrate adaptive immune response. Its relative
importance is unclear, but immunologists are working to find out.
Does immunologic memory require chronic exposure to antigens?
Yes, say a few prominent thinkers, but experiments with mice now challenge
the theory. Putting the debate to rest would require proving that something
is not there, so the question likely will not go away.
Why doesn't a pregnant woman reject her fetus?
Recent evidence suggests that the mother's immune system doesn't "realize"
that the fetus is foreign even though it gets half its genes from the
father. Yet just as Nobelist Peter Medawar said when he first raised
this question in 1952, "the verdict has yet to be returned."
What synchronizes an organism's circadian clocks?
Circadian clock genes have popped up in all types of creatures and in
many parts of the body. Now the challenge is figuring out how all the
gears fit together and what keeps the clocks set to the same time.
How do migrating organisms find their way?
Birds, butterflies, and whales make annual journeys of thousands of
kilometers. They rely on cues such as stars and magnetic fields, but
the details remain unclear.
Why do we sleep?
A sound slumber may refresh muscles and organs or keep animals safe
from dangers lurking in the dark. But the real secret of sleep probably
resides in the brain, which is anything but still while we're snoring
Why do we dream?
Freud thought dreaming provides an outlet for our unconscious desires.
Now, neuroscientists suspect that brain activity during REM sleep--when
dreams occur--is crucial for learning. Is the experience of dreaming
just a side effect?
Why are there critical periods for language learning?
Monitoring brain activity in young children--including infants--may
shed light on why children pick up languages with ease while adults
often struggle to learn train station basics in a foreign tongue.
Do pheromones influence human behavior?
Many animals use airborne chemicals to communicate, particularly when
mating. Controversial studies have hinted that humans too use pheromones.
Identifying them will be key to assessing their sway on our social lives.
How do general anesthetics work?
Scientists are chipping away at the drugs' effects on individual neurons,
but understanding how they render us unconscious will be a tougher nut
What causes schizophrenia?
Researchers are trying to track down genes involved in this disorder.
Clues may also come from research on traits schizophrenics share with
What causes autism?
Many genes probably contribute to this baffling disorder, as well as
unknown environmental factors. A biomarker for early diagnosis would
help improve existing therapy, but a cure is a distant hope.
To what extent can we stave off Alzheimer's?
A 5- to 10-year delay in this late-onset disease would improve old age
for millions. Researchers are determining whether treatments with hormones
or antioxidants, or mental and physical exercise, will help.
What is the biological basis of addiction?
Addiction involves the disruption of the brain's reward circuitry. But
personality traits such as impulsivity and sensation-seeking also play
a part in this complex behavior.
Is morality hardwired into the brain?
That question has long puzzled philosophers; now some neuroscientists
think brain imaging will reveal circuits involved in reasoning.
What are the limits of learning by machines?
Computers can already beat the world's best chess players, and they
have a wealth of information on the Web to draw on. But abstract reasoning
is still beyond any machine.
How much of personality is genetic?
Aspects of personality are influenced by genes; environment modifies
the genetic effects. The relative contributions remain under debate.
What is the biological root of sexual orientation?
Much of the "environmental" contribution to homosexuality
may occur before birth in the form of prenatal hormones, so answering
this question will require more than just the hunt for "gay genes."
Will there ever be a tree of life that systematists can agree on?
Despite better morphological, molecular, and statistical methods, researchers'
trees don't agree. Expect greater, but not complete, consensus.
How many species are there on Earth?
Count all the stars in the sky? Impossible. Count all the species on
Earth? Ditto. But the biodiversity crisis demands that we try.
What is a species?
A "simple" concept that's been muddied by evolutionary data;
a clear definition may be a long time in coming.
Why does lateral transfer occur in so many species and how?
Once considered rare, gene swapping, particularly among microbes, is
proving quite common. But why and how genes are so mobile--and the effect
on fitness--remains to be determined.
Who was LUCA (the last universal common ancestor)?
Ideas about the origin of the 1.5-billion-year-old "mother"
of all complex organisms abound. The continued discovery of primitive
microbes, along with comparative genomics, should help resolve life's
How did flowers evolve?
Darwin called this question an "abominable mystery." Flowers
arose in the cycads and conifers, but the details of their evolution
How do plants make cell walls?
Cellulose and pectin walls surround cells, keeping water in and supporting
tall trees. The biochemistry holds the secrets to turning its biomass
How is plant growth controlled?
Redwoods grow to be hundreds of meters tall, Arctic willows barely 10
centimeters. Understanding the difference could lead to higher-yielding
Why aren't all plants immune to all diseases?
Plants can mount a general immune response, but they also maintain molecular
snipers that take out specific pathogens. Plant pathologists are asking
why different species, even closely related ones, have different sets
of defenders. The answer could result in hardier crops.
What is the basis of variation in stress tolerance in plants?
We need crops that better withstand drought, cold, and other stresses.
But there are so many genes involved, in complex interactions, that
no one has yet figured out which ones work how.
What caused mass extinctions?
A huge impact did in the dinosaurs, but the search for other catastrophic
triggers of extinction has had no luck so far. If more subtle or stealthy
culprits are to blame, they will take considerably longer to find.
Can we prevent extinction?
Finding cost-effective and politically feasible ways to save many endangered
species requires creative thinking.
Why were some dinosaurs so large?
Dinosaurs reached almost unimaginable sizes, some in less than 20 years.
But how did the long-necked sauropods, for instance, eat enough to pack
on up to 100 tons without denuding their world?
How will ecosystems respond to global warming?
To anticipate the effects of the intensifying greenhouse, climate modelers
will have to focus on regional changes and ecologists on the right combination
of environmental changes.
How many kinds of humans coexisted in the recent past, and how did
The new dwarf human species fossil from Indonesia suggests that at least
four kinds of humans thrived in the past 100,000 years. Better dates
and additional material will help confirm or revise this picture.
What gave rise to modern human behavior?
Did Homo sapiens acquire abstract thought, language, and art gradually
or in a cultural "big bang," which in Europe occurred about
40,000 years ago? Data from Africa, where our species arose, may hold
the key to the answer.
What are the roots of human culture?
No animal comes close to having humans' ability to build on previous
discoveries and pass the improvements on. What determines those differences
could help us understand how human culture evolved.
What are the evolutionary roots of language and music?
Neuroscientists exploring how we speak and make music are just beginning
to find clues as to how these prized abilities arose.
What are human races, and how did they develop?
Anthropologists have long argued that race lacks biological reality.
But our genetic makeup does vary with geographic origin and as such
raises political and ethical as well as scientific questions.
Why do some countries grow and others stagnate?
From Norway to Nigeria, living standards across countries vary enormously,
and they're not becoming more equal.
What impact do large government deficits have on a country's interest
rates and economic growth rate?
The United States could provide a test case.
Are political and economic freedom closely tied?
China may provide one answer.
Why has poverty increased and life expectancy declined in sub-Saharan
Almost all efforts to reduce poverty in sub-Saharan Africa have failed.
Figuring out what will work is crucial to alleviating massive human
The following six mathematics questions are drawn from a list of seven
outstanding problems selected by the Clay Mathematics Institute. (The
seventh problem is discussed on p. 96.) For more details, go to www.claymath.org/millennium.
Is there a simple test for determining whether an elliptic curve has
an infinite number of rational solutions?
Equations of the form y2 = x3 ax b are powerful mathematical tools.
The Birch and Swinnerton-Dyer conjecture tells how to determine how
many solutions they have in the realm of rational numbers--information
that could solve a host of problems, if the conjecture is true.
Can a Hodge cycle be written as a sum of algebraic cycles?
Two useful mathematical structures arose independently in geometry and
in abstract algebra. The Hodge conjecture posits a surprising link between
them, but the bridge remains to be built.
Will mathematicians unleash the power of the Navier-Stokes equations?
First written down in the 1840s, the equations hold the keys to understanding
both smooth and turbulent flow. To harness them, though, theorists must
find out exactly when they work and under what conditions they break
Does Poincaré's test identify spheres in four-dimensional space?
You can tie a string around a doughnut, but it will slide right off
a sphere. The mathematical principle behind that observation can reliably
spot every spherelike object in 3D space. Henri Poincaré conjectured
that it should also work in the next dimension up, but no one has proved
Do mathematically interesting zero-value solutions of the Riemann zeta
function all have the form a bi?
Don't sweat the details. Since the mid-19th century, the "Riemann
hypothesis" has been the monster catfish in mathematicians' pond.
If true, it will give them a wealth of information about the distribution
of prime numbers and other long-standing mysteries.
Does the Standard Model of particle physics rest on solid mathematical
For almost 50 years, the model has rested on "quantum Yang-Mills
theory," which links the behavior of particles to structures found
in geometry. The theory is breathtakingly elegant and useful--but no
one has proved that it's sound.
Science, Vol 309, Issue 5731, 78-102 , 1 July 2005