As always, as the year comes to a close, there is an inevitable rush to produce top 10 lists. Top 10 movies, top 10 books, top 10 music albums. Not content to let Hollywood and the entertainment industry have all the fun, the news staff at Science magazine have compiled their year-end top 10 list of the scientific breakthroughs that broke through with the potential for lasting impact. These range in scale from protons to planets and include nearly everything in between.

Science 's Breakthrough of the Year: Reprogramming Cells

As the writers at Science spin the opening sentence, the breakthrough of the year is "a long-sought feat of cellular alchemy." Whereas the ancient alchemists sought to transmute mundane metals into gold or silver, modern scientific wizards have found ways to convert human skin cells—the base metal—into induced pluripotent stem cell (iPS)—the modern biological equivalent of gold. These iPS cells are capable of growing into a variety of tissues, which could ultimately lead to the capacity to cure certain diseases with a patient's own cells.

In a second cellular programming trick, scientists transformed mature cells in live mice from one specialized type to another. This bit of biological witchcraft flew in the face of years of results that suggested that cell development was a one-way street. It has provided much greater understanding into the nature of biological and chemical processes that enable cells to stably adopt a specialized role, and has opened the doors to the field that's now being called cellular programming. Both of these techniques potentially side stepp the political mine-field that surrounds human embryonic stem cells.

Ten years ago, a team from the University of Wisconsin-Madison developed a technique to get human embryonic stems cells (hES) from human blastocysts. This, not terribly surprisingly, ignited a large debate over bioethics since the procedure often destroys the blastocyst. The potential for a new source of embryonic-like stem cells came via breakthrough paper from a team of Japanese researchers. Named the number two breakthrough of the year by Science magazine, the Japanese team created iPS cells from mouse tail cells through the simple insertion of four genes. When the next logical step was taken—using the technique with human cells—researchers were off to the races.

Two groups announced stunning breakthroughs within weeks of each other this year. The first group derived iPS cells from the skin of an elderly woman suffering from amyotrophic lateral sclerosis (ALS, or Lou Gehrig's disease). They then directed the cells to develop into neurons and glia, two of the cell types most affected by ALS. Shortly after this announcement, a second group reported the creation of patient-specific iPS cell lines for 10 additional diseases. Many of these 10 disease are not well suited, or even possible, to study via animal models.

Ignoring the lure of stem cells, another group of researchers demonstrated that one does not need them to produce various mature cell types; instead, they forced mature cells to change their form and function. Working with live mice, an American research team demonstrated that pancreatic exocrine cells can be forced to function as beta cells. Using a trio of viruses as their gene delivery vectors, the team inserted a set of genes believed to be responsible for beta cell growth into the exocrine cells. Within days, they observed that the "treated mice formed insulin producing cells that acted like bona fide beta cells." Since beta cells are responsible for producing insulin and are destroyed in people suffering from type-I diabetes, this technique could have major ramifications if it can be modified for human use.

While these breakthroughs are major, much more work is needed before we start to see custom-made, individually constructed cures for diseases. We currently lack a reliable method of triggering developmental changes and need a more detailed understanding of how the conversion process works and a much more detailed understanding of the nature of the newly formed cells. Even though this field is not ready for human consumption, the potential it presents warranted it being named the biggest scientific breakthrough of the year, according to Science.

Runners-Up:



Direct

Views of Exoplanets:

Astronomers first found a planet orbiting another star in 1995, after

hundreds of years of speculation that the probability of other planets

must be infinitesimally close to unity. In the intervening 13 years, 332 more planets

have been found orbiting other stars. Until earlier this year, however, all were

found using indirect techniques. The vast majority of these

exoplanets—307

to be exact—were found not because we saw the

planet, but because we were able to observe the star it orbits wobbling

due to the planet's mass. Starting in the latter part of this year,

astronomers have been reporting on the direct observation of

exoplanets. Using adaptive optics and "virtual coronograph" software,

teams have found 11 planets by directly looking at them, rather than

relying on secondary effects.

Astronomers first found a planet orbiting another star in 1995, after hundreds of years of speculation that the probability of other planets must be infinitesimally close to unity. In the intervening 13 years, 332 more planets have been found orbiting other stars. Until earlier this year, however, all were found using indirect techniques. The vast majority of these exoplanets—307 to be exact—were found not because we saw the planet, but because we were able to observe the star it orbits wobbling due to the planet's mass. Starting in the latter part of this year, astronomers have been reporting on the direct observation of exoplanets. Using adaptive optics and "virtual coronograph" software, teams have found 11 planets by directly looking at them, rather than relying on secondary effects. The DNA of

Cancer: It is known that DNA mistakes can lead to cell

growth that is unregulated, which can produce a cancerous tumor. Thanks to the completion of

the human genome and affordable sequencing equipment, several groups have looked deeper

into the genetic mistakes that can cause cancer. Through the study of

various cancer genomes, scientists have concluded that treatments that block common cellular pathways could be more effective then a

'magic bullet' treatments directed at individual cancer genes.

It is known that DNA mistakes can lead to cell growth that is unregulated, which can produce a cancerous tumor. Thanks to the completion of the human genome and affordable sequencing equipment, several groups have looked deeper into the genetic mistakes that can cause cancer. Through the study of various cancer genomes, scientists have concluded that treatments that block common cellular pathways could be more effective then a 'magic bullet' treatments directed at individual cancer genes. New Class of

High-T Superconductors: since the discovery of high-temperature superconductors in 1986, all had been a ceramic made up of lanthanum-barium-copper oxides. Earlier this year, there was a flurry of papers from a number of research groups that announced they had found a new

class of high-temperature

superconductors, ceramics made of lanthanum, iron, arsenic,

oxygen, and fluorine. While their critical temperature is, by high-temperature superconducting standards, a not-so-hot 55 K, they have

opened a new pathway into the mystery of superconductor research. Follow

up work hasn't been able to determine whether these materials

behave the same as their more familiar cuprate cousins.

since the discovery of high-temperature superconductors in 1986, all had been a ceramic made up of lanthanum-barium-copper oxides. Earlier this year, there was a flurry of papers from a number of research groups that announced they had found a new class of high-temperature superconductors, ceramics made of lanthanum, iron, arsenic, oxygen, and fluorine. While their critical temperature is, by high-temperature superconducting standards, a not-so-hot 55 K, they have opened a new pathway into the mystery of superconductor research. Follow up work hasn't been able to determine whether these materials behave the same as their more familiar cuprate cousins. Protein

flopping and folding: How proteins dock with target

molecules has long been a subject of debate among biologists,

biochemists, and biophysicists. The leading theory is that, when a

protein molecule comes upon a target, it will change its shape so that

it will fit in a lock-and-key manner. However, some postulated

that proteins in solution randomly oscillate between a number of

related but slightly different conformations. New computational

biology work performed by teams in the US and Germany has given support to the

latter model. The researchers discovered that a oft-studied protein will "dance"

between many different configurations before finding the one that enables it to

interact with its target molecule.

How proteins dock with target molecules has long been a subject of debate among biologists, biochemists, and biophysicists. The leading theory is that, when a protein molecule comes upon a target, it will change its shape so that it will fit in a lock-and-key manner. However, some postulated that proteins in solution randomly oscillate between a number of related but slightly different conformations. New computational biology work performed by teams in the US and Germany has given support to the latter model. The researchers discovered that a oft-studied protein will "dance" between many different configurations before finding the one that enables it to interact with its target molecule. Splitting

Water: With the summer's historic rise in oil

prices, interest in renewable energy sources was front and center

view in the mind of many people. Even as technology for solar and wind

power advances and prices for the power they generate

falls, storing that energy remains a challenge. One suggestion is to

hydrolyze water into hydrogen and oxygen, which can later be burned

or used in a fuel cell setup. The problem is efficiently

spitting water; platinum is a good catalyst

for this reaction, but its scarcity and price are turn offs for large

scale work. This year saw the development of

a new catalyst, comprised of phosphorous and cobalt, that

can efficiently hydrolyze water on industrial scales.

With the summer's historic rise in oil prices, interest in renewable energy sources was front and center view in the mind of many people. Even as technology for solar and wind power advances and prices for the power they generate falls, storing that energy remains a challenge. One suggestion is to hydrolyze water into hydrogen and oxygen, which can later be burned or used in a fuel cell setup. The problem is efficiently spitting water; platinum is a good catalyst for this reaction, but its scarcity and price are turn offs for large scale work. This year saw the development of a new catalyst, comprised of phosphorous and cobalt, that can efficiently hydrolyze water on industrial scales. Beginning of

Life, the Movie: Most of us have have probably seen a video of the first cells of an embryo dividing, starting from a sperm+egg, then dividing to form the first few dozen individual

cells. When it comes to vertebrates, though, scientists only had, at best, a partial view of what comes next. This year, researchers from Germany created a

specialized microscope and observed the formation and growth of a zebrafish embryo. They watched it from a single cell until it reached a cluster of almost 16,000 individual cells. The

movies are freely

available on the Internet, and well worth watching.

Most of us have have probably seen a video of the first cells of an embryo dividing, starting from a sperm+egg, then dividing to form the first few dozen individual cells. When it comes to vertebrates, though, scientists only had, at best, a partial view of what comes next. This year, researchers from Germany created a specialized microscope and observed the formation and growth of a zebrafish embryo. They watched it from a single cell until it reached a cluster of almost 16,000 individual cells. The movies are freely available on the Internet, and well worth watching. Color Coded

Fat: It has been known for over 400 years that there are

two types of fat: white and brown. Brown fat cells

have a much higher concentration of mitochondria and burn energy for

heat; white fat cells are what many of us readily see in

our midsection. Both types of fat cells were assumed to be related and come from the same

progenitor cell type. Using the observation that the gene PRDM16 spurs

specialization of brown fat, US researchers expected that if they blocked PRDM16 activity, the brown

fat precursor cells would become white fat cells. They did not get what

they expected as, in the absence of PRDM16, the brown fat

cells of mice turned into muscle cells. The team was also able to reverse the process, turning cells

differentiating into muscle cells into brown fat. Using a

technique to trace cell linages, the team found that muscle and brown

fat cells in mice were related, but neither was related to white fat

cells.

It has been known for over 400 years that there are two types of fat: white and brown. Brown fat cells have a much higher concentration of mitochondria and burn energy for heat; white fat cells are what many of us readily see in our midsection. Both types of fat cells were assumed to be related and come from the same progenitor cell type. Using the observation that the gene spurs specialization of brown fat, US researchers expected that if they blocked activity, the brown fat precursor cells would become white fat cells. They did not get what they expected as, in the absence of the brown fat cells of mice turned into muscle cells. The team was also able to reverse the process, turning cells differentiating into muscle cells into brown fat. Using a technique to trace cell linages, the team found that muscle and brown fat cells in mice were related, but neither was related to white fat cells. Computing the

Basics: While protons, neutrons, and other light hadrons

are considered basic particles, the mathematics

describing their innards is incredibly complex. The simple picture of

the inside of any hadron is three quarks that exchange gluons,

the messenger particle of the strong nuclear force, among themselves.

Reality is much more complicated, and our best description of the strong force—quantum chromodynamics

(QCD)—requires incredibly powerful computers to have any hope of

accurately modeling even a "simple" hadron. Using massively parallel

computers and a technique known as lattice quantum chromodynamics,

researchers in Europe have predicted

the mass of a proton using only the theory behind the strong

force. The fact that their computed mass is within a few percent of the

experimental answer suggests that QCD properly describes the strong nuclear force.

While protons, neutrons, and other light hadrons are considered basic particles, the mathematics describing their innards is incredibly complex. The simple picture of the inside of any hadron is three quarks that exchange gluons, the messenger particle of the strong nuclear force, among themselves. Reality is much more complicated, and our best description of the strong force—quantum chromodynamics (QCD)—requires incredibly powerful computers to have any hope of accurately modeling even a "simple" hadron. Using massively parallel computers and a technique known as lattice quantum chromodynamics, researchers in Europe have predicted the mass of a proton using only the theory behind the strong force. The fact that their computed mass is within a few percent of the experimental answer suggests that QCD properly describes the strong nuclear force. DNA on the

Cheap: When the human genome was decoded a few years

ago, it used techniques that are now considered somewhat antiquated. Hardware from a number of companies has become available over the past few years

has blown the doors off genome sequencing. The "sequencing by

synthesis" technology from 454 Sequencing (now owned by Roche) has allowed researchers to to sequence partial genomes of extinct cave bears and

Neanderthals, along with 80 percent of a woolly mammoth's. As sequencing

technology advances, more and more genetic codes will be cracked and,

like in consumer technology and electronics, the price will continue to

fall.

Given this list, it would appear that 2008 was a productive year in the

natural sciences. To see how this list compares to last year's, have a

look at our past coverage.