Science's 8 Greatest Unsolved Mysteries: Progress Report

In the year 2000, PM asked how eight of the most profound questions in science might be answered before the dawn of the 22nd century. So where we stand now, a decade later?
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Science's 8 Greatest Unsolved Mysteries: Progress Report


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Will We Find a Cure for Cancer?
A million and a half Americans will be diagnosed with cancer this year, and one-third of them will succumb to it, according to the National Cancer Institute. Diet, tobacco use and other environmental factors and lifestyle choices have a well-documented role in causing many of these cancers­—significantly more so than family genetics. As PM reported 10 years ago, prevention appears to be the solution to the cancer scourge, not a miracle pill.

While new incidences and deaths from all types of malignancies have declined several percentage points over the past decade, some cancers, including melanoma, leukemia and pancreatic and kidney cancers, are statistically on the rise. Meanwhile, treatments—chemotherapy, radiation and surgery—remain woefully inadequate and unpleasant.

One new strategy for stopping cancer before it starts is to go after the mechanism many doctors have increasingly implicated in priming the pump: parasitic infections. Paul Ewald, an evolutionary biologist at the University of Louisville, believes that by 2050, as many as 95 percent of all cancers will be proved to stem partly from infection. (That figure today is just 15 to 20 percent.) Scientists already know that hepatitis viruses are linked to liver cancer; human papillomavirus (HPV) can lead to cervical, rectum, penis and head and neck cancers; infections of Helicobacter pylori, the same bacteria to blame for peptic ulcers, causes stomach cancer.

While a whole spectrum of pathogens can set our feet on the paths to cancer, Ewald says, viruses stand out as the major villain. That's because viruses have evolved to target genes involved with cell division; hijack those, and the viral invader sets itself up for a nice long stay in a host. Viruses might not necessarily spur the mutations that make cells proliferate out of control, but the viral agents can leave a cell far more vulnerable should such a mutation occur. In this way, viruses have "evolved to sabotage the barriers to cancer as a strategy for persisting within us," Ewald says.

In light of this, greater use of vaccinations and antibiotics as well as improved hygiene could significantly curb the incidence of cancer. Gardasil, the vaccine for HPV, approved in 2006, is a major step in this direction. "The best hope for safely curing and preventing cancers arises from the identification and targeting of their infectious causes," Ewald says. "If there is one thing that medical science is good at, it is controlling infection."

For those cancers that do persist, novel therapies are in works as well, including light-based, tumor-targeting drugs and "super" white blood cells that squash cancerous cells while sparing healthy ones. These have the potential to eradicate deep-seated cancers from the body without the devastating side effects of many treatments widely used today.
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Can We Achieve Immortality?
Common sense tells us that everything dies. But rather than face that dark truth, humankind continues to believe in mythological sources of infinite life: The quest for the fountain of youth has generated more hype (and quixotic expeditions) than perhaps any other realm of science and medicine.

Yet serious research continues into the life-extending properties of a host of compounds, including resveratrol (a substance found in grapes), rapamycin (derived from an Easter Island bacterium) and proteins made by the gene p21. These proteins inhibit other proteins in cells known to lead to amyloid plaque formation, which is implicated in Alzheimer's, and that promote cancer development. Senex Biotechnology, a company PM first reported on in 2000, has drugs in development that work in much the same way.

Research also continues on an enzyme called telomerase, which slows the shortening of telomeres—sequences of DNA that grow progressively shorter during cell division until the cell eventually mutates or dies. In theory, stop this countdown and cells should live indefinitely. (The 2009 Nobel Prize in Medicine went to the discoverers of how telomeres and telomerase work.) Recent findings allude to telomerase's promise: As reported in the journal Nature in November, mice stripped of and then re-exposed to telomerase showed dramatic signs of reverse aging. Nutritional supplements—which do not require Food and Drug Administration approval—based on boosting telomerase levels became available a few years ago but have yet to be clinically evaluated.

Meanwhile, the results from human trials of two new compounds called synthetic activators of SIRT1 (STACs) will be released this year. These drugs seem to mimic the benefits of caloric restriction—which slows metabolism and produces age-delaying effects in every species tested, from yeast to primates, according to David Sinclair, a pathologist at Harvard Medical School.

But Jay Olshansky, a professor of epidemiology at the School of Public Health at the University of Illinois at Chicago, doesn't think a cure for aging will come from a drug. "Resveratrol, telomerase, p21—all for the most part have fallen flat on their face," he says. "In the last 10 years, there hasn't been an intervention that slows aging in humans." Olshansky instead believes the genes of centenarians—people who reach the century mark—hold the key to arresting the aging process. The New England Centenarian Study (NECS), the largest study of the superannuated on the planet, is presently keeping tabs on some 1600 centenarians and hundreds of their similarly spry children.

"The reason it is so exciting is that we don't have to jump species to see results," Olshanksy, who isn't involved in the study, says. "We don't have to make the huge theoretical leap that if people could act like mice, they could live to 150. Another way of saying it is: The secret, if there is one, is already walking among us."

Ultimately, the fountain of youth of might not be chemical or biological but technological. Futurist Ray Kurzweil has prophesied the rise of nanotechnology as the means to immortality, enabled by tiny robots zipping through our bodies repairing damaged organs and tissues. Kurzweil wagers that anyone alive by midcentury has a good shot at never dying.
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Can We Create Life?
We still don't know how exactly life got its spark on our planet, or even if it sprung up elsewhere and was subsequently delivered here by comets. But at this point, it's fair to say we have a good handle on the recipe for life as we know it—the necessary components, the biomolecular structures they form and how the parts make up the whole. It's in the cooking instructions, if you will, that we remain a bit fuzzy.

As for creating life from scratch, a big step was taken last May when famed geneticist J. Craig Venter and his team unveiled the first synthetic organism. The scientists crafted an entire genome from chemicals in the lab. They then implanted this synthetic genome in an empty cell, after which the cell booted up and began cranking out copies of its modified self per the implanted genetic instructions.

This artificial life form, dubbed Synthia, required the leftover cellular machinery made by a natural, preexisting organism, so science hasn't reached back to square one yet. "Venter did not create life," says Arthur Caplan, a bioethicist at the University of Pennsylvania, who was involved in the research. "But he showed that an artificial genome can power a bacterium, thereby taking a crucial step toward the demonstration that synthesizing life is possible."

Venter and other geneticists are persevering in their efforts to boil life down to its very molecular essence—the minimal blueprint needed for an independent cell to persist and replicate. By studying the simple fatty and nucleic acids that make up the most basic forms of life, scientists hope to discover the boundary between mere chemical reactions and self-sustaining, evolving beings.

Along with these efforts to construct "wet," biochemical artificial life, computer scientists have already largely succeeded in creating life in digital form. The difference between the two is not as stark as you might think; after all, biological life's basic purpose is to make more copies of itself via instructions in DNA, and a computer program can be made to replicate itself in much the same way.

The digital organisms in the Avida project, based at the Digital Evolution Laboratory at Michigan State University, do just that—and like real critters, they compete, die and evolve. "The digital organisms in Avida are arguably as alive as natural viruses that trick a cell into doing most of the work for them," says Charles Ofria, the Digital Evolution lab's director. The first results from the Avida software program were published in 2003, three years after PM last checked in. The project has continued to produce ever-richer, lifelike entities that are helping tease apart the complexities of biological evolution. "The world of Avida may be a simulation," Ofria says, "but the evolution that occurs in that world is real."
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Will We Find the Soul?
The ability to create life on ever grander levels will bring to the fore that timeless quandary of what defines a unique individual, a unique mind and a unique consciousness—for lack of a better word, what defines a soul.

A developing field of inquiry known as neurotheology seeks to solve this mystery. "If the soul is the immaterial part of who we are, then at this point in time, science can only evaluate what happens within a person when they experience their soul in some way," says Andrew Newberg, a neuroscientist and author of the recent book Principles of Neurotheology.

To this end, Newberg and his colleagues have scanned the brains of Tibetan monks, Franciscan nuns and Pentecostal Christians while engaged in spiritual exercises such as meditation and speaking in tongues. In the 10 years since PM first spoke with Newberg, he and his colleagues have looked at activity in the brains of 130 people. The researchers continue to see that "a relatively extensive network of brain structures is involved with religious and spiritual states," Newberg says. By illuminating what the brain is up to in the throes of religious rapture, Newberg thinks neurotheology "can try to determine what brain and body functions appear to be associated with activities pertaining to the soul."

It might be that finding the wellspring of consciousness and the soul, as it were, will result from delving still deeper—into the quantum-mechanical realm. Conventional constructs of consciousness are based on classical physics, with our mind emerging from a network of billions of neurons electrically firing away in the three pounds of mush in our skulls. "Most views assume consciousness arises strictly from synaptic computation among brain neurons," says Stuart Hameroff, director of the Center for Consciousness Studies at the University of Arizona.

Along with Roger Penrose­—who will be mentioned again below—Hameroff co-created Orch OR (orchestrated objective reduction), a theory of quantum consciousness. Orch OR proposes an additional, major role for tiny cellular structures called microtubules. These hollow tubes partially compose the cytoskeleton that helps structure our cells' interiors. According to Orch OR, "consciousness also depends on quantum computations in microtubules inside brain neurons," Hameroff says.

At first blush, such a mechanism sounds unlikely; after all, the rudimentary quantum computers we've made in labs operate at extremely cold temperatures, not the toasty environment of upper 90s found in our brains. But results in the past five years point to quantum mechanics' involvement in a number of nonfrigid biological processes, including photosynthesis, Hameroff notes. And intriguing preliminary findings from Anirban Bandyopadhyay, a physicist at the Japanese National Institute for Materials Science in Tsukuba, imply that bits of quantum information, dubbed qubits, can maintain their coherence in single, warm microtubules in cells. Future work could assess whether certain gases used for anesthesia can scramble this coherence—a powerful demonstration of a basic on/off switch for consciousness.

The details of Orch OR are dense and provocative. That "objective reduction" part refers to the boiling down of the range of possible positions a particle could have to just one position. This follows as a natural result of a universe governed by the twin titans of physics—relativity and quantum mechanics—interlinking at an incomprehensibly small, yet mathematically valid, scale called the Planck length (1.6 x 10–35 meters, for those keeping count).

Therefore, Hameroff says, Orch OR, if true, would "connect the brain directly to the most basic level of the universe from which consciousness is said to arise." Such a link could have some profound ramifications, especially for believers in a soul. "The connection to space–time geometry also raises the intriguing possibility that Orch OR allows consciousness apart from the brain and body, distributed and entangled in space–time geometry," Hameroff says. This could perhaps account "for so-called out-of-body experiences and afterlife—the 'quantum soul.'"
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Are We Alone?






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Is Light the Ultimate Speed Limit?
As for communicating with far-flung alien civilizations or going to visit them ourselves, the situation appears far less optimistic.

For an area of research dealing with fantastic speeds, progress on faster-than-light (FTL) travel is ironically very slow. Since early last century, we've been hamstrung by Albert Einstein's proved-and-proved-again speed limit of light, which is 186,282 miles per second in a vacuum. Even if we could accelerate a spacecraft to this speed—which itself would require an improbable energy breakthrough—a round trip to Alpha Centauri, the nearest star system to us at 4.3 light-years away, would take almost a decade.

So to create a future resembling anything like the solar-system–hopping in Star Trek, we'll need to find a way around relativity. Several experiments, such as the one led by Princeton's Lijun Wang, which PM reported in 2000, and another by German researchers in 2007, have produced the appearance of light breaking its own racing rules. In the first case, the scientists readily admitted that no mass or information breached the speed of light, but that a pulse of light (a group of massless waves) did. In nonvacuum conditions, pulses of light measured at different points can seem to travel at "ludicrous speed," or faster than light for any Spaceballs fans—but that wouldn't actually help us reach for the stars. The 2007 experiment remains controversial and, given vagaries of measurement, has many physicists unconvinced that anything Einstein-defying has actually occurred.

Quantum entanglement, however, is one phenomenon "where information does seem to travel at faster-than-light speed," says Gerald Cleaver, a professor of physics at Baylor University. It works as follows: When a property of one of a pair of particles is measured, the second particle near simultaneously also assumes this property, apparently regardless of the distance separating the particles. In 2007, researchers set the record distance for entanglement of photons—some 89 miles (144 kilometers) between two of the Canary Islands—and an experiment in 2008 clocked the speed of entanglement as at least 10,000 times that of light. This "spooky action at a distance," as Einstein famously derided it, continues to fry brains, physicists' included, and it's not clear if it just might be the sort of window into new frontiers of physics that leave light in the dust someday.

Meanwhile, hopes for an Alcubierre (or warp) drive­ continue to be dashed. Such a setup involves propelling a pocket of space–time faster than light by scrunching up and expanding space–time behind and in front of it, respectively. Not only would we need science-fictional negative energy, we'd need gobs of it: Cleaver calculates that to initiate a faster-than-light "warp bubble" holding a spaceship not much bigger than Han Solo's Millennium Falcon would "be on par with the energy equivalent of the mass of Jupiter." To make matters worse, Spanish and Italian scientists suggested in a 2010 paper that deadly amounts of radiation would pervade such a bubble.

Perhaps the best hope for ever making the jump to hyperspace lies in our remaining ignorance. "There's certainly new physics left to be discovered," says Marc Millis, the former leader of NASA's Breakthrough Propulsion Physics program and founder and current president of the Tau Zero Foundation, a group dedicated to bringing about interstellar travel. Millis points to the two "dark" phenomena as clear examples: dark energy, the force swelling the cosmos at an ever-faster rate, and dark matter, the mysterious preponderance of the universe's material that, among other inferred effects, prevents rotating galaxies from disgorging their contents as they whirl. Add to those the fact that the cosmos, by our best reckoning, expanded much faster than the speed of light shortly after the Big Bang, and that general relativity is cool with space–time itself trumping light speed, and all hope is not yet lost for abolishing the current universal speed limit.
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Can We Travel Through Time?
Although the speed of light still remains sacrosanct, are we at least making progress toward profaning time?

In fact, breaking out of the shackles of the here and now can be done—but it's not terribly feasible. That's because, as Einstein instructed us, the passage of time is relative. Time moves faster at greater distances from the center of a massive object, such as the Earth; the clocks on satellites passing overhead have to be calibrated for these miniscule, albeit very real, relativistic discrepancies. Remarkably, this effect is detectable at a difference in height of a mere foot, as National Institutes for Standards and Technology scientists demonstrated with two atomic clocks last year. Ergo, our head ages quicker than our hearts... though only about 90 billionths of a second over a lifetime.

This phenomenon of time dilation can, however, start to pay dividends for an astronaut standing on a neutron star—the compact, super-massive remnant of a giant star. According to Paul Davies, a theoretical physicist and cosmologist at the University of Arizona, "70 years experienced by the astronaut would correspond to 100 years on Earth, so the astronaut will have reached the year 2110 in just seven decades." A nifty feat, until Davies drops the other shoe: "But of course, nobody could survive on the surface of a neutron star."

Speed also makes time fly: Stationary clocks (relative to, say, an earthbound observer) tick faster than clocks in motion. And the closer an object gets to the speed of light, the slower time passes for it. One wouldn't have to go on a long journey to reap a time-traveling benefit. "To get the big time-dilation factor, you just need to have motion in space, not necessarily over large distances," says Jeff Tollaksen, a professor of physics and director of the Center for Quantum Studies at Chapman University in Orange, Calif. So in principle, a time machine could be as simple as a big centrifuge that spins someone around at near-light speed. But, Tollaksen adds, good luck engineering a way to do that without scrambling the person inside.

Despite the considerable caveats, "going forward in time is just a matter of money and engineering," Davies says, "so big leaps could become a reality one day." As for going back in time, physicists are far less optimistic. For starters, basic logic would seem to preclude such an act. Consider the "grandfather paradox": A time traveler burrows into the past and kills his grandfather, thereby snuffing out his own eventual existence.

Yet in the quantum-mechanical sandbox Tollaksen plays in, the future can mind-bogglingly influence what comes before it. Recent experiments have shown that measuring a property of an object at a beginning and an end stage can alter the property's value at an intermediate stage. The use of so-called weak measurements that do not disturb a delicate quantum-mechanical system has begun to offer a peek into this backwards causality. Could such a phenomenon be the mechanism that allows us to modify the past, if not re-experience it? Tollaksen, for one, thinks not. "I don't see any conceivable breakthroughs that will get around the killing-your-grandfather paradoxes," he says. "It looks to us that the best nature can do to make the future relevant to the present is via the stuff we're doing with regard to weak measurements."

There does remain a wild card for time (and faster-than-light travel): wormholes, or hypothetical tunnels through space–time. But don't get your hopes up. "Their existence depends on anti-gravitating matter, which may exist only in microscopic amounts," Davies says. "For this reason, even if wormholes can be created, they are likely to be of subatomic dimensions and to evaporate in a split second."

So while the future beckons, the past might remain just that: the past. "Going back in time, for a human being, looks to be a much tougher proposition and may well be strictly impossible," Davies says. But this time he offers an encouraging caveat: "Of course, if there is new physics to be discovered, all bets are off."
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Will We Find Other Universes?
Even if we eventually solve all of the mysteries of our bodies, our planet and our universe, there remains yet another puzzle, and it is perhaps the most gobsmacking of all: the possibility of cosmic realms beyond our own.

Scientists have long proposed parallel universes with idiosyncratic laws of physics. Such a multiverse arises as an inevitability of quantum mechanics and its range of possible observations, or it might have bubbled out like soapsuds as our universe surged in size in its initial moments. Even string theory—the concept that infinitesimal strings vibrating in 10 dimensions constitute reality—points to universes by the bucketful.

These other universes, or any universe that preceded ours, might leave signatures of some sort in deep space. An intriguing new study from Roger Penrose of the University of Oxford and Vahe Gurzadyan of the Yerevan Physics Institute in Armenia suggests just that. The scientists have identified what they say are giant concentric circles in the cosmic microwave background (CMB) radiation. The CMB is a relic of the Big Bang's detonation 13.7 billion years ago—a supposedly smooth, random radiation that suffuses the universe everywhere we look.

The recently discovered rings denote regions where temperature variations in this background radiation read as smaller than average. According to Penrose, colliding super-massive black holes in a previous aeon of our universe could have created enormous gravitational waves, which are ripples in space–time; these ripples would then impart a remarkably uniform imprint on the dark matter in our current universe as this iteration of it unfolds.

Though other groups have confirmed these structures, the interpretation of them as signs of a cycle of cosmic rebirth has been strongly contested. Other anomalies detected this decade in the CMB—a streak here, a large cold spot there—courtesy of the best available maps by the Wilkinson Microwave Anisotropy Probe have similarly fueled speculation. Alien cosmoses may have bumped into ours and left such scars, researchers propose.

All agree that more detailed maps of the CMB from the European Space Agency's Planck spacecraft, due in about a year, will help move the debate forward—and perhaps toward a conclusion. "Notwithstanding how radical the views may sound to our ears for the time being," Gurzadyan says, "only the experiment, or equivalently the observations, in this case, are able to provide a decisive answer." Regardless of whether this far-out paradigm stands or crumbles, it is science on the edge, and that is the frontier of progress.
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In the Year 2000
In 2000, PM's science editor Jim Wilson posited eight questions that scientists would answer in the coming century. Here's a look at that original story.
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