Head Injuries and Football: A Crisis Too Long Ignored?

From the marquee names of the National Football League to the hundreds of college programs to the thousands of high school teams, football has carved a special place in America's psyche. This rests not only on its entertainment value — for a great many boys and men, football has taught the values of teamwork, discipline and sheer grit. But it is a sport with a significant risk of injury, and recent months have seen growing concern about a not immediately obvious, but particularly upsetting, kind of health threat: delayed brain damage from repeated concussions. In "Head Injuries and Football: A Crisis Too Long Ignored?" Today's Science takes an in-depth look at this problem, and how scientists and the public at large are responding to it.
In the macho, rough-and-tumble culture of the National Football League (NFL), injuries are accepted as an unfortunate but inevitable reality. Every NFL player endures bumps and bruises, cuts and contusions, and minor sprains and strains as the uncomfortable price of fame and fortune. Of course, some injuries are too debilitating to be considered routine. Broken and dislocated bones, severe sprains, and torn muscles, ligaments, or tendons force even the toughest players to miss multiple games, or even whole seasons.


Concussions are special; they are invisible and, in many instances, the immediate symptoms last only minutes. A concussion occurs when the brain is jarred inside the skull. A concussed person may lose consciousness for a brief period, and then will be disoriented for a while. Not long ago, a concussed NFL player would get a whiff of smelling salts to clear his head a bit and then eagerly get back into the game. It was a matter of showing his toughness.
In response to growing concerns about concussions, the NFL in 2007 instituted new rules and directives. Now, a player who suffers head trauma cannot return to action in the game in which the injury occurred. After the game, he is required to undergo a thorough battery of tests by his team's medical staff, and he cannot again practice or play until cleared to do so by the doctors. The NFL also banned intentional helmet-to-helmet contact, a cause of head injuries.
So, you ask, how often do concussions occur in the NFL these days? Well, no fewer than five players were concussed in regular-season games in October 2009: San Francisco 49ers linebacker Jeff Ulbrich on October 4, San Francisco safety Michael Lewis on October 11, Tampa Bay Buccaneers punt returner Clifton Smith and Buffalo Bills quarterback Trent Edwards on October 18, and Philadelphia Eagles running back Brian Westbrook on October 26. It was Lewis's third diagnosed concussion of 2009 (the two earlier ones happened during the summer preseason). Ulbrich is a 10-year NFL veteran with a double-digit history of concussions. When his latest head injury failed to respond to medical treatments, the 49ers in mid-October placed Ulbrich on injured reserve, meaning he would have to sit out the rest of the season.


An isolated concussion may be bothersome, but it is the cumulative effects of multiple concussions that are the focus of present concern — there are indications that these effects may be much more incapacitating and dangerous than anyone imagined. Medical specialists at Boston University recently have linked repetitive football head injuries to chronic traumatic encephalopathy, a degenerative brain disease characterized by dementia and, in some cases, suicidal depression. And, the scientists have found that the potential risks are not limited to pro players. The findings — contained in a paper published in the July 2009 issue of the Journal of Neuropathology and Experimental Neurology and described in press reports — have created a firestorm of controversy. The subject has even attracted the attention of a U.S. congressional committee. [See NFL Head Injuries, December 18, 2009]

A Survey Raises Questions

The latest controversy over concussions was triggered by a confidential telephone health survey of some NFL retired players commissioned by the league itself. The NFL did not make the poll public, but some elements apparently were leaked to New York Times reporter Alan Schwarz, who reported the findings on September 30, 2009. Over the past few years, Schwarz has published several articles in the Times on the lingering effects of football head injuries.
The league commissioned the poll to gather information in preparation for negotiations on a new Collective Bargaining Agreement with the players' union, the National Football League Players Association (NFLPA). The health benefits of retirees would be among the matters to be negotiated.
The survey was conducted by the Survey Research Center of the University of Michigan, in Ann Arbor. The center asked 1,063 retired NFL players a series of questions on a wide range of personal health issues. One question, paraphrased by Schwarz in the Times, was whether a player had been diagnosed with "dementia, Alzheimer's disease, or [another] memory-related disease" since retirement from football. According to the Times, some 6.1% of the respondents aged 50 and older, and 1.9% of the respondents aged 30-49, reported that they had received dementia-related diagnoses. Based on federal health statistics, the rate among the older respondents was five times higher than the national average for dementia, and the rate among the younger respondents was 19 times the national average. (Subsequent news stories revealed that the total number of respondents who answered "yes" to the question was 56.)
Dementia is an irreversible, progressive deterioration of mental function marked by confusion, impaired memory, and impaired judgment. Its most common — but not sole — cause is Alzheimer's disease, a degenerative brain affliction that manifests mainly in the elderly.
Medical experts cited by the Times agreed that the survey fell short of being valid medical research. (The findings were neither peer-reviewed nor published in any reputable science journal, two hallmarks of legitimate research.) But, as Amy Borenstein, an epidemiology professor at the University of South Florida, told Schwarz: "[The dementia responses] suggest something suspicious....It's something that must be looked into with a more rigorous study."
The NFL has been reluctant to acknowledge a direct link between football head injuries and impaired mental function. In reaction to the leaking of the survey results, NFL spokesman Greg Aiello told Schwarz, "There are thousands of retired players who do not have memory problems. Memory disorders affect many people who never played football or other sports."
David Weir, the University of Michigan professor who headed the survey, pointed out in a comment reported by the Associated Press, "The study was not designed to diagnose or assess dementia. The study did not conclude that football causes dementia."

Troubled Retirements, Troubling Deaths

The survey findings nudged the national media into taking a close look at the ongoing work of the Sports Legacy Institute and its partner, the Center for the Study of Traumatic Encephalopathy (CSTE). The institute, based in Tampa, Florida, is a nonprofit organization devoted to research on sports head injuries. It was founded in 2007 by Chris Nowinski, a former Harvard University football player whose career as a professional wrestler had been cut short by repeated concussions. The CSTE, part of the Boston University School of Medicine, was formed in 2008 to study the donated brains of deceased athletes. Since 2008, Nowinski has persuaded over 100 current and retired football players, ice hockey players, and other athletes to agree to donate their brains to the CSTE upon death.
Nowinski had been inspired to form the institute after learning of the pioneering research of Bennet Omalu, a brain specialist and forensic pathologist formerly attached to the University of Pittsburgh, in Pennsylvania. Omalu became the first scientist to identify chronic traumatic encephalopathy (CTE) in football players when he biopsied the brains of three NFL retirees who had died between 2002 and 2006. All three were known to have suffered many concussions over the course of their NFL careers.
CTE, once known as "dementia pugilistica," is a degenerative brain disease originally identified in deceased "punch-drunk" boxers in 1928. In boxers, the disease is the apparent result of taking too many punches to the head. Omalu found one of the telltale signs of CTE — abnormally high concentrations of a protein called tau — in the autopsied brains of all three deceased NFL ex-players. In normal concentrations, tau is necessary for the transfer of electrochemical signals between brain cells. Repetitive concussions apparently stimulate a toxic overproduction of tau. Alzheimer's disease, too, can stimulate an overproduction of tau. But Alzheimer's brains always show abnormal clumps or lesions of beta-amyloid protein. Excess tau in the absence of amyloid lesions points to CTE, not Alzheimer's.


Overabundant tau forms bundles of brown fibrous tendrils — in medical parlance, neurofibrillary tangles and neuropil threads — that damage, and then kill, entire regions of healthy brain cells. In turn, the diseased parts of the brain cause not only dementia, but , bizarre or erratic behavior, and sometimes parkinsonism. (Parkinsonism, a brain disorder that mimics Parkinson's disease, is characterized by muscle tremors, impaired balance, and speech difficulties, among other problems.) As yet, medical science has no way of detecting tau tangles in the brain of a living person; they can only be found by autopsying the brain of a dead person.
Omalu initially joined the Sports Legacy Institute, but left the organization in 2008 over personal disagreements with Nowinski. Omalu's research was validated and advanced by the CSTE, codirected by Massachusetts neuropathologists Ann McKee and Robert Cantu. In early 2009, they reported finding tau tangles in the biopsied brains of six of seven dead former professional football players, including the same three retirees initially studied by Omalu. The lone exception was Damien Nash, a former Denver Broncos running back who had died suddenly in 2007, at the age of 24, of a previously undiagnosed heart ailment. The specialists found no evidence at all of CTE in Nash's brain.
The brains of the other six NFL ex-players were riddled with tau tangles. (Only one of the six had traces of amyloid lesions, perhaps an indication that the retiree was in the initial stages of Alzheimer's disease in addition to having CTE.) All of the ex-players had died between the ages of 36 and 50 amid troubled retirements, and none had what could be regarded as a routine death. For example, Mike Webster, a Pro Football Hall of Fame center for the Pittsburgh Steelers, struggled with depression, cognitive difficulties, and financial hardships before succumbing to heart failure at age 50 in 2002. Andre Waters, an exuberant star defensive back with the Eagles, spiraled into a deep depression during retirement and shot himself to death in 2006, at age 44. Tom McHale, a Tampa Bay offensive lineman turned respected businessman, sank into alcoholism and drug addiction. In 2008, at age 45, McHale overdosed on a fatal combination of cocaine and prescription painkillers.


The CSTE also announced that it had found evidence of CTE in the brain of a deceased 18-year-old who had played high school football. (The youth's identity and cause of death were withheld from the public at the request of his family.) Later in the year, the neuropathologists reported that Mike Borich, a deceased former college football player and honored college coach who never played pro football, had CTE. (Borich, 42, died of a drug overdose in February 2009.) The implication of those announcements — that high school and college athletes could develop CTE — stirred nationwide concern.
The center published a summary of its CTE research in a paper in the July 2009 issue of the Journal of Neuropathology and Experimental Neurology, with Ann McKee as the lead author.

Congress Weighs In

The Judiciary Committee of the U.S. House of Representatives held a hearing on the issue of football head injuries on October 28, 2009, in Washington, D.C. The committee's chairman, John Conyers, a Democrat from Michigan, called the issue a matter of "life and death." He elaborated: "I say this not simply because of the impact of these injuries on the 2,000 current players and more than 10,000 retirees associated with the NFL . . . . I say it because of the effect on the millions of players at the college, high school, and youth levels."

 NFL Commissioner Roger Goodell testified before the committee. Under questioning, he declined to acknowledge a connection between concussions and brain disorders. Goodell contended that the league was willing to take unspecified new steps to make NFL games safer, and to improve disability benefits for retirees. He alluded to a current benefit, the "88 Plan," which now provides up to $88,000 a year to any retiree with diagnosed dementia, regardless of the cause. He also disclosed that a panel of NFL medical experts was preparing a detailed study on head trauma.


Robert Cantu, codirector of the Center for the Study of Traumatic Encephalopathy, told the committee that there was "growing and convincing evidence" that repetitive concussions cause irreversible brain damage. "The public health risk is already here, and we cannot afford to wait any longer to make changes to the way we play sports."
The committee's ranking Republican, Lamar Smith of Texas, argued that Congress should stay out of the matter. "Football, like soccer, rugby, and even basketball and baseball, involves contact that can produce injuries," he noted. "We cannot legislate the elimination of injuries from the games without eliminating the games themselves."

Discussion Questions

Assuming it has the power to do so, should the federal government intervene in amateur or professional sports to reduce the risk of head injuries? If yes, what form should that intervention take? If no, explain why not.
Batting helmets were not in common use in professional baseball during the first part of the 20th century, but are now mandatory (and of course are used in Little League and other youth leagues). Can you think of other changes in the way games are played that have been introduced for safety purposes? What specific steps, if any, do you think could be taken in football to reduce the risk of concussions? Would those steps substantially affect the character of the game?

Other 

{SEE ALSO HEAD INJURIES LEADING TO MEMORY PROBLEMS IN SOCCER}

Gut Feeling: Microbiome at Work

No one would dispute that what we eat, and how we eat, are important to our health. But in recent years, it has become increasingly clear that it's not enough to think simply in terms of a binary system — our bodies, and the food we put in them. The fact is, our bodies, or more particularly, our digestive tracts, are, it turns out, host to many other creatures: microorganisms that are in us, but not, strictly speaking, part of us. This community of microorganisms — the microbiome — has a profound impact on our health. Bacteria are the big players here — the mix of bacteria in our digestive systems influences the way we break down and process the foods we eat; it facilitates our absorption of nutrients and helps us obtain the vitamins that we need.


Because the bacteria inhabiting our digestive tracts, or guts, are so critical to our everyday life, it's not surprising that scientists have been delving into how all these bacteria function. There is a lot to know: our bodies (made up of roughly 10 trillion cells) house about 100 trillion microbes — so we are still in the early stages of teasing apart the processes at work.
A new paper has made an important breakthrough, bringing a little order to the chaos. Manimozhiyan Arumugam and Peer Bork, both of the European Molecular Biology Laboratory in Heidelberg, Germany, and Jeroen Raes at the University of Brussels, along with 82 colleagues from Japan, China, Brazil and a number of European countries, recently published a study in Nature that finds that there are apparently three distinct types of microbiomes in the human gut. Given the multiplicity of both microbes and humans, this is a striking result.

Looking for Hay in a Haystack

The research team was not so much searching for a needle in a haystack as trying to take every piece of hay in the stack, categorize it and sort it; instead of hay, though, the scientists were working with fragments of DNA. The group took fecal samples from 22 people (selected for diversity from Denmark, France, Spain and Italy) and extracted DNA fragments from the samples. After sequencing the DNA fragments, they found that the vast majority of the fragments belonged to bacteria (92.76%), with a few viruses (5.8%), archaea (0.8%), other eukaryotes (0.5%), and human contaminants (0.14%) thrown in.
Arumugam, Bork and colleagues focused on the bacterial DNA fragments. The study also looked at bacterial DNA fragments extracted from samples collected from 11 other people in a previous study (bringing the total sample size to 33 individuals). Then they compared the DNA fragments against genome databases, matching their DNA sequences to those of known species. They met with remarkable success; on average they were able to identify the phylum of 80% of the DNA fragments in a sample, and the genus of 52.8% of the fragments. (As a refresher, scientific taxonomy goes — from general to specific — in the following order: kingdom, phylum, class, order, family, genus, species; getting to the genus level is pretty impressive for something as diverse as bacteria). Once these identifications had been made, the fragments were sorted into their phylogenetic groups. (The phylogenetic group of a sample would be the group it belongs to, based on evolutionary development and history.)

Three's No Crowd

The results of this sorting were unexpected and remarkable. While everyone may, in fact, be as individual as a snowflake, it turns out that our gut microbiomes are not; only 3 types of gut microbiomes, or enterotypes, were found in the 33 people studied. Within each enterotype, members of one genus of bacteria vastly outnumbered members of all other genera. The three different enterotypes were named for the dominant genus of bacteria in that enterotype: Bacteroides, Prevotella, and Ruminococcus. The division into three enterotypes was based not just on the dominant genus; individuals who had the same dominant genus of bacteria in their gut also shared a characteristic makeup for the remaining bacteria — that is, the genera present in smaller amounts, and those that were missing, were specific to the enterotype. This finding implies that the enterotypes depend on the composition of the entire bacterial community in the digestive tract, not just the presence of one genus.


Using a small sample size (and 33 is fairly small) can confound data analysis; it can overlook certain features or give unwarranted importance to others. So although their results seemed to be conclusive, the researchers conducted additional analysis to try to ensure that the bacterial genera pattern they found was not an artifact of their relatively small sample size.
They performed the same analysis as above on data from two previously published gut microbiome studies (involving a total of 139 subjects from Denmark and America), and came up with the same results. Arumugam, Bork, and their collaborators then analyzed their original data (the first 33 individuals) from another perspective. They divided the bacterial DNA fragments by orthologous genes, genes that are shared between genera, because they were inherited from a common ancestor. Investigating orthologous genes allows the researchers to explore the possible functions performed by the bacteria, not just their relatedness (which the DNA sequencing analysis above does), because the genes possessed by a bacteria dictate what it is able to do. The distribution of orthologous gene groups was, with a few exceptions, the same as that of bacteria genera, further supporting the study's conclusion that human gut bacteria are separated into discrete groups (both functionally and phylogenetically) within a larger community and not just mixed together in a random assortment. This analytical approach also had a surprise in store for the researchers; although most of the more common functions performed by gut bacteria were found to be carried out by the dominant bacteria genera, as might be expected, some were performed by minor genera. This finding strengthens the idea that to really understand what is happening in the human gut, all of the bacteria and their contribution to the microbiome must be explored.

Only Skin Deep

The orthologous gene groups correlated with several different characteristics of the study group. Ten gene groups were found to vary with nationality, and 12 varied with age. One orthologous gene group and five other biomarkers correlated with gender, and three biomarkers correlated with the BMI (body mass index) of the experimental subjects.
Notwithstanding the correlation of some orthologous gene groups, there was no overall connection between enterotypes and common individual traits, such as nationality, age, gender and body mass index (BMI). The one exception to this observation was that the Japanese study participants had a higher likelihood of having the Bacteroides enterotype than either of the other two.


While the research has made an important contribution to the study of the human gut microbiome, it's too soon to know where further study of enterotypes will lead. Clearly, it can be hoped that the knowledge might ultimately permit more personalized diets and drug treatments, based on an individual's digestive microbial ecology. It is even conceivable that an improved understanding of enterotypes may even assist in the diagnosis of certain diseases.

Discussion Questions

What other steps could researchers take to try to nail down the claim that there are just three basic enterotypes? Can you think of other factors, besides those mentioned above (nationality, age, gender, etc.), that could be looked at for possible correlations with enterotypes? How might one investigate whether a person's enterotype remains unchanged throughout life or is subject to variation?

Carbon Dating New Neurons in Old Brains

In 1963, the Partial Nuclear Test Ban Treaty was signed, banning nuclear tests underwater, in the atmosphere and in outer space. Although underground detonations were still permitted and several countries refused to sign the treaty, it nonetheless helped slash radioactive fallout. Prior to the test ban treaty, the fallout from nuclear tests showered radioactive atoms across the Earth. Among these radioactive atoms was carbon-14, which was absorbed by plants, which were eaten by humans, who then had the carbon-14 atoms integrated into their DNA.


Fortunately, it appears that this spike in atmospheric carbon-14 did not have a substantial negative effect on the health of most humans. (For certain groups of humans, and for certain ecosystems, there were devastating effects linked to radioactive fallout from nuclear tests.) In fact, Jonas Frisén, of the Karolinska Institute in Sweden, and his colleagues have actually found a use for this pulse of atmospheric carbon-14: determining the age of human cells. Using this technique, they recently discovered, as detailed in Cell, that new neurons are produced in the striatum of adult humans, an area of the brain that had previously been overlooked in the search for adult-born neurons: neurons produced by adult brains.

Old Brains, New Tricks

For many years, most scientists believed that the human heart and brain could not produce new cells in adulthood. But in the late 1990s, researchers began to find evidence of neurons produced past infancy. Several years later, Frisén and colleagues were able to show that the human heart produces new muscles cells throughout adulthood. They determined that as many as half of the cells in the heart are replaced during an average lifetime.


Scientists had missed these remarkable phenomena for so long because it is unethical to perform the sort of experiments that could demonstrate the genesis of new heart or brain cells in adults. For instance, one way to test such a thing in mice is to feed them radiolabeled food for a certain period of time. Any cells produced during this time will incorporate the radiolabeled material into their DNA, which is stable for the life of the cell. Later, when researchers find a radiolabeled cell, they will know that the cell was created while the mouse was being fed the labeled food. This is sometimes called "pulse" labeling.
Of course, researchers are not generally allowed to feed humans radioactive food. But, as Frisén and colleagues realized, humans born throughout much of the 20th century had already been exposed to a known pulse of radiolabeled food as a result of the spike in atmospheric carbon-14 starting in 1955, when nuclear testing began to surge, peaking in 1963, and then slowly declining in the ensuing decades.

Radiocarbon Dating and Bomb Pulse Dating

Most people are familiar with radiocarbon dating, a technique frequently used to determine the age of ancient organisms. This is similar to the method used by Frisén and colleagues in that it focuses on the amount of carbon-14 in a sample. Radiocarbon dating relies on the radioactive decay of carbon-14 over time. If you know the approximate ratio of carbon-14 to carbon-12 in the atmosphere when an ancient organism was alive and you can measure the current ratio in a sample of the organism, then, using the half-life of carbon-14, you can calculate its age.
However, with a half-life of nearly 6,000 years, carbon-14 does not decay fast enough to mark individual phases in the life of a human. Instead, Frisén and colleagues gathered data on the rapidly rising and falling concentration of carbon-14 in the atmosphere before and after the Partial Test Ban and compared it to the amount of carbon-14 found in the neuronal DNA of humans who had lived and died during that time.


They found that neurons — specifically interneurons — in the striatum appeared to be much younger than the individuals whose brains the samples had been taken from. For instance, they found that people born before 1955 had interneurons containing DNA with high concentrations of carbon-14, suggesting that the interneurons had been created after their birth, during the heyday of atomic bomb testing.

Huntington's Disease and Neurogenesis

The striatum is an area at the crossroads of many of the brain's essential functions. In fact, cell death in the striatum is a primary characteristic of Huntington's disease, which results in extreme loss of coordination and dementia. Knowing this, Frisén and colleagues decided to take a closer look at the neurons of deceased individuals with Huntington's disease. Intriguingly, they found that neurons throughout the brain, including the striatum, appeared to be about the same age as the individual, indicating that either adult neurogenesis is suppressed in Huntington's disease or that adult-born neurons are destroyed by the disease's progression.


Although the exact relationship between adult neurogenesis and Huntington's disease is not clear, this finding does suggest that it might be possible to encourage or protect adult-born neurons, so that they might replace striatal neurons ravaged by the disease. More generally, massive cell death is the hallmark of many brain diseases, and it is the hope of scientists like Frisén and colleagues that research on adult neurogenesis will enable us to devise therapeutic strategies harnessing the brain's own ability to replenish neurons.

Discussion Questions

Imagine you are an archaeologist 1,000 years in the future. Will the bomb pulse of carbon-14 make radiocarbon dating easier or harder?
Frisén and colleagues also examined the neurons of deceased cancer patients who had been treated with a radiolabeled medicine as part of their treatment. This data provided provisional support for adult neurogenesis in the striatum, but Frisén and colleagues felt that this alone was not sufficient to support their hypothesis. What are the weaknesses of such cancer evidence as compared to the bomb-pulse evidence?

Knee Arthritis Surgery Fails to Outdo Placebo

A popular surgical procedure performed on thousands of patients suffering from arthritis of the knee may not be so effective after all. New research by the Veterans Affairs Medical Center in Houston, Texas contends that arthroscopic knee surgery for arthritis is a sham operation that is no better than a placebo treatment.
In a recent study, two groups of patients were put through one of two types of arthroscopic knee surgery, lavage or debridement. The former involves the flushing of joints with saline; the latter, the scraping of joint tissue. The goal of both is to remove unwanted inflammatory substances in the knee. A third group underwent a mock surgery. Since the study was blind, the subjects did not know to which of the three groups they belonged—all of them bore incision marks that commemorated their visit to the hospital.
For two years after the operation, researchers monitored the patients' progress, giving them questionnaires and testing their motor abilities. Those who did not receive either surgery recuperated just as well as those who received one or the other, in terms of pain and knee function.
The researchers did not mandate any formal physical rehabilitation after the surgery, or include it in the study. They only asked the patients to use ice and crutches to keep the swelling down for the first week.
Afterwards, patients performed routine daily activities as they were able to, given their post-surgical condition. Arthroscopic knee surgery is performed 300,000 times a year and costs $5000. Perhaps publication of this new finding in the July 11, 2002 issue of the New England Journal of Medicine will lead to the procedure being used only for arthritis-unrelated knee injuries, such as damaged meniscuses (cartilage tissues cushioning jointed bones) or torn ligaments, for which the surgery has been shown to be effective.

Cartilage Injections Repair Knee Damage

Swedish researchers have found a way to repair damaged cartilage in the knee. The new treatment involves growing patients' cartilage cells in a test tube, then injecting them into the damaged area.
Damaged cartilage often leads to osteoarthritis, the most common form of arthritis. The treatment seems to restore injured cartilage to almost-normal condition. It offers hope of nearly full recovery for young people who suffer cartilage damage in sports injuries.
Cartilage is a tough, slippery, flexible material that covers the ends of bones and lines joints. The material allows bones in joints to slip over each other smoothly, without pain or stiffness.
Cartilage cells, called chondrocytes, are distributed throughout a web of tough fibrous material. Cartilage has no blood vessels or nerves. For reasons that are not entirely clear to scientists, once cartilage is damaged or wears down over time, it does not repair itself.
Damage to cartilage can lead to osteoarthritis, characterized by joint pain and swelling. About 75% of elderly people suffer from osteoarthritis. Eventually the disease can lead to destruction of the entire joint. When this happens, doctors often replace the joint with an artificial one. About 95,000 people in the United States get artificial knees every year.
A recent study was done by Lars Petersen and Anders Lindahl at the Sahlgrenska University Hospital in Goteborg, Sweden, and their colleagues. They reported on 23 patients in the October 6, 1994, issue of the New England Journal of Medicine.
The patients ranged in age from 14 to 48. Most had relatively small knee-cartilage defects that were caused by accidents. "We started with knee injuries because they are the most common and easy to reach," Petersen told the Associated Press. "In principle, we could use this technique in any joint to repair and prevent further damage."

Chrondrocytes

In a preliminary operation, Petersen and Lindahl removed small pieces of healthy cartilage from the knees of their patients. They removed chondrocytes from the fibrous cartilage material and grew the cells in a test tube for 14 to 24 days.
During a second operation, the scientists removed a piece of the tough outer membrane, called periosteum, from a nearby bone. They sewed the periosteum over the damaged area of cartilage. Then they injected the cultured chondrocytes under it. Petersen and Lindahl examined the transplants three months after the second operation and again 12 to 48 months later.
In most cases the transplanted cells had grown into the previously damaged cartilage and formed normal-looking tissue. In all the patients, pain and swelling in the knee subsided to some degree.
Sixteen of the patients had defects in the cartilage that lines the bottom of the thigh bone. Fourteen of the 16 had good to excellent results. The other two required further surgery.
Seven patients had defects in the cartilage at the back of the kneecap. The procedure was less successful with these patients. Of those seven, only two had favorable results. Two others required further surgery.
Most elderly patients develop osteoarthritis due to normal wear and tear on their joints throughout their lives. The operation might not be as successful with them as with young accident victims.
Biosurface Technology Inc. in Cambridge, Massachusetts, is working with the Swedish team to refine the operation. Currently, the procedure requires open-knee surgery. Researchers hope to develop a way to perform the operation arthroscopically, using thin viewing tubes threaded into the knee through small incisions.
Clinical tests of the procedure are scheduled to begin in 1995 at Brigham and Women's Hospital in Boston.

Keeping Time with Quantum Entanglement

When scientists want to know what time it is, they can consult their local cesium atomic clock. And if they want to know whether their clock is accurate, at the end of each month they can check it against the Universal Coordinated Time (UTC) reading made by the International Bureau of Weights and Measures near Paris, France. But if they want to check UTC time in the middle of the month, they're out of luck, because UTC is not an actual clock.


Right now, about 200 cesium clocks around the world synchronize their time by bouncing microwave radiation off of global positioning system (GPS) satellites. UTC receives monthly readings from the clocks, averages the results, and determines what time it was when the process began. The report is sent back to the clocks, which are adjusted to come into sync with the average. No clock — no matter how fast — can communicate with another clock faster than the speed of light, and all these calculations and adjustments take time. The result is that no one knows what time it "really" is right now.
That may change, thanks to an innovative idea from a research group at Harvard University led by Mikhail Lukin. In the June 15, 2014 issue of Nature Physics, Peter Kómár, Lukin and other members of the group propose a global network of clocks with atoms in their cores linked to each other by quantum entanglement. Such a network would provide faster-than-light coordination and a global standard time.
Fully standardized time could benefit financial markets, physicists and geologists, or even reconnaissance drones. But serious logistical hurdles stand between entangled clocks and a takeover of the world's timekeeping. Still, the idea is intriguing because it combines methods already developed in two fields: atomic clocks and quantum entanglement.

The Tick, Tock of an Atomic Clock

Since their invention in 1949, atomic clocks have been the most accurate clocks on Earth. Yet they operate on the same principle as a pendulum clock: reliance on a steady oscillator. In a pendulum clock, the oscillator is the swinging pendulum. Counting the back-and-forth swings will give you a regular measure of the passage of time. The clock will be as accurate as the pendulum is steady.


Far more regular than a swinging pendulum is the frequency of microwave radiation emitted from a cesium atom. At the heart of an atomic clock, a microwave laser tuned to the correct frequency excites the electrons in a cesium atom. Each time the cesium atom absorbs a laser photon, one of its electrons jumps to a higher energy level and then falls back down, re-emitting a photon at a predictable frequency. For Cesium-133, that frequency is 9,192,631,770 cycles per second.
The atomic clock at the National Institute of Standards and Technology in Boulder, Colorado, is so precise that it will not gain or lose a second in 300 million years. And yet, however precise that clock may be, it is always essentially measuring local time, because coordinating with other clocks is imprecise and, well, takes time.

"Spooky Action at a Distance"

Hypothetically, though, that obstacle might be overcome by applying quantum mechanics. Indeed, Lukin's team hopes to use a concept called quantum entanglement to link atomic clocks around the world in a network that communicates faster than the speed of light.
Albert Einstein famously called entanglement a theory of "spooky action at a distance." He wasn't far off. At the quantum level, atoms are both waves and particles. Each atom exists in a "superposition of states" until it is measured. A superposition of states dictates that an unmeasured electron exists in many places at once, has a range of momentums, and spins in multiple directions. The probability that, when measured, a particle will be found in any one state is represented by its wave function, mathematically described by the Schrödinger equation. When one aspect of the particle is measured — to find out where it is, for example, or how fast it's moving — the wave function "collapses." The electron now exists in a particular place, and has a particular momentum and a particular spin. In other words, the measured electron loses its wave properties and acts solely as a particle at the moment of measurement. In the next moment, however, the electron's wave properties return.
Under certain circumstances, two particles may become entangled, which means their wave functions combine into one function that cannot be differentiated. Even after the particles are separated in space, this connection is maintained, so that measuring one particle will tell us something about the other particle.
For example, suppose a neutral particle called a pion decays into an electron and a positron. If we assume that the pion was initially at rest, then the electron and positron will fly off in opposite directions. A pion's spin is zero, so in order to conserve angular momentum, one product will be "spin up" and the other will be "spin down." So, if we measure the electron and find it spin up, the positron instantly becomes spin down. Yet before the measurement was taken, the electron and positron were both "spin up" and "spin down" at the same time, with their individual spin being a function of the two particles' relationship. In other words, the particles were entangled.
Recently, physicists have been getting better at creating entanglements experimentally. In 2007, a Viennese research team led by Anton Zeilinger transported the polarization state of one photon to another photon 143 kilometers (88 miles) away. And in 2011, Thomas Monz and his team at the University of Innsbruck entangled 14 calcium atoms by forcing them together with lasers.

Entangling Clocks, Creating Networks

Lukin's group hopes to use quantum entanglement to create a network of atomic clocks. At least one atom in the core of each clock would be entangled with atoms in other networked clocks. But because entanglement is often a fragile connection, redundancies would likely have to be built into the network.

In Lukin's proposed mechanism, one clock acts as the "central clock," sending out one photon from an entangled pair to each of the other node clocks via a process called quantum teleportation. Next, the now-entangled photon from the central clock expands the entangled state to other atoms in the node clock. The node clock measures the phase difference between the entangled atoms and its own local timekeeping atoms, which reveals how fast or slow the clock has been running. It then adjusts its own frequency and reports back the results to the central clock. The central clock can average the results from all the clocks and repeat the process to bring the clocks into phase with each other.


What Lukin's group proposes is roughly analogous to a network of pendulum clocks wherein a central clock would coordinate the pendulums for all the other clocks so that no matter where they were, they would swing back and forth in unison. If one pendulum started to slow down slightly, the central clock would give it a little push—just so—and it would come back into phase.

A Global Timekeeping System

An accurate clock network, especially if it could be extended to satellites, would have widespread benefits. For example, time moves slower near massive objects; GPS satellite clocks typically gain about 45 microseconds per day on Earth-bound clocks, since the pull of Earth's gravity is weaker at high altitude. And because an entangled clock network would be exquisitely sensitive to these differences in mass, it could help geologists and physicists with their research. Satellites with networked clocks could detect magma moving underground before volcanic eruptions or detect other subterranean features. The network could also detect small shifts in space and time, helping locate gravitational waves. More fancifully, the military could fly linked clocks over enemy territory to detect secret underground tunnels.
The possibilities seem both endless and a very long way off. Entangling 14 atoms in a lab, or two photons at a great distance, is impressive. But Lukin and his team would need to maintain the delicate entanglement across thousands of atoms around the globe — a far more stable connection than Monz or Zeilinger and their teams could manage. The engineering challenges of transporting entangled photons into Earth's orbit are daunting, to say the least.
Yet, in principle, the clock network should work: it uses no new technology, no new methods. It is an idea whose time has come.

Discussion Questions

What types of applications can you imagine for clocks linked by quantum entanglement?
 

Dinosaurs Get a New Family Tree

The dinosaurs left behind a treasure trove of fossils. Over 65 million years later, humans began gazing on these fossils with excitement and curiosity: what were these fearsome giants like? Early paleontologists, noting the apparent anatomical similarities between dinosaurs and modern reptiles, naturally assumed that dinosaurs were just like reptiles: cold-blooded, slow-moving beasts. This assumption went unchallenged for 150 years, and generations of children imagined an ancient Earth populated by lumbering, Godzilla-like creatures. But new research suggests these early behemoths were neither cold-blooded nor warm-blooded, but rather somewhere in between.

Knowing the true body temperature of dinosaurs would make it easier to understand how they lived and evolved. In a recent paper in Science, paleontologists John Grady and Felisa Smith from the University of New Mexico in Albuquerque suggest that dinosaurs belonged to a hitherto unknown metabolic category. Their findings may help explain how dinosaurs outcompeted other animals to rule the Earth for 135 million years.

Just Add Heat

Recently, several paleontologists challenged the 150-year-old assumption that dinosaurs were cold-blooded, and pointed to evidence that these ancient animals might actually have been warm-blooded. Strong support for this argument came from the theory that warm-blooded animals tend to grow quickly compared to cold-blooded animals. Because the dinosaurs ruled the Earth for so long, scientists reasoned they must have been comparable in growth speed to the endotherms that evolved during the age of the dinosaurs.
Called endotherms, from the Greek for "internal heat," warm-blooded animals enjoy rapid growth rates. These animals, including mammals and birds, generally have fast metabolisms, which allow them to quickly break down food and to produce large amounts of energy, much of it in the form of body heat. This allows endotherms to maintain a constant body temperature. Endotherms are active in places with a wide range of temperatures, but require a constant supply of food to maintain their body temperatures. Because they eat constantly, most endotherms grow steadily and quickly.

In contrast, the body temperature of cold-blooded ectotherms, whose name comes from the Greek for "external heat," is subject to the environment. These animals, among them crocodiles and turtles, must bask in the sun to warm up. Because of their slow metabolisms, ectotherms generate little body heat and energy, and are generally slow-growing. While ectotherms do not need to eat much or often, their activity is limited to the warmer hours of the day, after they have sunned themselves enough to raise their body temperatures. Based on these considerations, some scientists reasoned that dinosaurs would not have been able to compete with fast-growing endotherms if they themselves had been cold-blooded and slow-growing like many reptiles.


Dinosaur bone structure also suggests that these animals differ from modern ectothermic reptiles. Cold-blooded animals grow haltingly, experiencing more rapid growth during the warmer months and slower growth during the colder ones. As a result of this uneven growth, cross-sections of ectotherm bones contain rings similar to tree rings. Endotherms, which grow constantly, lack bone rings. Their bones instead take on a spongy appearance due to infiltrating blood vessels, which bring the nutrients necessary to sustain constant growth. While dinosaur bones have the growth rings associated with ectotherm bones, they also have the spongy appearance of endotherm bones.

The Metabolic Middle

Grady and Smith, along with a small team, decided that the best way to determine whether dinosaurs were endotherms or ectotherms was to compare the growth rates of dinosaurs to those of as many warm- and cold-blooded species as possible. The scientists examined pre-existing data from over 350 living species that were known to be either endothermic or ectothermic, and concluded that, as was to be expected, the endothermic animals all had faster growth rates than the ectothermic animals. Now the scientists simply had to determine the growth rates of various dinosaurs and compare them to those of the 350 living species in their study.


Luckily, the researchers could collect all the data they needed from the fossil record. Dinosaur bones contain many clues regarding growth rate: the animals' ages can be inferred from bone growth rings, similar to establishing the age of a tree, and their body sizes can be extrapolated from bone sizes. Thus, the researchers calculated the growth rates of 21 species of dinosaurs based on their inferred ages and sizes. Perhaps not so surprisingly, Grady and Smith came up with dinosaur growth rates that fell between those for endo- and ectotherms; dinosaurs, they found, grew faster than cold-blooded animals like reptiles, but slower than warm-blooded animals like mammals and birds. Because growth rate is a strong predictor of ecto- or endothermy, the scientists created a new category of animals, which they called mesotherms, from the Greek for "middle heat"; the new category was populated almost — but not quite — entirely by dinosaurs.

Mesothermy Is Not Extinct

Besides dinosaurs, the new mesotherm category includes a small but interesting assortment of living species. Among them are tuna and some species of sharks and turtles; these creatures are able to raise their body temperature from within, but, unlike endotherms, do not keep it constant. The only mammalian example of a mesotherm turned out to be the spiny anteater or echidna; it maintains a constant internal temperature, but, unlike normal endotherms, can tolerate dramatic changes in that temperature. Besides having similar metabolisms, these latter-day mesotherms also resemble dinosaurs by appearing to have growth rates falling between those of endotherms and ectotherms.


Grady, Smith and their colleagues also concluded that feathered dinosaurs like Archaeopteryx and Troodon had growth rates similar to those of other, non-feathered dinosaurs. This is surprising because it suggests that the evolution of feathers and flight, traits found in both modern birds and certain dinosaurs, can be separated from the evolution of other birdlike traits such as extremely fast growth rates, which are characteristic of modern birds but not of dinosaurs.

Is a Middling Metabolism the Way to Go?

Dinosaurs ruled the Earth for over 135 million years. It now appears likely that this domination was due in part to dinosaur mesothermy. Perhaps dinosaurs, neither warm-blooded nor cold-blooded, enjoyed an advantageous middle road: a metabolism fast enough to provide some body heat and comfort over a wide range of temperatures, but slow enough that the dinosaurs did not have to constantly search for food. Although we may never know for sure what these giant creatures were like, clues from their bones suggest that they were not simply lumbering giant reptiles. Instead, it appears they were something much more unique.

Discussion Questions

How do you think mesothermy evolved separately in species as different as dinosaurs, tuna and anteaters? Some birds have extremely fast growth rates, even compared to other endotherms, while primates have relatively slow growth rates. If growth rates fall along a spectrum, how can they be limited to three categories: endothermic, ectothermic and mesothermic?