Science Tuesday - Pigeons, Science Funding, Weight Loss

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Researchers have found that mutations in pigeon DNA can control a variety of traits, including the directions their feathers grow, like in this Jacobin pigeon. Charles Darwin raised pigeons and was interested in their breeding as an extreme example of domestic selection. More Photos Here

Pigeons Get a New Look
By CARL ZIMMER, The New York Times, February 4, 2013

In 1855, Charles Darwin took up a new hobby. He started raising pigeons.

In the garden of his country estate, Darwin built a dovecote. He filled it with birds he bought in London from pigeon breeders. He favored the fanciest breeds — pouters, carriers, barbs, fantails, short-faced tumblers and many more.

“The diversity of the breeds is something astonishing,” he wrote a few years later in “On the Origin of Species” — a work greatly informed by his experiments with the birds.

Pigeon breeding, Darwin argued, was an analogy for what happened in the wild. Nature played the part of the fancier, selecting which individuals would be able to reproduce. Natural selection might work more slowly than human breeders, but it had far more time to produce the diversity of life around us.

Yet to later generations of biologists, pigeons were of little more interest than they are to, say, New Yorkers. Attention shifted to other species, like fruit flies and E. coli.

Now Michael D. Shapiro, a biologist at the University of Utah, is returning pigeons to the spotlight.



In an article published online last week by the journal Science, an international team of scientists led by Dr. Shapiro reports that it has delved into a source of information Darwin didn’t even know about: the pigeon genome. So far, they have sequenced the DNA of 40 breeds, seeking to pinpoint the mutations that produced their different forms.

The scientists are following Darwin’s example by using the birds to find clues to the way evolution works in general. They are particularly interested in the mutations that produce radically new kinds of anatomy.

“Pigeons are an ideal way to look at these things,” Dr. Shapiro said.

The new work supports Darwin’s original claim that all pigeon breeds descend from the rock pigeon, whose range stretched from Europe to North Africa and east into Asia.

“It’s a brilliant bit of investigative science, the type of research that hopefully will come to define the genomic era,” said Beth Shapiro (no relation to Michael), an evolutionary molecular biologist at the University of California, Santa Cruz.

Archaeologists have speculated that rock pigeons flocked to the first farms in the Fertile Crescent in the Middle East, where they pecked at loose grain. Farmers then domesticated them for food.

Later, humans bred the birds to carry messages. By the eighth century B.C., Greeks were using pigeons to send the results of Olympic Games from town to town. Genghis Khan used pigeons to create a communication network across his empire in 12th century A.D.

Eventually, people began breeding pigeons simply for pleasure. Akbar the Great, a 16th-century Mughal emperor, always traveled with his personal colony of 10,000 pigeons. He bred some of the birds for their ability to tumble through the air, and others for their extravagant beauty.

Dr. Shapiro and his colleagues have been able to work out the genealogy of these breeds. They found, for example, that fantail pigeons, one of Akbar’s favorite breeds, are closely related to breeds from Iran. Dr. Shapiro suspects that their kinship is a result of trade along the Silk Route between the Mughal Empire and Persia.

Some of these breeds would escape from their owners and mate with wild rock pigeons. As a result, Dr. Shapiro and his colleagues have struggled to find a pigeon with “pure” rock pigeon DNA. In search of wild birds, they sampled the DNA of pigeons from remote islands off the coast of northern Scotland. “If there’s going to be any truly wild pigeons left, those are going to be a good place to look for them,” he said.

The Scottish pigeons turned out to be closely related to Modena pigeons, an old Italian breed that may have interbred with the ancestors of wild pigeons in Scotland. Or perhaps Modena pigeons were domesticated directly from wild ancestors, rather than another breed. “We just can’t distinguish between the two possibilities yet,” Dr. Shapiro said.

European colonists brought their domesticated pigeons to the New World, where they raised them once more for food, messages and diversion. Thomas Jefferson designed a grand dovecote for Monticello, complete with pillars. Some of America’s tame immigrant pigeons escaped yet again and evolved into a new population of feral pigeons — the ones that thrive in American cities.

“It looks like European and North American ferals are quite distinct,” Dr. Shapiro said.

Like Darwin, Dr. Shapiro came late to the world of pigeon breeding. From 2001 to 2006, as a postdoctoral researcher at Stanford, he studied how stickleback fish in Canadian lakes evolved into strikingly different shapes in just a few thousands of years. While giving a talk for the position at the University of Utah, he had waxed poetic about how some of the fish had lost their armored spikes.

His host was not impressed.

“He said, ‘You think sticklebacks are diverse?’ ” Dr. Shapiro recalled. “And he plunked down an 800-page encyclopedia on pigeon breeding and said, ‘Take a look at this.’ ”

Dr. Shapiro started leafing through the book. “I knew a little bit about pigeons from Darwin, but this was insane,” he recalled.

When he got the job in Utah, Dr. Shapiro decided to split his lab’s efforts between fish and pigeons. He set out to discover what Darwin could not: the genetic basis of the birds’ evolution.

When he explained the project to pigeon breeders he met on a visit to the Utah State Fair, they allowed him and his colleagues to draw blood from their birds to get their DNA. Before long, Dr. Shapiro was following Darwin’s steps and raising pigeons of his own at the university, crossing the breeds to produce hybrids.

Once he and his colleagues worked out the genealogy of pigeons, they could then investigate how they had evolved into so many different forms. To begin this stage of the project, Dr. Shapiro picked out a particularly extravagant trait to study: head crests.

“There are many different kinds of crests,” he said. “Some birds just have just a little peak, some have what looks like an inverted shell, some have a mane, and some have their entire head engulfed in feathers.” Photos of a variety of pigeons.

Dr. Shapiro and his colleagues have found that the closest relatives of crested breeds are uncrested breeds. In other words, pigeon breeders produced crests on the birds on five separate occasions. The scientists compared the genomes of the crested pigeons with one another, as well as with other pigeons and with chickens, turkeys and other species. They hunted for mutated genes unique to the crested breeds, and found that all of them shared precisely the same mutation in precisely the same gene, EphB2.

Bird embryos develop placodes, little disks of tissue on their skin from which feathers will grow. The scientists found that in ordinary pigeons without crests, EphB2 became active on the bottom edge of the placodes; in crested pigeons it was active on the top edge.

The experiment suggests that EphB2 tells the placode which way is up. In most pigeons, it instructs the feathers to grow down the neck; but the mutation changes the location where EphB2 switches on, effectively turning the feathers upside down and producing a crest.

“They grow the wrong way,” Dr. Shapiro said. “They’re even pointing the wrong way in the embryo, before they become feathers.”

The new research suggests that the crested version of EphB2 arose in a surprising way. It mutated only once, rather than five separate times.

Dr. Shapiro came to this conclusion in part because he found that it takes two copies of the mutant gene to reverse the feathers. When the mutation arose, it was passed down invisibly from pigeon to pigeon. Only when two carriers happened to mate did they suddenly produce a crested chick.

Adam Boyko, a Cornell geneticist who studies dogs, has found similar results in his own research.

Several dog breeds have short legs, for example, but only a single mutant gene is responsible for the change. Like the crested-feather mutation, it worked its way into each of the short-legged breeds. “There’s clearly a parallel,” Dr. Boyko said.

Dr. Shapiro is moving ahead with studies on the many other traits of pigeon breeds to see if this pattern is an exception or the rule.

“The more examples that we have,” he said, “the more we can understand what the general trends in evolutionary change are.”





Study Flags Duplicate Financing
By DOUGLAS QUENQUA, The New York Times, February 4, 2013

The government may be wasting millions of dollars by paying for the same research projects twice, according to a new analysis of grant and contract records.

Researchers from Virginia Tech and Duke University compared more than 600,000 grant summaries issued to federal agencies since 1985. What they found was almost $70 million that might have been spent on projects that were already at least partly financed. The results were published in the journal Nature.



Harold R. Garner, director of medical informatics and systems at Virginia Tech, was inspired to perform the study after reading a 2012 Government Accountability Office report on reducing duplication and overlap in federal services. He had long used software to find plagiarism and duplicate publications, he said, “so I thought, what a great thing to do.”

To hunt for duplicate grants, Dr. Garner looked for similar or identical language in grant summaries. His team then manually searched the flagged grants.

While he acknowledges that the government may already have identified some of the overlap he discovered, he believes the amount of fraud found in the study makes a strong case for doing a more thorough investigation.

The problem is not that there is too much money in scientific research, he emphasized, but not enough.

“Funding of government grants is at an all-time low, so people are getting desperate in finding the money to fund their labs,” he said. “I would hope that this would be used to improve how we distribute funds and not be used to cut the budget.”




Myths of Weight Loss Are Plentiful, Researcher Says
By GINA KOLATA, The New York Times, JANUARY 30, 2013

If schools reinstated physical education classes, a lot of fat children would lose weight. And they might never have gotten fat in the first place if their mothers had just breast fed them when they were babies. But be warned: obese people should definitely steer clear of crash diets. And they can lose more than 50 pounds in five years simply by walking a mile a day.

Those are among the myths and unproven assumptions about obesity and weight loss that have been repeated so often and with such conviction that even scientists like David B. Allison, who directs the Nutrition Obesity Research Center at the University of Alabama at Birmingham, have fallen for some of them.

Now, he is trying to set the record straight. In an article published online today in The New England Journal of Medicine, he and his colleagues lay out seven myths and six unsubstantiated presumptions about obesity. They also list nine facts that, unfortunately, promise little in the way of quick fixes for the weight-obsessed. Example: "Trying to go on a diet or recommending that someone go on a diet does not generally work well in the long term."

Obesity experts applauded this plain-spoken effort to dispel widespread confusion about obesity. The field, they say, has become something of a quagmire.



"In my view," said Dr. Jeffrey M. Friedman, a Rockefeller University obesity researcher, "there is more misinformation pretending to be fact in this field than in any other I can think of."

Others agreed, saying it was about time someone tried to set the record straight.

"I feel like cheering," said Madelyn Fernstrom, founding director of the University of Pittsburgh Weight Management Center. When it comes to obesity beliefs, she said, "We are spinning out of control."

Steven N. Blair, an exercise and obesity researcher at the University of South Carolina, said his own students believe many of the myths. "I like to challenge my students. Can you show me the data? Too often that doesn't come into it."

Dr. Allison sought to establish what is known to be unequivocally true about obesity and weight loss.

His first thought was that, of course, weighing oneself daily helped control weight. He checked for the conclusive studies he knew must exist. They did not.

"My goodness, after 50-plus years of studying obesity in earnest and all the public wringing of hands, why don't we know this answer?" Dr. Allison asked. "What's striking is how easy it would be to check. Take a couple of thousand people and randomly assign them to weigh themselves every day or not."

Yet it has not been done.

Instead, people often rely on weak studies that get repeated ad infinitum. It is commonly thought, for example, that people who eat breakfast are thinner. But that notion is based on studies of people who happened to eat breakfast. Researchers then asked if they were fatter or thinner than people who happened not to eat breakfast - and found an association between eating breakfast and being thinner. But such studies can be misleading because the two groups might be different in other ways that cause the breakfast eaters to be thinner. But no one has randomly assigned people to eat breakfast or not, which could cinch the argument.

So, Dr. Allison asks, why do yet another study of the association between thinness and breakfast? "Yet, I can tell you that in the last two weeks I saw an association study of breakfast eating in Islamabad and another in Inner Mongolia and another in a country I never heard of."

"Why are we doing these?" Dr. Allison asked. "All that time and effort is essentially wasted. The question is: 'Is it a causal association?'" To get the answer, he added, "Do the clinical trial."

He decided to do it himself, with university research funds. A few hundred people will be recruited and will be randomly assigned to one of three groups. Some will be told to eat breakfast every day, others to skip breakfast, and the third group will be given vague advice about whether to eat it or not.

As he delved into the obesity literature, Dr. Allison began to ask himself why some myths and misconceptions are so commonplace. Often, he decided, the beliefs reflected a "reasonableness bias." The advice sounds so reasonable it must be true. For example, the idea that people do the best on weight-loss programs if they set reasonable goals sounds so sensible.

"We all want to be reasonable," Dr. Allison said. But, he said, when he examined weight-loss studies he found no consistent association between the ambitiousness of the goal and how much weight was lost and how long it had stayed off. This myth, though, illustrates the tricky ground weight-loss programs have to navigate when advising dieters. The problem is that on average people do not lose much - 10 percent of their weight is typical - but setting 10 percent as a goal is not necessarily the best strategy. A very few lose a lot more and some people may be inspired by the thought of a really life-changing weight loss.

"If a patient says, 'Do you think it is reasonable for me to lose 25 percent of my body weight,' the honest answer is, 'No. Not without surgery,'" Dr. Allison said. But, he said, "If a patient says, 'My goal is to lose 25 percent of my body weight,' I would say, 'Go for it.'"

Yet all this negativism bothers people, Dr. Allison conceded. When he talks about his findings to scientists, they often say: "O.K., you've convinced us. But what can we do? We've got to do something." He replies that scientists have an ethical duty to make clear what is established and what is speculation. And while it is fine to recommend things like bike paths or weighing yourself daily, scientists must make sure they preface their advice with the caveat that these things seem sensible but have not been proven.

Among the best established methods is weight-loss surgery, which, of course, is not right for most people. But surgeons have done careful studies to show that on average people lose substanial amounts of weight and their health improves, Dr. Allison said. For dieters, the best results occur with structured programs, like ones that supply complete meals or meal replacements.

In the meantime, Dr. Allison said, it is incumbent upon scientists to change their ways. "We need to do rigorous studies," he said. "We need to stop doing association studies after an association has clearly been demonstrated."

"I never said we have to wait for perfect knowledge," Dr. Allison said. But, as John Lennon said, "Just give me some truth."

Here is an overview of the obesity myths looked at by the researchers and what is known to be true:


MYTHS

Small things make a big difference. Walking a mile a day can lead to a loss of more than 50 pounds in five years.

Set a realistic goal to lose a modest amount.

People who are too ambitious will get frustrated and give up.

You have to be mentally ready to diet or you will never succeed.

Slow and steady is the way to lose. If you lose weight too fast you will lose less in the long run.


Ideas not yet proven TRUE OR FALSE

Diet and exercise habits in childhood set the stage for the rest of life.

Add lots of fruits and vegetables to your diet to lose weight or not gain as much.

Yo-yo diets lead to increased death rates.

People who snack gain weight and get fat.

If you add bike paths, jogging trails, sidewalks and parks, people will not be as fat.


FACTS - GOOD EVIDENCE TO SUPPORT

Heredity is important but is not destiny.

Exercise helps with weight maintenance.

Weight loss is greater with programs that provide meals.

Some prescription drugs help with weight loss and maintenance.

Weight-loss surgery in appropriate patients can lead to long-term weight loss, less diabetes and a lower death rate.