Some Traits (Including Some Diseases) Depend on Many Genes Rather than a Single Gene

(p. D3) A new exploration of how evolution works at the genomic level may have a significant impact on drug development and other areas of medicine.
The report, published in Nature last week, offers new evidence in a longstanding debate about how organisms evolve. One well-known path to change is a heavily favorable mutation in a single gene. But it may be well known only because it is easy to study. Another path is exploitation of mildly favorable differences that already exist in many genes.
. . .
Three biologists at the University of California, Irvine, Molly K. Burke, Michael R. Rose and Anthony D. Long, followed populations of fruit flies through 600 generations and studied the whole genome of some 250 flies in order to see what kinds of genetic change they had undergone.
. . .
The conventional view is that evolutionary change is generally mediated by a favorable mutation in a gene that then washes through the whole population, a process called a hard sweep because all other versions of the gene are brushed away. The alternative, called a soft sweep, is that many genes influence a trait, in this case the rate of maturation, and that the growth-accelerating versions of each of these genes become just a little more common. Each fly has a greater chance of inheriting these growth-promoting versions and so will mature faster.
In sequencing their subjects’ genomes, the researchers found that a soft sweep was indeed responsible for the earlier hatching. No single gene had swept through the population to effect the change; rather, the alternative versions of a large number of genes had become slightly more common.
. . .
Haldane favored the single mutation mechanism, but Fisher and Wright backed multiple gene change.
. . .
The demise of the Haldane view “is very bad news for the pharmaceutical industry in general,” Dr. Rose said. If disease and other traits are controlled by many genes, it will be hard to find effective drugs; a single target would have been much simpler.

For the full story, see:
NICHOLAS WADE. “Natural Selection Cuts Broad Swath Through Fruit Fly Genome.” The New York Times (Tues., September 21, 2010): D3.
(Note: ellipses added.)
(Note: the online version of the article is dated September 20, 2010.)

Global Warming Reduces Bubonic Plague in U.S.

(p. D6) Global warming may have one minor but previously unknown benefit, scientists said this month: it may be cutting down cases of bubonic plague in the United States.
. . .
A study in this month’s issue of The American Journal of Tropical Medicine and Hygiene tracked climatic conditions in 195 counties in 13 Western states, from Washington to Texas, that reported even one plague case since 1950.
Cases have dropped over time, and the study concluded that rising nighttime temperatures since 1990 had helped. Warmer nights melt winter snowpacks earlier, leading to drier soil in rodent burrows. When the soil gets too dry, fleas die.

For the full story, see:
DONALD G. McNEIL Jr. “GLOBAL UPDATE; United States: Decrease in Bubonic Plague Cases May Be an Effect of Climate Change.” The New York Times (Tues., September 21, 2010): D6.
(Note: ellipsis added.)
(Note: the online version of the article is dated September 20, 2010.)

Chocolate Reduces Risk of Cardiovascular Disorder by 37%

(p. D6) An analysis of studies including more than 100,000 subjects has found that high levels of chocolate consumption are associated with a significant reduction in the risk of certain cardiovascular disorders.
. . .
Over all, the report, published Monday in the British medical journal BMJ, showed that those in the group that consumed the most chocolate had decreases of 37 percent in the risk of any cardiovascular disorder and 29 percent in the risk for stroke.

For the full story, see:
NICHOLAS BAKALAR. “VITAL SIGNS; Prevention: Evidence of Heart Benefits From Chocolate.” The New York Times (Tues., August 30, 2011): D6.
(Note: ellipsis added.)
(Note: the online version of the article is dated August 29, 2011.)

“What Happens in America Is Defined by Tort Lawyers”

JungleGymRelic2011-11-09.jpg “CHILDHOOD RELIC; Jungle gyms, like this one in Riverside Park in Manhattan, have disappeared from most American playgrounds in recent decades.” Source of caption and photo: online version of the NYT article quoted and cited below.

(p. D3) “There is no clear evidence that playground safety measures have lowered the average risk on playgrounds,” said David Ball, a professor of risk management at Middlesex University in London. He noted that the risk of some injuries, like long fractures of the arm, actually increased after the introduction of softer surfaces on playgrounds in Britain and Australia.

“This sounds counterintuitive, but it shouldn’t, because it is a common phenomenon,” Dr. Ball said. “If children and parents believe they are in an environment which is safer than it actually is, they will take more risks. An argument against softer surfacing is that children think it is safe, but because they don’t understand its properties, they overrate its performance.”
Reducing the height of playground equipment may help toddlers, but it can produce unintended consequences among bigger children. “Older children are discouraged from taking healthy exercise on playgrounds because they have been designed with the safety of the very young in mind,” Dr. Ball said. “Therefore, they may play in more dangerous places, or not at all.”
Fear of litigation led New York City officials to remove seesaws, merry-go-rounds and the ropes that young Tarzans used to swing from one platform to another. Letting children swing on tires became taboo because of fears that the heavy swings could bang into a child.
“What happens in America is defined by tort lawyers, and unfortunately that limits some of the adventure playgrounds,” said Adrian Benepe, the current parks commissioner.

For the full story, see:
JOHN TIERNEY. “FINDINGS; Grasping Risk in Life’s Classroom.” The New York Times (Tues., July 19, 2011): D1 & D3.
(Note: the online version of the article is dated July 18, 2011, and has the title “FINDINGS; Can a Playground Be Too Safe?.”)

No Evidence that Parents Were Ever Indifferent to the Well-Being of Their Children

(p. 404) No one expressed parental loss better (as no one expressed most things better) than William Shakespeare. These lines are from King John, written soon after his son Hamnet died at the age of eleven in 1596:
Grief fills the room up of my absent child
Lies in his bed, walks up and down with me,
Puts on his pretty looks, repeats his words,
Remembers me of all his gracious parts,
Stuffs out his vacant garments with his form.

(p. 405) These are not the words of someone for whom children are a product, and there is no reason to suppose – no evidence anywhere, including that of common sense – that parents were ever, at any point in the past, commonly indifferent to the happiness and well-being of their children. One clue lies in the name of the room in which we are now. ‘Nursery’ is first recorded in English in 1330 and has been in continuous use ever since. A room exclusively dedicated to the needs and comforts of children would hardly seem consistent with the belief that children were of no consequence within the household. No less significant is the word ‘childhood’ itself. It has existed in English for over a thousand years (the first recorded use is in the Lindisfarne Gospels circa AD 950), so whatever it may have meant emotionally to people, as a state of being, a condition of separate existence, it is indubitably ancient. To suggest that children were objects of indifference or barely existed as separate beings would appear to be a simplification at best.

Source:
Bryson, Bill. At Home: A Short History of Private Life. New York: Doubleday, 2010.
(Note: italics in original.)

Increase in Cholera Not Caused by Global Warming

(p. D6) Cholera outbreaks seem to be on the increase, but a new study has found they cannot be explained by global warming.
A bigger factor may be the cycle of droughts and floods along big rivers, according to Tufts University scientists who published a study in The American Journal of Tropical Medicine and Hygiene this month.

For the full story, see:
DONALD G. McNEIL Jr. “GLOBAL UPDATE; Cholera: Climate Change Isn’t a Culprit in Increasing Outbreaks, Study Finds.” The New York Times (Tues., August 30, 2011): D6.
(Note: the online version of the article is dated August 29, 2011.)

“The World Before the Modern Era Was Overwhelmingly a Place of Tiny Coffins”

(p. 404) There is no doubt that children once died in great numbers and that parents had to adjust their expectations accordingly. The world before the modern era was overwhelmingly a place of tiny coffins. The figures usually cited are that one-third of children died in their first year of life and half failed to reach their fifth birthdays. Even in the best homes death was a regular visitor. Stephen Inwood notes that the future historian Edward Gibbon, growing up rich in healthy Putney, lost all six of his siblings in early childhood. But that isn’t to say that parents were any less devastated by a loss than we would be today. The diarist John Evelyn and his wife had eight children and lost six of them in childhood, and were clearly heartbroken each time. ‘Here ends the joy of my life,’ Evelyn wrote simply after his oldest child died three days after his fifth birthday in 1658. The writer William Brownlow lost a child each year for four years, a chain of misfortune that ‘hast broken me asunder and shaken me to pieces’, he wrote, but in fact he and his wife had still more to endure: the tragic pattern of annual deaths continued for three years more until they had no children left to yield.

Source:
Bryson, Bill. At Home: A Short History of Private Life. New York: Doubleday, 2010.

Black Death Microbe Same as in Middle Ages But Now Does Much Less Harm

LondonMedievalMap2011-11-07.jpg

Source of map: online version of the NYT article quoted and cited below.

If the Black Death microbe is the same today as in the Middle Ages, maybe the difference in effects is partly due to our better nutrition, health, hygiene, and housing?

(p. D4) The agent of the Black Death is assumed to be Yersinia pestis, the microbe that causes bubonic plague today. But the epidemiology was strikingly different from that of modern outbreaks. Modern plague is carried by fleas and spreads no faster than the rats that carry them can travel. The Black Death seems to have spread directly from one person to another.

Victims sometimes emitted a deathly stench, which is not true of plague victims today. And the Black Death felled at least 30 percent of those it inflicted, whereas a modern plague in India that struck Bombay in 1904, before the advent of antibiotics, killed only 3 percent of its victims.
. . .
If Yersinia pestis was indeed the cause of the Black Death, why were the microbe’s effects so different in medieval times? Its DNA sequence may hold the answer. Dr. Poinar’s team has managed to reconstruct a part of the microbe’s genetic endowment. Yersinia pestis has a single chromosome, containing the bulk of its genes, and three small circles of DNA known as plasmids.
The team has determined the full DNA sequence of the plasmid known as pPCP1 from the East Smithfield cemetery. But, disappointingly, it turns out to be identical to the modern-day plasmid, so it explains none of the differences in the microbe’s effects.

For the full story, see:
NICHOLAS WADE. “Hunting for a Mass Killer in Medieval Graveyards.” The New York Times (Tues., August 30, 2011): D4.
(Note: ellipsis added.)
(Note: the online version of the article is dated August 29, 2011.)

Of Mice and Men and Health and Longevity

MiceSenescentCells2011-11-04.jpg“Two 9-month-old mice from the study. The one on the right received the drug to eliminate senescent cells.” Source of caption and photo: online version of the NYT article quoted and cited below.

(p. A1) In a potentially fundamental advance, researchers have opened up a novel approach to combating the effects of aging with the discovery that a special category of cells, known as senescent cells, are bad actors that promote the aging of the tissues. Cleansing the body of the cells, they hope, could postpone many of the diseases of aging.

The findings raise the prospect that any therapy that rids the body of senescent cells would protect it from the ravages of aging. But many more tests will be needed before scientists know if drugs can be developed to help people live longer.
Senescent cells accumulate in aging tissues, like arthritic knees, cataracts and the plaque that may line elderly arteries. The cells secrete agents that stimulate the immune system and cause low-level inflammation. Until now, there has been no way to tell if the presence of the cells is good, bad or indifferent.
The answer turns out to be that (p. A4) the cells hasten aging in the tissues in which they accumulate. In a delicate feat of genetic engineering, a research team led by Darren J. Baker and Jan M. van Deursen at the Mayo Clinic in Rochester, Minn., has generated a strain of mouse in which all the senescent cells can be purged by giving the mice a drug that forces the cells to self-destruct.
Rid of the senescent cells, the Mayo Clinic researchers reported online Wednesday in the journal Nature, the mice’s tissues showed a major improvement in the usual burden of age-related disorders. They did not develop cataracts, avoided the usual wasting of muscle with age, and could exercise much longer on a mouse treadmill. They retained the fat layers in the skin that usually thin out with age and, in people, cause wrinkling.

For the full story, see:
NICHOLAS WADE. “Prospect of Delaying Aging Ills Is Raised in Cell Study of Mice.To Challenges For Obama, Add Another.” The New York Times (Thur., November 3, 2011): A1-A4.
(Note: the online version of the article is dated November 2, 2011 and has the title “Purging Cells in Mice Is Found to Combat Aging Ills.”)
(Note: thanks to Luis Locay for sending me the link to this.)

Another worthwhile article summarizing the same research, is:
SHIRLEY S. WANG. “Cell Study Finds a Way to Slow Ravages of Age.” The Wall Street Journal (Thur., November 3, 2011): A2.

“A Landmark Achievement for Regenerative Medicine”

TracheaMadeInLab2011-08-09.jpg “A lab-made windpipe was implanted June 9 into a 36-year-old patient whose own windpipe was obstructed by a tumor.” Source of caption and photo: online version of the WSJ article quoted and cited below.

(p. A3) Doctors have replaced the cancer-stricken windpipe of a patient with an organ made in a lab, a landmark achievement for regenerative medicine. The patient no longer has cancer and is expected to have a normal life expectancy, doctors said.

“He was condemned to die,” said Paolo Macchiarini, a professor of regenerative surgery who carried out the procedure at Sweden’s Karolinska University Hospital. “We now plan to discharge him [Friday].”
The transplantation of an entirely synthetic and permanent windpipe had never been successfully done before the June 9 procedure. The researchers haven’t yet published the details in a scientific journal.

For the full story, see:
GAUTAM NAIK. “Lab-Made Trachea Saves Man; Tumor-Blocked Windpipe Replaced Using Synthetic Materials, Patient’s Own Cells.” The Wall Street Journal (Fri., July 8, 2011): C8.

Easter Island Was Ravaged by Rats, Peruvian Slaving Parties and Nonnative Diseases, Not by Ecocide

Statues-That-WalkedBK.jpg

Source of book image: http://0.tqn.com/d/archaeology/1/0/g/L/1/Statues-That-Walked-sm.jpg

The natives call Easter Island “Rapa Nui.”

(p. C5) With the forest gone, Rapa Nui’s soil degraded; unable to feed themselves, Mr. Diamond argued in his best-selling “Collapse” (2005), Easter Islanders faced “starvation, a population crash, and a descent into cannibalism.” The fall was abrupt and overwhelming; scores of giant statues were abandoned, half-finished. Roggeveen had discovered a ruin–and a powerful eco-parable.

Books and articles by the hundred have pointed to Rapa Nui as the inevitable result of uncontrolled population growth, squandered resources and human fecklessness. “The person who felled the last tree could see it was the last tree,” wrote Paul G. Bahn and John Flenley in “Easter Island, Earth Island” (1992). “But he (or she) still felled it.” “The parallels between Easter Island and the whole modern world are chillingly obvious,” Mr. Diamond proclaimed. “The clearest example of a society that destroyed itself by overexploiting its own resources,” he said, Rapa Nui epitomizes “ecocide,” presenting a stark image of “what may lie ahead of us in our own future.”
No, it doesn’t, write archaeologists Terry Hunt and Carl Lipo in “The Statues That Walked,” a fascinating entry in the pop-science genre of Everything You Know Is Wrong. Messrs. Hunt and Lipo had no intention of challenging Mr. Diamond when they began research on Rapa Nui. But in their fourth year of field work, they obtained radiocarbon dates from Anakena Beach, thought to be the island’s oldest settlement. The dates strongly indicated that the first settlers appeared around A.D. 1200–eight centuries later than Heyerdahl and other researchers had thought.
Wait a minute, the authors in effect said. Rapa Nui is so remote that researchers believe it must have been settled by a small group of adventurers–a few dozen people, brave or crazy, in boats. The new evidence suggested that their arrival had precipitated catastrophic deforestation “on the scale of decades, not centuries.” The island then probably had only a few hundred inhabitants. Some ecologists estimate that the island originally had 16 million palm trees. How could so few people have cut down so much so fast?
. . .
The real culprit, according to “The Statues That Walked,” was the Polynesian rat (Rattus exulans), which stowed away on the boats of the first Polynesian settlers. In laboratory settings, Polynesian rat populations can double in 47 days. Throw a breeding pair into an island with no predators and abundant food and arithmetic suggests the result: ratpocalypse. If the animals multiplied as they did in Hawaii, the authors calculate, Rapa Nui would quickly have housed between two and three million. Among the favorite food sources of R. exulans are tree seeds and tree sprouts. Humans surely cleared some of the forest, but the real damage would have come from the rats that prevented new growth.
“Rather than a case of abject failure,” the authors argue, “Rapa Nui is an unlikely story of success.” The islanders had migrated, perhaps accidentally, to a place with little water and “fundamentally unproductive” soil with “uniformly low” levels of phosphorus, an essential mineral for plant growth. To avoid the wind’s dehydrating effects, the newcomers circled their gardens with stone walls known as manavai. Today, the researchers discovered, abandoned manavai occupy about 6.4 square miles, a tenth of the island’s total surface.
More impressive still, about half of the island is covered by “lithic mulching,” in which the islanders scattered broken stone over the fields. The uneven (p. C6) surface creates more turbulent airflow, reducing daytime surface temperatures and warming fields at night. And shattering the rocks exposes “fresh, unweathered surfaces, thus releasing mineral nutrients held within the rock.” Only lithic mulching produced enough nutrients–just barely–to make Rapa Nui’s terrible soil cultivable. Breaking and moving vast amounts of stone, the islanders had engineered an entirely new, more productive landscape.
Their success was short-lived. As Messrs. Hunt and Lipo point out, the 18th and 19th centuries were terrible times to reside in a small, almost defenseless Pacific nation. Rapa Nui was repeatedly ravaged by Peruvian slaving parties and nonnative diseases.
. . .
Easter Island’s people did not destroy themselves, the authors say. They were destroyed.
. . .
Oral tradition said that the statues walked into their places. Oral tradition was correct, the authors say. By shaping the huge statues just right, the islanders were able to rock them from side to side, moving them forward in a style familiar to anyone who has had to move a refrigerator. Walking the statues, the authors show in experiments, needed only 15 or 20 people.
In a 2007 article in Science, Mr. Diamond estimated that hundreds of laborers were needed to move the statues, suggesting that the eastern settlements of the island alone had to have “a population of thousands”–which in turn was proof of the island’s destructive overpopulation. By showing that the statues could have been moved by much fewer people, Messrs. Hunt and Lipo have removed one of the main supports of the ecocide theory and the parable about humankind it tells.

For the full review, see:
CHARLES C. MANN. “Don’t Blame the Natives; It was a rat that caused the sudden collapse of Easter Island’s civilization.” The Wall Street Journal (Sat., JULY 30, 2011): C5-C6.
(Note: ellipses added; italics in original.)

Source of book under review:
Hunt, Terry, and Carl Lipo. The Statues That Walked: Unraveling the Mystery of Easter Island. New York: Free Press, 2011.