In 1778, Founding Father Benjamin Franklin was in France attempting to secure support for the United States Colonies during the War for Independence.
Great Britain and France had been at odds with one another for many years as the two most powerful nations in the world.
The American Continental Congress knew that enlisting aid from France would further infuriate King George III.
The Americans were fully aware they could not win the war with Great Britain alone. They had no navy, and military supplies such as guns and ammunition were hard to come by as the Colonies depended on Great Britain for most of their supplies.
The British had recruited North American Indian tribes to fight for their cause — promising if Britain retained control of the Colonies, the Native Americans would be left alone. The only hope the Colonists had was to enlist foreign aid.
The Colonies were forbidden to trade with foreign countries, but smuggling had been going on for years. American rice and tobacco were to be shipped only to Britain but were secretly shipped to northwestern France and Amsterdam in exchange for much-needed items such as tea, fabric for clothing, gunpowder, arms, wig powder and other necessities.
Great Britain was aware of the illegal trading but mostly ignored the situation until they found out about the weapons and gunpowder. In 1774, the British sent ships to Texel Island in northern Holland to curtail the trade with Amsterdam. According to Aermican Herritage by the beginning of 1775, the British had unknowingly sent almost six million dollars’ worth of war munitions to the Colonies.
At the age of seventy-one Benjamin Franklin was sent to France, along with Silas Deane and Arthur Lee, to gain help from Louis XVI. On May 2, 1776, the French King signed documents making France an American ally which dishonored her treaties with Britain.
In 1770 Massachusetts appointed Franklin as the first foreign ambassador to France. By 1778, Franklin, Deane and Lee had negotiated the Treaty of Alliance and the Treaty of Amity and Commerce with their new ally.
Franklin had already proved his worth in the Colonies by his writings, inventions, research of electricity, and his brilliant use of diplomacy. Although he was self-taught, Franklin held honorary degrees from Harvard, Yale, the University of St. Andrews in Scotland, and Oxford University in England.
He also helped found the University of Pennsylvania in his hometown of Philadelphia. The French, fascinated by Franklin, welcomed him with open arms. He learned French and was set up in a house in the Parisian suburb of Passy.
His charm, wit and humble dress made him one of the most popular people in Paris. He wore a coonskin cap to play up the French belief that Americans were wild frontiersmen. In fact, Franklin was so popular in France that even today some French citizens think he was an American president. Franklin was criticized by his contemporaries for living the high life, going to balls and parties and hobnobbing with the wealthiest of society.
For Franklin to have mixed with the poorer people would have alienated him from the king and wealthy potential donors to the cause. It was the eve of the French Revolution, and the public had had about enough of squalid living conditions while the wealthy flaunted their money in over the top decadence.
At the end of the Revolutionary War Franklin successfully negotiated the Treaty of Paris in 1783.
Having spent about ten years in France, Franklin returned to Philadelphia in 1785. He assisted in the creation of both the Bill of Rights and the United States Constitution.
In April of 1790, Franklin died at the age of eighty-four at the Philadelphia home of his daughter, Sarah. According to Biography, Franklin had written his own epitaph when he was twenty-two:
“The body of B. Franklin, Printer (Like the Cover of an Old Book Its Contents torn Out And Stript of its Lettering and Gilding) Lies Here, Food for Worms. But the Work shall not be Lost; For it will (as he Believ’d) Appear once More In a New and More Elegant Edition Revised and Corrected By the Author.”
Alas, the inscription on his headstone in Christ Church Burial Ground reads “Benjamin and Deborah Franklin 1790.” The Poor Richard Club mounted a plaque near the grave with Franklin’s epitaph for himself and another with a timeline of Franklin’s life.
In 1963 Alfred Hitchcock released The Birds, one of his most iconic thrillers. The movie considered what would happen if flocks of birds, animals that linger in the background of many of our daily lives, suddenly rose up and attacked a small coastal town in California. The film was inspired by a real-life event, namely an attack by sooty shearwaters on Capitola, California, in 1961. It was linked to diatompoisoning of the anchovies eaten by the birds. The shearwaters crashed into rooftops, and their carcasses were found on the streets and throughout the town.
Movies like The Birds (1963) or The Happening (2008) that explore the possibility of nature suddenly becoming vindictive pop into theaters from time to time, but the prospect of injuries and even deaths caused by aggressive birds is not fiction. Territoriality and defending young from predators remains serious business, and even the smallest birds will lash out at threats. The list below highlights some of the world’s most dangerous birds.
Cassowaries are the only members of the family Casuariidae and belong to the order Casuariiformes, which also includes the emu. Three species (counted by some experts as six), each with several races, live in habitats that span parts of Australia and New Guinea. The cassowary has been known to kill human beings with slashing blows of its feet, as the innermost of its three toes bears a long daggerlike nail. The bird has been observed moving rapidly along narrow tracks in the bush, sprinting as fast as 50 km (31 miles) per hour.
Cassowaries are curious, and they do attack from time to time, but attacks on humans are relatively rare. Those attacks that do occur overwhelmingly involve soliciting food from people. One of the most recent incidents came in 2012, when a tourist in Queensland, Australia, was kicked by a cassowary off a ledge and into a body of water but remained unharmed otherwise. One of the most famous attacks (and the only one known to result in a confirmed death) occurred in 1926: one member of a group of teenaged boys hunting cassowaries was killed after a cassowary leapt upon him while he was on the ground. The bird slashed the boy’s jugular vein with its long toenail.
Ostrich (Struthio camelus)
Ostriches are flightless birds found only in open country in Africa. The largest living birds, adult males may be 2.75 meters (about 9 feet) tall—almost half of that height being in the neck—and weigh more than 150 kilograms (330 pounds). Ostriches are seen individually, in pairs, in small flocks, or in large aggregations, depending on the season. The ostrich relies on its strong legs—uniquely two-toed, with the main toe developed almost as a hoof—to escape its enemies, chiefly humans and the larger carnivores. A frightened ostrich can achieve a speed of 72.5 kilometers (45 miles) per hour. If cornered, it can deliver dangerous kicks capable of killing lions and other large predators. Deaths from kicks and slashes are rare, with most attacks resulting from humans provoking the birds.
One of the most interesting ostrich-attack stories involved the American musician Johnny Cash, who kept an exotic animal park with ostriches on his property. Cash encountered an aggressive male ostrich several times during his walks in the woods in 1981. On one occasion, Cash brandished a 6-foot stick and swung it at the bird, who dodged the swipe and slashed at Cash with its foot. Cash noted that the blow struck him in the stomach, and if it weren’t for a strong belt buckle, he said that the ostrich’s toe claw would have cut his abdomen open and killed him.
Emu (Dromaius [or Dromiceius] novaehollandiae)
The common emu, the only survivor of several forms exterminated by settlers, is stout-bodied and long-legged like its relative the cassowary. Emus can dash away at nearly 50 km (30 miles) per hour; if cornered, they kick with their big three-toed feet. Like cassowaries and ostriches, the toe claws of emus are capable of eviscerating animals under the right conditions; however, human fatalities are extremely rare. Reports of emu attacks resulting in a range of injuries in Australia and in wild-animal parks, emu farms, and zoos across the world are not uncommon, with more than 100 occurring in 2009 alone.
Lammergeier (Gypaetus barbatus)
Lammergeiers, which are also called bearded vultures, are big eaglelike vultures of the Old World (family Accipitridae). These birds often reach lengths of more than 1 meter (40 inches), with a wingspread of nearly 3 meters (10 feet). They inhabit mountainous regions from Central Asia and eastern Africa to Spain and dine on carrion, especially bones, which they drop from heights as great as 80 meters (260 feet) onto flat rocks below. This cracks open the victim’s bones and allows the birds access to the marrow. Attacks on humans are either rare or even anecdotal; however, the Athenian dramatist Aeschylus is said to have died at Gela (on Sicily’s south coast) when a lammergeier dropped a tortoise on his bald head after mistaking it for a stone. Although Aeschylus did die at Gela, experts believe that the story describing the strange cause of his death was fabricated by a later comic writer.
Great horned owl (Bubo virginianus)
Owls of all kinds have been known to attack people when defending their young, their mates, or their territories. Frequent targets include unsuspecting joggers and hikers. Often victims escape without injury, and deaths from owl attacks are extremely rare. Great horned owls (Bubo virginianus) and barred owls (Strix varia), in particular, have received attention from high-profile attacks.
In 2012 a number of people in a Seattle-area park reported being attacked by a great horned owl that swooped down from the trees. A similar swooping attack occurred in Salem, Oregon, in 2015 when a great horned owl repeatedly struck the scalp of a jogger, who ran and later escaped. Great horned owls are powerful predators that often grow to more than 2 feet (60 cm) in length, with wingspans that often approach 200 cm (80 inches). These owls, which are found across the Americas, usually eat small rodents and birds but have been known to carry off larger prey. The clutching force of their talons can be as strong as 500 psi (which is similar to the bite of a large guard dog and thus great enough to permanently disfigure, blind, or kill). Great horned owls, like most owl species, tend to concentrate on the face and head in battles with larger animals.
Barred Owl (Strix varia)
Barred owls, whose habitat includes much of the eastern United States and southeastern Canada, are smaller than great horned owls. They weigh between 630 and 800 grams (1.4 to 1.8 pounds) and have a wingspan of about 110 cm (43 inches). Attacks by barred owls on hikers have been reported from Texas to British Columbia.
A barred owl was thought to have played a part in a bizarre high-profile North Carolina murder case. In 2003 a man was convicted of murdering his second wife with a fireplace blow poke. In 2011, after the man had served several years in prison, a judge tossed out the forensic evidence related to the murder weapon. Shortly thereafter, news of barred-owl attacks in the Pacific Northwest, combined with a reexamination of the wounds on the victim’s scalp, face, and wrists, prompted the defendant’s attorneys to suggest that a barred owl was to blame for the victim’s death. The defense argued that the victim, who was under the influence of pain medication and alcohol at the time, was attacked by a barred owl in her front yard. The owl had become entangled in the victim’s hair and continued to scratch and peck before the victim was able to fight it off and free it as she ran into the house. After climbing the stairs to the second floor, the attorneys suggested that the victim had then fallen backwards down the stairs to her death, breaking her neck. In 2017 the defendant plead guilty to voluntary manslaughter, which allowed him to maintain his innocence.
Antarctica, Earth’s coldest continent, is known for its remoteness, its unique fauna, and its frigid surface of ice. Around Antarctica’s periphery, dozens of ice shelves (that is, masses of glacier-fed floating ice that are attached to land) project outward into the Southern Ocean. The two largest ice shelves, the Ross Ice Shelfand the Ronne Ice Shelf, span a combined area of nearly 350,000 square km (about 135,000 square miles)—an area roughly equivalent to Venezuela—but Antarctica’s Larsen Ice Shelf, the continent’s fourth largest, has received the bulk of the attention over the last 25 years because it is slowly coming apart. The latest episode in this saga occurred between July 10 and July 12, 2017, when a one-trillion-metric-ton chunk of ice—possibly critical to holding back a large section of the remaining shelf—calved (that is, broke away).
The Larsen Ice Shelf is located on the eastern side of the Antarctic Peninsula and juts out into the Weddell Sea. It originally covered an area of 86,000 square km (33,000 square miles), but its footprint has declined dramatically, possibly as a result of warming air temperatures over the Antarctic Peninsula during the second half of the 20th century. In January 1995 the northern portion (known as Larsen A) disintegrated, and a giant iceberg calved from the middle section (Larsen B). Larsen B steadily retreated until February–March 2002, when it too collapsed and disintegrated. The southern portion (Larsen C) made up two-thirds of the ice shelf’s original extent, covering an area of about 50,000 square km (19,300 square miles) alone. Its thickness ranges from 200 to 600 meters (about 660 to 1,970 feet). Sometime between July 10 and July 12, 2017, a 5,800-square-km- (~2,240-square-mile-) section—some 12% of the Larsen C—broke away. Signs of Larsen C’s impending fracture date back to 2012, when satellite monitoring detected a steadily growing crack near the Joerg Peninsula at the southern end of the shelf. NASA and ESA satellites tracked the rift as it grew to more than 200 km (124 miles) in length and the huge iceberg separated from the continent.
Although some 88% of Larsen C remains, many scientists worry that it will fall apart like Larsen A and Larsen B, because the loss of such a huge area of the shelf’s ice front may make the remainder of the ice shelf less stable. The shelf’s mass, along with the fact that it is pinned behind shallow undersea outcrops of rock below, creates a natural dam that significantly slows the flow of the ice into the Weddell Sea. Scientists note that the section that calved was not held back by rock, so they are less worried that the loss of the calved section will result in the shelf’s wholesale disintegration in the near term. Some scientists even concede that the calved area could regrow to form a new ice dam that reinforces the shelf. However, the results of ice-calving and glacier-flow models predict that the shelf will continue to break apart over the course of years and decades.
Calving is a natural process driven, in part, by seasonal changes in temperature and the pressures associated with the build-up of compressional stress on the ice. Some studies argue that spring and summer foehns (warm dry gusty winds that periodically descend the leeward slopes of mountain ranges) have also contributed to the weakening of the ice. As investigations into ice shelf dynamics continue, such large iceberg calving events are often regarded as symptoms of climate changeassociated with global warming. While global warming may turn out to play a part in ice shelf calving events, scientists disagree on the role, if any, the phenomenon has played in recent developments on Larsen C.
The partnership between humans and animals dates back to the first domestication of animals in the Stone Age, as long as 9,000 years ago. But never have animals provided such dedicated and particular help to humans as they do today in the form of trained service, or assistance, to people with disabilities. These animals, usually dogs, help people accomplish tasks that would otherwise be prohibitively difficult or simply impossible. Service animals are not pets but working animals doing a job. Thus, legislation—such as the Americans with Disabilities Act (1990) in the United States and the Disability Discrimination Act (1995) in the United Kingdom—makes service animals exempt from rules that prohibit animals from public places and businesses.
The most familiar service animals are guide dogs who help visually impaired people move about safely. Systematic training of guide dogs originated in Germany during World War I to aid blindedveterans. In the late 1920s Dorothy Harrison Eustis, an American dog trainer living in Switzerland, heard of the program and wrote a magazine article about it. The publicity led her to her first student, Morris Frank, with whose help she established a similar training school in the United States in 1929, the Seeing Eye (now located in Morristown, New Jersey).
Puppies are often bred for the purpose by the various organizations that train guide dogs. German shepherds, Labrador retrievers, and Labrador-golden retriever crosses are the most widely used breeds because of their calm temperaments, intelligence, natural desire to be helpful, and good constitutions. Puppies spend their first year with foster families who socialize them and prepare them for later training by teaching them basic obedience skills. At the age of approximately 18 months, guide dogs enter formal training, which lasts from about three to five months. During this period the dogs learn to adjust to a harness, stop at curbs, gauge the human partner’s height when traveling in low or obstructed places, and disobey a command when obedience will endanger the person.
In recent years, hearing dogs have become increasingly common. These dogs, usually mixed-breed rescues from animal shelters, are trained to alert their human partners to ordinary sounds, such as an alarm clock, a baby’s cry, or a telephone. The dogs raise the alert by touching the partner with a paw and then leading him or her to the source of the sound. They are also trained to recognize danger signals—such as fire alarms and sounds of intruders—and to raise the alert by touching with a paw and then lying down in a special “alert” posture, at which time the human partner can take appropriate action.
Dogs can be trained for a great variety of assistance purposes. For example, Service Dogs for America (SDA)/Great Plains Assistance Dogs Foundation, Inc., trains several categories of assistance animals, including service dogs who help people who use wheelchairs and other mobility devices; hearing dogs; seizure-alert or seizure-response dogs, who help persons with seizure disorders by activating an electronic alert system when symptoms occur (some can even predict the onset of a seizure); and therapeutic companion dogs, who provide emotional support for people in hospices, hospitals, and other situations in which loneliness and lack of stimulation are continual problems. There are many programs that train and certify pet animals, especially dogs and cats, as therapy animals who visit such institutions and bring much-welcomed companionship to patients.
Animals are also used in programs such as animal-assisted therapy (AAT). In the words of the Australia-based Delta Society, AAT is a “goal-directed intervention” that utilizes the motivating and rewarding presence of animals, facilitated by trained human professionals, to help patients make cognitive and physical improvements. For example, an elderly patient in a nursing home might be given the task of buckling a dog’s collar or feeding small treats to a cat, activities that enhance fine motor skills. Goals are set for the patients, and their progress is measured.
Dogs and cats are not the only animals who can assist humans with disabilities. Capuchin monkeys—small, quick, and intelligent—can help people who are paralyzed or have other severe impairments to their mobility, such as multiple sclerosis. These monkeys perform essential tasks such as turning on lights and picking up dropped objects. One of the more unusual assistance animals is the guide horse. An experimental program in the United States trains miniature horses to guide the visually impaired in the same way that guide dogs do. The tiny horses may be an alternative for people who are allergic to dogs or who have equestrian backgrounds and are more comfortable with horses.
Certain dogs and other animals have special skills similar to those of the seizure-assistance dogs, such as the ability to detect a diabetic’s drop in blood sugar and alert the person before danger occurs. The sometimes uncanny natural abilities of animals can benefit humans in many ways. Reputable organizations that train assistance animals also take steps to ensure that the animals are cherished and lead rewarding, enjoyable, and healthy lives. When the animals’ helping careers are over, provision is made for their well-deserved retirement.
Sperm whales (Physeter catodon), or cachalots, are the largest of the toothed whales, with males up to 19 meters (62 feet) long—more than five times the length of a large elephant—and females up to 12 meters (39 feet) in length. They are easily recognized by their enormous square head and narrow lower jaw. Probably the most famous sperm whale was Moby Dick, the great white whale from Herman Melville’s classic novel of the same name. (As far as we can tell, Moby Dick was the only sperm whale that delivered a unique brand of karmic justice to one-legged sea captains bent on vengeance.) Despite the public’s passing familiarity with sperm whales, many people have wondered why they are so named. Are they called sperm whales because their body shape is similar to that of male sex cells, or is there another reason?
The whale’s common name originated during the heyday of the commercial whaling industry, from the end of the 18th century through the 19th century. The head of the sperm whale contains an enormous fluid-filled organ (which whalers called the case). During whale harvests, this organ, now called the spermaceti organ, was discovered to contain a white liquid that whalers mistook for the sperm of the whale. The spermaceti organ is unique to sperm whales, although bottlenose whales possess a similar organ. It has a volume as large as 2,000 liters (530 gallons) and can extend through 40 percent of the whale’s length.
Whalers valued spermaceti (the name of the material within the spermaceti organ) because it could be cooled into a wax that could be made into ointments, cosmetic creams, fine wax candles, pomades, textile finishing products, and industrial lubricants. The whale’s spermaceti organ and blubber also hold sperm oil, a pale yellow oil that was used as a superior lighting oil and later as a lubricant and in soap manufacturing.
Imagine the thrill of discovery when more than 10 years of research on the origin of a common genetic disease, cystic fibrosis (CF), results in tracing it to a group of distinct but mysterious Europeans who lived about 5,000 years ago.
CF is the most common, potentially lethal, inherited disease among Caucasians—about one in 40 carry the so-called F508del mutation. Typically only beneficial mutations, which provide a survival advantage, spread widely through a population.
CF hinders the release of digestive enzymes from the pancreas, which triggers malnutrition, causes lung disease that is eventually fatal and produces high levels of salt in sweat that can be life-threatening.
In recent years, scientists have revealed many aspects of this deadly lung disease which have led to routine early diagnosis in screened babies, better treatments and longer lives. On the other hand, the scientific community hasn’t been able to figure out when, where and why the mutation became so common. Collaborating with an extraordinary team of European scientists such as David Barton in Ireland and Milan Macek in the Czech Republic, in particular a group of brilliant geneticists in Brest, France led by Emmanuelle Génin and Claude Férec, we believe that we now know where and when the original mutation arose and in which ancient tribe of people.
We share these findings in an article in the European Journal of Human Genetics which represents the culmination of 20 years’ work involving nine countries.
What is cystic fibrosis?
My quest to determine how CF arose and why it’s so common began soon after scientists discovered the CFTR gene causing the disease in 1989. The most common mutation of that gene that causes the disease was called F508del. Two copies of the mutation—one inherited from the mother and the other from the father—caused the lethal disease. But, inheriting just a single copy caused no symptoms, and made the person a “carrier.”
I had been employed at the University of Wisconsin since 1977 as a physician-scientist focusing on the early diagnosis of CF through newborn screening. Before the gene discovery, we identified babies at high risk for CF using a blood test that measured levels of protein called immunoreactive trypsinogen (IRT). High levels of IRT suggested the baby had CF. When I learned of the gene discovery, I was convinced that it would be a game-changer for both screening test development and epidemiological research.
That’s because with the gene we could offer parents a more informative test. We could tell them not just whether their child had CF, but also whether they carried two copies of a CFTR mutation, which caused disease, or just one copy which made them a carrier.
One might ask what is the connection between studying CF newborn screening and learning about the disease origin. The answer lies in how our research team in Wisconsin transformed a biochemical screening test using the IRT marker to a two-tiered method called IRT/DNA.
Because about 90 percent of CF patients in the U.S. and Europe have at least one F508del mutation, we began analyzing newborn blood for its presence whenever the IRT level was high. But when this two-step IRT/DNA screening is done, not only are patients with the disease diagnosed but also tenfold more infants who are genetic carriers of the disease are identified.
As preconception-, prenatal- and neonatal screening for CF have proliferated during the past two decades, the many thousands of individuals who discovered they were F508del carriers and their concerned parents often raised questions about the origin and significance of carrying this mutation themselves or in their children. Would they suffer with one copy? Was there a health benefit? It has been frustrating for a pediatrician specializing in CF to have no answer for them.
The challenge of finding origin of the CF mutation
I wanted to zero in on when this genetic mutation first starting appearing. Pinpointing this period would allow us to understand how it could have evolved to provide a benefit—at least initially—to those people in Europe who had it. To expand my research, I decided to take a sabbatical and train in epidemiology while taking courses in 1993 at the London School of Hygiene and Tropical Medicine.
The timing was perfect because the field of ancient DNA research was starting to blossom. New breakthrough techniques like the Polymerase Chain Reaction made it possible to study the DNA of mummies and other human archaeological specimens from prehistoric burials. For example, early studies were performed on the DNA from the 5,000-year-old Tyrolean Iceman, which later became known as Ötzi.
I decided that we might be able to discover the origin of CF by analyzing the DNA in the teeth of Iron Age people buried between 700-100 B.C. in cemeteries throughout Europe.
Using this strategy, I teamed up with archaeologists and anthropologists such as Maria Teschler-Nicolaat the Natural History Museum in Vienna, who provided access to 32 skeletons buried around 350 B.C. near Vienna. Geneticists in France collected DNA from the ancient molars and analyzed the DNA. To our surprise, we discovered the presence of the F508del mutation in DNA from three of 32 skeletons.
This discovery of F508del in Central European Iron Age burials radiocarbon-dated to 350 B.C. suggested to us that the original CF mutation may have arisen earlier. But obtaining Bronze Age and Neolithic specimens for such direct studies proved difficult because fewer burials are available, skeletons are not as well-preserved and each cemetery merely represents a tribe or village. So rather than depend on ancient DNA, we shifted our strategy to examine the genes of modern humans to figure out when this mutation first arose.
Why would a harmful mutation spread?
To find the origin of CF in modern patients, we knew we needed to learn more about the signature mutation—F508del—in people who are carriers or have the disease.
This tiny mutation causes loss of one amino acid out of the 1,480 amino acid chain and changes the shape of a protein on the surface of the cell that moves chloride in and out of the cell. When this protein is mutated, people carrying two copies of it—one from the mother and one from the father—are plagued with thick sticky mucus in their lungs, pancreas and other organs. The mucus in their lungs allows bacteria to thrive, destroying the tissue and eventually causing the lungs to fail. In the pancreas, the thick secretions prevent the gland from delivering the enzymes the body needs to digest food.
So why would such a harmful mutation continue to be transmitted from generation to generation?
A mutation as harmful as F508del would never have survived among people with two copies of the mutated CFTR gene because they likely died soon after birth. On the other hand, those with one mutation may have a survival advantage, as predicted in Darwin’s “survival of the fittest” theory.
Perhaps the best example of a mutation favoring survival under stressful environmental conditions can be found in Africa, where fatal malaria has been endemic for centuries. The parasite that causes malaria infects the red blood cells in which the major constituent is the oxygen-carrying protein hemoglobin. Individuals who carry the normal hemoglobin gene are vulnerable to this mosquito-borne disease. But those who are carriers of the mutated “hemoglobin S” gene, with only one copy, are protected from severe malaria. However two copies of the hemoglobin S gene causes sickle cell disease, which can be fatal.
Here there is a clear advantage to carrying one mutant gene—in fact, about one in 10 Africans carries a single copy. Thus, for many centuries an environmental factor has favored the survival of individuals carrying a single copy of the sickle hemoglobin mutation.
Similarly we wondered whether there was a health benefit to carrying a single copy of this specific CF mutation during exposures to environmentally stressful conditions. Perhaps, we reasoned, that’s why the F508del mutation was common among Caucasian Europeans and Europe-derived populations.
Clues from modern DNA
To figure out the advantage of transmitting a single mutated F508del gene from generation to generation, we first had to determine when and where the mutation arose so that we could uncover the benefit this mutation conferred.
We obtained DNA samples from 190 CF patients bearing F508del and their parents residing in geographically distinct European populations from Ireland to Greece plus a Germany-derived population in the U.S. We then identified a collection of genetic markers—essentially sequences of DNA—within the CF gene and flanking locations on the chromosome. By identifying when these mutations emerged in the populations we studied, we were able to estimate the age of the most recent common ancestor.
Next, by rigorous computer analyses, we estimated the age of the CF mutation in each population residing in the various countries.
We then determined that the age of the oldest common ancestor is between 4,600 and 4,725 years and arose in southwestern Europe, probably in settlements along the Atlantic Ocean and perhaps in the region of France or Portugal. We believe that the mutation spread quickly from there to Britain and Ireland, and then later to central and southeastern European populations such as Greece, where F508del was introduced only about 1,000 years ago.
Who spread the CF mutation throughout Europe?
Thus, our newly published data suggest that the F508del mutation arose in the early Bronze Age and spread from west to southeast Europe during ancient migrations.
Moreover, taking the archaeological record into account, our results allow us to introduce a novel concept by suggesting that a population known as the Bell Beaker folk were the probable migrating population responsible for the early dissemination of F508del in prehistoric Europe. They appeared at the transition from the Late Neolithic period, around 4000 B.C., to the Early Bronze Age during the third millennium B.C. somewhere in Western Europe. They were distinguished by their ceramic beakers, pioneering copper and bronze metallurgy north of the Alps and great mobility. All studies, in fact, show that they were into heavy migration, traveling all over Western Europe.
Over approximately 1,000 years, a network of small families and/or elite tribes spread their culture from west to east into regions that correspond closely to the present-day European Union, where the highest incidence of CF is found. Their migrations are linked to the advent of Western and Central European metallurgy, as they manufactured and traded metal goods, especially weapons, while traveling over long distances. It is also speculated that their travels were motivated by establishing marriage networks. Most relevant to our study is evidence that they migrated in a direction and over a time period that fit well with our results. Recent genomic data suggest that both migration and cultural transmission played a major role in diffusion of the “Beaker Complex” and led to a “profound demographic transformation” of Britain and elsewhere after 2400 B.C.
Determining when F508del was first introduced in Europe and discovering where it arose should provide new insights about the high prevalence of carriers—and whether the mutation confers an evolutionary advantage. For instance, Bronze Age Europeans, while migrating extensively, were apparently spared from exposure to endemic infectious diseases or epidemics; thus, protection from an infectious disease, as in the sickle cell mutation, through this genetic mutation seems unlikely.
As more information on Bronze Age people and their practices during migrations become available through archaeological and genomics research, more clues about environmental factors that favored people who had this gene variant should emerge. Then, we may be able to answer questions from patients and parents about why they have a CFTR mutation in their family and what advantage this endows.
This article was originally published on The Conversation.Matthew E. Baker, Professor of Geography and Environmental Systems, University of Maryland, Baltimore County