Toulouse Lautrec

An Artist despite His Genes

In the summer of 1997, I had the good fortune to take my family on holiday to Paris. Among the small souvenirs we brought home was a set of coasters for drinks, each depicting a famous Parisian landmark. They were the Eiffel Tower, Notre Dame, Sacre Coeur, the Arc de Triomphe, Saint Chapelle, and the Moulin Rouge. That the last, a tawdry dance hall set up in the 1880s on the outskirts of Paris, should hold rank with the other five is in one sense a measure of the impact of a talented, unconventional, and tortured painter whose meteoric career lasted less than 20 years.

Fate spun out an unusually complex web for Henri Marie-Raymond Toulouse-Lautrec Montfa, who was destined to scandalize and then win over the art world with bold paintings and posters of the seamy side of life in Montmartre. Born in 1864 to great wealth, he was the first and only surviving son of an avid horseman and huntsman who lived a life unconstrained by social rules and a pious, retiring mother who could not have been more opposite. The night of his wife's delivery, her husband, Count Alphonse, is reliably reported to have prayed feverishly for a son, mainly so that he could train a future hunting companion. Famous for his wild life, Alphonse was a descendant of the ancient Counts of Toulouse and Viscounts of Lautrec whose ancestors had been the cousins of kings. Adele Tapie de Celeyrais, the future painter's mother, was from a less illustrious family, but her grandfather owned a magnificent estate with 3500 acres of vineyards. She was swept off her feet by her future husband's dashing military ways, and her parents, putting social class and economics ahead of character, encouraged a marriage that would soon turn sour. Crucial to our tale is that Henri's parents were first cousins.

Consanguinity and Recessive Genes

Long before geneticists began to do research, folk wisdom recognized that there was some danger (as measured by infertility and birth defects) to consanguineous marriages. Most states in the United States still forbid first-cousin marriages, and to this day, second-cousin marriages are permitted within the Catholic Church only by special dispensation. Some peoples, however, such as the Druze who favor uncle-niece marriages, still regard consanguinity as a way to strengthen family ties. Indeed, Christianity is the only major religion to proscribe cousin marriages. Until recently, the Chinese prized cousin marriage if the couple were the children of two brothers (geneticists call this parallel cousin marriage), but not if the unions were between offspring of a brother on the one hand and a sister on the other (cross-over cousin marriage). There is no genetic logic here, for in both cases, each marriage carries the same coefficient of relationship—husband and wife share an average one out of eight alleles (particular versions of genes) by descent. Of the roughly 100,000 genes they will each contribute to sperm or egg, about 12,500 will be the same alleles (the word refers to variants of any one gene).

The children of first-cousin marriages are more likely than those who are the offspring of unrelated persons to inherit two identical copies of the same gene. Products of even closer genetic unions, what we would call incestuous matings, share a much higher percentage of alleles. In the rare case of brother-sister unions, a child would have exactly the same two copies of a particular gene (be homozygous for them) in one-quarter of his or her total number of gene pairs. The few published studies of incest confirm that the offspring have a very high risk for being born with serious genetic diseases. Popular thinking has long held that marriage between relatives has the potential for producing children who are sublimely gifted or who are badly handicapped. In the case of Henri Marie-Raymond Toulouse-Lautrec Montfa, both predictions were realized.

The views held by geneticists about the impact of intermarriage on the health of offspring have vacillated significantly since 1900, and it is still difficult to estimate the magnitude of the risk (the theoretical benefits are now almost never discussed) associated with consanguinity. In the early 1900s, many scientists already believed that inbreeding conferred a very high risk of producing children who were mentally retarded, but there were few studies to support their opinion. The reasoning was that each of us must carry some alleles (gene variants) that in single doses pose no risk (and may even provide a benefit) but that if paired together (through inheritance from each parent) can have very harmful results.

Population geneticists estimate that our individual load of genetic lethals—gene variants that although harmless if only one copy is present either kill the individual or make it extremely unlikely that he or she will reproduce (infertility is genetic death) if two copies are present—is about 4-5. The reason that having one copy of any particular genetic lethal does not cause illness is simple. The protein made by the "normal" counterpart of the particular gene is sufficient to offset the lack of or malfunction of the other. In most cases that have been studied, it seems that people only need about 10% of the usual level of the normal protein to get by, so there is an adequate safety margin if one "bad" allele causes a 50% reduction in the output.

Children who are born of cousin marriages begin life with a set of genes that are drawn from parents with comparatively similar genomes (sets of genes). If a common ancestor of the cousins carried one of the harmful variants, it is statistically more likely that each cousin will have a copy than would be the case if they were unrelated. Therefore, the children of their union are more likely than the children of unrelated parents to inherit two copies of the "bad" gene. The very few studies of children who are born of highly incestuous matings, such as father-daughter rape, suggest that they are at much higher than average risk (perhaps 40%) of having a genetic disorder. This supports the argument for a genetic risk in cousin marriage, but says little about its magnitude.

Because humans have spent most of their history living in small groups, it is likely that matings between cousins were extremely common for eons. Our species tolerated this, but we have no idea at what cost. Almost certainly, there were many offspring of close genetic matings that did not survive. As recently as a century ago, until the rise of the automobile, first-cousin marriages were much more common in Europe and the United States than they are today. Studies from church records in Europe show that in the late 19th century, most people tended to choose spouses who had grown up within 15 miles of them, and many married neighbors within their small villages. Spouses were frequently second or third cousins, and not infrequently they were first cousins.

Throughout this century there has been a steady decline in first-cousin marriages, a trend that has made it possible to study their impact on the health of the offspring. Alan Bittles and James Neel, two leading population geneticists, recently reviewed the world literature on the effects of first-cousin marriage. They concluded that, contrary to earlier estimates, the average person carries only about 1 or 2 lethal genes that manifest in late pregnancy or childhood. If true, this suggests that first-cousin marriages in general pose relatively little danger for bringing out hidden genetic defects. However, any reassurance that one can draw about the risks of first-cousin marriage is of no solace to a particular couple who have a child burdened by a pair of genes that together cause severe disability.

Bittles and Neel could not rule out the possibility that there are many lethal alleles which kill the embryo so early that the pregnancy is not even recognized. It would be possible to investigate this by comparing the fertility (within the same culture) of cousin marriages with exogamous (out-bred) marriages. A significantly lower fertility rate in cousin marriages would suggest the impact of early lethal genes. Another interesting conclusion that one can draw from their study is that the majority of changes (mutations) in human germ-line DNA are of no functional consequence.

Toulouse-Lautrec: A Sketch

The inbreeding in the Toulouse-Lautrec family was not at all atypical, especially for 19th century French nobility. The painter's grandmothers were sisters, and his mother's brother married his father's sister. Such unions, along with the law of primogeniture (that land passes to the first-born son), were essential for keeping together the vast estates that formed the basis of most great wealth.

Before he was three, it was apparent that Henri, the adored center of a powerful, doting, and, on his father's side, physically rugged, artistic, and profoundly eccentric, family, was not growing normally. He was not sickly, but he was frail. Contemporary photos, family letters, and the memories of those who knew him evoke an image of a tiny child with an unusually large head. At the age of six months he weighed only 10 pounds.

One of his biographers reports that Henri's mother was worried that his fontanel (the opening at the top of the head of newborns that normally closes during the first year) was still widely open when he was four, a sign suggesting a skeletal abnormality. Photos of him in early childhood show a large and unusually wide head. He spoke with a lisp, and his arms and legs were very short. Within his extended family Henri was 1 of 4 children from among 16 born in two marriages to suffer with a serious skeletal disorder that was almost certainly caused by having inherited two copies of a "bad" gene (a recessive disorder).

Throughout his childhood, Henri, who showed a penchant for drawing by the age of 3, grew slowly. At school, where he excelled in his studies, he was nicknamed "the little man." Fellow students, who loved the devil-may-care attitude with which he regarded his disability, used to carry Henri about so he would not exhaust or endanger himself chasing after them. As the years passed, he fell farther behind. At the age of 13 he was only 4 feet, 8 inches tall. Despite the boy's exuberant, charming personality, Henri's father, unable to control his disappointment that he had not sired a rugged hunter, distanced himself from his son, conduct that would continue through his life. His mother, devoted to Henri until his death, consulted doctor after doctor, none of whom offered more than reassurance and quack interventions, such as stretching him on a rack, to spur his growth.

On May 30, 1878, Henri, who at 13 was so frail that he walked with a cane, fell as he was rising from a low chair. The fall, which would not have harmed the average person, left him with a fractured left femur. Less than two years later, while walking in the garden, he slipped into a small ditch and fractured his right femur. With strict bed rest and splinting, the bones mended on both occasions. His growth, however, was over. He stood just shy of 4 feet, 11 inches tall.

As he moved through adolescence, Toulouse-Lautrec seemed to grow uglier. His nose broadened, his lips thickened, his legs bowed, and, some say that his hands grew much too large for his tiny arms. He nobly fought the disability. One summer in Nice he walked, swam, and rode for weeks on end. He swam he said, "like a toad, but fast and well." But still he could not take up his father's passions—riding and hunting. By the time he was 14, it was apparent that Henri would be burdened by a lifelong physical disability, one that was incompatible with the family traditions. Despite his mother's devotion, others began to push him outside the family circle. No doubt thinking that his son would never make a good marriage, Count Alphonse early on took the decisive step of writing a will in which he left his vast tracts of land in southern France to Henri's younger sister, Alix.

It was about then that Henri began to disappear into his art. In 1880 when he was 15, he made 300 drawings and about 50 paintings. In the autumn of that year he and his mother (who was estranged from his father) moved to Paris. Henri was to sit for his baccalaureate exams in the spring of 1881, in that era typically the end point for the education of a son of a wealthy family. But soon after arriving Henri began to spend his days in the studio of a family friend, Rene Princeteau, a connection which his father had made for him. The solid artistic reputation enjoyed by Princeteau, who was then 37 years old, was especially remarkable because he had been born deaf. The degree to which he had triumphed over his disability impressed everyone. He could read lips well, and with a bit of practice one could understand his speech. Throughout Henri's first years in Paris, Princeteau treated him like a son and by example showed him what he might become. Henri quickly abandoned his formal schooling to pursue painting, a course that caused him to fail his first try at the baccalaureate. To please his mother, he did manage to buckle down enough to pass on his second attempt.

Henri's presence in the art world grew quickly. Within a year, at Princeteau's urging, he had enrolled in the studio of Leon Bonnat, a member of the French Academy of Beaux Art and a leading teacher. Along with his fellow young artists, Henri soon immersed himself in cafe life, started a lifelong pattern of heavy drinking, and became an afficionado of the darker sides of Paris. More and more he was drawn to the bohemian section of the city known as Montmartre.

In the late 1880s, Henri turned to lithography. His first poster, The Moulin Rouge, appeared in 1891 and, although (or perhaps because) it broke sharply from the dominant style, was immediately hailed as a tremendous success. His bold compositions in which the subject dominates the foreground, usually in three-quarter profile, ruled the French poster-making world for more than a decade. Not burdened by convention, Toulouse-Lautrec was willing to create on commission for virtually anyone who wanted his services. During the 1890s he illustrated song books for composers and menus for restaurateurs, designed posters for books and journals, crafted billboards for theatre productions, and sketched advertisements for furniture stores and bicycle factories. His work was decidedly antiacademic, and the Parisians loved it.

As he grew older and realized that hopes of normal relationships with women were remote, he took his solace more and more in alcohol and the brothels that dotted that quarter of Paris. He befriended many prostitutes, spent lavishly on them, and on occasion disappeared into bordellos for weeks on end. He is, for example, known to have lived for months at a time in an upscale bordello at 5, rue des Moulins, near the Opera, a luxurious establishment famous for having rooms decorated in different historical periods, apparently to satisfy the fantasies of some of the regular clients. Affectionately known as "Monsieur Henri," he took his meals with the women when they were off duty, and painted many of them and the lavish rooms in which they plied their trade. His scenes of those interiors, of the madams, the laundrymen, the prostitutes submitting to medical exams or sitting idly while waiting for their next clients, are among the most important artistic records of that life. He painted many of the women, and it is fair speculation that he tossed off hundreds of sketches in those times that never saw the light of day. On one occasion toward the end of a life by then dominated by drinking, he moved his studio and left 87 works behind for the landlord, saying, "They are of no importance."

Even though he had abused alcohol for two decades, Toulouse-Lautrec remained functional until his mid-30s. He did suffer from severe dental problems, and he broke one more bone, his clavicle, during a drunken fall downstairs. He also almost certainly contracted syphilis and may have suffered from neurosyphilis. On one occasion his alcohol abuse became so severe that his friends and family had him committed to an asylum in a last-ditch effort to save his life. After a bout of delirium tremens, he emerged improved, only to relapse quickly.

In 1901 Lautrec, his health worn down by two decades of alcohol abuse and the insidious march of syphilis, left Paris to spend the winter in Bordeaux with his friend, Paul Viaud, whom his mother had hired to stop him from drinking. His art works from this period seem all too obviously to reflect a deep depression. The clear bright colors of the famous posters have given way to gray, dark, heavy sketches, images that suggest despair and death. In August, while staying in a small coastal town, Lautrec suf fered a stroke. He was taken to his mother's estate at Malrome, where he fell into a coma and died on September 9. As she had been figuratively his whole life, his mother was at his side. His father too was nearby. According to one story, Henri's last words were to call him an "old fool."

Despite his disability (or perhaps because of it) and dissolute life, Henri left behind hundreds of oil paintings and the posters that soon garnered him fame, as well as thousands of sketches. His father rejected any suggestion that his son's work was important and enduring and signed away his paternal rights to them. Today, two of the paintings that he rejected grace the entrance to the top floor at the Musee D'Orsay in Paris, which houses the greatest collection of Postimpressionist French painting in the world. His mother, who lived until 1930, worked devotedly to create the Musée Toulouse-Lautrec in Albi, France, where today many of his works hang.


There are many genetic causes of dwarfism—a term used originally to describe a person with short stature whose limbs and torso are not proportionate. Until recently, the main tools used by clinical geneticists to categorize and study affected persons were radiographs and close attention to clinical features. Some conditions, such as diastrophic dwarfism, are often fatal. An affected infant may die of respiratory failure if the rib cage is too weak to help the lungs to expand properly. Other forms, such as the relatively common and well-recognized achondroplasia (a diagnosis that one early medical detective erroneously applied to Toulouse-Lautrec), are compatible with a long, healthy, productive life, limited all too often only by the prejudice of strangers.

Periodically for the last 80 years physicians have speculated about the cause of Henri's disabilities. Most of the guesses—achondroplasia, osteo-genesis imperfecta (the bones of affected persons break almost without being stressed), and epiphyseal dysplasia (a disorder of the growth plates of the long bones)—were not strongly supported. In 1962 Maroteaux and Lamy, two prominent French doctors, described a form of dwarfism that they called pycnodysostosis (the term means dense bones), and then garnered more than the usual attention by claiming that Toulouse-Lautrec, by then a star in the French artistic pantheon, had been afflicted with the con dition. The records of Henri's physical condition seemed to match with the features of their living patients. In addition to a tendency to fracture their leg bones, persons with pycnodysostosis have small stature, a large head with a prominent forehead, and dental problems. Although many doctors doubted the posthumous diagnosis, it stuck, and Toulouse-Lautrec was inducted into a second select group—famous people who have been given genetic diagnoses long after death. He was sometimes mentioned in genetics courses as an example of the dangers of consanguinity. Professors speculated that each of his parents had contributed a copy of the allele which causes pycnodysostosis or some other allele which affects the growth and strength of long bones.

In 1995 a group of geneticists, including Bruce Gelb and Bob Desnick, who work at Mount Sinai School of Medicine in New York, rekindled interest in pycnodysostosis when, using new DNA mapping techniques in an Arab family with many affected members and in which there had been many consanguineous marriages, they showed that the culprit gene was located somewhere within a small region on the long arm of chromosome 1. Their scientific report on the mapping of the pycnodysostosis gene was accompanied by an essay by Julia Frey, an art historian who wrote a fine biography of Toulouse-Lautrec. Although she interpreted the historical data to cast doubt on the diagnosis, on balance I think the material supports it.

In 1996 the New York team successfully cloned the gene responsible for pycnodysostosis, showing that the disorder is caused by defects in a gene that makes a protein called cathepsin K. This protein is used by cells called osteoclasts that are primarily responsible for remodeling bone, especially during growth. The osteoclasts of people with this very rare disease are able to perform part of the remodeling process, but because their cathepsin K does not work properly, the cells are unable to finish their job. Because pycnodysostosis is essentially a disease that only affects osteo-clasts, it may turn out to be treatable, either by transplanting normal os-teoclasts or through gene therapy (see Chapter 20).

Can we be sure that Toulouse-Lautrec suffered from pycnodysostosis? No. Could the diagnosis be made definitively or excluded? Yes. There are two possibilities. If descendants of his sister (who, assuming the diagnosis is correct, would have had a 2 in 3 chance of having inherited one copy of the allele) provided blood samples in which DNA analysis showed the presence of a copy of a mutated cathepsin K gene, it would by inference clinch the historical diagnosis. If descendants were to successfully petition a court for permission to exhume the artist's remains, then DNA analysis of a bone fragment might provide a definitive answer. Dr. Robert Desnick, the physician-researcher who led the team that worked out the molecular basis of pycnodysostosis, thinks that Toulouse-Lautrec was affected with it. He has discussed the possibility of resolving the diagnostic question with the family, but the descendants were reluctant to be tested and have ruled out exhumation of the artist's remains.

Those geneticists who are fond of offering Henri Toulouse-Lautrec as an example of inbreeding gone awry rarely mention the many talented artists among his ancestors. Julia Frey wrote that, "For three generations Henri's forebears had shown a marked artistic talent. His great-grandfather, Jean-Joseph de Toulouse-Lautrec, had done a number of small, but excellent, family portraits." Naturally, since he was a nobleman, that talent served him only as a hobby. It would have been unthinkable for him to become a professional artist. According to family letters, two of Henri's uncles were also gifted amateur painters. There is, of course, no single gene that governs whether one is capable of becoming a talented painter. But Henri was drawing well without benefit of a tutor by age 3. As an adult, his art is all the more impressive given the deformity of his limbs, which surely must have affected his brush strokes. He actually had to use unusually long brushes so he would not have to sit too close to the canvas. Nevertheless, his paintings and sketches are wonderfully vibrant.

Given the family history, it is hard to avoid wondering whether there was also a genetic basis for the Toulouse-Lautrec line's legendary history of alcohol abuse. Fantastic stories of their love of and capacity for drink stretch back through the centuries, but Henri's drinking seemed to eclipse all the ancestral tales. Did his parents' union provide a genetic basis for that predisposition? We will never know. The many well-documented stories of his behavior also suggest that Henri's father suffered from manic-depressive illness. If so, Henri had a fairly good chance (family studies put the risk to sons of affected parents at about 10%) of himself suffering from this disorder, an illness that drives many persons to alcohol abuse. Severe alcohol abuse is encountered more often among those with bipolar disorder than among persons who suffer from depression. Perhaps the

Toulouse-Lautrecs were driven to drink in part to cope with the genetic burden of madness. If so, Henri's alcoholism was not necessarily a response to having inherited the two defective cathepsin K genes that destined him to suffer from pycnodysostosis.

Today, through advances in physical therapy and orthopedic surgery, persons with pycnodysostosis do moderately well. But it seems highly unlikely that another affected person will ever live so on the edge or paint with such fervor or manage to capture the spirit of Paris so well as did Toulouse-Lautrec at the Moulin Rouge. In a span lasting less than 20 years and hampered by physical deformity and severe alcohol abuse, he produced 737 canvases, 275 watercolors, 368 prints and posters, and 5,084 drawings. Almost certainly, he created hundreds of other works that he destroyed or simply left behind in the brothels and dance halls of late 19th century Paris. As one turns the pages of an art book or strolls through the museum at Albi, it is hard to think of Toulouse-Lautrec as a man with a disability.

Czar Nicholas II and his family. (© Illustrated London News/Archive Photos/Picture quest.)

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Alcohol No More

Do you love a drink from time to time? A lot of us do, often when socializing with acquaintances and loved ones. Drinking may be beneficial or harmful, depending upon your age and health status, and, naturally, how much you drink.

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