Scientists Zoom In on Genetic Causes of Inflammatory Bowel Disease

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Study by study, researchers are pushing ever closer toward identifying the gene variants to blame for inflammatory bowel disease (IBD). The latest and most promising findings were published in the journal Nature.

There are two forms of IBD: ulcerative colitis, which affects only the colon and is more common in women; and Crohn's disease, which can affect any part of the gastrointestinal tract and is slightly more common in men. Today, IBD affects between 1 and 1.3 million Americans, yet we understand very little about why it happens or why some groups of people are more susceptible than others.

It's possible and even likely, scientists say, that the root of the illness could lie in our genes. Previous studies have linked IBD to hundreds of different genetic variants, but that's as specific as they could get.

To take a closer look, researchers at three institutions collaborated to build a massive, high-resolution genetic map. They collected the genomes of 67,852 different people—18,967 with Crohn's disease, 14,628 with ulcerative colitis, and 34,257 healthy people for a control group—and combed through, looking for variants unique to the folks with IBD.

Like previous researchers, they found plenty. But the new map was so detailed that its creators could zoom in further and further down, checking how likely it was that any given variant could actually cause the disease. From hundreds, they narrowed it down to just 18 variants, and had at least 95 percent certainty that these were the ones responsible. Some of these gene variants were related to processing amino acids; some seemed to interfere with healthy molecule binding; and some were tied to the switching on and off of immune or gut cells.

"We need to be careful in deciding when we are sure we have the right variant," first author Hailiang Huang, of Massachusetts General Hospital and the Broad Institute, said in a statement. "This new technique helps us to pinpoint which genetic variants are implicated in IBD with greater confidence."

The authors say that isolating IBD-related gene variants will help develop new drugs, and could someday even aid in personalized medicine by helping doctors identify which existing drugs will be most effective for their patients.

Watch: Woman Plays Violin During Brain Surgery to Help Doctors Avoid Damaging Her Fine Motor Skills

Violinist Dagmar Turner played George Gershwin's "Summertime" and other selections during her brain surgery performance.
Violinist Dagmar Turner played George Gershwin's "Summertime" and other selections during her brain surgery performance.
Furtseff/iStock via Getty Images

When 53-year-old Dagmar Turner told neurosurgeons she was right-handed, they said that was no problem—the brain surgery they were planning to remove a tumor only ran the risk of affecting fine motor skills in her left hand. To Turner, a lifelong violinist and member of the Isle of Wight Symphony Orchestra, that was still very much a problem.

Turner told ITV News she suggested playing the violin during the procedure so the surgeons at King’s College Hospital in London could ensure they weren’t damaging coordination in either hand. They agreed.

According to NBC News, the violinist played George Gershwin's “Summertime” and selections by Gustav Mahler and Julio Iglesias while surgeons extracted the tumor from the right frontal lobe of her brain. BBC News reports that she’s been living with the growth since 2013, and doctors decided it was time to operate in November 2019.

You can watch her play in the video below. (The top of Turner’s head is completely obscured by plastic and other surgical materials, so there’s nothing graphic in the clip. Having said that, anyone who’s especially squeamish about the inside of an operating room should proceed with caution.)

Professor Keyoumars Ashkan, a neurosurgeon who helped plan the procedure, said in a statement from the hospital that the mid-surgery performance was a first for him.

“We perform around 400 resections (tumor removals) each year, which often involves rousing patients to carry out language tests, but this was the first time I’ve had a patient play an instrument,” he said. “We managed to remove over 90 percent of the tumor, including all the areas suspicious of aggressive activity, while retaining full function in her left hand.”

[h/t BBC News]

15 Historic Diseases that Competed with Bubonic Plague

Jan Josef Horemans, Interior with a surgeon and his apprentice attending to a patient (1722), Wellcome Collection // CC BY-NC 4.0
Jan Josef Horemans, Interior with a surgeon and his apprentice attending to a patient (1722), Wellcome Collection // CC BY-NC 4.0

In 1665, about a quarter of all Londoners died of the Great Plague—but bubonic plague was not the only deadly disease circulating in the city. A published register, called London’s Dreadful Visitation, or, A Collection of All the Bills of Mortality, recorded the causes of death and the number of victims in London between December 20, 1664 and December 19, 1665. The systematic, parish-by-parish tally reveals the rapid spread of plague throughout the capital: a total of one victim, recorded in the first week, increased to 7165 during the week of September 12-19, 1665.

But quite a few Londoners met their fates in other ways. Here’s a look into the antiquated diseases that managed to kill those that Yersinia pestis couldn’t catch.

1. Winde

Winde is listed throughout the Bills as a constant cause of death. According to the Oxford English Dictionary, winde referred to paroxysms of severe gastrointestinal pain, which could have been symptoms of numerous diseases.

2. Purples

Purples described purple blotches on the skin caused by broken blood vessels, indicative of an underlying illness, such as scurvy or a circulation disorder. It could also mean the most severe stage of smallpox.

3. Livergrown

People who died of livergrown suffered from an enlarged (or failing) liver. Doctors could diagnose it through the combination of other symptoms, like jaundice and abdominal pain. It was commonly a result of alcoholism, but could be caused by a number of disorders.

4. Chrisomes

Infant mortality was extremely high before the advent of modern medicine. The Bills distinguished abortive (miscarried), stillborn, infant, and chrisom deaths—the latter term specified infants who died within the first month of life, around the time they were baptized with special white cloths (which were called chrisomes).

5. Rising of the Lights

18th century illustration of lungs and heart
Jacques-Fabien Gautier d'Agoty, The Lungs and the Heart (1754), Wellcome Collection // CC BY-NC 4.0

Physicians and scholars have debated the origin of the term rising of the lights. According to the OED, the condition indicated any kind of illness characterized by a hoarse cough, difficulty breathing, or a choking sensation. Croup, asthma, pneumonia, and emphysema were all culprits.

6. Timpany

The condition of having serious swelling or bloating in the digestive tract, which produces a hollow sound when tapped, is still called tympany today. The sort that would have proven fatal to humans could have been caused by kidney disease, intestinal infections, or cancerous tumors.

7. Tissick

The term tissick, a corruption of phthisis, originated in ancient Greek and persisted through Latin, French, and English for thousands of years, only to end up an obsolete word referring to a “wasting disease of the lungs,” according to the Online Etymology Dictionary. In the 17th century, that could indicate the wheezing and coughing associated with asthma, bronchitis, or possibly tuberculosis.

8. Meagrome or Megrim

We recognize this obscurely spelled ailment as migraine. During the years of the Great Plague, any internal head trauma, from an aneurysm to a brain tumor, would be filed under megrim.

9. Imposthume

Imposthume was a swelling, cyst, or abscess, usually filled with pus or other putrescence. At the same time that it was being recorded as a cause of death, imposthume took on a metaphorical meaning and referred to an egotistical or corrupt person “swollen” with pride.

10. Head Mould Shot

In newborns, the bony plates of the skull are not fused together, which makes it easier to fit through the birth canal. Head mould shot described a condition where the cranial bones were so compressed by delivery that they overlapped (or overshot) each other and caused fatal pressure on the brain. Today, the condition, now known as craniosynostosis, is treatable with surgery.

11. Quinsie

18th century illustration of a woman getting her throat examined in a pharmacy

Quinsie, which evolved from a Latin word meaning “choke,” is still occasionally used in modern England. It describes a complication of tonsillitis in which an abscess grows between the tonsil and the throat. Unless the abscess was removed, a patient could suffocate from the blockage.

12. Surfeit

A surfeit means an excess of something. In the Bills of Mortality, it’s hard to identify the substance in question. Sometimes, as in the case of King Henry I and his lampreys, it can refer to overeating a food that becomes poisonous if taken in large enough quantities.

13. French Pox

When people across Europe came down with syphilis beginning in the 1490s, they blamed the French. (Perhaps they should have blamed Christopher Columbus and the Spanish, whom historians believe brought the bacterial infection back from the New World.) Rightly or wrongly, French pox is what the Bills of Mortality lists for deaths by advanced syphilis, whose symptoms included rash, blindness, organ failure, and tissue necrosis.

14. Bloody Flux

Dysentery, a.k.a. bloody flux, was common among densely crowded Londoners without clean drinking water. People contracted dysentery from food or water contaminated with one of several pathogens, and its main symptom was bloody diarrhea (the aforementioned flux) and severe dehydration.

15. Plannet

Plannet is likely a shorthand for “planet-struck.” Many medical practitioners believed the planets influenced health and sanity. A person who was planet-stricken had been suddenly maligned by the forces of particular planets. They would likely present symptoms also associated with aneurysms, strokes, and heart attacks.

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