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The Uterus: A Natural History

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The human body is an amazing thing. For each one of us, it’s the most intimate object we know. And yet most of us don’t know enough about it: its features, functions, quirks, and mysteries. That’s why we’re launching a new series called The Body, which will explore human anatomy, part by part. Think of it as a mini digital encyclopedia with a dose of wow.
 

At only 3 inches long and weighing about 60 grams, the uterus isn’t a flashy, attention-grabbing organ. When it comes to human health, the heart usually comes first, followed by the brain, then perhaps the digestive system. Yet the uterus plays an outsized role. It’s the carrier of all life, the subject of scrutiny in political forums, and a source of delight and despair for sexually mature women. It causes bleeding and pain, allows 211 million women to get pregnant every year, and is partially responsible for the 10 to 20 percent of those pregnancies that end in miscarriage.

Despite its ability to create life, there are dozens of crucial things we have yet to learn about the uterus. At least we’ve abandoned the theory that it travels freely around the body, causing hysteria, and that it can be manipulated by smelling salts.

Today we know the uterus sits low in the abdomen, held in place by muscles and ligaments. It is connected to the vagina by the cervix and receives unfertilized eggs from the ovaries via the fallopian tubes, which are connected to both sides of the uterus. It expands from 3 inches to the size of a watermelon by the end of a pregnancy in order to hold the baby and placenta—and, luckily for new mothers, naturally deflates about six weeks after the child is born.

But how did we develop this organ, how does it operate—or malfunction—in the body, and what's the outlook for the future?

THE EXTRAORDINARY EVOLUTION OF THE MAMMALIAN UTERUS

Until recently, scientists didn’t even understand how mammals evolved uteruses that allowed for live birth. Soft tissue is rarely preserved in the fossil record, which means scientists can study the bone structure of past organisms but are often left guessing when it comes to organs.

Up until marsupial ancestors appeared 220 million years ago, new life came out of eggs. Before that time, even the earliest mammalian predecessors, the group called monotremes (like echidnas and platypuses) were still laying eggs. But by 105 million years ago, placental mammals had evolved elaborate uteruses that allowed for invasive placentas, maternal tolerance of the fetus, and long gestation periods. What caused this evolution? Why did mammals suddenly appear?

In 2015, a team of researchers from the University of Chicago, Yale, and several other universities found a major clue in the hunt to discover the origin of mammals: genetic parasites. Called transposons, these snippets of non-protein-coding DNA regularly changed positions in the genome, an action called “jumping genes.” The leap-frogging transposons caused genes from other tissues—like the brain and digestive system—to be activated in the uterus. As more and more genes were expressed in the uterus, organisms shifted from producing eggs to giving live birth. The shift began sometime between 325 and 220 million years ago with the appearance of monotremes, and continued for hundreds of millions of years until placental mammals appeared, sometime between 176 and 105 million years ago.

During the genetic shift, more than 1000 genes turned on in therians, common ancestors to marsupials and placental mammals (like us). Many of these genes related to maternal-fetal communication, and especially the suppression of the maternal immune system in the uterus so it didn't reject the developing fetus. Because many of the transposons had progesterone binding sites that regulated the process, the uterus evolved to be extremely sensitive to that hormone (which is produced by the ovaries during the release of a mature egg; it prepares the uterine lining to receive a fertilized egg). The study appeared in the journal Cell Reports. In a press statement, Vincent Lynch, one of the study’s authors, said the discovery shed light on how “something completely novel evolves in nature.”

“It’s easy to imagine how evolution can modify an existing thing, but how new things like pregnancy evolve has been much harder to understand,” Lynch continued. “We now have a new mechanistic explanation of this process that we’ve never had before.”

THE MYSTERIES OF MENSTRUATION

While live birth defines mammals, including everything from whales to dogs to bats, there’s one thing that sets humans apart from most other species: menstruation. We’re part of an exclusive club that’s limited to old world primates, elephant shrews, and fruit bats. All other species remodel and reabsorb the endometrium, or uterine lining. So why do humans have to deal with the hassle of a period? Scientists aren’t quite sure. One theory is that the process protects us from abnormal pregnancies. The human gestation period is so long and requires so many biological resources that it’s better to reject all but the best candidates. And the reason we have periods is far from the only thing we don’t understand about menstruation.

“There is so much we don’t know,” says Hilary Critchley, OB/GYN and professor of reproductive sciences at the University of Edinburgh. “Not only why do we have normal periods, but particularly why does a woman have heavier periods?” Critchley and her colleagues published a paper that compiled years’ worth of studies in Human Reproduction Update in July 2015. They found far more questions than answers. Their research confirmed what is known: that a decline in progesterone triggers menstruation, and that the endometrial coagulation system plays a part in stopping the bleeding. But plenty of questions remain about the mechanics of the process.

Doctors don’t know what regulates inflammation during menstruation, what causes the bleeding to stop, or how the uterus repairs itself so quickly without creating any scar tissue. They also don’t understand the causes of diseases associated with menstruation, like polycystic ovary syndrome and endometriosis. Neither currently has a cure, and they afflict around 1 in 10 women. In the most extreme cases of endometriosis, women have no choice but to undergo hysterectomies.

“If you’re in the workforce, period problems can be really embarrassing and really difficult to deal with. This is where I see the unmet need for new treatments,” Critchley tells mental_floss. “A woman now has 400 periods in a lifetime. A woman (100 years ago) had 40. If you’ve got more periods, you’ve got more opportunity for it to be a problem.” This increase in the number of periods by a factor of 10 in the past 100 years is due to contraception and improved nutrition. The downside is that's a lot more opportunity for menstruation to cause problems.

GROWING AN EXTRA ORGAN TO MAKE A BABY

Menstruation isn’t the only area of female reproductive health that has researchers scratching their heads. Perhaps even more confounding is the placenta, a transient organ created during pregnancy by the embryo.

“I’d say the placenta is probably the least studied and the least understood organ in the body,” says Catherine Spong, acting director of the National Institute of Child and Human Development. She oversees the Human Placenta Project (HPP), which aims to develop new tools to monitor the placenta throughout its development. “If you could understand how the placenta allows two genetically distinct entities not only to grow, but also thrive, the implications for enhancing our understanding of immunology and transplant medicine would be pretty remarkable.”

Stacy Zamudio, a recipient of a grant from the HPP and director of research at Hackensack University Medical Center, calls the placenta “the most wonderful organ ever.” Her research focuses on placenta accreta (when the placenta grows too deeply into the mother’s uterine wall and even outside organs).

“It breathes, it produces hormones, it produces immunologic factors that protect the baby against infection. It acts like a skin, a liver, a kidney, a lung—it does all the functions of the other organs in one organ,” Zamudio says.

Human Placenta Project

The placenta achieves this by hooking into arteries in the uterus, essentially hijacking the mother’s body so the embryo can have a constant stream of nutrients and oxygen as it develops. When it’s functioning normally, the placenta ensures a positive outcome: healthy baby, healthy mother. But when things go wrong with the placenta, they quickly go from bad to worse.

The placenta can be under-invasive, meaning the connection to the mother’s blood isn’t strong enough. The baby stops developing because it’s not getting nutrients, and in the worst cases the mother can suffer from preeclampsia, which causes life-threateningly high blood pressure and can only be treated by immediate delivery of the baby. Or, as with the cases Zamudio studies, the placenta can be over-invasive, infiltrating the uterus and other organs beyond it like a cancer. Finally, in a complication known as placental abruption, the placenta can peel away from the uterus before delivery, removing the baby’s source of oxygen and nutrients and causing heavy bleeding in the mother.

Pregnancy can be a dangerous balancing act, and if doctors had better ways of monitoring the placenta’s development over the course of pregnancy, they might be able to prevent or avert the worst outcomes.

FROM WOMB TRANSPLANTS TO TRICORDERS

In October 2014, a baby born to a Swedish couple became an exciting example of the possible future of maternity—he was the first child ever born of a transplanted uterus. (The first pregnancy from a womb transplant, in Turkey, was terminated in 2013 when the fetus had no heartbeat.) The 36-year-old mother, who was herself born without a uterus, received a donation from a woman in her 60s, and had a frozen embryo successfully implanted in the transplanted organ. Although the child was born prematurely, he and the mother were otherwise healthy after the pregnancy. Since then, four more women who received uterus transplants from doctors at the University of Gothenburg have gotten pregnant. 

The pioneering surgery is now spreading across the world. Doctors at Cleveland Clinic performed the first successful uterus transplant in the U.S. just last week. The 9-hour surgery was performed on a 26-year-old patient with uterine factor infertility (an irreversible condition affecting 3 to 5 percent of women that prevents pregnancy). If the patient heals and can become pregnant, the surgery could offer new hope to women who previously thought they were doomed to infertility.

Despite the enormous advances made in the last decades concerning women's health, many questions about the uterus remain unanswered. Scientists don’t know why the placenta sometimes grows too little or too much, or how it communicates with the rest of the organs in the mother’s body. They don’t know why some women have debilitating cramps during their periods that have been likened to the pain of having a heart attack. But with scientists around the globe investing time and resources into such questions, it might not be long before we have real answers and solutions to these problems.

"We're not that far away from the tricorder in Star Trek," Zamudio says, referring to developing technologies like nanomagnetics. "I'm hoping that I'll be alive long enough to see a doctor be able to wave the instrument over the woman's abdomen and tell me what the glucose level is in that body."

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Scientists Accidentally Make Plastic-Eating Bacteria Even More Efficient
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In 2016, Japanese researchers discovered a type of bacteria that eats non-biodegradable plastic. The organism, named Ideonella sakaiensis, can break down a thumbnail-sized flake of polyethylene terephthalate (PET), the type of plastic used for beverage bottles, in just six weeks. Now, The Guardian reports that an international team of scientists has engineered a mutant version of the plastic-munching bacteria that's 20 percent more efficient.

Researchers from the U.S. Department of Energy's National Renewable Energy Laboratory and the University of Portsmouth in the UK didn't originally set out to produce a super-powered version of the bacteria. Rather, they just wanted a better understanding of how it evolved. PET started appearing in landfills only within the last 80 years, which means that I. sakaiensis must have evolved very recently.

The microbe uses an enzyme called PETase to break down the plastic it consumes. The structure of the enzyme is similar to the one used by some bacteria to digest cutin, a natural protective coating that grows on plants. As the scientists write in their study published in the journal Proceedings of the National Academy of Sciences, they hoped to get a clearer picture of how the new mechanism evolved by tweaking the enzyme in the lab.

What they got instead was a mutant enzyme that degrades plastic even faster than the naturally occurring one. The improvement isn't especially dramatic—the enzyme still takes a few days to start the digestion process—but it shows that I. sakaiensis holds even more potential than previously expected.

"What we've learned is that PETase is not yet fully optimized to degrade PET—and now that we've shown this, it's time to apply the tools of protein engineering and evolution to continue to improve it," study coauthor Gregg Beckham said in a press statement.

The planet's plastic problem is only growing worse. According to a study published in 2017, humans have produced a total of 9 billion tons of plastic in less than a century. Of that number, only 9 percent of it is recycled, 12 percent is incinerated, and 79 percent is sent to landfills. By 2050, scientists predict that we'll have created 13 billion tons of plastic waste.

When left alone, PET takes centuries to break down, but the plastic-eating microbes could be the key to ridding it from the environment in a quick and safe way. The researchers believe that PETase could be turned into super-fast enzymes that thrives in extreme temperatures where plastic softens and become easier to break down. They've already filed a patent for the first mutant version of the enzyme.

[h/t The Guardian]

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15 Overlooked Facts about Rosalind Franklin
Robin Stott, via Flickr // CC BY-SA 2.0
Robin Stott, via Flickr // CC BY-SA 2.0

Today is the 60th anniversary of the death of English chemist Rosalind Franklin, a brilliant and dedicated scientist best known for the honor denied her: the 1962 Nobel Prize for discovering the structure of DNA. Here are 15 facts about her.

1. SHE KNEW HER CALLING EARLY, BUT HER FATHER RESISTED EDUCATING A DAUGHTER.

Rosalind Elsie Franklin was born in London in 1920. She was one of five children born into a wealthy Jewish family. She decided she wanted to become a scientist at 15, and passed the admissions exam for Cambridge University. However, her father, Ellis, a merchant banker, objected to women going to college and refused to pay her tuition. Her aunt and mother finally managed to change his mind, and she enrolled at Cambridge's all-female Newnham College in 1938.

2. SHE ATTENDED COLLEGE WITH ANOTHER WOMAN WHO DIDN'T GET FULL CREDIT FOR HER WORK.

Bletchley Park cryptanalyst Joan Clarke was a few years older than Franklin, but they were both at Newnham in the late 1930s. Clarke would go on to be recruited for the war effort, cracking the German Enigma codes. The full scope of Clarke's work is still unknown, due to government secrecy.

3. HER SCHOLASTIC ACHIEVEMENTS WERE DENIED BY HER UNIVERSITY FOR YEARS.

Newnham College, Cambridge
Azeira, Wikimedia Commons // Public Domain

Despite Newnham College having been at Cambridge since 1871, the university refused to accept women as full members until 1948, seven years after Franklin earned the title of a degree in chemistry. Oxford University started granting women's degrees in 1920.

4. HER RESEARCH ON COAL HELPED THE AEROSPACE INDUSTRY.

After graduation, Franklin got a job at the British Coal Utilization Research Association (BCURA), where she researched coal and charcoal, and how it could be used for more than fuel. Her research formed the basis for her 1945 doctoral dissertation; it and several of her later papers on the micro-structures of carbon fibers played a role in the eventual use of carbon composites in air- and spacecraft construction.

5. HER MALE COLLEAGUES WERE HOSTILE AND UNDERMINED HER RESEARCH.

Franklin had a direct nature and was unwilling to be traditionally feminine. One reason she left Cambridge to work on coal was that her doctoral supervisor did not like her and believed women would always be less than men. When she was hired in 1951 at King's College, London, to work on DNA, she clashed with researcher Maurice Wilkins, who had thought she was his assistant, not his equal. Meanwhile, Franklin was under the impression that she'd be completely independent. Their relationship got worse and worse the longer they worked together. Wilkins went so far as to share Franklin's research without telling her with James Watson and Francis Crick—even though they were technically his competitors, funded by Cambridge University. Watson was particularly nasty about Franklin in his 1968 book, The Double Helix, criticizing her appearance and saying she had to be “put in her place.”

6. HOW EVENTS UNFOLDED IN THE DISCOVERY OF DNA'S STRUCTURE IS STILL DEBATED TODAY.

Double helix of DNA
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Many books have been written hashing over events, either criticizing Watson and Crick, saying they stole Franklin's research, or defending the duo, saying her research helped them but that Franklin would not ultimately have reached their conclusions on her own. Though Franklin and Watson never became friendly, Crick and his wife welcomed Franklin into their home while she was being treated for ovarian cancer.

7. HER WORK MAY HAVE LED TO HER UNTIMELY DEATH.

Franklin died of cancer in 1958. She was 37. Though genetics likely played a part in her illness, her work with crystal x-ray diffraction, which involved constant exposure to radiation, did not help. She is not the first woman in science to risk her health for her research. Marie Curie died from aplastic anemia, which has been tied to radiation exposure. Many of Curie's personal belongings, including her cookbooks, are too radioactive to handle even today.

8. HAD SHE LIVED LONGER, SHE MAY HAVE QUALIFIED FOR MORE THAN ONE NOBEL PRIZE.


Maurice Wilkins (on left), Francis Crick (third from left), and James Watson (fifth from left) accept their Nobel Prize in 1962.
Keystone, Getty Images

The first, of course, would have been awarded with Watson, Crick, and Wilkins, had they been made to share credit with her. (Pierre Curie had to ask the Nobel Committee to add his wife to the nomination in 1903.) As for the second, chemist Aaron Klug won the prize in 1982, carrying on work he and Franklin had started on viruses in 1953, after she left King's College. Because of the rules at the time of her death about awarding prizes posthumously (and in 1974 all posthumous awards were eliminated, the sole exception being in 2011), Franklin has none.

9. DESPITE BEING DENIED HER PRIZE, SHE'S BEEN HONORED BY MANY ACADEMICS.

In 2004, the Chicago Medical School renamed itself the Rosalind Franklin University of Medicine and Science. She has also had a number of academic programs, auditoriums, and labs named for her. In 2013, Newnham College principal Dame Carol Black helped install a plaque commemorating Franklin at the Eagle Pub in Cambridge. Crick and Watson, who already had a plaque in the pub, drank there often while working on the DNA project, and allegedly boasted about discovering “the secret of life” to other patrons.

10. SHE IS THE SUBJECT OF SEVERAL BIOGRAPHIES.

The first, 1975's Rosalind Franklin and DNA, was written by her friend Anne Sayre, largely as a reaction to Watson's The Double Helix. In 2002, Brenda Maddox published Rosalind Franklin: The Dark Lady of DNA.

11. AN OBJECT IN SPACE IS NAMED AFTER HER.

In 1997, amateur Australian astronomer John Broughton discovered an asteroid, which he named 9241 Rosfranklin.

12. AT LEAST ONE HISTORY RAP BATTLE IS ABOUT HER.

It was produced by seventh graders in Oakland, California (with some help from teacher Tom McFadden). And it is delightful.

13. SHE HAS BEEN IMMORTALIZED ON THE SMALL SCREEN AND THE BIG STAGE.

In 1987, BBC's Horizon series aired The Race for the Double Helix, starring Juliet Stevenson as Franklin. Jeff Goldblum played Watson. In 2011, playwright Anna Ziegler premiered a one-act about Franklin called Photograph 51. It opened on the West End in 2015, starring Nicole Kidman as Franklin.

14. THE 2015 RUN OF PHOTOGRAPH 51 RE-IGNITED THE OLD CONTROVERSY.

While Kidman got much praise from critics for her turn as Franklin in Photograph 51, Maurice Wilkins' friends and former colleagues have taken exception to a scene where Wilkins takes a photograph—the titular Photo 51, which showed evidence of DNA's structure—from Franklin's desk when she isn't there, saying he would never have done something so dishonorable.

15. THE PLAY MAY COME TO THE BIG SCREEN IN THE NEXT FEW YEARS.

In 2016, the West End production's director, Michael Grandage, told The Hollywood Reporter that he hopes to turn the play into a film, with Kidman reprising the role.

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