- Nobel recognizes breakthrough insights into cell's perception and response to changes in oxygen levels.
- Too title oxygen is a problem. Also too much.
- Their research unveiled a genuine "textbook discovery."
The 2019 Nobel Prize in Medicine has just been awarded to three scientists from the U.S. and U.K. working independently on the same problem: How cells sense and adapt to oxygen availability. They've unveiled the series of molecular events that allow cells to assess and respond to changing levels of available oxygen, with implications in the treatment of cancer, heart attacks, strokes, anemia, and other diseases.
According to the Nobel Assembly, these seminal discoveries "revealed one of life's most essential adaptive processes." The Assembly's Randall Johnson says, "Scientists often toss around this phrase 'textbook discovery.' But I'd say this is really essentially a textbook discovery." He envisions the discovery as "something basic biology students will be learning about when they study — at aged 12 or 13 or younger — biology, and learn the fundamental ways cells work."
Three scientists with three questions
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The three scientists who received the 5 a.m. call from Stockholm are Gregg Semenza (Johns Hopkins University), Sir Peter Ratcliffe (Oxford University), and William Kaelin, Jr. (Dana-Farber Cancer Institute/Harvard University). The three shared their work informally over the years in an ongoing conversation that moved the whole field of study forward. Each had his own reason for pursuing his research area, and their interests reflect the far-ranging impact of their findings.
Semenza wondered exactly what it was that cancer cells were seeking when they spread to new areas in the body. He suspected it was oxygen.
As a kidney specialist, Ratcliffe was intrigued by the manner in which the kidney regulated the production of a particular hormone, erythropoietin (EPO), which affects the production of red, oxygen-carrying blood cells in response to changes in levels of available oxygen. Others considered this to be a not-very-interesting question, but Ratcliffe was intrigued.
For Kaelin, it was a pursuit of answers behind a rare genetic form of cancer, Von Hippel-Lindau syndrome (VHL disease), known to involve exaggerated production levels of EPO, and an excess of blood vessels. He had a hunch it was something in cells' then-mysterious oxygen-sensing mechanism malfunctioning.
Why this is important
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Cells need oxygen to live, and Earth's air-breathing organisms have developed ways to ensure their cells get the amount of oxygen they need. At high altitudes, for example, we produce more red blood cells to accommodate the relative scarcity of air and combat the onset of hypoxia. While a lack of oxygen can be deadly, so too can too much — it may be that an excess of oxygen can be exploited by some cancers, among other issues.
Human bodies have developed a couple of ways to monitor and respond to changes in oxygen levels. The carotid body associated with the large vessels on both sides of the neck have unique cells that sense oxygen levels, and, as noted above, the body produces more oxygen-carrying cells to maximize delivery of what O2 there is when there's not enough. Production of these oxygen-carrying cells is triggered by the production of erythropoietin (EPO) — it's this system that the Nobel winners explored.
A technical glimpse into a three-part puzzle
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The research that led to the Nobel-awarded discovery began back in the 1990s when, Semenza started studying the EPO gene to learn how its production was being controlled. He identified a DNA segment near the EPO gene that appeared to be regulating its production in response to hypoxia. Most interestingly, this DNA, also spotted around the same time by Ratcliffe, wasn't only in kidney cells known to produce EPO, but in all cells.
Eventually Semenza discovered a protein complex that binds to the DNA depending on the amount of oxygen available, and named it hypoxia-inducible factor, or HIF. HIF turned out to be a pair of different DNA-binding proteins, HIF-1α and ARNT.
The amount of HIF-1α increases when oxygen levels are low, apparently due to an oxygen-related reduction in the effect of ubiquitin, a peptide that normally would bind with and quickly decay HIF-1α.
As a result of his immersion in Von Hippel-Lindau research, Ratcliffe discovered why a lack of oxygen could dampen ubiquitin's bite: HIF-1α is tagged for destruction by ubiquitin via the VHL gene. (An absence of the VHL gene causes the disease by allowing the presence of too much HIF-1α.)
This implied an unknown interaction between the VHL gene and HIF-1α and Kaelin and Ratcliffe worked it out. They realized that at normal oxygen levels, two hydroxyl groups were added to two locations in HIF-1α. Aided by oxygen-sensitive enzymes, VHL thus binds to HIF-1α and moderates the production of EPO and the number red blood cells. With either too little or too much oxygen, this balance is upset.
In all, this daisy-chained sets of research has given us a new insight about our bodies — specifically, of the series of molecular events that constantly help our cells assess and respond to changing levels of oxygen. "Textbook discovery," indeed.
We're learning more new things about death everyday. Much has been said and theorized about the great divide between life and the Great Beyond. While everyone and every culture has their own philosophies and unique ideas on the subject, we're beginning to learn a lot of new scientific facts about the deceased corporeal form.
An Australian scientist has found that human bodies move for more than a year after being pronounced dead. These findings could have implications for fields as diverse as pathology to criminology.
Dead bodies keep moving
Credit: Flickr
Researcher Alyson Wilson studied and photographed the movements of corpses over a 17 month timeframe. She recently told Agence France Presse about the shocking details of her discovery.
Reportedly, she and her team focused a camera for 17 months at the Australian Facility for Taphonomic Experimental Research (AFTER), taking images of a corpse every 30 minutes during the day. For the entire 17 month duration, the corpse continually moved.
"What we found was that the arms were significantly moving, so that arms that started off down beside the body ended up out to the side of the body," Wilson said.
The researchers mostly expected some kind of movement during the very early stages of decomposition, but Wilson further explained that their continual movement completely surprised the team:
"We think the movements relate to the process of decomposition, as the body mummifies and the ligaments dry out."
During one of the studies, arms that had been next to the body eventually ended up akimbo on their side.
The team's subject was one of the bodies stored at the "body farm," which sits on the outskirts of Sydney. (Wilson took a flight every month to check in on the cadaver.)
Her findings were recently published in the journal, Forensic Science International: Synergy.Implications of the study
The researchers believe that understanding these after death movements and decomposition rate could help better estimate the time of death. Police for example could benefit from this as they'd be able to give a timeframe to missing persons and link that up with an unidentified corpse. According to the team:
"Understanding decomposition rates for a human donor in the Australian environment is important for police, forensic anthropologists, and pathologists for the estimation of PMI to assist with the identification of unknown victims, as well as the investigation of criminal activity."
While scientists haven't found any evidence of necromancy. . . the discovery remains a curious new understanding about what happens with the body after we die.
Warp speed!
Ah, the warp drive, that darling of science fiction plot devices. So, what about a warp drive? Is that even a really a thing?
Let's start with the "warping" part of a warp drive. Without doubt, Albert Einstein's theory of general relativity ("GR") represents space and time as a 4-dimensional "fabric" that can be stretched and bent and folded. Gravity waves, representing ripples in the fabric of spacetime, have now been directly observed. So, yes spacetime can be warped. The warping part of a warp drive usually means distorting the shape of spacetime so that two distant locations can be brought close together — and you somehow "jump" between them.
This was a basic idea in science fiction long before Star Trek popularized the name "warp drive." But until 1994, it had remained science fiction, meaning there was no science behind it. That year, Miguel Alcubierre wrote down a solution to the basic equations of GR that represented a region that compressed spacetime ahead of it and expanded spacetime behind to create a kind of traveling warp bubble. This was really good news for warp drive fans.
The problems with a warp drive
There were some problems though. Most important was that this "Alcubierre drive" required lots of "exotic matter" or "negative energy" to work. Unfortunately, there's no such thing. These are things theorists dreamed up to stick into the GR equations in order to do cool things like make stable open wormholes or functioning warp drives.
It's also noteworthy that researchers have raised other concerns about an Alcubierre drive — like how it would violate quantum mechanics or how when you arrived at your destination it would destroy everything in front of the ship in an apocalyptic flash of radiation.
Warp drives: A new hope
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Recently, however, there seemed to be good news on the warp drive front with the publication this April of a new paper by Alexey Bobrick and Gianni Martre entitled "Introducing Physical Warp Drives." The good thing about the Bobrick and Martre paper was it was extremely clear about the meaning of a warp drive.
Understanding the equations of GR means understanding what's on either side of the equals sign. On one side, there is the shape of spacetime, and on the other, there is the configuration of matter-energy. The traditional route with these equations is to start with a configuration of matter-energy and see what shape of spacetime it produces. But you can also go the other way around and assume the shape of spacetime you want (like a warp bubble) and determine what kind of configuration of matter-energy you will need (even if that matter-energy is the dream stuff of negative energy).
Warp drives are simpler and much less mysterious objects than the broader literature has suggested.
What Bobrick and Martre did was step back and look at the problem more generally. They showed how all warp drives were composed of three regions: an interior spacetime called the passenger space; a shell of material, with either positive or negative energy, called the warping region; and an outside that, far enough away, looks like normal unwarped spacetime. In this way they could see exactly what was and was not possible for any kind of warp drive. (Watch this lovely explainer by Sabine Hossenfelder for more details). They even showed that you could use good old normal matter to create a warp drive that, while it moved slower than light speed, produced a passenger area where time flowed at a different rate than in the outside spacetime. So even though it was a sub-light speed device, it was still an actual warp drive that could use normal matter.
That was the good news.
The bad news was this clear vision also showed them a real problem with the "drive" part of the Alcubierre drive. First of all, it still needed negative energy to work, so that bummer remains. But worse, Bobrick and Martre reaffirmed a basic understanding of relativity and saw that there was no way to accelerate an Alcubierre drive past light speed. Sure, you could just assume that you started with something moving faster than light, and the Alcubierre drive with its negative energy shell would make sense. But crossing the speed of light barrier was still prohibited.
So, in the end, the Star Trek version of the warp drive is still not a thing. I know this may bum you out if you were hoping to build that version of the Enterprise sometime soon (as I was). But don't be too despondent. The Bobrick and Martre paper really did make headway. As the authors put it in the end:
"One of the main conclusions of our study is that warp drives are simpler and much less mysterious objects than the broader literature has suggested"
That really is progress.
Late Medieval England had its share of problems. The Wars of Roses raged, the Black Death killed off large parts of the population, and passing ruffians could say "Ni" at will to old ladies.
To make matters worse, a first of its kind study published in the International Journal of Paleopathology has demonstrated that much of the population suffered from another plague — a plague of bunions likely caused by a ridiculous medieval fashion trend.
If the shoe fits, it won't cause bunions
The outlines of a leather shoe from the King's Ditch, Cambridge. It is easy to see how these shoes might be constricting. Copyright Cambridge Archaeological Unit.
The bunion, known to medicine as "hallux valgus," is a deformity of the joint connecting the big toe to the rest of the foot. It is painful and can cause other issues including poor balance. The condition is associated with having worn constrictive shoes for a long period of time as well as genetic factors. Today, it is often caused by wearing high heeled shoes.
The medieval English didn't care for high heeled shoes as much as modern fashionistas, but there was a major fashion trend toward shoes with long, pointed toes called "poulaines" or "crakows" for their supposed place of origin, Krakow, Poland.
This trend, already silly-looking to a modern observer, got out of hand in a hurry. According to some records, the points on nobleman's shoes could be so long as to require tying them to the leg with string so the wearer could walk. At one point, King Edward IV had to ban commoners from wearing points longer than two inches. A couple years later, he saw fit to ban the shoes altogether.
But, just knowing that people back in the day made poor fashion choices doesn't prove they suffered for it. That is where digging up old skeletons to look at their feet comes in.
Beauty is pain: the price of high medieval fashion
To learn how bad the bunion epidemic was, the researchers looked to four burial sites in and around Cambridge. One was a rural cemetery where poor peasants were buried. Another was the All Saints by the Castle parish, which had a mixed collection of people that tended toward poverty. The Hospital of St. John's burial ground contained both the poor charges of a charity hospital and wealthy benefactors. Lastly, they considered the cemetery of a local Augustinian friary, home to monks and well-to-do philanthropists.
The team considered 177 adult skeletons that were at least a quarter complete and still had enough of their feet to make studying them possible. The remains were classified by age and sex by observation and DNA testing. Each was examined for evidence of bunions and signs of complications from the condition, such as falling.
Those buried in the monastery's graveyard were the most affected. Nearly half, 43 percent, of the remains found there had bunions. This includes five of the eleven members of the clergy they found. Twenty-three percent of those laid to rest at the Hospital of St. John had bunions, though only 10 percent of those at the All Saints by the Castle parish graveyard did.
The rural cemetery had a much lower rate of instances, only three percent, suggesting that these peasants were able to avoid at least one plague.
Overall, eighteen percent of the individuals examined had bunions, with men more likely to have them than women. Those at cemeteries known for exclusivity were more likely to have them as well, though it is clear that the condition also affected members of other classes. This makes sense, as it is known that these shoes had mass appeal.
The authors note that the rural cemetery having fewer cases is partly because that cemetery "went out of use prior to the wide adoption of pointed shoes, and it is likely that those residing in the parish predominately wore soft leather shoes, or possibly went barefoot."
Those skeletons with evidence of bunions were more likely to have fractures indicative of a fall. This was more common on those estimated or recorded as having lived past age 45.
In our much more enlightened times, 23 percent of the population currently endures having bunions, most of them women, and one of the leading culprits behind this is the high heeled shoe.
Some things never change.
