from the world's big
Hypoxia researchers win 2019 Nobel Prize in Medicine
Three scientist friends, working separately, share the prestigious prize.
- 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
Image source: Paramonov Alexander/Shutterstock
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
Image source: Daniel Prudek /Shutterstock
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
Image source: DragonTiger8/Shutterstock
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.
Ever since we've had the technology, we've looked to the stars in search of alien life. It's assumed that we're looking because we want to find other life in the universe, but what if we're looking to make sure there isn't any?
Here's an equation, and a rather distressing one at that: N = R* × fP × ne × f1 × fi × fc × L. It's the Drake equation, and it describes the number of alien civilizations in our galaxy with whom we might be able to communicate. Its terms correspond to values such as the fraction of stars with planets, the fraction of planets on which life could emerge, the fraction of planets that can support intelligent life, and so on. Using conservative estimates, the minimum result of this equation is 20. There ought to be 20 intelligent alien civilizations in the Milky Way that we can contact and who can contact us. But there aren't any.
Building a personal connection with students can counteract some negative side effects of remote learning.
- Not being able to engage with students in-person due to the pandemic has presented several new challenges for educators, both technical and social. Digital tools have changed the way we all think about learning, but George Couros argues that more needs to be done to make up for what has been lost during "emergency remote teaching."
- One interesting way he has seen to bridge that gap and strengthen teacher-student and student-student relationships is through an event called Identity Day. Giving students the opportunity to share something they are passionate about makes them feel more connected and gets them involved in their education.
- "My hope is that we take these skills and these abilities we're developing through this process and we actually become so much better for our kids when we get back to our face-to-face setting," Couros says. He adds that while no one can predict the future, we can all do our part to adapt to it.
Frequent shopping for single items adds to our carbon footprint.
- A new study shows e-commerce sites like Amazon leave larger greenhouse gas footprints than retail stores.
- Ordering online from retail stores has an even smaller footprint than going to the store yourself.
- Greening efforts by major e-commerce sites won't curb wasteful consumer habits. Consolidating online orders can make a difference.
A pile of recycled cardboard sits on the ground at Recology's Recycle Central on January 4, 2018 in San Francisco, California.
Photo by Justin Sullivan/Getty Images<p>A large part of the reason is speed. In a competitive market, pure players use the equation, <em>speed + convenience</em>, to drive adoption. This is especially relevant to the "last mile" GHG footprint: the distance between the distribution center and the consumer.</p><p>Interestingly, the smallest GHG footprint occurs when you order directly from a physical store—even smaller than going there yourself. Pure players, such as Amazon, are the greatest offenders. Variables like geographic location matter; the team looked at shopping in the UK, the US, China, and the Netherlands. </p><p>Sadegh Shahmohammadi, a PhD student at the Netherlands' Radboud University and corresponding author of the paper, <a href="https://www.cnn.com/2020/02/26/tech/greenhouse-gas-emissions-retail/index.html" target="_blank">says</a> the above "pattern holds true in countries where people mostly drive. It really depends on the country and consumer behavior there."</p><p>The researchers write that this year-and-a-half long study pushes back on previous research that claims online shopping to be better in terms of GHG footprints.</p><p style="margin-left: 20px;">"They have, however, compared the GHG emissions per shopping event and did not consider the link between the retail channels and the basket size, which leads to a different conclusion than that of the current study."</p><p>Online retail is where convenience trumps environment: people tend to order one item at a time when shopping on pure player sites, whereas they stock up on multiple items when visiting a store. Consumers will sometimes order a number of separate items over the course of a week rather than making one trip to purchase everything they need. </p><p>While greening efforts by online retailers are important, until a shift in consumer attitude changes, the current carbon footprint will be a hard obstacle to overcome. Amazon is trying to have it both ways—carbon-free and convenience addicted—and the math isn't adding up. If you need to order things, do it online, but try to consolidate your purchases as much as possible.</p><p>--</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
Chronic irregular sleep in children was associated with psychotic experiences in adolescence, according to a recent study out of the University of Birmingham's School of Psychology.