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
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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.
Researchers documented the most common negative side effects of smoking weed, and who might be most susceptible.
- A team of researchers identified a total of 26 possible adverse reactions to cannabis use.
- Coughing fits, anxiety, and paranoia are among the top three most common adverse reactions to smoking weed.
- It was the people who smoke on a less frequent basis who were more likely to have had the bad experiences.
The most common adverse effects of pot<p>As it turns out, coughing fits are among the top three most common adverse reactions to cannabis use, along with anxiety and paranoia, according to a new study published in the <em>Journal</em><a href="https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-019-0013-x" target="_blank"><em> of Cannabis Research</em></a>. </p><p>Now that weed is legal in the state, a team of researchers at Washington State University sought to document potential negative reactions to cannabis in order to paint a detailed picture of the effects of smoking weed for newbies. The authors surveyed more than 1,500 college students on the specific type and frequency of adverse reactions they had experienced while using pot. Additionally, the students in the study were surveyed about their demographics, personality traits, reasons for using cannabis and their use patterns. </p><p>Despite marijuana's <a href="https://bigthink.com/sex-relationships/marijuana-sex" target="_self">numerous benefits</a>, the team identified a total of <a href="https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-019-0013-x/tables/2" target="_blank">26 possible adverse reactions to</a> the drug. More than half of the study participants reported having coughing fits along with anxiety and/or paranoia while using cannabis. The most frequently occuring of these were the coughing fits, along with chest/lung discomfort and body humming. A subset of the study group reported these reactions occurring around 30–40% of the time they were using pot. On the flip side, the three <em>least</em>-commonly reported reactions to cannabis use were fainting, visual hallucinations and cold sweats. </p><p>"There's been surprisingly little research on the prevalence or frequency of various adverse reactions to cannabis and almost no research trying to predict who is more likely to experience these types of adverse reactions," <a href="https://news.wsu.edu/2020/03/30/new-research-sheds-light-potentially-negative-effects-cannabis/" target="_blank">said Carrie Cuttler</a>, assistant professor of psychology and an author on the paper, according to WSU News. "With the legalization of cannabis in Washington and 10 other states, we thought it would be important to document some of this information so that more novice users would have a better sense of what types of adverse reactions they may experience if they use cannabis."</p><p>The most distressing of the 26 negative reactions were panic attacks, fainting, and vomiting. Yet, the survey data suggested that cannabis users generally do not find even acute adverse reactions to cannabis to be severely distressing.</p>
What causes a bad reaction?<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwOTEwOC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNTQ5MDQ2Mn0.S2Pkbh3VAgB4Gk5tkavamMv0_4t76dg65yGWpCHG17U/img.jpg?width=1245&coordinates=0%2C1872%2C0%2C1252&height=700" id="dee45" class="rm-shortcode" data-rm-shortcode-id="df6e30ecae156ba0012f4773a374800c" data-rm-shortcode-name="rebelmouse-image" />
But most city dwellers weren't seeing the science — they were seeing something out of Blade Runner.
On Sept. 9, many West Coast residents looked out their windows and witnessed a post-apocalyptic landscape: silhouetted cars, buildings and people bathed in an overpowering orange light that looked like a jacked-up sunset.
A study finds 1.8 billion trees and shrubs in the Sahara desert.
- AI analysis of satellite images sees trees and shrubs where human eyes can't.
- At the western edge of the Sahara is more significant vegetation than previously suspected.
- Machine learning trained to recognize trees completed the detailed study in hours.
Why this matters<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2MDQ1OC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzOTkyODg5NX0.O3S2DRTyAxh-JZqxGKj9KkC6ndZAloEh4hKhpcyeFDQ/img.jpg?width=980" id="3770d" class="rm-shortcode" data-rm-shortcode-id="3c27b79d4c0600fb6ebb82e650cabec0" data-rm-shortcode-name="rebelmouse-image" />
Area in which trees were located
Credit: University of Copenhagen<p>As important as trees are in fighting climate change, scientists need to know what trees there are, and where, and the study's finding represents a significant addition to the global tree inventory.</p><p>The vegetation Brandt and his colleagues have identified is in the Western Sahara, a region of about 1.3 million square kilometers that includes the desert, <a href="https://en.wikipedia.org/wiki/Sahel" target="_blank">the Sahel</a>, and the <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/subhumid-zones" target="_blank" rel="noopener noreferrer">sub-humid zones</a> of West Africa.</p><p>These trees and shrubs have been left out of previous tabulations of carbon-processing worldwide forests. Says Brandt, "Trees outside of forested areas are usually not included in climate models, and we know very little about their carbon stocks. They are basically a white spot on maps and an unknown component in the global carbon cycle."</p><p>In addition to being valuable climate-change information, the research can help facilitate strategic development of the region in which the vegetation grows due to a greater understanding of local ecosystems.</p>
Trained for trees<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2MDQ3MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNTk5NTI3NH0.fR-n1I2DHBIRPLvXv4g0PVM8ciZwSLWorBUUw2wc-Vk/img.jpg?width=980" id="e02c0" class="rm-shortcode" data-rm-shortcode-id="79955b13661dca8b6e19007935129af1" data-rm-shortcode-name="rebelmouse-image" />
Credit: Martin Brandt/University of Copenhagen<p>There's been an assumption that there's hardly enough vegetation outside of forested areas to be worth counting in areas such as this one. As a result the study represents the first time a significant number of trees — likely in the hundreds of millions when shrubs are subtracted from the overall figure — have been catalogued in the drylands region.</p><p>Members of the university's Department of Computer Science trained a machine-learning module to recognize trees by feeding it thousands of pictures of them. This training left the AI be capable of spotting trees in the tiny details of satellite images supplied by NASA. The task took the AI just hours — it would take a human years to perform an equivalent analysis.</p><p>"This technology has enormous potential when it comes to documenting changes on a global scale and ultimately, in contributing towards global climate goals," says co-author Christian Igel. "It is a motivation for us to develop this type of beneficial artificial intelligence."</p><p>"Indeed," says Brandt says, "I think it marks the beginning of a new scientific era."</p>
Looking ahead and beyond<p>The researchers hope to further refine their AI to provide a more detailed accounting of the trees it identifies in satellite photos.</p><p>The study's senior author, Rasmus Fensholt, says, "we are also interested in using satellites to determine tree species, as tree types are significant in relation to their value to local populations who use wood resources as part of their livelihoods. Trees and their fruit are consumed by both livestock and humans, and when preserved in the fields, trees have a positive effect on crop yields because they improve the balance of water and nutrients."</p><p>Ahead is an expansion of the team's tree hunt to a larger area of Africa, with the long-term goal being the creation of a more comprehensive and accurate global database of trees that grow beyond the boundaries of forests.</p>
Younger Americans support expanding the Supreme Court and serious political reforms, says new poll.