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.
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.
India finishes last of 60 countries in environment and sustainability, as ranked by the expats who work there.
- How 'green' is life in your work country?
- That's the question InterNations asked its network of expats.
- The United States ended 30th out of 60 countries.
Nordics on top<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2NjgyNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NTczNzkyOX0.VgfqyjAa9avw6gFOE0qlgSgKuBN7DJmzOc5lzFGLm8g/img.jpg?width=980" id="1f0dc" class="rm-shortcode" data-rm-shortcode-id="b27458cf472d26cf1f87cb91623a0621" data-rm-shortcode-name="rebelmouse-image" alt="Evo Hiking Area, H\u00e4meenlinna, Finland." />
Evo Hiking Area in Hämeenlinna, Finland. Great nature, clean air, clean water? Check, check and check.
Credit: Kanta-Hämeen kuvapankki on Flickr/ Public Domain.<p><br><strong>1. Finland</strong></p><p>The Nordic country scores at or near the top in all categories surveyed, including the quality of the natural environment (say 96 percent of expats in Finland), water and sanitation (96 percent) and air (95 percent). <br></p><p><strong>2. Sweden</strong></p><p>Swedes lead the world in environmental awareness (84 percent versus just 48 percent globally). Perhaps not surprising, for the homeland of <a href="https://bigthink.com/politics-current-affairs/greta-effect" target="_blank">Greta Thunberg</a>. This is reflected by government policy. Sweden currently gets more than 50 percent of its power from renewable sources and wants to go 100% renewable before 2040. "I've been here for over 20 years and I clearly see the benefits of my taxes paid coming back to me and the rest of society," says one American expat.<br></p><p><strong>3. Norway</strong></p><p>"The beautiful nature, the clean air and tap water, and the focus on the environment," are what one Ukrainian expat enjoys most about Norway. With 76 percent of expats happy with the availability of green goods and services, Norway's 'weakest' category is still 13 percentage points above the global average. <br></p><p><strong>4. Austria</strong></p><p>The first non-Nordic in the global ranking, Austria places in the Top 10 for each category and comes in first for the availability of green goods and services (90 percent). <br></p><p><strong>5. Switzerland</strong></p><p>Swiss nature is the most appreciated in the world (98 percent versus 83 percent on average). Switzerland also gets stellar results for air and water quality and the availability of green energy and green goods and services. </p><p><strong>6. Denmark</strong></p><p>Danes are very much into green causes, as is their government, say 83 percent resp. 84 percent of expats. "Organic food is readily available, and they are good with recycling," observes a South African expat. And they love cycling: 9 out of 10 Danes own a bike.</p><p><strong>7. New Zealand</strong></p><p>85 percent of expats agree that the New Zealand government takes green issues seriously. In fact, New Zealand plans to use 90 percent electricity from renewables by 2025. The country also scores high on the quality of its natural environment and all other categories – albeit slightly less on the quality of its water and sanitation.</p><p><strong>8. Germany</strong></p><p>"I enjoy the rising awareness about environmental issues and the alternatives the government and society are developing," says one Colombian expat. Indeed, 80 percent of expats agree the German government is pro-environment (versus 55 percent globally). <br></p><p><strong>9. Canada</strong></p><p>The only North American destination in the Top 10, thanks especially to expat appreciation of Canada's natural environment (96 percent), but also the quality of its water and sanitation (90 percet) and the availability of green goods and services (80 percent). <br></p><p><strong>10. Luxembourg</strong></p><p>"Access to nature for hiking and bicycling" is a definite boon for one American expat. In fact, the country's natural environment, although ranking 13th out of 60, is its lowest-rated subcategory. Luxembourg does even better when it comes to green energy, waste management, and the quality of its air and water.</p>
Taiwan, most sustainable destination in Asia<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2Njg1Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1NzkxMDAxNH0.Roy7h_Od1cmaqBmamk-DP4rKMpLjTM-qIajG96alZAg/img.jpg?width=980" id="00799" class="rm-shortcode" data-rm-shortcode-id="dab52370e1edb5da5ebb0f5631027b1c" data-rm-shortcode-name="rebelmouse-image" alt="\u200bEternal Spring Shrine in the Taroko Gorge, Hualien County, Taiwan." />
Eternal Spring Shrine in the Taroko Gorge, Hualien County. Outside of Taipei, Taiwan can be surprisingly green and beautiful.
Credit: Zairon, CC BY-SA 4.0<p><strong>11. Taiwan</strong></p><p>The highest-scoring expat destination in Asia, Taiwan boasts 92 percent approval of its waste management and recycling, and 80 percent of the availability of green goods and services. But "the air pollution (in Taipei) is getting worse because it is too crowded," one expat complains.</p><p><strong>12. Netherlands</strong></p><p>Green goods and services are widely available, agree 82 percen of expats, as is green energy. However, 13 percent rate the Dutch environment negatively, 4 percet above the global average. <br></p><p><strong>13. Portugal</strong></p><p>Well ahead of its neighbor Spain (#20), the country scores high for air quality (91 percent) and natural environment (95 percent). "I like the opportunity for gardening and growing our own food," says one expat. <br></p><p><strong>14. Estonia</strong></p><p><strong></strong>Estonia scores in the Top 20 for every category and gets its highest marks for its natural environment. "A beautiful country with excellent air quality and open spaces," praises an Indian expat.<br></p><p><strong>15. Costa Rica</strong></p><p><strong></strong>Both the government and the people are very supportive of green policies, find 82 percent, resp. 67 percent of expats. "It's easy to live a healthy lifestyle with regard to the food, climate, clean air and water," says one. Costa Rica won the 2019 UN Champion of the Earth award and has pledged to go carbon neutral by 2050.<br></p><p><strong>16. Czechia</strong></p><p><strong></strong>"The beauty of the environment" is one of the best things about living in Czechia, says a Russian expat. No less than 97 percent of expats agree.<br></p><p><strong>17. France</strong></p><p><strong></strong>77 percent of expats are happy about the availability of green goods and services in France, which is 14 percentage points above average. The country also scores well for waste management and recycling. In short, France has a "good, green and clean environment," one Iranian expat finds. <strong><br></strong></p><p><strong>18. Australia</strong></p><p><strong></strong>While ranking high on the quality of its nature, water and air, Australia scores low when it comes to government support for green issues (51 percent). Fortunately, expats see more interest among the general population (68 percent). </p><p><strong>19. Singapore</strong></p><p><strong></strong>Expats rate the government's interest in green issues higher than globally average (77 percent versus 55 percent), but the Singaporean public's engagement for the same less than average (40 percent versus 48 percent). Of course, in a small, crowded place like Singapore, "(nature) spots are limited."<br></p><p><strong>20. Spain</strong></p><p>Spain's "scenery, diversity of places to visit and healthier environment" are what rate highly with one British expat. Its weak point is governmental and public support for green issues – but still slightly above the global average. <br></p>
London is "polluted and noisy"<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2Njg4Ni9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NDg3NjkyOH0.3ySSD7jFBfAWA07u-EN-oL9x9cq9FZn06iz5aV0hEOw/img.jpg?width=980" id="f5630" class="rm-shortcode" data-rm-shortcode-id="80c9fa119e7ff3acc91e027b7529bfed" data-rm-shortcode-name="rebelmouse-image" alt="\u200bEven at 2:30pm, London gets clogged." />
Afternoon traffic jam in London.
World map for the 'sustainable expat'<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2Njg5MC9vcmlnaW4ucG5nIiwiZXhwaXJlc19hdCI6MTYzMzAyNjQ2MH0.hjRiMDmOSnn9EvKJtx_tlzql3Gf7ph8lt8bL6dPCft4/img.png?width=980" id="def5d" class="rm-shortcode" data-rm-shortcode-id="149be2f5a19cc625cb555d8078f62ce2" data-rm-shortcode-name="rebelmouse-image" alt="The best & worst destiations for the sustainable expat" />
Sixty expat destinations ranked for sustainability, from best (orange) to worst (light blue). In between: fairly okay (brown), middling (grey) and not that great (dark blue).
South Korea's "rather horrible" air<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2NjkxNS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY2MTY1MjIwNn0.2e6eBIc38sAZLFQGKw4UL3-SY3hA9NthX0Uj9L4ibZA/img.jpg?width=980" id="c10db" class="rm-shortcode" data-rm-shortcode-id="cba918e6e5455c2e5ff4f9d5caf54775" data-rm-shortcode-name="rebelmouse-image" alt="\u200bSmoggy Seoul" />
Seoul's air quality is so bad you can picture it. Only India's air is perceived as worse than South Korea's, according to the expat survey.
Bad, worse, India<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDU2Njk0MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0NTcyMTczMH0.Pt2bGDrpSKSwVjimMK_iK0Jejpu8ILn77VEzHTdzQQ4/img.jpg?width=980" id="28411" class="rm-shortcode" data-rm-shortcode-id="8b8b602261a168a46b05c53e09ab1b02" data-rm-shortcode-name="rebelmouse-image" alt="man standing surrounded by garbage" />
India scores worst in all three categories, but to be fair – some of its problems were imported from more developed countries.