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The Promise of iPS
Earlier this week, the Nobel Prize for Medicine was awarded to John B. Gurdon and Shinya Yamanaka for their pioneering work in cell reprogramming. The decision was not without controversy. Since Gurdon's early work was used as the basis for cloning projects (including Dolly the sheep), cell reprogramming, or pluripotent stem cells (iPS) technology, has been viewed with quite a bit of suspicion and fear.
Of course, much of that fear is rooted in a future that is far, far away from now. The science fiction version of cell reprogamming has us cloning ourselves (and maybe our pets), "designing" our babies and generally defying nature. And while many have talked about potential stem cell therapies, like replacing neurons in the substantia nigras of individuals with Parkinson's disease, we aren't there--and aren't likely to be there for a long, long time. There's still quite a bit of work to be done--and a lot of ethical considerations to be hashed out--before those kinds of programs are realized.
But, for me, the real promise of iPS, at this juncture, is to be able to better model neuropsychiatric disease--and test personalized treatments for those disorders.
Let me give you an example. When Shinya Yamanaka first transformed a skin cell into a stem cell back in 2006 by altering 4 genes, he inspired thousands of other researchers to embark on similar projects. One of his colleagues at the Gladstone Institute, Yadong Huang, took the idea and ran with it--managing to turn a skin cell into a neuron by simply changing one gene, Sox2. And with just one factor at play, Huang's group can reprogram cells with "zero tumor formation"--an issue that many other reprogramming techniques have.
Huang says that, ideally, one day, we might be able to replace cells obliterated by Alzheimer's disease. "Scientists like myself are very careful about talking about this. We know the brain is very different from other organs and there are many hurdles that must be overcome before we can begin to talk about using stem cell therapy in the brain," he said. And he's right.
But that doesn't mean iPS is not valuable now. Huang and other researchers are using these iPS cells to better understand the molecular mechanics of many neuropsychiatric disorders like Alzheimer's.
"Many of the cell culture studies done in Alzheimer's research do not involve human neurons," he told me. "It's hard to get human neurons. Sometimes you can get some after brain surgery. But it's just a small piece and you are taking that piece from someone with damage to the brain. This technique allows us to really study human neurons in culture and see if we can replicate many of the studies that are currently conducted in animal models."
Furthermore, these generated, living neural networks may help clinicians understand which treatments are best for individual patients. More and more, neuroscientists are learning that neuropsychiatric disorders are not single diseases but collections of various rare genetic disorders. One drug will not fit all. Huang can imagine a future where a patient donates a few skin cells in order to determine which drug is best for their version of the disease. "This is something that will help us make sure that we are giving patients safe, effective drugs in the future.”
Even without scientists running to inject stem cells into our brains, Gurdon and Yamanaka's win is an exciting coup for medicine. And I'm excited to see what the real, as opposed to the imagined, future of iPS will bring to the table.
Photo Credit: nobeastsofierce/Shutterstock.com
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Richard Feynman once asked a silly question. Two MIT students just answered it.
Here's a fun experiment to try. Go to your pantry and see if you have a box of spaghetti. If you do, take out a noodle. Grab both ends of it and bend it until it breaks in half. How many pieces did it break into? If you got two large pieces and at least one small piece you're not alone.
But science loves a good challenge<p>The mystery remained unsolved until 2005, when French scientists <a href="http://www.lmm.jussieu.fr/~audoly/" target="_blank">Basile Audoly</a> and <a href="http://www.lmm.jussieu.fr/~neukirch/" target="_blank">Sebastien Neukirch </a>won an <a href="https://www.improbable.com/ig/" target="_blank">Ig Nobel Prize</a>, an award given to scientists for real work which is of a less serious nature than the discoveries that win Nobel prizes, for finally determining why this happens. <a href="http://www.lmm.jussieu.fr/spaghetti/audoly_neukirch_fragmentation.pdf" target="_blank">Their paper describing the effect is wonderfully funny to read</a>, as it takes such a banal issue so seriously. </p><p>They demonstrated that when a rod is bent past a certain point, such as when spaghetti is snapped in half by bending it at the ends, a "snapback effect" is created. This causes energy to reverberate from the initial break to other parts of the rod, often leading to a second break elsewhere.</p><p>While this settled the issue of <em>why </em>spaghetti noodles break into three or more pieces, it didn't establish if they always had to break this way. The question of if the snapback could be regulated remained unsettled.</p>
Physicists, being themselves, immediately wanted to try and break pasta into two pieces using this info<p><a href="https://roheiss.wordpress.com/fun/" target="_blank">Ronald Heisser</a> and <a href="https://math.mit.edu/directory/profile.php?pid=1787" target="_blank">Vishal Patil</a>, two graduate students currently at Cornell and MIT respectively, read about Feynman's night of noodle snapping in class and were inspired to try and find what could be done to make sure the pasta always broke in two.</p><p><a href="http://news.mit.edu/2018/mit-mathematicians-solve-age-old-spaghetti-mystery-0813" target="_blank">By placing the noodles in a special machine</a> built for the task and recording the bending with a high-powered camera, the young scientists were able to observe in extreme detail exactly what each change in their snapping method did to the pasta. After breaking more than 500 noodles, they found the solution.</p>
The apparatus the MIT researchers built specifically for the task of snapping hundreds of spaghetti sticks.
(Courtesy of the researchers)
What possible application could this have?<p>The snapback effect is not limited to uncooked pasta noodles and can be applied to rods of all sorts. The discovery of how to cleanly break them in two could be applied to future engineering projects.</p><p>Likewise, knowing how things fragment and fail is always handy to know when you're trying to build things. Carbon Nanotubes, <a href="https://bigthink.com/ideafeed/carbon-nanotube-space-elevator" target="_self">super strong cylinders often hailed as the building material of the future</a>, are also rods which can be better understood thanks to this odd experiment.</p><p>Sometimes big discoveries can be inspired by silly questions. If it hadn't been for Richard Feynman bending noodles seventy years ago, we wouldn't know what we know now about how energy is dispersed through rods and how to control their fracturing. While not all silly questions will lead to such a significant discovery, they can all help us learn.</p>
A study looks at the performance benefits delivered by asthma drugs when they're taken by athletes who don't have asthma.
- One on hand, the most common health condition among Olympic athletes is asthma. On the other, asthmatic athletes regularly outperform their non-asthmatic counterparts.
- A new study assesses the performance-enhancement effects of asthma medication for non-asthmatics.
- The analysis looks at the effects of both allowed and banned asthma medications.
WADA uncertainty<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzUzNzU0OS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMDc4NjUwN30.fFTvRR0yJDLtFhaYiixh5Fa7NK1t1T4CzUM0Yh6KYiA/img.jpg?width=980" id="01b1b" class="rm-shortcode" data-rm-shortcode-id="2fd91a47d91e4d5083449b258a2fd63f" data-rm-shortcode-name="rebelmouse-image" alt="urine sample for drug test" />
Image source: joel bubble ben/Shutterstock<p>When inhaled β-agonists first came out just before the 1972 Olympics, they were immediately banned altogether by the WADA as possible doping substances. Over the years, the WADA has reexamined their use and refined the organization's stance, evidence of the thorniness of finding an equitable position regarding their use. As of January 2020, only three β-agonists are allowed — salbutamol, formoterol, and salmeterol —and only in inhaled form. Oral consumption appears to have a greater effect on performance.</p>
The study<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzUzNzU0Ny9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY1MTIzMDQyMX0.Gk4v-7PCA7NohvJjw12L15p7SumPCY0tLdsSlMrLlGs/img.jpg?width=980" id="d3141" class="rm-shortcode" data-rm-shortcode-id="ebe7b30a315aeffcb4fe739095cf0767" data-rm-shortcode-name="rebelmouse-image" alt="runner at starting position on track" />
Image source: MinDof/Shutterstock<p>Of primary interest to the authors of the study is confirming and measuring the performance improvement to be gained from β-agonists when they're ingested by athletes who don't have asthma.</p><p>The researchers performed a meta-analysis of 34 existing studies documenting 44 randomized trials reporting on 472 participants. The pool of individuals included was broad, encompassing both untrained and elite athletes. In addition, lab tests, as opposed to actual competitions, tracked performance. The authors of the study therefore recommend taking its conclusions with just a grain of salt.</p><p>The effects of both WADA-banned and approved β-agonists were assessed.</p>
Approved β-agonists and non-asthmatic athletes<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzUzNzU1MC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMzkxODk0M30.3RssFwk_tWkHRkEl_tIee02rdq2tLuAePifnngqcIr8/img.jpg?width=980" id="39a99" class="rm-shortcode" data-rm-shortcode-id="b1fe4a580c6d4f8a0fd021d7d6570e2a" data-rm-shortcode-name="rebelmouse-image" alt="vaulter clearing pole" />
Image source: Andrey Yurlov/Shutterstock<p>What the meta-analysis showed is that the currently approved β-agonists didn't significantly improve athletic performance among those without asthma — what very slight benefit they <em>may</em> produce is just enough to prompt the study's authors to write that "it is still uncertain whether approved doses improve anaerobic performance." They note that the tiny effect did increase slightly over multiple weeks of β-agonist intake.</p>
Banned β-agonist and non-asthmatic athletes<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMzUzNzU1Mi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzNjI3ODU5Mn0.vyoxSE5EYjPGc2ZEbBN8d5F79nSEIiC6TUzTt0ycVqc/img.jpg?width=980" id="de095" class="rm-shortcode" data-rm-shortcode-id="02fdd42dfda8e3665a7b547bb88007ef" data-rm-shortcode-name="rebelmouse-image" alt="swimmer mid stroke" />
Image source: Nejron Photo/Shutterstock<p>The study found that for athletes without asthma, however, the use of currently banned β-agonists did indeed result in enhanced performance. The authors write, "Our meta-analysis shows that β2-agonists improve anaerobic performance by 5%, an improvement that would change the outcome of most athletic competitions."</p><p>That 5 percent is an average: 70-meter sprint performance was improved by 3 percent, while strength performance, MVC (maximal voluntary contraction), was improved by 6 percent.</p><p>The analysis also revealed that different results were produced by different methods of ingestion. The percentages cited above were seen when a β-agonist was ingested orally. The effect was less pronounced when the banned substances were inhaled.</p><p>Given the difference between the results for allowed and banned β-agonists, the study's conclusions suggest that the WADA has it about right, at least in terms of selection of allowable β-agonists, as well as the allowable dosage method.</p>
Takeaway<p>The study, say its authors, "should be of interest to WADA and anyone who is interested in equal opportunities in competitive sports." Its results clearly support vigilance, with the report concluding: "The use of β2-agonists in athletes should be regulated and limited to those with an asthma diagnosis documented with objective tests."</p>
Certain water beetles can escape from frogs after being consumed.
- A Japanese scientist shows that some beetles can wiggle out of frog's butts after being eaten whole.
- The research suggests the beetle can get out in as little as 7 minutes.
- Most of the beetles swallowed in the experiment survived with no complications after being excreted.