Researchers from Karolinska University have discovered a gene that reduces the severity of Covid infections by 20%. In theirpaper the scientists state that this explains why the disease’s symptoms are so variable, hitting some harder than others.
Why do some people fall severely ill from COVID-19 while others don’t? In addition to risk factors like age or obesity and plenty of other environmental factors, it also comes down to our varying genetic makeup. Therefore, researchers across the globe have begun the mammoth task of mapping the genes involved in making people more susceptible to catching SARS-CoV-2 (COVID-19) and developing a severe infection.
These large-scale efforts have thrown up more than a dozen genomic regions along the human chromosome containing large clusters of genes associated with severe COVID-19. However, the specific causal genes in these regions are yet to be identified, hampering our ability to understand COVID-19’s often selective pathology.
Now, scientists build on these findings to pinpoint a gene that confers protection from critical illness.
Neanderthal DNA protects against severe COVID-19
The previous studies from 2020 concentrated on the genetic data of people of European ancestry recorded by multi-disciplinary teams all over the world for the 1000 Genomes Project. This monumental collaboration uncovered a specific segment of DNA known as the OAS1/2/3 cluster, which lowers the risk of developing an acute COVID-19 infection by 20%. Inherited from Neanderthals in roughly half of all people outside of Africa, this segment is responsible for encoding genes in the immune system.
The genetic array came about as a result of the migration of an archaic human species out of the African continent about 70,000 years ago who mated and mingled DNA with Neanderthals reproduced in their offspring’s haplotypes, a set of inheritable DNA variations close together along a chromosome.
However, most human haplotypes outside Africa now include DNA from Neanderthals and Denisovans (an ancient human originating in Asia). Consequently, this ancient region of DNA is heaving with numerous genetic variants, making it challenging to distinguish the exact protective gene that could serve as a target for medical treatment against severe COVID-19 infection.
A possible solution is that people of African descent do not contain these archaic genes in their haplotypes, making them shorter and easier to decipher.
To test this theory, the researchers checked the 1000 Genomes project database for individuals carrying only parts of this DNA segment – focusing on individuals with African ancestry who lack heritage from the Neanderthals. Remarkably, the researchers found that individuals of predominantly African ancestry had the same protective gene cluster as those of European origin.
Genetic studies should be a multi-cultural affair
Once they established this, the researchers collated 2,787 COVID-19 cases with the genetic data of 130,997 individuals of African ancestry to reveal the gene variant rs10774671 G thought to convey protection against COVID-19 hospitalization. Their results correspond to a previous, more extensive study of individuals of European heritage, with analysis suggesting it is likely the only causal variant behind the protective effect.
Surprisingly, this previously ‘useless’ ancient variant was found to be widespread, present in one out of every three people of white European ancestry and eight out of ten individuals of African descent.
In evolutionary terms, the researchers write that the variant exists today in both these gene pools “as a result of their inheritance from the ancestral population common to both modern humans and Neanderthals.” Accordingly, their data adds more weight to the standard held theory that a common ancestor originated in Africa millions of years ago before sharing their DNA across the globe.
And while there’s much more to uncover regarding the newly discovered variant, the researchers can firmly suggest at this stage that the protective gene variant (rs10774671 G) works by determining the length of a protein encoded by the gene OAS1. As the longer version of the protein is more effective at breaking down the virus than the unaltered form, a life-threatening infection is less likely to occur.
Using genetic risk factors to design new COVID-19 drugs
Despite their promising results, the team cautions that the 1000 Genomes Project does not provide a complete picture of this genomic region for different ancestries. Nevertheless, it’s clear that the Neanderthal haplotype is virtually absent among individuals of primarily African ancestry, adding, “How important it is to include individuals of different ancestries” in large-scale genetic studies.
Senior researcher Brent Richards from McGill University says that it is in this way “we are beginning to understand the genetic risk factors in detail is key to developing new drugs against COVID-19.”
If these results are anything to go by, we could be on the cusp of novel treatments that can harness the immune system to fight this disease.
Nootropics are drugs that have a stimulating effect on our minds and brains. They’re meant to improve our cognitive abilities in various ways. On the face of it, that sounds awesome; who doesn’t want to get smarter by taking a pill? But many drugs touted with having a nootropic effect have no evidence to show for it. Some are complete swindles.
All of this doesn’t help give nootropics, which are a genuine category of drugs, a good name. Despite the undeniable appeal of being referred to as ‘cognitive enhancers’.
Today, we’re going to take a look at what nootropics are, talk about a few that we know are genuine, their effects, and some of the controversy around this subject.
So what are they?
The term was coined in 1972 by Romanian-born chemist and psychologist Corneliu Giurgea. At the time, he stated that to qualify as a nootropic, a compound should do the following:
Improve learning and memory.
Make learned behaviors or memories more resilient in the face of factors or conditions that disrupt them, such as hypoxia.Protect the brain against chemical or physical injuries.
Increase the efficacy of the tonic cortical/subcortical control mechanisms.
Have extremely low levels of toxicity, produce few (ideally no) side-effects, and to not induce the same effects of other psychotropic drugs (i.e. not get you high).
All of these are very useful pointers. However, I’ve found that the best way to explain what a certain family of drugs is to someone is to point at the examples people have direct experience with. We’re lucky, then, since virtually every one of us uses nootropics. Caffeine, nicotine, or L-theanine in various types of tea are some of the most-used nootropics in the world. Caffeine is the single most widely-used one. Besides coffee, caffeine is also naturally present in chocolate and tea. Many processed items such as food supplements, energy drinks, or sodas also contain caffeine.
All of these compounds influence our cognitive abilities in one form or another. Caffeine is notorious for helping pick us up when we’re feeling sleepy. But it also has a direct influence on the levels of various neurotransmitters in the brain. Past research has noted this leads to improved short-term memory performance and learning ability. These effects were not related to the stimulating effects of caffeine but occurred alongside it. According to Stephanie M. Sherman et al., 2016:
“Participants who drank caffeinated coffee were significantly more awake by the end of the experiment, while participants who drank decaffeinated coffee did not experience the same increase in perceived wakefulness”, it notes, adding that caffeine also “increased explicit memory performance for college-aged adults during early morning hours. Young adults who drank caffeinated coffee showed a 30% benefit in cued recall performance compared to the decaffeinated coffee drinkers, and this effect was independent of the perceived positive effect of the caffeine.”
Nicotine, an active ingredient in tobacco plants, also seems to have nootropic potential. D M Warburton, 1992, reports on a range of effects nicotine has on the (healthy) brain, including improvements in attention “in a wide variety of tasks” and improvements in short- and long-term memory. It further explains that nicotine can help improve attention in “patients with probable Alzheimer’s Disease”. Some of these effects were attributed to the direct effect nicotine has on attention, while others “seem to be the result of improved consolidation as shown by post-trial dosing” — meaning the compound likely also helps strengthen memories after they are formed.
Please do keep in mind here that I do not, in any way, condone that you pick up smoking. There isn’t any scenario under which I’d estimate that the potential nootropic effect of nicotine outweighs the harm posed by smoking. There are other ways to introduce nicotine into your system if you’re really keen on it.
L-theanine is very similar in structure to the neurotransmitter glutamate — which has the distinction of being the most abundant neurotransmitter in the human brain. Glutamate is our main excitatory neurotransmitter, and a chemical precursor for our main inhibitory neurotransmitter, as well. To keep things short, glutamate is an important player in our brains.
Because of how similar they are chemically, L-theanine can bind to the same sites as glutamate, although to a much lower extent. We’re not very sure what effects L-theanine has on the brain exactly, there is some evidence that it can work to reduce acute stress and anxiety in stressful situations by dampening activation in the sympathetic nervous system (Kenta Kimura et al., 2006).
How they work
A wide range of chemically distinct substances can have nootropic effects. As such, it’s perhaps impossible to establish a single, clear mechanism through which they act. But in very broad lines, their end effect is that of boosting one or several mental functions such as memory, creativity, motivation, and attention.
The nootropic effects of caffeine come from it interacting with and boosting activity in brain areas involved in the processing and formation of short-term memories. It does this, as we’ve seen, by tweaking neurotransmitter levels in the brain. Others, like nicotine and L-theanine, also influence neurotransmitter levels, or bind to receptor sites themselves, thus influencing how our minds and brains function. Others still influence our mental capacity through more mechanical means. As noted byNoor Azuin Suliman et al., 2016:
“Nootropics act as a vasodilator against the small arteries and veins in the brain. Introduction of natural nootropics in the system will increase the blood circulation to the brain and at the same time provide the important nutrient and increase energy and oxygen flow to the brain”. Furthermore, “the effect of natural nootropics is also shown to reduce the inflammation occurrence in the brain […] will protect the brain from toxins and [minimize] the effects of brain aging. Effects of natural nootropics in improving brain function are also contributed through the stimulation of the new neuron cell. [Through this] the activity of the brain is increased, enhancing the thinking and memory abilities, thus increasing neuroplasticity”.
The brain is a very complicated mechanism, one whose inner workings we’re only beginning to truly understand. Since there are so many moving parts involved in its functions, there are many different ways to tweak its abilities. Way too many to go through them all in a single sitting. One thing to keep in mind here is that nootropics can be both natural and synthetic in nature. In general — and this is a hard ‘in general’ — we understand the working mechanisms of natural nootropics a bit more than those of synthetic nootropics.
Still, even with caffeine, we start seeing one of the main drawbacks — most of which remain poorly understood — of nootropics. The word ‘nootropic’ is a compound of two Ancient Greek root words and roughly translates to “mind growers”. But, just as tuning a guitar’s strings alters what chords it can play overall, nootropics affect our minds and brains in their entirety. They often act on multiple systems in the body at the same time to produce these effects.
We separate nootropics by their effects in three classes. These are eugeroics, which promote wakefulness and alertness. One prominent eugeroic is Modafinil, currently used to treat narcolepsy, obstructive sleep apnea, and shift work sleep disorder. It’s also being investigated as a possible avenue for the treatment of stimulant drug withdrawal.
The second class is part of the ADHD medication family, which includes Methylphenidate, Lisdexamphetamine, Dexamfetamine. Ritalin is a drug in this category. It was originally used to treat chronic fatigue, depression, and depression-associated psychosis. Today, Ritalin is the most commonly prescribed medication for ADHD as it addresses the restlessness, impulsive behaviour, and inattentiveness associated with the disorder.
Finally, we have nootropic supplements. These include certain B vitamins, fish oil, and herbal supplements such as extracts of Gingko biloba and Bacopa monnieri. Supplements tend to be the more contested than the rest, with the plant extracts themselves being the most contested overall. One thing to keep in mind here is that the FDA doesn’t regulate nootropic supplements the same way it does for prescription drugs, so buyer beware. Another is that there is little reliable evidence that these supplements actually help boost memory or cognitive performance beyond a placebo effect. A review of literature on the efficacy of supplements (Scott C. Forbes et al., 2015) concludes that:
“Omega-3 fatty acids, B vitamins, and vitamin E supplementation did not affect cognition in non-demented middle-aged and older adults. Other nutritional interventions require further evaluation before their use can be advocated for the prevention of age-associated cognitive decline and dementia”.
One final point here is that the nutrients these supplements provide — if they work — shouldn’t produce meaningful effects unless you’ve been taking them for a while. Dr. David Hogan, co-author of that review and a professor of medicine at the University of Calgary in Canada, toldTime.com that age also plays a factor, and that such nutrients may not be of much help if taken “beyond the crucial period” of brain development.
No side effects?
“Caffeine has been consumed since ancient times due to its beneficial effects on attention, psychomotor function, and memory,” notesFlorian Koppelstaetter et al., 2010. “Caffeine exerts its action mainly through an antagonism of cerebral adenosine receptors, although there are important secondary effects on other neurotransmitter systems”.
Adenosine receptors in the brain play a part in a number of different processes, but a few that are important to our discussion right now are: regulating myocardial (heart) activity, controlling inflammation responses in the body, and keeping tabs on important neurotransmitters in the brain such as dopamine.
Caffeine helps make us be more alert by impairing the function of these receptors; one of the things that happen when adenosine binds to these sites is that we start feeling drowsy, even sleepy. But our brains come equipped with these receptors for a very important reason — they keep us alive and healthy. Messing with their activity can lead us to some very dangerous situations. Caffeine intake, for example, increases blood pressure and heart rate, at least in part by interfering with these adenosine receptors. Heavy caffeine intake has been linked to tachycardia (rapid heart contractions) in certain cases.
The risk posed by nootropics comes down to their very nature. By design, these are drugs meant to tweak the way our brains work. But our brains are so essential to keeping our bodies alive that any wrong tweak can lead to a lot of problems. There is some evidence that the use of certain nootropics comes at “a neuronal, as well as ethical, cost”. Revving our brains ever harder could mean they wear out more quickly.
“Altering glutamate function via the use of psychostimulants may impair behavioral flexibility, leading to the development and/or potentiation of addictive behaviors”, Kimberly R. Urban, Wen-Jun Gao, 2014, reports. “Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve. Finally, recent studies have begun to highlight potential damaging effects of stimulant exposure in healthy juveniles.”
“This review explains how the main classes of cognitive enhancing drugs affect the learning and memory circuits, and highlights the potential risks and concerns in healthy individuals, particularly juveniles and adolescents. We emphasize the performance enhancement at the potential cost of brain plasticity that is associated with the neural ramifications of nootropic drugs in the healthy developing brain”.
This leads us neatly to:
Although nootropics are still poorly understood, they have an undeniable allure. And there’s no shortage of people willing to capitalize on that demand.
There are valid uses for nootropics, and there is research to support these uses. ADHD medication being a prime example of that. But there is also a lot of false advertising, inflated claims, false labeling, and general snake-oilery going on in the field of nootropics.
We live in a world where cognitive ability and academic achievement have a large impact on our livelihoods, and the quality of our lives. As such, there is a lot of incentive for us to boost these abilities, and nootropics seem to offer an easy way to achieve them. So, naturally, there’s a lot of incentive for people to try and sell them to you. There is a growing trend of use of nootropics by students trying to make it through the curriculum — or to get an edge over their peers — in universities around the world. Factor in the fact that we still have a poor understanding of nootropics, and a poorer understanding still of their side- and long-term effects on our brains, and it becomes worrying.
The Federal Drug Administration and Federal Trade Committee have sent multiple warnings to manufacturers and distributors of nootropic drugs and supplements over the years over charges of misleading marketing, the manufacture and distribution of unapproved drugs or no proven safety or efficiency at the marketed doses, even over the use of illegal substances.
In closing, nootropics are a valid and real class of drugs. While there is still much we don’t yet understand about them, we know that they exist and they can work in the way we envision them, as long as we do so responsibly. In many ways, however, they suffer from their fame. Everybody wants a pill that would make them smarter, sharper, more focused. That in itself isn’t damnable. The trouble starts when we’re willing to overlook potential risks or even willingly ignore known side-effects in chasing that goal.
Harvey J. Alter, Michael Houghton and Charles M. Rice have been awarded for the discovery of hepatitis C virus, a breakthrough that led to tests and cures for the dangerous disease.
“For the first time in history, the disease can now be cured, raising hopes of eradicating hepatitis C virus from the world,” the Nobel Committee said in announcing the prize in Stockholm.
Scientists had long known about the hepatitis A and B viruses, but they were poking in the dark trying to find the hepatitis (hep) C virus. It took decades of work from Americans Harvey J. Alter and Charles M. Rice and British-born scientist Michael Houghton to make that breakthrough.
As is often the case, the Nobel Prize was awarded to breakthroughs that made a practical difference in the world — and this certainly fit the bill. Identifying the hepatitis C virus has led to efficient screens for the virus, making blood supplied for transfusions much safer than it was in the past. Up until the 1960s, medics were gravely concerned about a number of people receiving blood transfusions containing a mysterious infectious agent. That turned out to be the hep C virus.
“We take it for granted that if you get a transfusion, you’re not going to get sick from that transfusion. That was not the case before but is certainly the case now,” Rice said in an interview with AP. Before the tests, the risk of contracting the disease from a transfusion was about 1 in 10, now it’s closer to 1 in a million.
The discovery paved the way for treatments to save thousands every year. This is currently the only chronic viral infection that can be reliably cured, using one of several potent drugs. Without treatment, the virus can cause liver scars, cancer, or even damage requiring a liver transplant.
However, despite remarkable progress, the disease still affects over 70 million people every year, killing 400,000. We have the technology to save these people, it’s all about making the drugs cheaper and more available.
“What we need is the political will to eradicate it” and to make the drugs affordable enough to do it, Alter said.
The award comes at a very important time for the medical community around the world. In a statement, the Nobel Assembly said the isolation of Hepatitis C had marked a “landmark achievement in the ongoing battle against viral diseases”.
“It takes time before it’s fully apparent how beneficial a discovery is,” said Thomas Perlmann, secretary-general of the Nobel Committee.
This serves as a stark reminder that dealing with COVID-19 isn’t something that will happen overnight — even for a disease that’s been studied for decades and for which treatment exists, making it really go away with treatment alone is turning to be a massive challenge.
“To control an epidemic, you need to have a vaccine,” Houghton said. For “diseases like gonorrhea, syphilis, chlamydia, we’ve had cheap drugs available for decades, and yet we still have big epidemics of those diseases.”
As for the three new laureates, they weren’t exactly hugging the phone in expectation. Perlmann struggled to reach Alter and Rice by phone.
“I had to call a couple of times before they answered,” Perlmann said. “They seemed very surprised and very, very happy.”
The Nobel Prize for Medicine is pretty much the highest recognition you can obtain in the field. The prize honors great minds that made breakthrough discoveries that better the world, with an emphasis on science that paved the way for practical applications. The prize also comes with 10 million Swedish kronor (over $1.1 million), as was requested by the prize’s creator, Swedish inventor Alfred Nobel, 124 years ago.
Researchers at the University of Bristol (UoB) have created a robot for a peculiar purpose: chewing gum.
Robots keep coming for our jobs. Today, they’ve taken one of the easier ones — gum chewer. However, rest assured, it’s all in the name of science.
The robot is dentated to become a new gold standard for the testing of drug release from chewing gum. It has built-in humanoid jaws which closely replicate our chewing motions, and releases artificial saliva to allow researchers to estimate the transfer of substances from the gum to a potential user.
I have a mouth and I must chew
“Bioengineering has been used to create an artificial oral environment that closely mimics that found in humans,” says Dr Kazem Alemzadeh, Senior Lecturer in the UoB Department of Mechanical Engineering, who led the study.
“Our research has shown the chewing robot gives pharmaceutical companies the opportunity to investigate medicated chewing gum, with reduced patient exposure and lower costs using this new method.”
Chewing gum is recognized as a possible drug delivery method, but there currently aren’t any reliable ways of testing how much of a particular compound they can release during use.
The team’s theoretical work showed that a robot could be useful for this role — so they set out to build it and test it out.
The team explains that the robot can “closely replicate” the human chewing process. Its jaws are fully enclosed, allowing for the amount of released xylitol (a type of sweetener common in gum) to be measured.
In order to assess the robot, the team had human participants chew the gum and then measured the amount of xylitol it contained after different chewing times. The team also took saliva and artificial saliva samples after 5, 10, 15, and 20 minutes of continuous chewing. The robot’s gum was then tested similarly and compared to that of the human participants.
The release rates between these two chewed gums were pretty similar, the team found. The greatest release of xylitol occurred during the first five minutes. After 20 minutes of chewing, only a low level of this compound remained in the gum, regardless of how it was chewed.
All in all, this suggests that the robot is a reliable estimation tool for chewing gum. It uses the same motions and chewing patterns as humans, and its artificial saliva seems to interact with the gum in a very similar way. As such, it could serve as the cornerstone of medical chewing gum.
“The most convenient drug administration route to patients is through oral delivery methods,” says Nicola West, Professor in Restorative Dentistry in the Bristol Dental School and co-author of the study.
“This research, utilizing a novel humanoid artificial oral environment, has the potential to revolutionize investigation into oral drug release and delivery.”
The paper “Development of a Chewing Robot with Built-in Humanoid Jaws to Simulate Mastication to Quantify Robotic Agents Release from Chewing Gums Compared to Human Participants” has been published in the journal IEEE Transactions on Biomedical Engineering.