The bristle worm, also known as polychaetes, has been around for an estimated 500 million years. Scientists believe that the super-resilient species has survived five mass extinctions, and there are some 10,000 species of them.
Be glad if you haven't encountered a bristle worm. Getting stung by one is an extremely itchy affair, as people who own saltwater aquariums can tell you after they've accidentally touched a bristle worm that hitchhiked into a tank aboard a live rock.
Bristle worms are typically one to six inches long when found in a tank, but capable of growing up to 24 inches long. All polychaetes have a segmented body, with each segment possessing a pair of legs, or parapodia, with tiny bristles. ("Polychaeate" is Greek for "much hair.") The parapodia and its bristles can shoot outward to snag prey, which is then transferred to a bristle worm's eversible mouth.
The jaws of one bristle worm — Platynereis dumerilii — are super-tough, virtually unbreakable. It turns out, according to a new study from researchers at the Technical University of Vienna, this strength is due to metal atoms.
Metals, not minerals
Fireworm, a type of bristle wormCredit: prilfish / Flickr
This is pretty unusual. The study's senior author Christian Hellmich explains: "The materials that vertebrates are made of are well researched. Bones, for example, are very hierarchically structured: There are organic and mineral parts, tiny structures are combined to form larger structures, which in turn form even larger structures."
The bristle worm jaw, by contrast, replaces the minerals from which other creatures' bones are built with atoms of magnesium and zinc arranged in a super-strong structure. It's this structure that is key. "On its own," he says, "the fact that there are metal atoms in the bristle worm jaw does not explain its excellent material properties."
Just deformable enough
Credit: by-studio / Adobe Stock
What makes conventional metal so strong is not just its atoms but the interactions between the atoms and the ways in which they slide against each other. The sliding allows for a small amount of elastoplastic deformation when pressure is applied, endowing metals with just enough malleability not to break, crack, or shatter.
Co-author Florian Raible of Max Perutz Labs surmises, "The construction principle that has made bristle worm jaws so successful apparently originated about 500 million years ago."
Raible explains, "The metal ions are incorporated directly into the protein chains and then ensure that different protein chains are held together." This leads to the creation of three-dimensional shapes the bristle worm can pack together into a structure that's just malleable enough to withstand a significant amount of force.
"It is precisely this combination," says the study's lead author Luis Zelaya-Lainez, "of high strength and deformability that is normally characteristic of metals.
So the bristle worm jaw is both metal-like and yet not. As Zelaya-Lainez puts it, "Here we are dealing with a completely different material, but interestingly, the metal atoms still provide strength and deformability there, just like in a piece of metal."
Observing the creation of a metal-like material from biological processes is a bit of a surprise and may suggest new approaches to materials development. "Biology could serve as inspiration here," says Hellmich, "for completely new kinds of materials. Perhaps it is even possible to produce high-performance materials in a biological way — much more efficiently and environmentally friendly than we manage today."
In March 2019, the FDA approved ketamine, under the trade name Spravato (esketamine), for clinical use in treatment-resistant depression therapy. Alongside racemic ketamine, which is commonly used in ketamine infusion therapy, ketamine is the first hallucinogen approved for therapeutic usage in the United States.
Technically, ketamine is not a psychedelic but rather a hallucinogen and dissociative. (While ketamine has psychedelic effects, traditional psychedelics bind to the 5-HT2B receptor.) Still, advocates for psychedelic therapy recognize ketamine as a gateway for traditional psychedelics, such as psilocybin and LSD, to be considered for therapeutic usage.
To understand the proliferation of ketamine clinics across North America, the origins of this peculiar substance — one that went from battlefields to veterinary clinics to dance clubs in the span of two decades — must be discussed.
History of ketamine
In 1962, chemistry professor Calvin Stevens synthesized ketamine while researching alpha-hydroxyimine rearrangements. The first human tests were conducted on prisoners in 1964. Ketamine soon replaced phencyclidine (PCP) as the go-to anesthetic in hospitals. It was initially used on soldiers during the Vietnam War following FDA approval in 1970. Thanks to its success on the battlefield, ketamine was placed on the World Health Organization's List of Essential Medicines.
Ketamine has been used broadly as a sedative and anesthetic; to aid in emergency surgeries in war zones; as a bronchodilator for severe asthmatics; to treat certain types of seizures; and in postoperative pain management. Now, ketamine infusions and nasal sprays are being used for depression. Ketamine is also showing potential efficacy in treating chronic pain and suicidal ideation, though more research needs to be done.
Of all of those uses, ketamine has predominantly been used as an anesthetic in humans and animals. While it restricts breathing less than other similar medications, ketamine also produces hallucinations (thus, it's labeled as a dissociative anesthetic). The list of potential side effects from using ketamine is long, including nausea, double vision, breathing problems, impaired memory, liver enzyme abnormalities, urinary tract problems, and even increased depression — an alarming possibility given its growing use as an antidepressant replacement.
Small-scale studies on using ketamine to treat depression were conducted in 2000 and 2006. Further research confirmed its role in alleviating depressive symptoms, including the possibility that the antidepressant effects of a single dose can persist for weeks. In 2016, the FDA fast-tracked ketamine trials for depression.
A chair is seen in a therapy room at Field Trip, a psychedelic therapy clinic in Toronto, Ontario, Canada.Credit: Cole Burston/AFP via Getty Images
Ketamine infusion therapy
There has yet to be a consensus on how ketamine addresses depression. Antidepressants act on the body's serotonin and noradrenaline systems. Ketamine seems to interfere with an amino acid derivative, NMDA. As a 2017 study published in the journal Nature explains:
"Ketamine is responsible for blocking the N-methyl-D-aspartate (NMDA) receptor, which causes an immediate alleviation of depressive effects, while another metabolite in the drug helps the effects last for hours. This blockage is also what causes the hallucinogenic effects."
Small intravenous doses of esketamine — an enantiomer of ketamine and the substance actually approved by the FDA — seem to lift depressed patients out of their funk. So does Spravato, a nasal spray that can only be administered under supervision in a doctor's office or clinic.
Patients that have tried two different antidepressant medications with no success (the definition of treatment-resistant depression) can legally receive ketamine infusions or Spravato at clinics located all over the country. Since the therapy is generally not covered by insurance, treatments range from $300 to $2,000 per session; the Field Trip Treatment Program, which includes psychotherapy and six infusions, runs $4,700.
The process of ketamine infusion therapy is varied depending on which clinic you attend. Companies like Field Trip and organizations such as MAPS require psychotherapy sessions to coincide with infusions.
Unfortunately, therapeutic implementation has not always lived up to federal requirements. Reports of patients quitting antidepressants and psychotherapy to use esketamine as their primary source of treatment abound. Since medical professionals with no mental health training, such as nurse practitioners, anesthesiologists, and pain physicians, can legally administer ketamine, patients are left to process the drug's effects with little to no guidance.
Thus far, efficacy has been mixed. As STAT News editor Megan Thielking writes, people with minor depressive issues are likely better candidates for ketamine therapy than those with treatment-resistant depression, the very cohort the drug is purported to target.
"Studies vary but have found response rates to ketamine as high as 70 percent among people with major depression who have failed a few other antidepressants. But the rate is lower for patients with extremely treatment-resistant depression, and how long any improvement lasts varies from one patient to the next."
Was ketamine approved too quickly?
While ketamine therapy is certainly promising, the FDA-approved trials raise a number of red flags. A recent analysis in The British Journal of Psychiatry concludes that we're moving too fast. Author Mark Horowitz writes:
"Out of the three short-term trials conducted by Janssen only one showed a statistically significant difference between esketamine and placebo. These were even shorter than the 6-8 week trials the FDA usually requires for drug licensing."
Trials usually last three months; the approved ketamine trials only lasted four weeks and barely showed efficacy above placebo. More concerning, the FDA allowed Janssen to submit a discontinuation trial with a study design flaw as evidence of efficacy — side effects were treated as evidence of relapse, not withdrawal symptoms. Even more alarmingly, six people in the esketamine group died during the trials, including three by suicide, two of which had previously shown no signs of suicidal ideation.
When Janssen stated that the problem wasn't esketamine but underlying conditions, the FDA accepted the reasoning even though no conclusive evidence was provided. This doesn't mean ketamine therapy isn't potentially therapeutic, though it does suggest that its approval by the FDA was rushed.
Psychiatrist Lori Calabrese, who offers ketamine infusion for depression and anxiety in her clinic, puts it best when stating, "The pace of ketamine treatment in real-world practices has outstripped what researchers are able to do and publish." Time will tell if this treatment proves more beneficial than dangerous in mental health treatments.
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Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
Due to stigma, their illegal status and difficulty in finding control groups, research with psychedelics has been a challenge. But research increasingly shows that this class of drug has legitimate medicinal uses, and they may be just as good or even better than more traditional therapies.
Now, the Centre for Psychedelic Research at Imperial College London reports in the New England Journal of Medicine that when pitted against escitalopram (brand name: Lexapro), psilocybin was as effective as the popular SSRI (selective serotonin reuptake inhibitor) in treating moderate to severe depression. Perhaps most significantly, these results were obtained when comparing 6 weeks of daily doses of escitalopram to just two administrations of psilocybin.
Robin Carhart-Harris, head of the center who has published over 100 papers on psychedelics, is confident this study represents another step forward in applying psychedelics to mental health treatment protocols while also reducing fears a lot of citizens have around these substances. In a press release, he said:
"One of the most important aspects of this work is that people can clearly see the promise of properly delivered psilocybin therapy by viewing it compared with a more familiar, established treatment in the same study. Psilocybin performed very favorably in this head-to-head."
Credit: Robin Carhart-Harris et al, NEJM, 2021.
As depicted above, the phase 2 clinical trial included 59 volunteers. The escitalopram (control) group received six weeks of daily escitalopram in addition to two tiny (1-mg) doses of psilocybin — a dose so low that it is unlikely to produce hallucinogenic effects. The psilocybin (experimental) group received two 25-mg doses of psilocybin three weeks apart with placebo given on all the other days.
At the end of the study, both groups saw a decrease in depressive symptoms, though the results were not statistically significant. (That isn't necessarily bad because if the two drugs have similar effects, then they would not produce statistically significant results. Still, a larger study is needed to confirm that psilocybin is "just as good as" escitalopram.)
Additionally, several other outcomes favored psilocybin over escitalopram. For instance, 57 percent in the psilocybin group saw a remission of symptoms compared to 28 percent in the escitalopram group. This result was significant.
Psychedelics without tripping
As psychedelics become decriminalized and potentially legalized for therapeutic use, however, a large population of people might desire the antidepressant effects without the hallucinations. For example, the psychedelic ibogaine may be useful for treating addiction, so the company Mindmed is developing an analog that works without producing the unwanted hallucinogenic side effects.
A new research article, published in the journal PNAS, investigated the antidepressant effects of psilocybin on a group of chronically stressed mice. (Under immense stress, mice develop something resembling human depression.) As with humans, depressed mice lose a sense of joy, which can be assessed by determining their preference for sugar water over tap water. Normal mice prefer sugar water, but depressed mice simply don't care.
Once the mice were no longer juicing up on the sweetened water, the team dosed them with psilocybin alongside a drug called ketanserin, a 5-HT2A serotonin receptor antagonist that eliminates psychedelic effects. Within 24 hours of receiving the dose, the mice were rushing back to the sugar water, indicating that tripping is not necessary for psilocybin to work as an antidepressant.
While the team is excited about these results, they realize it needs to be replicated in a different population.
"The possibility of combining psychedelic compounds and a 5-HT2AR antagonist offers a potential means to increase their acceptance and clinical utility and should be studied in human depression."
Photo: Cannabis_Pic / Adobe Stock
The future of psychedelic therapy
Psychedelics such as psilocybin and LSD have a long track record of efficacy in clinical trials and anecdotal experiences. Almost all volunteers of the famous Marsh Chapel experiment claimed their experience on Good Friday in 1962 was one of the most significant events of their lives — and this was a quarter-century after the fact. A more recent, controlled study found that a single dose of psilocybin showed antidepressant effects six months later.
Proponents of macrodosing and ritualistic experiences sometimes argue that the full-blown mystical trip is the therapy, though this is anecdotal, not clinical research. As the Maryland team noted, a number of people are contraindicated for psychedelics, whether through a family history of schizophrenia or current antidepressant treatments.
Senior author Scott Thompson is excited for future research on this topic. As he said of his team's findings:
"The psychedelic experience is incredibly powerful and can be life-changing, but that could be too much for some people or not appropriate… These findings show that activation of the receptor causing the psychedelic effect isn't absolutely required for the antidepressant benefits, at least in mice."
Hopefully, with more research occurring in psychedelics than even in the 1950s (when studies predominantly relied on anecdotal evidence and little government support), the longstanding stigmatization of psychedelics is beginning to recede. This could open up new possibilities for both clinical research and, for those curious about the ritual effects, a continuation of introspective experiences.
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Stay in touch with Derek on Twitter and Facebook. His most recent book is "Hero's Dose: The Case For Psychedelics in Ritual and Therapy."
Neanderthals' image has undergone quite an upgrade in recent years. Where we once we thought of them as knuckle-dragging just-slightly-more-evolved apes, we now know that they were not so very unlike us. Evolutionarily more primitive, yes, but not by that much. They buried their dead, painted cave art, developed wooden tools, and even made string. We also know that their genetic traces remain in many modern humans. A new study from researchers at the University of Binghamton in New York State and Universidad de Alcalá in Spain pretty conclusively demonstrates they had the physical apparatus required for speaking and for understanding speech.
"This is one of the most important studies I have been involved in during my career," says co-author Ralph Quam. "The results are solid and clearly show the Neanderthals had the capacity to perceive and produce human speech. This is one of the very few current, ongoing research lines relying on fossil evidence to study the evolution of language, a notoriously tricky subject in anthropology."
The study is published in the journal Nature Ecology & Evolution.
Long-standing questions
Neanderthal reconstruction (right), 2014
Credit: Cesar Manso/Getty Images
"For decades, one of the central questions in human evolutionary studies has been whether the human form of communication, spoken language, was also present in any other species of human ancestor, especially the Neanderthals," says co-author Juan Luis Arsuaga.
The key to answering these questions, say the researchers, has to do first with Neanderthals' physical ability to hear in the frequency ranges typically involved in speech. In addition, while it's known that these ancient people had the physiological capacity for producing vowel sounds, the new research adds consonants to the Neanderthal repertoire, greatly expanding the possibilities for conveying a wide variety of meaning through the production of more types of sounds.
Neanderthal hearing
The authors made high-resolution CT scans of fossilized Neanderthal skulls—and skulls from some of their ancestors—found at UNESCO's archaeological site in northern Spain's Atapuerca Mountains. These scans served as the basis for virtual 3D models of the fossils' ear structures. Similar models of modern human ear structures were also created for comparison purposes.
Auditory bioengineering software assessed the hearing capabilities of the models. The software is capable of identifying sensitivity to frequencies up to 5 kHz, the midrange and low-midrange frequencies at which homo sapien speech primarily occurs. (We can hear much higher and lower frequencies, but that's where speech lies.)
Of particular importance is the "occupied bandwidth," the frequency region of greatest sensitivity, and therefore the spectrum most capable of accommodating enough different audio signals to represent a multitude of meanings. The occupied bandwidth is considered a critical requirement for speech since being able to produce and hear many different sounds—and understand their many different meanings—is the cornerstone of efficient communication.
Compared to their ancestors, the Neanderthal models turned out to have better hearing in the 4-5 kHz range, making their hearing more comparable to our own. In addition, the Neanderthals were found to have a wider occupied bandwidth than their predecessors, again more closely resembling modern humans.
Lead author of the study Mercedes Conde-Valverde says, "This really is the key. The presence of similar hearing abilities, particularly the bandwidth, demonstrates that the Neanderthals possessed a communication system that was as complex and efficient as modern human speech."
Consonants
Credit: sakura/Adobe Stock/Big Think
The study also suggests that Neanderthal vocalization were more advanced than previously thought. Says Quam: "Most previous studies of Neanderthal speech capacities focused on their ability to produce the main vowels in English spoken language."
However, he says, "One of the other interesting results from the study was the suggestion that Neanderthal speech likely included an increased use of consonants."
This is important, since "the use of consonants is a way to include more information in the vocal signal and it also separates human speech and language from the communication patterns in nearly all other primates. The fact that our study picked up on this is a really interesting aspect of the research and is a novel suggestion regarding the linguistic capacities in our fossil ancestors."
Bottom line
The study concludes that Neanderthals had the physiological hardware to produce a complex range of vocalizations, and the ability to understand them through ear structures not very unlike our own. This fits neatly with other recent insights as to the sophistication of the Neanderthals, a people who now seem to have been developing an expansive set of advanced capabilities simultaneously.
The authors of the study have been investigating the Neanderthals for almost 20 years, and others have been at it even longer. The work continues, and the study's publication marks a significant milestone in the much longer journey.
"These results are particularly gratifying," says co-author Ignacio Martinez. "We believe, after more than a century of research into this question, that we have provided a conclusive answer to the question of Neanderthal speech capacities."
When it comes to senses like ours, tiny single-celled organisms floating in the ocean don't have much going on. And yet, as Sacha Coesel, the lead author of a new study from University of Washington researchers, puts it: "If you look in the ocean environment, all these different organisms have this day-night cycle. They are very in tune with each other, even as they get moved around. How do they know when it's day? How do they know when it's night?"
The answer, according to Coesel and her colleagues, is four previously unknown groups of photoreceptors that may help these organisms detect day, night, and each other.
Light and dark are vital to these organisms. When the sun is up, they become energized and grow. Cell division occurs at night when the darkness' ultraviolet wavelengths are less damaging to their DNA.
"Daylight is important for ocean organisms," says senior author Virginia Armbrust, "we know that, we take it for granted. But to see the rhythm of genetic activity during these four days, and the beautiful synchronicity, you realize just how powerful light is."
Photoreceptors and optogenetics
Credit: ktsdesign/Adobe Stock
Aside from being fascinating in their own right, these little "light switches" are likely to be of great interest to people working in optogenetics, a transformative area of scientific research.
This combination of optical technologies and genetics is giving researchers new insights into the workings of the brain, allowing them to, for example, turn on and off single neurons as they explore the brain's myriad pathways and interactions. Optogenetics also holds promise for better management of pain, and has cast new light on brain motor decision-making.
These new-found, naturally occurring photoreceptors may substitute for, or complement, human-made photoreceptors currently used in optogenetics. It's hoped that these newcomers will prove more sensitive and better equipped to respond to particular light wavelengths. Possibly because water filters out red light—the reason the ocean looks blue—the new photoreceptors are sensitive to blue and green wavelengths of light.
"This work dramatically expanded the number of photoreceptors — the different kinds of those on-off switches — that we know of," offers Armbrust.
Finding the new photoreceptors
Credit: Dror Shitrit/Simons Collaboration on Ocean Processes and Ecology/University of Washington
The researchers identified the previously undiscovered groups of photoreceptors by analyzing RNA they'd filtered from seawater samples taken far from shore. The samples were collected every four hours over the course of four days from the Northern Pacific Ocean near Hawaii. One set of samples was collected from currents running about 15 meters beneath the surface. A second set sampled deeper down, gathering water from between 120 and 150 meters, in the "twilight zone" where organisms get by with little sunlight.
Filtering the samples produced protists—single-celled organisms with a nucleus—measuring from 200 nanometers to one tenth of a millimeter across. Among these were light-activated algae as well as simple plankton that derive their energy from the organisms they consume.
Under-appreciated, tiny drivers of sea health
The new photoreceptors help fill in at least one of the blanks in our knowledge of the countless floating communities of microscopic creatures in our seas, communities that have a far greater impact on our planet than many people realize.
Says Coesel, "Just like rainforests generate oxygen and take up carbon dioxide, ocean organisms do the same thing in the world's oceans. People probably don't realize this, but these unicellular organisms are about as important as rainforests for our planet's functioning."
