Bacterial spores can likely survive in dormancy for over hundreds of millions of years. This ability to remain viable without detectable metabolism blurs the line between life, death, and deep sleep. (Photo credit – Iuliia Morozova)
Back in the 1990s, at the turn of the century, scientists discovered a tiny brine pocket in a salt crystal within an underground cavern used to store nuclear waste. This pocket contained a droplet of water with trapped bacterial spores. The analysis of these spores revealed that they represented two bacterial species, Bacillus marismortui and Virgibacillus pantothenticus, which have likely remained dormant but viable for approximately 250 million years! To date, these spore samples hold the documented record for how long a living cell can remain viable in a state of dormancy.
Although some scientists have expressed skepticism about this discovery, noting that reports of ancient bacteria found in rock, coal, and Egyptian temples have not stood up to scientific scrutiny, similar findings have been made for other organisms. For instance, in one subsequent study, 100-million-year-old samples of dormant aerobic bacteria from ancient sea-floor sediments were successfully brought to life—providing another demonstration of the exceptional longevity of dormant microbial cells.
The question, however, stands regardless of any imaginable skepticism: For how long can an organism remain viable in a state of dormancy? If we find a way to protect biological molecules from damage caused by oxygen or radiation, can “simple” organisms, such as bacteria, remain viable forever?
While the answer to this question remains to be found (ironically, supported by research funded through grants that typically last about 5 years), let’s consider several documented examples of these longevity:
Human oocytes – remain dormant but viable for up to ~40 years …
We, humans, cannot sense magnetism and many other natural forces. But some animals can. These differences in sensory aptitude show that we are surrounded by phenomena and forces that we cannot directly perceive. Thus, although we do not think of ourselves as deaf and blind, we are actually deaf and blind—in more ways we can imagine.
Umwelt. In German, Umwelt simply means “environment” or “surroundings,” but in biology, it carries a more specific meaning: “perceived environment” — referring to only that part of your surroundings that you can actually sense (and care about).
It’s easy to understand why the concept of Umwelt is so important, thought-provoking, powerful. Consider any pair of living organisms that coexist in the same physical environment. For instance, you and a mosquito in the same room (sorry). Your Umwelten (the plural of Umwelt) will be vastly different. As humans, we will perceive our room (or a phone screen) but may not notice the odors present. Whereas, the mosquito (a blind animal) will not see anything but will smell our breath by sensing the carbon dioxide we exhale. Two species. Same place and time. Two worlds.
I like to extend the concept of Umwelt beyond the biology of senses—towards the realm of attention and concern. As humans, our “Umwelt of concern” primarily revolves around other humans: we care about social standing and how much we are liked, included, recognized, and cherished. By other humans, of course. And we can go through an entire day or even a week without thinking of anything else but other humans. Even indirectly, our concerns about career progress and financial wealth are deeply rooted in our social standing. “If you want to get rich, find a way to serve many,” says the old wisdom, and by “many,” they mean, of course, many other people.
This selective attention creates a colossal blindness. For instance, while our planet hosts over 2 million species, we ignore nearly all of them in our daily thought processes. Our usual concerns revolve around humans, occasionally dogs, cats (and maybe dinosaurs). We do not even think about the animals we eat or those that populate the surfaces of our bodies (unless they bother us through itch and inflammation). More importantly, of all the things that exist in the immensely vast universe, we are primarily focused on our immediate neighbors, the infamous Joneses. And rarely do we stop to gaze at the stars, despite their presence in our plain sight every single clear night.
In hindsight, I am convinced that one major reason I became a scientist was the exhilarating sense of wonder that science can dramatically expand our Umwelt—far beyond the humble limits (and fallacies) of our sensory systems, and far beyond our day-to-day thinking, burdened by worries about our social status and the pressure to perform or fit in.
As a kid (completely free from these worries) I would meet my dear friends late in the evening in our neighborhood to gaze at the quiet, mesmerizing light of the stars. This light fascinated us. It turned the gears of our our imagination. We would eagerly debate: What are the boundaries of the universe? If the universe is so vast or infinite, then why don’t we see the entire sky ablaze with light? And when and how did it all begin? How old are our sun and planet? We would then share share everything we had read, and heard, and—most importantly—thought about space and the origin of life on our planet.
Now, as someone who studies nature for a living, I do not have the luxury of believing in eternal life. I, therefore, acutely feel that—in this unimaginably vast, largely silent, and seemingly indifferent universe, where stars and galaxies emerge and fade away without a trace—we, the human race, have a chance to enjoy love and life—and nurture a world of culture, a world of meaning, a world of emotional maturity and warmth, where people take loving, tender care of each other and their fragile environment, and celebrate this improbable gift of being alive and self-aware.
While we are not immortal individually—and have a very decent chance of vanishing without a trace in the distant future (e.g., in response to a cosmic cataclysm)—we can enjoy this moment and share the joy of living with others. We also can use our intelligence as a gift to continually improve this world for ourselves and future generations—to keep the fire of life burning and growing, if not in size, then in quality. So, let’s make it happen or literally die trying. We have nothing to lose and everything to gain.
Among natural proteins, there is a class known as LEA proteins. These proteins, likely of plant origin, protect living cells from death due to desiccation and possibly other environmental stresses. Some of these proteins exist in bacteria. In E. coli, one of the best-studied bacterial LEA proteins is known as RMF (Ribosome Modulation Factor). This protein appears to protect ribosomes from degradation in metabolically inactive cells of E. coli. RMF is conserved in nearly half of the currently known gamma-proteobacteria, although its origin in bacteria remains unknown.
How did plants emerge on our planet? Fossil evidence suggests that the first plant-type organisms initially emerged in the form of algae, likely around 1.2 billion years ago. And for more than 700 million years, they remained exclusively marine, thriving while submerged in water (possibly following the famous crab’s advice: “Darling, it’s better down where it’s wetter”). This is especially remarkable because current evidence indicates that the first masses of land emerged above sea level about 3.7 billion years ago. This means that for over 3 billion years, land was completely devoid of plants. However, about 470 million years ago, marine plants began to transition to terrestrial living, with ferns being among the pioneers of these early conquerors of the land.
We can imagine that terrestrial living provided plenty of benefits to these early plants: little competition for space, much more sunlight, and access to mineral nutrients. Perhaps there were also fewer predators. However, with these advantages came the real risk of death from dehydration, which likely promoted the selection of plant variants capable of tolerating prolonged lack of water. It took some lineages of plants a gradual evolution into seed plants around 350 million years ago during the Late Devonian period. The invention of seeds has provided a colossal advantage for plant survival. For many higher plants, seeds can lose up to 95% of their water content and still remain viable, entering a state of dormancy that protects them from desiccation damage. This allows plants to pause their life cycle until the environment is suitable for active growth.
According to current estimates, the emergence of seed plants coincided with (or preceded by) the origin of so called LEA proteins, which is a special class of protective proteins in plant genomes: . These proteins, through a poorly understood mechanism, allow seeds to remain viable in the face of desiccation. We currently know that most known LEA proteins are highly hydrophilic and often non-globular proteins that protect seeds, as well as mature plant tissues, from desiccation damage. Their name stands for Late Embryogenesis Abundant proteins, which stems from their discovery in cotton seeds, where LEA proteins accumulate during the late stages of embryo development. In plants, LEA proteins enable organisms to survive severe and reversible dehydration, a phenomenon termed “anhydrobiosis.” Furthermore, the ability of LEA proteins can be replicated in other organisms. For example, LEA proteins can confer desiccation tolerance when recombinantly expressed in mammalian cells. In one particular study, mammalian skin cells were shown to become almost completely nonviable (with only 1% of cells alive) after 4 hours of air drying. However, more than 58% of these cells survived if they expressed the protein dehydrin from maize, the cold acclimation protein WCOR410 from wheat, and LEA protein group 3 from brine shrimp.
The evolutionary origin of LEA proteins in nature has likely been driven by the spread of plants from marine to terrestrial environments, which occurred around 470 million years ago during the Ordovician period. As plants transitioned to land, they faced the risk of desiccation and gradually evolved into seed plants, around 350 million years ago during the Late Devonian period. According to current estimates, it is during this time that LEA proteins emerged as small, highly hydrophilic proteins that protect seeds (but also mature plant tissues) from desiccation damage.
Although “canonical” LEA proteins originate from plants, they appear to have spread to other species via horizontal gene transfer. As a result, LEA are present not only in plants but also in other eukaryotes and many bacteria. In tested species, LEA proteins help cells survive harsh environmental conditions, such as desiccation, cold shock, and possibly many other unfavorable circumstances.
In E. coli, there are at least five LEA proteins, but we understand the biology of just one of them, the RMF protein. This protein binds to ribosomes in metabolically inactive (stationary or transiently stressed) cells and prevents ribosomes from being degraded by cellular nucleases and proteases. This allows E. coli to remain inactive with a lower risk of digesting their essential molecular machinery, making it possible for these bacteria to survive prolonged states of metabolic inactivity and recover when conditions improve or when the cells adapt to a new environment.
When we talk about hibernation, we typically mean surviving winter times. However, many organisms use hibernation to survive heat, not cold.
To survive in desert heat, Selaginella lepidophylla may lose up to 97% of its body weight and remain dormant and viable for many years. Given this exceptional heat tolerance through hibernation, it is included in our list of the Top 100 most remarkable hibernators.
If you visit the Chihuahuan Desert—one of the most fascinating places on our planet for anyone interested in biodiversity—you may find one of its most resilient residents, a moss-like plant commonly known as the Resurrection Plant. Here are some remarkable and mind-boggling facts about it:
Its actual growth period lasts only a small fraction of the year, primarily occurring during the wet months (~2-3 months per year) when conditions are optimal for growth.
For the rest of the year, this plant remains dormant: when the rains stop, it dries out and shrinks into a tight ball that weighs only about 3% of its initial weight. So, technically, this plant turns into viable but dormant hay.
In this dry form, it can remain dormant for up to several years, effectively suspending its growth until it receives sufficient moisture. When rehydrated, it quickly resumes growth, often in under an hour.
This plant species arose about 250 million years ago (which makes it approximately a thousand times older than humans) and is called Selaginella lepidophylla, where Selaginella refers to selāgō—a Latin name for a type of juniper—and lepidophylla means “scaly” (from lepidus) and “leaf” (from phyllon). This name highlights the plant’s unique feature of having scaly leaves that enable it to survive in extremely dry conditions.
Thus, when you think about dormancy next time, imagine not only a bear’s den but also a hot, dry desert.
When cells reduce their metabolic activity, some of their key enzymes enter various states of molecular hibernation. This state allows cells to prevent degradation of their most essential enzymes by cellular proteases and nucleases and thereby put their life on pause. Hibernating RNA polymerase (the image from Irina Artsimovitch’s laboratory)
A superpower we take for granted.
Scientists say it is impossible for a human body to go without food for longer than 8 days, with some optimists claiming that up to 21 days is sometimes possible. Even the Bible considers 40 days of fasting the ultimate feat of bodily strength. Yet what’s not possible for a human — even the legendary Christ — appears to be fairly mundane for creatures that are comparable to us in size, anatomy and lifespan. These creatures are bears.
Bears have a remarkable knack for starvation. Unlike humans, they can enjoy their breakfast in mid-September to have their lunch only in April! I guess if they would be into academic research or the literary career, it would be easy for them to implement this golden rule by Kingsley Amis: “A bad review may spoil your breakfast, but you shouldn’t allow it to spoil your lunch.”
— Hey bear, a bad review may spoil your breakfast, but you shouldn’t allow it to spoil your lunch.
— Easy as pie, pal. Just give it to me in September (proceeds to reading comments by Reviewer 2, yawns, and falls asleep).
So, what’s the trick? What makes bears so good in their ability to cope with starvation? The answer is hibernation.
All animals are equal? You’ve got to be kidding. Hibernation. We sort of know what hibernation is, but really — not quite. When I was a kid, my understanding of hibernation — mainly learned from Fozzie Bear — was plain and simple: a long nap. Over the years, however, I learned that the actual state of hibernation is much deeper and more complex than usual sleep. Although we do not fully understand this process, we now know that hibernation has many unique metabolic signatures that distinguish it from ordinary sleep, and mechanisms of hibernation appear to be wildly distinct in different species. This suggests that the ability to hibernate has evolved many times in the history of life on Earth, with many species inventing their own unique ways of hibernating.
For instance, when grizzly bears hibernate, their body temperature decreases from 38 to 31°C; their heart rate drops from 40-50 to just 8-19 beats per minute; their respiration decreases from 6-10 to just about 1 breath per minute; their circadian clocks get shut off; and their metabolism not only slows down but changes in such a way that bears do not release bodily waste for several weeks. Instead, they turn their urine into protein through a urea recycling process, along with other metabolic changes that allow them to survive cold, despondent winters.
But in other species, like Arctic ground squirrels, the process of hibernation looks strikingly different. These animals undergo the process of “supercooling,” in which their average body temperature drops to -3°C, with only their heart and brain remaining slightly warmer. Unlike most other animals, these squirrels can somehow prevent the nucleation of ice crystals in their bodies. This allows them to remain alive and soft, yet technically frozen, when the air temperature drops to -26°C. Just imagine if we, humans, would have such a skill!
Even a more impressive example of hibernation can be found in smaller animals, ironically known as water bears or tardigrades. While actively growing tardigrades are highly sensitive to various stressors, including heat and cold, things totally change as they hibernate. When these caterpillar-looking creatures encounter starvation or stress, they rapidly purge most of the water from their bodies. This “dry hibernation” allows these (not-so-much-)water bears to survive prolonged stress for decades and possibly much longer. In this state, tardigrades can survive exposure to extreme environments, including temperatures as low as -200°C and as high as 150°C, or high doses of radiation, or life in the open space outside our planet.
Thus, hibernation is a superpower: when organisms hibernate, they can do things impossible in their ordinary sleep or alert state: being able to enter a state of hibernation allows organisms to survive in some of the most extreme conditions known to science. No wonder, we, humans, would gain a lot if we could understand this process better and learn how to induce hibernation at a desired time in a target organism, including our own bodies. Putting gravely ill people or astronauts to sleep would be one immediate application of such a hibernation by design.
More common than you think. What is even more important about hibernation is how common it occurs in nature. Contrary to popular belief, hibernation is not limited to large animals or “weird” insects. In fact, hibernation is routinely exercised by practically all known microorganisms, including most studied bacteria.
One reason we know little about the hibernation of microorganisms merely stems from semantics. When bacteria hibernate, we usually do not call them ‘hibernating’. Instead, we call them ‘dormant’ or ‘persistent’. Semantics frequently screws us up. Remeber George Carlin’s ‘Soft language’? While not deliberate or malicious, this use of different terms for hibernation of animals as opposed to hibernation of germs creates a common and wrong perception that hibernation is rare, and the ability to hibernate is limited to just a handful of animal species that need to survive harsh winters.
Instead, we actually know that when bacteria face starvation or stress, including exposure to certain drugs and therapies, they undergo a conceptually similar transformation to the one observed in grizzly bears, squirells or tardigrades: some bacteria lose their water, some shut off most (but not all) of their metabolism, some produce special anti-freeze agents that prevent formation of ice crystals when bacteria are exposed to sub-freezing temperatures. This allows bacteria to survie in hostile environments for a very long time. For example, recent studies of the Greenland ice sheet have identified and ‘resurrected’ a specimen of the bacterium Chryseobacterium greenlandensis that are 120,000 years old! And it is possible that 120,000 years is very far from the actual survival limit for a hibernating microorganism.
This example goes to show that hibernation — frequently viewed as something exotic — is in fact one of the most common survival strategies of modern microorganisms. What is even more important: at least in the microbial world, the process of hibernation shows that life can be put on hold, paused, or at least marginally suspended for thousands and thousands of years without loss of viability. Thus, a typical germ can easily outperform Briar Rose, making bacteria extremely successful in surviving not only starvation and stress but also clinical drugs that we use to cure bacterial infections.
When organisms hibernate, their molecules can hibernate too. What happens inside a living cell when an organism hibernates? It was believed until recently that when a living cell encounters environmental stress, it ceases most of its metabolic activities and its key enzymes remain vacant and idle until conditions improve. However, it has become clear in recent years that organisms, from bacteria to humans, can employ a special mechanism to protect their key enzymes from degradation or unwanted activity under conditions of stress. This mechanism is based on putting their enzymes into a state akin hibernation of animals, known as molecular hibernation. Typically, molecular hibernation involve enzyme association with a specialized inhibitor/partner that occupies the active site of this enzyme.
One example of hibernating enzymes includes protasome. Proteasome is an enzyme complex that catalyzes the degradation of proteins. In some species of animals, the activity of proteasome decreases during hibernation, allowing the animal to conserve energy. This is accomplished by the binding of an inhibitor called lactacystin to the active site of proteasome, which prevents it from catalyzing the degradation of proteins.
Another example is calcineurin, an enzyme that catalyzes the dephosphorylation of target proteins in response to calcium signals. In some species of animals, the activity of calcineurin decreases during hibernation, allowing the animal to conserve energy. This is accomplished by the binding of an inhibitor called cyclosporin A, FK506, and Tacrolimus to the active site of calcineurin, which prevents it from catalyzing the dephosphorylation of target proteins.
Every time I hear people ranting about life being unfair, huffing and puffing if things don’t go their way, I recall this stunning visual: “What are the odds”. It estimates our odds of being alive, showing they are just a fraction above zero, or 1 in 102,685,000 if you like math.
Imagine: 1 in 102,685,000. As someone put it, “that probability is the same as if you handed out 2 million dice, each dice with one trillion sides… then rolled those 2 million dice and had them all land on 439,505,270,846.” It seems we are damn good at gambling! At least for once. So, when next time your dumb classmate gets into Harvard and you fail as a valedectorian, please recall this absurdly slim chance of your existance, and take a moment to appreciate this unique gift of luck — to be alive as a concious human being, to share this transient journey we call life with people we love, to get a chance to understand and explore ourselves and the universe around us, to breath air and enjoy warm rays of the morning Sun — all those things we take for granted while being obsessed with the cherry on top. Because, if scientists got it right, our life is highly improbable, and it won’t last for long. Thus, luckily for us, life is tremendously unfair, if you see what I mean.
Apparently there is an amazingly simple and elegant trick to help people interact with new people at conferences (and other social events). And I am not talking about chutzpah (although this is a great quality to have, at least within reason). What I am talking about is the Pac-Man rule: https://www.ericholscher.com/blog/2017/aug/2/pacman-rule-conferences/
In late 1970s, agriculture encountered a major crisis in pesticide resistance leading to the near-collapse of the cotton industry in several countries. This crisis forced the industry to devise the Integrated Pest Management (IPM), an approach that aims to minimize the risk of pesticide resistance by limiting pesticide use and by trying to manage pests rather than trying to eradicate them. Our recent paper provides a small “stone” for the emerging “building” of a similar approach – adaptive therapy – that aims to improve the way use antimicrobial and anticancer drugs: https://www.pnas.org/content/early/2020/07/10/2003132117
Please check out this wonderful blog post by Maria O’Hanlon discussing our work and this emerging new trend in more sustainable drug application: https://bit.ly/3fs45sr
Grants and Fellowships: Nature's ad of the three searchable databases of global funding opportunities for graduate students, postdocs and junior faculty members: https://t.co/7KHJ0k0xx1
Every time I hear people ranting about life being unfair, huffing and puffing if things don’t go their way, I recall this stunning visual: 
