In 1988, Richard Lenski, a thirty-one-year-old biologist at UC Irvine, started an experiment. He divided a population of a common bacterium, E. coli, into twelve flasks. Each flask was kept at thirty-seven degrees Celsius, and contained an identical cocktail of water, glucose, and other nutrients. Each day, as the bacteria replicated, Lenski transferred several drops of each cocktail to a new flask, and every so often he stored samples away in a freezer. His goal was to understand the mechanics of evolution. How quickly, effectively, creatively, and consistently do microorganisms improve their reproductive fitness?
Lenski’s flasks produced about six new generations of E. coli a day; the bacteria woke up as babies and went to bed as great-great-great-grandparents. In this way, Lenski and his team have studied more than seventy thousand generations of E. coli over thirty-three years. Compared with their distant ancestors, the latest versions of the bacterium reproduce seventy per cent faster; it once took them an hour to double their ranks, but now they can do it in less than forty minutes. Different populations have taken different paths to enhanced fitness, but, after decades, most have arrived at reproduction rates within a few percentage points of one another.
Lenski’s Long-Term Evolution Experiment, or L.T.E.E., as it’s called, has yielded fundamental insights into the mutational capabilities of microorganisms. For his work, Lenski, now in his sixties and at Michigan State University, has received a MacArthur “genius” grant and a Guggenheim Fellowship. “I’m not sure I can tell you how it’s affected my thinking, because I’m not sure I can conceive of being in this field without this experiment existing,” Michael Baym, an evolutionary biologist at Harvard Medical School, recently told Discover.
Three of the experiment’s key findings are especially relevant today. The first is that, in general, there were diminishing returns to mutation over time: the bacteria made many of their most reproductively advantageous moves early on. A second finding, however, was that the bacteria never stopped getting fitter. Seventy thousand generations in, they’re still finding new ways to improve, albeit at a somewhat slower rate. “I had sort of imagined that things would have flatlined,” Lenski told me recently, when we spoke over Zoom. “But there seem to be endless possibilities for tinkering and progress. If there is a hard limit, it’s so, so far away that it’s impractical to consider on an experimental timescale—maybe even a geological timescale.”
Lenski has a friendly, expressive face, with pale blue eyes and a neat beard; his voice pulses with excitement when he considers a provocative question or explains the implications of his research. He told me about a third major finding: in 2003, some fifteen years and thirty thousand generations into the experiment, Lenski arrived at his lab to find that, overnight, a flask that was normally fairly translucent had turned cloudy. The bacteria it contained had experienced an explosive surge in growth. Normally, E. coli eat mainly glucose, but this population had unlocked an entirely new source of energy: a chemical compound called citrate. The capacity to metabolize citrate is so unusual that no population in the study had developed it until that point, and none have attained it since. It’s as if a family of humans could suddenly drink salt water.
sars-CoV-2, the virus that causes covid-19, has already had one citrate moment: the instant, probably sometime in 2019 but possibly earlier, when it developed the ability to leap into humans. Since then, the virus has accumulated innumerable mutations, some of which allow it to generate copies of itself more efficiently—by altering how it binds to our cells, for instance, or by finding new ways to slip past our immune systems. It’s a process that has occurred with every infectious disease in history—measles, tuberculosis, bubonic plague, influenza, and untold others. The difference with the coronavirus is that the world is now watching every mutational move as it happens.
During this pandemic, we’ve developed and deployed vaccines in real time. Meanwhile, sars-CoV-2 is replicating not in a dozen flasks but in tens of millions of people, some of whom have been immunized, all of whom exert selective pressure for the virus to find new, more efficient replication strategies. The virus will continue to mutate every moment of every day, for years, for decades. The fear is that it will hit upon a second citrate moment: a mutation, or set of mutations, that enables it to circumvent our vaccines, which so far have proved spectacularly effective and resilient. For those who remain unvaccinated—the majority of humankind—there is also the horrifying prospect of a variant that is vastly more contagious or deadly. Every few months, we learn of a version of the virus that seems somehow worse: Alpha, Beta, Gamma, Delta. The coronavirus appears destined to march its way through the Greek alphabet—a prizefighter getting quicker, slicker, stronger with each opponent. What are the limits to its evolutionary fitness? Are they knowable? And, if so, how close are we to reaching them?
These were the questions on my mind as I spoke with experts in an effort to understand the future of the pandemic. With questions so complex, it’s helpful to start by figuring out what, exactly, we want to know. For each new coronavirus variant, we want to find out if it’s more transmissible, if it will make us sicker, and if it will more effectively get around our immune defenses. On that last front, we want to understand two more questions: How much will it succeed in hiding from our antibodies (which recognize and bind to the virus, preventing infection) and from our T cells (which recognize chopped-up viral fragments displayed by infected cells, and specialize not in preventing infection but in controlling and terminating it).
Roberto Burioni, a physician and professor at Vita-Salute San Raffaele University, in Milan, has been called the most famous virologist in Italy; he has written about the prospects for a “final” variant, a version of the coronavirus that has reached maximum transmissibility, and which becomes “the dominant strain, experiencing only occasional, minimal variations.” As Burioni sees it, there are three potential futures for the coronavirus. The first—the most optimistic for us—is one in which the virus simply can’t evolve its way around the vaccines. This is not an unlikely possibility. Many viruses—measles, mumps, rubella, polio, smallpox—have never meaningfully circumvented their vaccines, and so far the best of our current jabs have remained remarkably protective against new coronavirus variants, including Delta….
![](https://www.nanoappsmedical.com/wp-content/uploads/2017/05/spacer.jpg)
News
The Silent Battle Within: How Your Organs Choose Between Mom and Dad’s Genes
Research reveals that selective expression of maternal or paternal X chromosomes varies by organ, driven by cellular competition. A new study published today (July 26) in Nature Genetics by the Lymphoid Development Group at the MRC [...]
Study identifies genes increasing risk of severe COVID-19
Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in [...]
Small regions of the brain can take micro-naps while the rest of the brain is awake and vice versa
Sleep and wake: They're totally distinct states of being that define the boundaries of our daily lives. For years, scientists have measured the difference between these instinctual brain processes by observing brain waves, with [...]
Redefining Consciousness: Small Regions of the Brain Can Take Micro-Naps While the Rest of the Brain Is Awake
The study broadly reveals how fast brain waves, previously overlooked, establish fundamental patterns of sleep and wakefulness. Scientists have developed a new method to analyze sleep and wake states by detecting ultra-fast neuronal activity [...]
AI Reveals Health Secrets Through Facial Temperature Mapping
Researchers have found that different facial temperatures correlate with chronic illnesses like diabetes and high blood pressure, and these can be detected using AI with thermal cameras. They highlight the potential of this technology [...]
Breakthrough in aging research: Blocking IL-11 extends lifespan and improves health in mice
In a recent study published in the journal Nature, a team of researchers used murine models and various pharmacological and genetic approaches to examine whether pro-inflammatory signaling involving interleukin (IL)-11, which activates signaling molecules such [...]
Promise for a universal influenza vaccine: Scientists validate theory using 1918 flu virus
New research led by Oregon Health & Science University reveals a promising approach to developing a universal influenza vaccine—a so-called "one and done" vaccine that confers lifetime immunity against an evolving virus. The study, [...]
New Projects Aim To Pioneer the Future of Neuroscience
One study will investigate the alterations in brain activity at the cellular level caused by psilocybin, the psychoactive substance found in “magic mushrooms.” How do neurons respond to the effects of magic mushrooms? What [...]
Decoding the Decline: Scientific Insights Into Long COVID’s Retreat
Research indicates a significant reduction in long COVID risk, largely due to vaccination and the virus’s evolution. The study analyzes data from over 441,000 veterans, showing lower rates of long COVID among vaccinated individuals compared [...]
Silicon Transformed: A Breakthrough in Laser Nanofabrication
A new method enables precise nanofabrication inside silicon using spatial light modulation and laser pulses, creating advanced nanostructures for potential use in electronics and photonics. Silicon, the cornerstone of modern electronics, photovoltaics, and photonics, [...]
Caught in the actinium: New research could help design better cancer treatments
The element actinium was first discovered at the turn of the 20th century, but even now, nearly 125 years later, researchers still don't have a good grasp on the metal's chemistry. That's because actinium [...]
Innovative Light-Controlled Drugs Could Revolutionize Neuropathic Pain Treatment
A team of researchers from the Institute for Bioengineering of Catalonia (IBEC) has developed light-activated derivatives of the anti-epileptic drug carbamazepine to treat neuropathic pain. Light can be harnessed to target drugs to specific [...]
Green Gold: Turning E-Waste Into a Treasure Trove of Rare Earth Metals
Scientists are developing a process inspired by nature that efficiently recovers europium from old fluorescent lamps. The approach could lead to the long-awaited recycling of rare earth metals. A small molecule that naturally serves [...]
Cambridge Study: AI Chatbots Have an “Empathy Gap,” and It Could Be Dangerous
A new study suggests a framework for “Child Safe AI” in response to recent incidents showing that many children perceive chatbots as quasi-human and reliable. A study has indicated that AI chatbots often exhibit [...]
Nanoparticle-based delivery system could offer treatment for diabetics with rare insulin allergy
Up to 3% of people with diabetes have an allergic reaction to insulin. A team at Forschungszentrum Jülich has now studied a method that could be used to deliver the active substance into the [...]
Nanorobot kills cancer cells in mice with hidden weapon
Researchers at Karolinska Institutet in Sweden have developed nanorobots that kill cancer cells in mice. The robot's weapon is hidden in a nanostructure and is exposed only in the tumor microenvironment, sparing healthy cells. [...]