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Scientists build tiny biological robots from human cells
Researchers at Tufts University and Harvard University’s Wyss Institute have created tiny biological robots that they call Anthrobots from human tracheal cells that can move across a surface and have been found to encourage the growth of neurons across a region of damage in a lab dish.
The work follows from earlier research in the laboratories of Michael Levin, Vannevar Bush Professor of Biology at Tufts University School of Arts & Sciences, and Josh Bongard at the University of Vermont in which they created multicellular biological robots from frog embryo cells called Xenobots, capable of navigating passageways, collecting material, recording information, healing themselves from injury, and even replicating for a few cycles on their own. At the time, researchers did not know if these capabilities were dependent on their being derived from an amphibian embryo, or if biobots could be constructed from cells of other species.
In the current study, published in Advanced Science, Levin, along with PhD student Gizem Gumuskaya discovered that bots can in fact be created from adult human cells without any genetic modification and they are demonstrating some capabilities beyond what was observed with the Xenobots. The discovery starts to answer a broader question that the lab has posed — what are the rules that govern how cells assemble and work together in the body, and can the cells be taken out of their natural context and recombined into different “body plans” to carry out other functions by design?
In this case, researchers gave human cells, after decades of quiet life in the trachea, a chance to reboot and find ways of creating new structures and tasks. “We wanted to probe what cells can do besides create default features in the body,” said Gumuskaya, who earned a degree in architecture before coming into biology. “By reprogramming interactions between cells, new multicellular structures can be created, analogous to the way stone and brick can be arranged into different structural elements like walls, archways or columns.” The researchers found that not only could the cells create new multicellular shapes, but they could move in different ways over a surface of human neurons grown in a lab dish and encourage new growth to fill in gaps caused by scratching the layer of cells.
Exactly how the Anthrobots encourage growth of neurons is not yet clear, but the researchers confirmed that neurons grew under the area covered by a clustered assembly of Anthrobots, which they called a “superbot.”
“The cellular assemblies we construct in the lab can have capabilities that go beyond what they do in the body,” said Levin, who also serves as the director of the Allen Discovery Center at Tufts and is an associate faculty member of the Wyss Institute. “It is fascinating and completely unexpected that normal patient tracheal cells, without modifying their DNA, can move on their own and encourage neuron growth across a region of damage,” said Levin. “We’re now looking at how the healing mechanism works, and asking what else these constructs can do.”
The advantages of using human cells include the ability to construct bots from a patient’s own cells to perform therapeutic work without the risk of triggering an immune response or requiring immunosuppressants. They only last a few weeks before breaking down, and so can easily be re-absorbed into the body after their work is done.
In addition, outside of the body, Anthrobots can only survive in very specific laboratory conditions, and there is no risk of exposure or unintended spread outside the lab. Likewise, they do not reproduce, and they have no genetic edits, additions or deletions, so there is no risk of their evolving beyond existing safeguards.
How Are Anthrobots Made?
Each Anthrobot starts out as a single cell, derived from an adult donor. The cells come from the surface of the trachea and are covered with hairlike projections called cilia that wave back and forth. The cilia help the tracheal cells push out tiny particles that find their way into air passages of the lung. We all experience the work of ciliated cells when we take the final step of expelling the particles and excess fluid by coughing or clearing our throats. Earlier studies by others had shown that when the cells are grown in the lab, they spontaneously form tiny multicellular spheres called organoids.
The researchers developed growth conditions that encouraged the cilia to face outward on organoids. Within a few days they started moving around, driven by the cilia acting like oars. They noted different shapes and types of movement — the first. important feature observed of the biorobotics platform. Levin says that if other features could be added to the Anthrobots (for example, contributed by different cells), they could be designed to respond to their environment, and travel to and perform functions in the body, or help build engineered tissues in the lab.
The team, with the help of Simon Garnier at the New Jersey Institute of Technology, characterized the different types of Anthrobots that were produced. They observed that bots fell into a few discrete categories of shape and movement, ranging in size from 30 to 500 micrometers (from the thickness of a human hair to the point of a sharpened pencil), filling an important niche between nanotechnology and larger engineered devices.
Some were spherical and fully covered in cilia, and some were irregular or football shaped with more patchy coverage of cilia, or just covered with cilia on one side. They traveled in straight lines, moved in tight circles, combined those movements, or just sat around and wiggled. The spherical ones fully covered with cilia tended to be wigglers. The Anthrobots with cilia distributed unevenly tended to move forward for longer stretches in straight or curved paths. They usually survived about 45-60 days in laboratory conditions before they naturally biodegraded.
“Anthrobots self-assemble in the lab dish,” said Gumuskaya, who created the Anthrobots. “Unlike Xenobots, they don’t require tweezers or scalpels to give them shape, and we can use adult cells — even cells from elderly patients — instead of embryonic cells. It’s fully scalable — we can produce swarms of these bots in parallel, which is a good start for developing a therapeutic tool.”
Little Healers
Because Levin and Gumuskaya ultimately plan to make Anthrobots with therapeutic applications, they created a lab test to see how the bots might heal wounds. The model involved growing a two-dimensional layer of human neurons, and simply by scratching the layer with a thin metal rod, they created an open ‘wound’ devoid of cells.
To ensure the gap would be exposed to a dense concentration of Anthrobots, they created “superbots” a cluster that naturally forms when the Anthrobots are confined to a small space. The superbots were made up primarily of circlers and wigglers, so they would not wander too far away from the open wound.
Although it might be expected that genetic modifications of Anthrobot cells would be needed to help the bots encourage neural growth, surprisingly the unmodified Anthrobots triggered substantial regrowth, creating a bridge of neurons as thick as the rest of the healthy cells on the plate. Neurons did not grow in the wound where Anthrobots were absent. At least in the simplified 2D world of the lab dish, the Anthrobot assemblies encouraged efficient healing of live neural tissue.
According to the researchers, further development of the bots could lead to other applications, including clearing plaque buildup in the arteries of atherosclerosis patients, repairing spinal cord or retinal nerve damage, recognizing bacteria or cancer cells, or delivering drugs to targeted tissues. The Anthrobots could in theory assist in healing tissues, while also laying down pro-regenerative drugs.
Making New Blueprints, Restoring Old Ones
Gumuskaya explained that cells have the innate ability to self-assemble into larger structures in certain fundamental ways. “The cells can form layers, fold, make spheres, sort and separate themselves by type, fuse together, or even move,” Gumuskaya said. “Two important differences from inanimate bricks are that cells can communicate with each other and create these structures dynamically, and each cell is programmed with many functions, like movement, secretion of molecules, detection of signals and more. We are just figuring out how to combine these elements to create new biological body plans and functions — different than those found in nature.”
Taking advantage of the inherently flexible rules of cellular assembly helps the scientists construct the bots, but it can also help them understand how natural body plans assemble, how the genome and environment work together to create tissues, organs, and limbs, and how to restore them with regenerative treatments.
An experimental drug originally developed to treat cancer may help clear HIV from infected cells in the brain, according to a new Tulane University study.
Published in the journal Brain, this discovery marks a significant step toward eliminating HIV from hard-to-reach reservoirs where the virus evades otherwise effective treatment.
“This research is an important step in tackling brain-related issues caused by HIV, which still affect people even when they are on effective HIV medication,” said lead study author Woong-Ki Kim, PhD, associate director for research at Tulane National Primate Research Center. “By specifically targeting the infected cells in the brain, we may be able to clear the virus from these hidden areas, which has been a major challenge in HIV treatment.”
Antiretroviral therapy (ART) is an essential component of successful HIV treatment, maintaining the virus at undetectable levels in the blood and transforming HIV from a terminal illness into a manageable condition. However, ART does not completely eradicate HIV, necessitating lifelong treatment. The virus persists in “viral reservoirs” in the brain, liver, and lymph nodes, where it remains out of reach of ART.
The brain has been a particularly challenging area for treatment due to the blood-brain barrier — a protective membrane that shields it from harmful substances but also blocks treatments, allowing the virus to persist. In addition, cells in the brain known as macrophages are extremely long-lived, making them difficult to eradicate once they become infected.
Infection of macrophages is thought to contribute to neurocognitive dysfunction, experienced by nearly half of those living with HIV. Eradicating the virus from the brain is critical for comprehensive HIV treatment and could significantly improve the quality of life for those with HIV-related neurocognitive problems.
Researchers focused on macrophages, a type of white blood cell that harbors HIV in the brain. By using a small molecule inhibitor to block a receptor that increases in HIV-infected macrophages, the team successfully reduced the viral load in the brain. This approach essentially cleared the virus from brain tissue, providing a potential new treatment avenue for HIV.
The small molecule inhibitor used, BLZ945, has previously been studied for therapeutic use in amyotrophic lateral sclerosis (ALS) and brain cancer, but never before in the context of clearing HIV from the brain.
The study, which took place at the Tulane National Primate Research Center, utilized three groups to model human HIV infection and treatment: an untreated control group, and two groups treated with either a low or high dose of the small molecule inhibitor for 30 days. The high-dose treatment lead to a notable reduction in cells expressing HIV receptor sites, as well as a 95-99% decrease in viral DNA loads in the brain .
In addition to reducing viral loads, the treatment did not significantly impact microglia, the brain’s resident immune cells, which are essential for maintaining a healthy neuroimmune environment. It also did not show signs of liver toxicity at the doses tested.
The next step for the research team is to test this therapy in conjunction with ART to assess its efficacy in a combined treatment approach. This could pave the way for more comprehensive strategies to eradicate HIV from the body entirely.
This research was funded by the National Institutes of Health, including grants from the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke, and was supported with resources from the Tulane National Primate Research Center base grant of the National Institutes of Health, P51 OD011104.
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Chemical analyses find hidden elements from renaissance astronomer Tycho Brahe’s alchemy laboratory
In the Middle Ages, alchemists were notoriously secretive and didn’t share their knowledge with others. Danish Tycho Brahe was no exception. Consequently, we don’t know precisely what he did in the alchemical laboratory located beneath his combined residence and observatory, Uraniborg, on the now Swedish island of Ven.
However, during an excavation in 1988-1990, some pottery and glass shards were found in Uraniborg’s old garden. These shards were believed to originate from the basement’s alchemical laboratory. Five of these shards — four glass and one ceramic — have now undergone chemical analyses to determine which elements the original glass and ceramic containers came into contact with.
The chemical analyses were conducted by Professor Emeritus and expert in archaeometry, Kaare Lund Rasmussen from the Department of Physics, Chemistry, and Pharmacy, University of Southern Denmark. Senior researcher and museum curator Poul Grinder-Hansen from the National Museum of Denmark oversaw the insertion of the analyses into historical context.
Enriched levels of trace elements were found on four of them, while one glass shard showed no specific enrichments. The study has been published in the journal Heritage Science.
“Most intriguing are the elements found in higher concentrations than expected — indicating enrichment and providing insight into the substances used in Tycho Brahe’s alchemical laboratory,” said Kaare Lund Rasmussen.
The enriched elements are nickel, copper, zinc, tin, antimony, tungsten, gold, mercury, and lead, and they have been found on either the inside or outside of the shards.
Most of them are not surprising for an alchemist’s laboratory. Gold and mercury were — at least among the upper echelons of society — commonly known and used against a wide range of diseases.
“But tungsten is very mysterious. Tungsten had not even been described at that time, so what should we infer from its presence on a shard from Tycho Brahe’s alchemy workshop?,” said Kaare Lund Rasmussen.
Tungsten was first described and produced in pure form more than 180 years later by the Swedish chemist Carl Wilhelm Scheele. Tungsten occurs naturally in certain minerals, and perhaps the element found its way to Tycho Brahe’s laboratory through one of these minerals. In the laboratory, the mineral might have undergone some processing that separated the tungsten, without Tycho Brahe ever realizing it.
However, there is also another possibility that Professor Kaare Lund Rasmussen emphasizes has no evidence whatsoever — but which could be plausible.
Already in the first half of the 1500s, the German mineralogist Georgius Agricola described something strange in tin ore from Saxony, which caused problems when he tried to smelt tin. Agricola called this strange substance in the tin ore “Wolfram” (German for Wolf’s froth, later renamed to tungsten in English).
“Maybe Tycho Brahe had heard about this and thus knew of tungsten’s existence. But this is not something we know or can say based on the analyses I have done. It is merely a possible theoretical explanation for why we find tungsten in the samples,” said Kaare Lund Rasmussen.
Tycho Brahe belonged to the branch of alchemists who, inspired by the German physician Paracelsus, tried to develop medicine for various diseases of the time: plague, syphilis, leprosy, fever, stomach aches, etc. But he distanced himself from the branch that tried to create gold from less valuable minerals and metals.
In line with the other medical alchemists of the time, he kept his recipes close to his chest and shared them only with a few selected individuals, such as his patron, Emperor Rudolph II, who allegedly received Tycho Brahe’s prescriptions for plague medicine.
We know that Tycho Brahe’s plague medicine was complicated to produce. It contained theriac, which was one of the standard remedies for almost everything at the time and could have up to 60 ingredients, including snake flesh and opium. It also contained copper or iron vitriol (sulphates), various oils, and herbs.
After various filtrations and distillations, the first of Brahe’s three recipes against plague was obtained. This could be made even more potent by adding tinctures of, for example, coral, sapphires, hyacinths, or potable gold.
“It may seem strange that Tycho Brahe was involved in both astronomy and alchemy, but when one understands his worldview, it makes sense. He believed that there were obvious connections between the heavenly bodies, earthly substances, and the body’s organs. Thus, the Sun, gold, and the heart were connected, and the same applied to the Moon, silver, and the brain; Jupiter, tin, and the liver; Venus, copper, and the kidneys; Saturn, lead, and the spleen; Mars, iron, and the gallbladder; and Mercury, mercury, and the lungs. Minerals and gemstones could also be linked to this system, so emeralds, for example, belonged to Mercury,” explained Poul Grinder-Hansen.
Kaare Lund Rasmussen has previously analyzed hair and bones from Tycho Brahe and found, among other elements, gold. This could indicate that Tycho Brahe himself had taken medicine that contained potable gold.
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Nitrogen emissions have a net cooling effect: But researchers warn against a climate solution
An international team of researchers has found that nitrogen emissions from fertilisers and fossil fuels have a net cooling effect on the climate. But they warn increasing atmospheric nitrogen has further damaging effects on the environment, calling for an urgent reduction in greenhouse gas emissions to halt global warming.
The paper was led by the Max Planck Institute in Germany and included authors from the University of Sydney. It comes one day after new data from the European Union’s Copernicus Climate Change Service indicated that Sunday, 21 July was the hottest day recorded in recent history.
The net cooling effect occurs in four ways:
- Short-lived nitrogen oxides produced by the combustion of fossil fuels pollute the atmosphere by forming fine suspended particles which shield sunlight, in turn cooling the climate;
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ammonia (a nitrogen and hydrogen-based compound) released into the atmosphere from the application of manure and artificial fertilisers has a similar effect;
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nitrogen applied to crops allows plants to grow more abundantly, absorbing more CO2 from the atmosphere, enabling a cooling effect;
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nitrogen oxides also play a role in the breakdown of atmospheric methane, a potent greenhouse gas.
The researchers warned that increasing atmospheric nitrogen was not a solution for combatting climate change.
“Nitrogen fertilisers pollute water and nitrogen oxides from fossil fuels pollute the air. Therefore, increasing rates of nitrogen in the atmosphere to combat climate change is not an acceptable compromise, nor is it a solution,” said Professor Federico Maggi from the University of Sydney’s School of Civil Engineering.
Sönke Zaehle from the Max Planck Institute said: “This may sound like good news, but you have to bear in mind that nitrogen emissions have many harmful effects, for example on health, biodiversity and the ozone layer. The current findings, therefore, are no reason to gloss over the harmful effects, let alone see additional nitrogen input as a means of combatting global warming.”
Elemental nitrogen, which makes up around 78 percent of the air, is climate-neutral, but other reactive nitrogen compounds can have direct or indirect effects on the global climate — sometimes warming and at other times cooling. Nitrous oxide (N2O) is an almost 300 times more potent greenhouse gas than CO2. Other forms of nitrogen stimulate the formation of ozone in the troposphere, which is a potent greenhouse gas and enhances global warming.
Professor Maggi said the research was important as it helped the team gain an understanding of the net-effect of the distribution of nitrogen emissions from agriculture.
“This work is an extraordinary example of how complex interactions at planetary scales cannot be captured with simplistic assessment tools. It shows the importance of developing mathematical models that can show the emergence of nonlinear — or unproportional — effects across soil, land, and atmosphere,” he said.
“Even if it appears counter-intuitive, reactive nitrogen introduced in the environment, mostly as agricultural fertilisers, can reduce total warming. However, this is minor compared with the reduction in greenhouse gas emissions required to keep the planet within safe and just operational boundaries.
“New generation computational tools are helping drive new learnings in climate change science, but understanding is not enough — we must act with great urgency to reduce greenhouse gas emissions.”
Gaining a holistic understanding of the impacts of nitrogen
The scientists determined the overall impact of nitrogen from human sources by first analysing the quantities of the various nitrogen compounds that end up in soil, water and air.
They then fed this data into models that depict the global nitrogen cycle and the effects on the carbon cycle, for example the stimulation of plant growth and ultimately the CO2 and methane content of the atmosphere. From the results of these simulations, they used another atmospheric chemistry model to calculate the effect of man-made nitrogen emissions on radiative forcing, that is the radiant energy that hits one square metre of the Earth’s surface per unit of time.
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