After years of failed attempts, researchers have successfully cloned human stem cells from adult cells – a breakthrough that could one day lead to diseased or damaged cells being regenerated in patients.
A report in the journal Cell Stem Cell describes how the same cloning technique that produced Dolly the sheep was applied, but with adult human cells. Last year, a team at Oregon Health & Science University used this method to clone stem cells from fetuses.
This time, the cells were derived from adults – 35 and 75 years old, respectively.
Nuclear transfer, as the process is called, involves taking a donor's DNA – in this case from skin cells – then inserting that DNA into an "empty" egg cell with its DNA stripped out. The resulting hybrid cell is stimulated to fuse and begin dividing, with a new line of stem cells being created within a few days from the donor DNA. These stem cells are then extracted in the laboratory, where further treatments enable them to develop into specific types of cells, like neurons, muscle, insulin-producing cells, or whatever is required. Type 1 diabetics, for example, unable to make enough insulin, could in theory generate their own cells that produced the hormone.
Key to the success of this latest breakthrough was the use of caffeine to prevent the hybrid egg from dividing prematurely. The eggs were made to rest for about two hours – rather than 30 minutes – giving the DNA extra time to adjust and interact with its new environment. This delayed reaction apparently "erased" the cell's history, causing it to behave like an entirely new structure.
Of the 77 samples, however, only two fully developed into clone stem cells. The process remains highly inefficient and expensive, meaning that only extremely rich individuals could benefit at present. Despite this, lead researcher Dr. Robert Lanza and his team at biotech firm Advanced Cell Technology are optimistic that progress will continue. Their experiments have now proved, for the first time, that successful cloning of human stem cells is possible with donors of any age – even the elderly. Lanza now hopes to create a virtual library of cells, using carefully selected DNA donors taken from millions of different samples.
This breakthrough also reignites the debate on full human cloning, its ethical implications and potential for abuse. Marcy Darnovsky, a director at the Center for Genetics and Society, has commented: "If we're going to be having cloned embryos in laboratories around the country, we really need to get our act together and have a law that prohibits human reproductive cloning. Sixty countries have done that."
As to the question of when human cloning might happen – Dr. Paul Knoepfler, from UC Davis School of Medicine, says: "I don't believe that's coming anytime soon, but certainly this kind of technology could be abused by some kind of rogue scientist."
Researchers have published the first comprehensive, large-scale data set on how the brain of a mammal is wired, providing a groundbreaking new data resource and fresh insights into how the nervous system processes information.
Credit: Allen Institute for Brain Science
While the human brain contains over 100 billion individual neurons, the mouse brain contains 75 million. However, the two structures are very similar, making it possible to compare them and identify many important processes. As computer power continues to advance exponentially, it is becoming possible to model networks of neurons in greater and greater detail. The first complete simulation of a single neuron was perfected in 2005; this was followed by a neocortical column with 10,000 neurons in 2008; then a cortical mesocircuit with 1,000,000 neurons in 2011. Now, a team of researchers from the Allen Institute in Seattle has achieved a major milestone by simulating an entire mouse brain, containing 75 million neurons. If trends continue, entire human brains could be modelled within the next decade.
A landmark study published this month in the journal Nature both describes the publicly available Allen Mouse Brain Connectivity Atlas, and demonstrates the exciting new knowledge that can be gleaned from this valuable resource.
"Understanding how the brain is wired is among the most crucial steps to understanding how the brain encodes information," explains Hongkui Zeng, Senior Director of Research Science at the Allen Institute for Brain Science. "The Allen Mouse Brain Connectivity Atlas is a standardised, quantitative, and comprehensive resource that will stimulate exciting investigations around the entire neuroscience community, and from which we have already gleaned unprecedented details into how structures are connected inside the brain."
Using the data – which took four years of work to collect – the researchers were able to demonstrate highly specific patterns in the connections among different brain regions. The strengths of these connections were found to vary with greater than five orders of magnitude, balancing a small number of strong connections with a large number of weak connections.
The researchers set out to create a wiring diagram of the brain – known as a "connectome" – to illustrate short and long-range connections using genetically-engineered viruses, able to trace and illuminate individual neurons. To get a truly comprehensive view, imaging data was collected at resolutions smaller than a micrometre from over 1,700 mouse brains.
"The data for the Allen Mouse Brain Connectivity Atlas was collected in a way that’s never been done before," says Zeng. "Standardising the data generation process allowed us to create a 3D common reference space, meaning we could put the data from all of our thousands of experiments next to each other and compare them all in a highly quantitative way at the same time."
The Allen Mouse Brain Connectivity Atlas contains over 1.8 petabytes of data – equivalent to 24 years of continuous HD video. The team behind it has been steadily releasing new data since November 2011; and in March, they released the last major update, though the resource will continue to be updated as technology develops and researchers are able to add more new types of connectivity data.
"The Allen Mouse Brain Connectivity Atlas provides an initial road-map of the brain, at the level of interstate highways and major cities that they link," explains David Anderson, Professor of Biology at the California Institute of Technology. "Smaller road networks and their intersections with the interstates will be the next step, followed by maps of local streets in different municipalities. This information will provide a framework for what we ultimately want to understand: ‘traffic patterns’ of information flow in the brain during various activities such as decision-making, mapping of the physical environment, learning and remembering, and other cognitive or emotional processes."
With the Nature publication, Allen Institute scientists have already begun to demonstrate the power of analysis contained within the Atlas. By analysing their data, Zeng and her team were able to discover several interesting properties of the mouse brain's connectome. For example, there are extensive connections across the two hemispheres with mirror-image symmetry. Pathways belonging to different functional circuits in the brain can be identified and their relationships and intersections visualised in 3D.
The Atlas will serve as an invaluable tool for neuroscientists all over the world, long into the future. "Previously, the scientific community had to rely on incomplete, fragmented data sets, like small pieces of a map but at different scales and resolutions, so it was impossible to see the bigger picture," explains Professor Ed Callaway, in the Systems Neurobiology Laboratories at the Salk Institute for Biological Studies. “Now, we have instant access to complete and consistent data across the entire brain, and the suite of web-based analytic and display tools make it easy to find what you need and to see it in 3D.
"Who you are – all your thoughts and actions your entire life – is based on connections between neurons," Callaway continues. "So if we want to understand any of these processes or how they go wrong in disease, we have to understand how those circuits function. Without an atlas, we couldn’t hope to gain that understanding."
The first evidence that CRISPR can reverse a disease in living animals has been demonstrated. Using this new gene-editing technique, MIT researchers cured mice of a rare liver disorder.
Illustration: Christine Daniloff/MIT
CRISPR is a revolutionary new technique for editing DNA. It is much faster and more accurate than previous methods, enables many genes to be modified at once, and can reduce the times needed for animal studies from months to weeks. Gene therapy often involves using modified viruses that insert DNA at random places on the genome – a haphazard and risky process that is unsuitable for many patients. With CRISPR, however, extreme precision allows detailed alterations of any specific position on the genome, without introducing unintended mutations or flaws. Last year, it was described by Nobel-winning scientist Craig Mello as "jaw-dropping", "a real game-changer" and "a tremendous breakthrough with huge implications for molecular genetics."
Now, researchers at the Massachusetts Institute of Technology (MIT) have used CRISPR to snip out faulty DNA in mice and replace it with the correct sequence – curing them of a rare liver disorder. This new study, published yesterday in Nature Biotechnology, offers the first evidence that CRISPR is able to reverse disease symptoms in living animals.
Professor Daniel G. Anderson, senior author of the paper: "What's exciting about this approach is that we can actually correct a defective gene in a living adult animal."
When bacteria come under attack from viral infection, they rely on a type of cellular machinery to defend themselves. Researchers have copied this system to create gene-editing complexes. This includes a DNA-cutting enzyme called Cas9, which is bound to a short RNA guide strand – programmed to bind to a specific genome sequence and tell Cas9 where to make its cut. At the same time, the researchers also deliver a DNA template strand. When the cell repairs the damage produced by Cas9, it copies from this template, introducing new genetic material into the genome.
This method holds potential for treating many genetic disorders in humans, say the researchers. Other gene-editing systems based on DNA-slicing enzymes have been created in the past – but using those complexes, it is much harder and more expensive to make a nuclease that's specific to your target of interest.
"The CRISPR system is very easy to configure and customise," says Anderson.
In experiments with adult mice carrying a mutated form of the FAH enzyme, researchers delivered RNA guide strands and the gene for Cas9, along with a 199-nucleotide DNA template for the correct sequence. The healthy gene was inserted in about 0.4 percent of hepatocytes – the cells that make up most of the liver. Over the next 30 days, those healthy cells began to spread and replace diseased liver cells, eventually accounting for one-third of all hepatocytes. This was enough to cure the disease, allowing the mice to survive after being taken off medication.
"We can do a one-time treatment and totally reverse the condition," says Hao Yin, a postdoc at the Koch Institute and one of the lead authors of the Nature Biotechnology paper.
"This work is an exciting first step to using modern gene-editing tools to correct devastating genetic diseases for which there are currently no options for affected patients," says Charles Gersbach at Duke University, who was not part of the research team.
To deliver the CRISPR components, the researchers employed a technique known as high-pressure injection, which uses a high-powered syringe to rapidly discharge material into a vein. This approach delivers material successfully to liver cells – but Anderson envisions that better delivery approaches are possible. His lab is now working on methods that may be safer and more efficient – including targeted nanoparticles.
In the last year, thousands of research labs around the world have started using the CRISPR system to create their own genetically modified cell lines. IVF doctors believe it could be used to prevent inherited diseases in families by changing an embryo's DNA before implantation into the womb. In addition to medical cures, CRISPR may accelerate the development of GM crops and livestock.
DNA can already tell us the sex and ancestry of unknown individuals, but now an international team of researchers is beginning to connect genetics with facial features, degrees of femininity and racial admixture.
Image: Shriver Claes/Penn State
"By jointly modelling sex, genomic ancestry and genotype, the independent effects of particular alleles on facial features can be uncovered," the researchers state in PLOS Genetics. They add that "by simultaneously modelling facial shape variation as a function of sex and genomic ancestry along with genetic markers in craniofacial candidate genes, the effects of sex and ancestry can be removed from the model thereby providing the ability to extract the effects of individual genes."
In essence, by including sex and racial admixture, researchers can learn about how certain genes and their variations influence the shape of the face and its features.
"We use DNA to match to an individual or identify an individual, but you can get so much more from DNA," says Mark D. Shriver, professor of anthropology, Penn State. "Currently we can't go from DNA to a face or from a face to DNA, but it should be possible."
The researchers looked at both actual physical face shape and genetic markers of face shape. They then validated their study by asking individuals to look at faces and determine four things. Is this face male or female? How feminine is it? What proportion of this person is West African? What group would you put this person in, Black African or African-American; White, European or European-American; or Mixed?
To look at the physical face shape, the researchers used populations of mixed West African and European ancestry from the U.S., Brazil and Cape Verde. They placed a grid on 3-D images of the faces of the subjects and measured the spatial coordinates of the grid points. They then used statistical methods to determine the relationship between the variation in the faces and the effects of sex, genomic ancestry and genes that affect the shape of the head and face.
To identify these genes, the researchers looked at known genetic mutations that cause facial and cranial deformation because these genes in their normal variations might also affect the face and head. For example, one gene affects the lips, another changes the shape and configuration of the bones around the eyes, and another influences the shape of the mid face and skull.
"Probably only 5 percent of genes show a difference between populations," said Shriver. "We are using different populations because they have had different environments and different social environments."
The researchers look at the face because it is the most visible part of humans, and characteristics are likely to be influenced by selection. The environment, the local temperatures, rainfall, elevation or other factors in the surroundings may influence certain physical features. Other facial characteristics may be influenced by sexual selection, a recognised or unrecognised preference for a certain look. This changes from group to group and may have no influence on survivability but are instead related to mate choice and contest competition. Both forms of selection will concentrate certain variations in geological areas over time. By looking at groups of mixed ancestry, the researchers can more easily identify the different variations.
"The environment and social environment are major driving factors in changing a whole set of genes that make up how a person looks," said Peter Claes, postdoctoral researcher and expert in morphometrics at Medical Imaging Research Centre, KU Leuven, Belgium.
Eventually, the researchers think that they might approximate the image of a parent from the DNA of children or better visualise some of Homo sapiens' ancestors by looking at DNA. On a more practical level, law enforcement groups might be able to create a "mug shot" from DNA to identify both victims and criminals. These predictive models taken from DNA would be forensically very useful.
Brain implants today are where laser eye surgery was several decades ago – fraught with risk, and applicable only to a narrowly defined set of patients... but a sign of things to come. Professor of Psychology, Gary Marcus, discusses this emerging area of science and its future possibilities. Video courtesy of the Wall Street Journal.
Human Longevity Inc. (HLI) – a new company focused on extending healthy, high performance human lifespan – was announced this week by co-founders Peter Diamandis, Craig Venter and Robert Hariri.
The company, based in San Diego, California, is being capitalised with an initial $70 million investment. These funds will be used to build the most comprehensive and complete human genome, microbiome, and phenotype database in the world – available to tackle the diseases associated with age-related human biological decline. HLI is also leading the development of cell-based therapeutics to address age-related decline in endogenous stem cell function. Revenue streams will be derived from database licensing to pharmaceutical, biotechnology and academic organisations, sequencing and development of advanced diagnostics and therapeutics.
"Using the combined power of our core areas of expertise– genomics, informatics and stem cell therapies, we are tackling one of the greatest medical/scientific and societal challenges – aging and aging related diseases," said Dr. Venter. "HLI is going to change the way medicine is practiced by helping to shift to a more preventive, genomic-based medicine model which we believe will lower healthcare costs. Our goal is not necessarily lengthening life, but extending a healthier, high performing, more productive lifespan."
HLI has purchased two Illumina HiSeq X Ten Sequencing Systems (with an option to acquire three additional systems) to sequence up to 40,000 human genomes per year, with plans to rapidly scale up to 100,000 human genomes per year. HLI will sequence a variety of humans – children, adults and super centenarians, those with diseases and those without.
HLI is focusing its initial clinical sequencing efforts on cancer. While many are tackling this area using gene sequencing and other advanced technologies, there has not been a comprehensive clinical effort to combine germ line, human genome and tumour genome sequencing along with comprehensive biochemical information from each patient. Later, the company plans to extend its efforts to diabetes and obesity, heart and liver diseases, as well as dementia.
The goal of HLI is to analyse, utilise and share data, to enhance diagnostic abilities and improve patient outcomes in medical centres worldwide. This will involve strategic collaborations with Metabolon Inc., the J. Craig Venter Institute (JCVI) and the University of California, San Diego. Together, they will undertake an ambitious multi-pronged effort utilising stem cell therapy advances to enhance and improve the healthy life span. HLI’s work is premised on the theory that as the human body ages, many biological changes occur – including substantial changes and degradation to the genome of the differentiated, specialised cells found in all body tissues. There is also a depletion and degradation of healthy regenerative stem cell populations in the body over time. HLI will monitor genomic changes that occur during stem cell differentiation, normal aging, and in association with the onset of disease.
“The global market for healthy human longevity is enormous, with total healthcare expenditures in those 65 and older running well over $7 trillion,” said Dr. Hariri. “We believe that HLI’s unique science and technology, along with our business leadership, will positively impact the healthcare market with novel diagnostics and therapeutics.”
“Between 1910 and 2010, improvements in medicine and sanitation increased the human lifespan by 50 percent – from 50 to 75 years,” said Dr. Diamandis. “Today, with the emergence of exponential technologies such as those being pioneered and advanced by HLI, we have the potential to meaningfully extend the lifespan even further.”
Using an inexpensive 3-D printer, biomedical engineers have developed a custom-fitted, implantable device with embedded sensors that could transform treatment and prediction of cardiac disorders.
An international team of biomedical engineers and materials scientists have created a 3-D elastic membrane made of a soft, flexible, silicon material, precisely shaped to match the heart's epicardium (its outer layer). Current technology is two-dimensional and cannot cover the full surface of the epicardium or maintain reliable contact for continual use without sutures or adhesives.
Tiny sensors can be printed onto this membrane that precisely measure temperature, mechanical strain and pH level, among other markers, or deliver a pulse of electricity in cases of arrhythmia. These sensors could assist physicians with determining the health of the heart, deliver treatment or predict an impending heart attack before a patient exhibits any physical signs.
"Each heart is a different shape, and current devices are one-size-fits-all and don't at all conform to the geometry of a patient's heart," says Professor Igor Efimov, at Washington University in St. Louis. "With this application, we image the patient's heart through MRI or CT scan, then computationally extract the image to build a 3-D model that we can print on a 3-D printer. We then mold the shape of the membrane that will constitute the base of the device deployed on the surface of the heart."
The video below shows a rabbit heart, kept beating outside the body in a nutrient and oxygen-rich solution. The new cardiac device – with its flexible network of sensors and electrodes – has been custom-designed to fit over the heart and contract and expand as it beats. If all goes well, a version for humans is expected in the next 10-15 years.
Ultimately, this membrane could be used to treat diseases of the ventricles in the lower chambers of the heart or could be inserted inside the heart to treat a variety of disorders – including atrial fibrillation, which affects 3 to 5 million patients in the United States.
"Currently, medical devices to treat heart rhythm diseases are essentially based on two electrodes inserted through the veins and deployed inside the chambers," says Efimov. "Contact with the tissue is only at one or two points, and it is at a very low resolution. What we want to create is an approach that will allow you to have numerous points of contact and to correct the problem with high-definition diagnostics and high-definition therapy."
Recently, Google announced it was developing a contact lens embedded with sensors to monitor glucose levels in diabetes patients. Efimov says the membrane his team has developed is a similar idea, but much more sophisticated.
"Because this is implantable, it will allow physicians to monitor vital functions in different organs and intervene when necessary to provide therapy," he says. "In the case of heart rhythm disorders, it could be used to stimulate cardiac muscle or the brain, or in renal disorders, it would monitor ionic concentrations of calcium, potassium and sodium."
The membrane could even hold a sensor to measure troponin – a protein expressed in heart cells and a hallmark of an impending heart attack. Ultimately, such devices will be combined with ventricular assist devices, Efimov says.
"This is just the beginning," he adds. "Previous devices have shown huge promise and have saved millions of lives. Now we can take the next step and tackle some arrhythmia issues that we don’t know how to treat."
Researchers have developed the technology for a catheter-based device that would provide forward-looking, real-time, 3-D imaging from inside the heart, coronary arteries and peripheral blood vessels. With its volumetric imaging, the new device could better guide surgeons working in the heart, and potentially allow more of patients' clogged arteries to be cleared without major surgery.
Credit: Georgia Tech/Rob Felt
The device integrates ultrasound transducers with processing electronics on a single 1.4 millimetre silicon chip. On-chip processing of signals allows data from more than 100 elements on the device to be transmitted using just 13 tiny cables, permitting it to easily travel through circuitous blood vessels. The forward-looking images produced by the device would provide significantly more information than existing cross-sectional ultrasound.
Researchers have developed and tested a prototype, able to provide image data at 60 frames per second, and plan next to conduct animal studies that could lead to commercialisation of the device.
Professor Degertekin, Georgia Institute of Technology: "Our device will allow doctors to see the whole volume that is in front of them within a blood vessel. This will give cardiologists the equivalent of a flashlight so they can see blockages ahead of them in occluded arteries. It has the potential for reducing the amount of surgery that must be done to clear these vessels."
“If you’re a doctor, you want to see what is going on inside the arteries and inside the heart, but most of the devices being used for this today provide only cross-sectional images. If you have an artery that is totally blocked, for example, you need a system that tells you what’s in front of you. You need to see front, back and sidewalls altogether. That kind of information is basically not available at this time.”
This device, on a single chip, includes 56 ultrasound transmit elements and 48 receive elements, with a 430-micron hole in the centre for a guide wire. Power-saving circuitry in the array shuts down sensors when they are not needed, allowing operation with just 20 milliwatts of power and reducing the amount of heat generated inside the body.
Credit: Gokce Gurun et al./IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control
“You want the most compact and flexible catheter possible,” Degertekin explained. “We could not do that without integrating the electronics and the imaging array on the same chip.”
Based on their prototype, the researchers expect to conduct animal trials and ultimately hope to gain FDA approval for use in humans. Further into the future, Degertekin hopes to develop a version of the device that could guide interventions in the heart under magnetic resonance imaging (MRI). Other plans include further reducing the size of the device to place it on a 400-micron diameter guide wire. Their work is described in IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control.
Diseases like Alzheimer’s and Huntington’s are often associated with aging. However, the biological link between the two is less certain. Researchers at Rutgers University–Camden are seeking insight into this connection by studying very small RNA molecules in the common fruit fly.
“As the flies in our experiment age, we’re able to detect specific patterns of microRNAs – which help to regulate genes – when they are bound to specific proteins,” says Ammar Naqvi, a doctoral student in computational and integrative biology at Rutgers–Camden.
MicroRNAs are connected to various developmental stages and disease states, and their proper modulation is required for the integrity and maintenance of cells.
The research is being done under the supervision of Andrey Grigoriev, a professor of biology at Rutgers–Camden, and in collaboration with a research team at the University of Pennsylvania. Computational and bioinformatics analysis for the project is performed at Rutgers–Camden.
In flies, microRNAs are “loaded” onto one of two protein complexes known as Ago1 or Ago2, which then guide it to repress gene expression. The team found that as fruit flies age, more microRNAs accumulate on the Ago2 protein complex, and therefore impact age-associated events in the flies.
“We were able to connect the two processes,” Naqvi says. “Studies have shown that there is some change in the microRNA population with age, but no one was sure how they were partitioned with the protein complexes. We observed such partitioning and also an increase in neurodegeneration, which resulted in a shorter lifespan for these flies.”
Grigoriev explains: “Neurodegeneration and aging go hand-in-hand — but we are the first to have shown the details of this change in regulation with aging. This tells us that there are different mechanisms of regulation in different stages of development. Is aging a byproduct of development? I cannot tell you. It’s possible that this could be relevant for other diseases. That’s what we want to find out.”
For the first time, scientists at King's College London have identified a gene linking thickness of the grey matter in the brain to intelligence. The study is published in Molecular Psychiatry and may help scientists understand biological mechanisms behind some forms of intellectual impairment.
The researchers looked at the cerebral cortex – the outermost layer of the human brain. It is known as 'grey matter' and plays a key role in memory, attention, perceptual awareness, thought, language and consciousness. Previous studies have shown that the thickness of the cerebral cortex, or 'cortical thickness', strongly correlates with intellectual ability. However, no genes had been identified until now.
An international team of scientists, led by King's, analysed DNA samples and MRI scans from 1,583 healthy 14 year olds. These teenagers also underwent a series of tests to determine their verbal and non-verbal intelligence.
Dr Sylvane Desrivières, from King's College London's Institute of Psychiatry and lead author of the study: "We wanted to find out how structural differences in the brain relate to differences in intellectual ability. The genetic variation we identified is linked to synaptic plasticity – how neurons communicate. This may help us understand what happens at a neuronal level in certain forms of intellectual impairments, where the ability of the neurons to communicate effectively is somehow compromised.
"It's important to point out that intelligence is influenced by many genetic and environmental factors," she added. "The gene we identified only explains a tiny proportion of the differences in intellectual ability, so it's by no means a 'gene for intelligence'."
The researchers looked at 54,000 genetic variants possibly involved in brain development. They found that, on average, teenagers carrying a particular gene variant had a thinner cortex in the left cerebral hemisphere, especially in the frontal and temporal lobes, and performed less well on tests for intellectual ability. The genetic variation affects expression of the NPTN gene, which encodes a protein acting at neuronal synapses and therefore affects how brain cells communicate.
To confirm their findings, the NPTN gene was studied in both mouse and human brain cells. The scientists found that the NPTN gene had a different activity in the left and right hemispheres of the brain, which may cause the left hemisphere to be more sensitive to the effects of NPTN mutations. Their findings suggest that some differences in intellectual abilities can result from a decreased function of the NPTN gene in particular regions of the left brain hemisphere.
The genetic variation identified in this study only accounts for an estimated 0.5% of total variation in human intelligence. However, the findings may have important implications for the understanding of biological mechanisms underlying several psychiatric disorders, such as schizophrenia and autism, where impaired cognitive ability is a key feature of the disorder.
For the first time anywhere, a team of researchers at Penn State University has placed tiny synthetic motors directly inside live human cells, propelled them with ultrasonic waves and steered them magnetically.
Credit: Mallouk Lab/ Penn State
"As these nanomotors move around and bump into structures inside the cells, the live cells show internal mechanical responses that no one has seen before," said Tom Mallouk, Professor of Materials Chemistry and Physics. "This research is a vivid demonstration that it may be possible to use synthetic nanomotors to study cell biology in new ways. We might be able to use nanomotors to treat cancer and other diseases, by mechanically manipulating cells from the inside. Nanomotors could perform intracellular surgery and deliver drugs noninvasively to living tissues."
Until now, Mallouk said, nanomotors have been studied only "in vitro" in a laboratory apparatus – not in living human cells. Chemically powered nanomotors were first developed 10 years ago at Penn State by a team that included chemist Ayusman Sen and physicist Vincent Crespi, in addition to Mallouk.
"Our first-generation motors required toxic fuels and they would not move in biological fluid, so we couldn't study them in human cells," Mallouk said. "That limitation was a serious problem." When Mallouk and physicist Mauricio Hoyos discovered that nanomotors could be powered by ultrasonic waves, the door was open to studying the motors in living systems.
For their experiments, the team used HeLa cells, an immortal line of human cervical cancer cells that is typically used in research studies. These cells ingest the nanomotors, which then move about inside, powered by ultrasonic waves. At low ultrasonic power, the nanomotors have little effect on the cells. But when the power is turned up, the nanomotors spring into action, bumping into organelles – structures within a cell that perform specific functions. The nanomotors can act as egg beaters to homogenise the cell's contents, or they can act as battering rams to puncture the cell membrane.
While ultrasound pulses control whether the nanomotors spin around or whether they move forward, the researchers can control them even further by steering them, using magnetic forces. Mallouk and his colleagues also found that the nanomotors can move autonomously – independently of one another – an ability that is important for future applications.
"Autonomous motion might help nanomotors selectively destroy the cells that engulf them," Mallouk said. "If you want these motors to seek out and destroy cancer cells, for example, it's better to have them move independently. You don't want a whole mass of them going in one direction."
"One dream application of ours is Fantastic Voyage-style medicine, where nanomotors cruise around inside the body, communicating with each other and performing various kinds of diagnoses and therapy. There are lots of applications for controlling particles on this small scale, and understanding how it works is what's driving us."
New research predicts that rats will continue to grow and fill a 'significant chunk' of Earth's emptying ecospace. Their global influence is likely to grow in the future as larger mammals continue to become extinct.
Credit: Avinashmaurya (CC BY-SA 3.0)
Dr Jan Zalasiewicz, from the Department of Geology at the University of Leicester, suggests that we better get used to having rats around: "Rats are one of the best examples of a species that we have helped spread around the world, and that have successfully adapted to many of the new environments that they found themselves in.
"They are now on many, if not most, islands around the world – and once there, have proved extraordinarily hard to eradicate. They're often there for good, essentially. Once there, they have out-competed many native species and at times have driven them to extinction. As a result, ecospace is being emptied – and rats are in a good position to re-fill a significant chunk of it, in the mid- to far-geological future."
As rats fill the newly opened ecospace left in the wake of other extinct mammals, over time they, like many other species of animal, experience evolutionary adaptation. Gigantism can occur in animals as they adapt to their environment and Zalasiewicz believes that rats will prove to be no exception to this timeless rule.
"Animals will evolve, over time, into whatever designs will enable them to survive and to produce offspring," he continued. "For instance, in the Cretaceous Period, when the dinosaurs lived, there were mammals – but these were very small, rat and mouse-sized, because dinosaurs occupied the larger ecological niches.
"Only once the dinosaurs were out of the way did these tiny mammals evolve into many different forms, including some very large and impressive ones: brontotheriums, horses, mastodons, mammoths, rhinoceri and more.
"Given enough time, rats could grow to be at least as large as the capybara, the world's largest rodent, that lives today – that can reach 80 kilos. If the ecospace was sufficiently empty, then they could get larger still."
While looking to what may happen in the future, occurrences of gigantism in rodents in the past can show the scope for evolution – the largest extinct rodent discovered so far, named the Josephoartigasia monesi, was larger than a bull, and weighed over a ton.
Scale image of human and Josephoartigasia monesi. Credit: Nobu Tamura (CC BY 3.0)
As another comparison, roughly 50 million years ago, the ancestors of today's blue whale was a wolf-sized creature living close to shore – showing how mammals can grow in size and stature considerably over time.
The variations in future rat sizes will not simply involve them blowing up to epic proportions, however. Dr Zalasiewicz suggests that there will be many types of evolutionary adaptations in rats over time.
"Animals can evolve to smaller as well as larger sizes," he said. "This will depend on what particular circumstances they find themselves in and what the selective pressures on them are. Each island that rats are now present on is in effect a laboratory of future evolution – and each will produce different results.
"So there will be future thin rats, future fat rats, slow and heavy rats, fast and ferocious rats, maybe future aquatic rats – the list goes on. Other animals will likely follow the same pattern, such as domestic cats, rabbits, goats and more."
While Dr Zalasiewicz admits it is difficult to predict exactly what may happen in the future, he suspects that rats will be major players in the geological future of planet Earth, and over time will produce some remarkable descendants.
Japanese researchers have converted adult cells from mice into stem cells by exposing them to acid. This could pave the way for routine use of stem cells in medicine with a technique that is cheaper, faster and more efficient than before.
An unusual reprogramming phenomenon by which the fate of somatic cells can be drastically altered through changes to the external environment is described in two new articles.
Postnatal somatic cells committed to a specific lineage are shown to be converted into a pluripotent state (capable of differentiating into nearly all cell types) when exposed to an environmental stress, in this case short exposure to low pH. This reprogramming process does not need nuclear manipulation or the introduction of transcription factors – thought to be necessary to induce pluripotency – so the work may have important implications for regenerative medicine.
Reprogramming in response to environmental stress has been observed in plants, whereby mature cells can become immature cells capable of forming a whole new plant structure, including roots and stalks. Whether animal cells have a similar potential has been a challenging question, but one that Haruko Obokata and co-authors have addressed. They demonstrate that mammalian somatic cells can be reprogrammed when stressed by low-pH conditions, and have named this phenomenon Stimulus-Triggered Acquisition of Pluripotency (STAP).
So-called STAP cells have some characteristics that resemble embryonic stem cells, but the STAP cells only have a limited capacity for self-renewal. In a second paper, Obokata and colleagues investigate the nature of STAP cells and suggest that they represent a unique state of pluripotency. The researchers also demonstrate that under pluripotent stem-cell culture conditions, STAP cells can be transformed into robustly self-renewing stem cells, similar to embryonic stem cells.
Together, these findings reveal that cells in the body have the potential to become pluripotent and provide new insights into the diverse cellular states.
Professor Chris Mason, an expert in regenerative medicine at University College London: "If it works in man, this could be the game changer that ultimately makes a wide range of cell therapies available using the patient's own cells as starting material – the age of personalised medicine would have finally arrived.
"Who would have thought that to reprogram adult cells to an embryonic stem cell-like (pluripotent) state just required a small amount of acid for less than half an hour? An incredible discovery."
STAP cells generated an entire fetus body. Credit: Haruko Obokata.
Japanese researchers have discovered a species of leech able to survive for 24 hours at -196°C (-321°F) and for 32 months at -90°C (-130°F). This finding could provide insights into cryopreservation for humans. It also increases the chances of life elsewhere in the universe.
Credit: Dai Suzuki et al / PLOS ONE
Pictured above is Ozobranchus jantseanus, a parasitic leech that feeds on the blood of freshwater turtles in East Asia. These creatures typically reach up to 15 mm (0.6") in length, attaching themselves externally and relying on their hosts for all of their life stages, from egg to adult.
A team from Tokyo University of Marine Science and Technology – working on a separate project – had pulled a frozen, dead turtle out of storage, when they noticed several of these parasites clinging to the animal. The leeches appeared to be still alive, wriggling as they began to warm up. The researchers knew they had found something highly unusual, as it was rare for any organism to withstand such low temperatures. A new study was undertaken to investigate this further and to determine the full extent of their cold tolerance.
Prior to the experiment, only two other animals were known to survive in liquid nitrogen – a microscopic invertebrate known as the waterbear and the larvae of a drosophilid fly – with maximum recorded submersion times of 15 minutes and one hour, respectively.
Cryoexposure tests were conducted on seven different species of leech, at -90°C and -196°C, for a period of 24 hours. Ozobranchus jantseanus was the only one to survive both temperatures. In fact, it could withstand multiple freezes and repeated freeze-thaw cycles, without needing time to acclimatise.
An even more amazing discovery was to follow, however. Every single leech from this species placed at -90°C (-130°F) survived at least nine months, with some lasting in storage for 32 months, or more than 2.5 years. This is colder than the average temperature on Mars.
At present, it is unknown how these creatures are managing to cope with such an extreme environment. "It is likely that this cryotolerant ability has arisen in response to some as yet unclarified adaptation," the researchers state. "It is hoped that these findings will contribute to the development of new cryopreservation methods that do not require additives, and also to the resuscitation of organisms that have been frozen underground in permafrost areas, on Antarctica, and possibly on other planets."
Globally, an estimated 285 million people have diabetes – a chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. Its incidence is growing rapidly, and by 2030, the number of cases is predicted to almost double. By 2050, as many as one in three U.S. adults could be affected if current trends continue.
To keep their blood sugar levels under control, sufferers need to constantly monitor themselves. This can involve pricking their finger to get a blood sample, two to four times per day. For many people, managing this condition is therefore a painful and disruptive process.
To address this problem, Internet giant Google has announced it is developing a smart contact lens. This wearable tech will measure glucose levels in tears, using a tiny wireless chip and miniaturised sensor, embedded between two layers of soft contact lens material. When glucose levels fall below a certain threshold, tiny LED lights will activate themselves to function as a warning system for the wearer.
Google admits it is still "early days" for this technology, but there is clearly great potential for improving the lives of diabetes sufferers around the world. To achieve their goal, they intend to partner with other technology companies who have previous experience of bringing products like this to market. You can read more at the Google Official Blog.
U.S. biotechnology company, Illumina, has demonstrated the first machine capable of sequencing a complete human genome for less than $1,000. This landmark opens the floodgates to mass genome sequencing and will lead to cheaper and faster medical research.
The Human Genome Project – an international effort to identify and map every gene in the body – was initiated in 1990 at a cost of $3 billion. It was the largest collaborative biological project ever undertaken, involving hundreds of laboratories and requiring 13 years to complete.
In the first decade of the 21st century, new sequencing methods led to costs plummeting at a rate even faster than Moore's Law, the trend of exponentially improving power seen in computer chips. In addition to price, the length of time needed to scan DNA was falling rapidly. By the early 2010s, thousands of human genomes had been decoded worldwide.
In recent years, however, this trend appeared to reach a plateau with costs hovering at between $3-5,000. Hopes for a $1,000 genome seemed unrealistic. The industry had surely experienced the law of diminishing returns.
That apparent stagnation has now ended, with U.S. company Illumina achieving a major breakthrough in the form of their HiSeq X Ten Sequencing System. In a press release, they claim to have "broken the sound barrier of human genomics", by enabling $1,000 whole genome sequencing for the first time.
HiSeq X Ten will be released in March 2014 at $1m each, in a minimum of 10 units. The figure of $1,000 per genome takes into account the cost of the machines and the chemicals needed to do the sequencing. It is, therefore, not yet economical for smaller research labs, hospitals, or doctor's offices. However, larger research institutes have already expressed an interest – including the Broad Institute in Cambridge, Massachusetts; Macrogen in Seoul, South Korea; and the Garvan Institute of Medical Research in Sydney, Australia. In the coming years, costs will continue to go down while speed and accuracy go up, and the average person will be able to scan their genome at a very affordable price.
Other companies, such as 23andMe, have been offering personalised DNA analysis for some time now. These tests, however, only do partial sequencing for a tiny fraction of total genes. The new machine from Illumina, on the other hand, scans the entire human genome, all 3.2 billion base pairs. Five complete genomes can be delivered in a day, or potentially 1,825 per year. Several advanced design features are utilised to generate this massive throughput, an order of magnitude faster than before: patterned flow cells (which contain billions of nanowells at fixed locations), combined with a new clustering chemistry (for high occupancy and monoclonality), and state-of-the art optics.
Jay Flatley, CEO of Illumina: “With the HiSeq X Ten, we’re delivering the $1,000 genome, reshaping the economics and scale of human genome sequencing, and redefining the possibilities for population-level studies in shaping the future of healthcare. The ability to explore the human genome on this scale will bring the study of cancer and complex diseases to a new level. Breaking the ‘sound barrier’ of human genetics not only pushes us through a psychological milestone, it enables projects of unprecedented scale. We are excited to see what lies on the other side.”
A new way to potentially stop cancer cells from spreading and moving throughout the bloodstream has been discovered by researchers at Cornell University.
By attaching a protein to white blood cells, biomedical engineers at Cornell University have demonstrated the annihilation of metastasizing cancer cells moving through the bloodstream. The study, “TRAIL-Coated Leukocytes that Kill Cancer Cells in the Circulation,” is published in the 6th January edition of the journal PNAS.
“These circulating cancer cells are doomed,” said Michael King, Cornell professor of biomedical engineering and the study’s senior author. “About 90% of cancer deaths are related to metastases, but now we’ve found a way to dispatch an army of killer white blood cells that cause apoptosis – the cancer cell’s own death – obliterating them from the bloodstream. When surrounded by these guys, it becomes nearly impossible for the cancer cell to escape.”
Metastasis is the spread of cancer cells to other parts of the body. Surgery and radiation can be effective at treating primary tumors – but difficulty in detecting metastatic cancer cells has made treatment of spreading cancer problematic, say the scientists.
King and his colleagues injected human blood samples, and later mice, with two proteins: E-selectin (an adhesive) and TRAIL (Tumor Necrosis Factor Related Apoptosis-Inducing Ligand). The TRAIL protein joined together with the E-selectin protein stick to leukocytes – white blood cells – ubiquitous in the bloodstream. When a cancer cell comes into contact with TRAIL, which becomes unavoidable in the chaotic blood flow, the cancer cell essentially kills itself.
“The mechanism is surprising and unexpected in that this repurposing of white blood cells in flowing blood is more effective than directly targeting the cancer cells with liposomes or soluble protein,” say the authors.
In the laboratory, King and his colleagues tested this concept’s efficacy. When treating cancer cells with the proteins in saline, they found a 60 percent success rate in killing the cancer cells. In normal laboratory conditions, the saline lacks white blood cells to serve as a carrier for the adhesive and killer proteins. Once the proteins were added to flowing blood, which models forces, mixing and other human-body conditions, however, the success rate in killing the cancer cells jumped to nearly 100 percent.
As this research is newly announced, King says animal trials will continue and he hopes that the research will proceed to human clinical trials sometime in the future.
Implantation of a sleep apnea device called Inspire Upper Airway Stimulation (UAS) therapy can lead to significant improvements for patients with obstructive sleep apnea (OSA), according to a study published in the New England Journal of Medicine. After one year, patients using the device had an average 70 percent reduction in sleep apnea severity, as well as significant reductions in daytime sleepiness.
Sleep apnea is a disorder characterised by pauses in breathing, or shallow and infrequent breathing, during sleep. Each of these pauses in breathing, called an apnea, can last from seconds to minutes, and may occur 30 times or more an hour. When normal breathing returns (sometimes accompanied by a loud snort or choking sound), the body moves out of deep sleep and into a lighter sleep. This results in poor overall quality of sleep and excessive tiredness during the daytime – increasing a person's risk for heart attack, stroke, high blood pressure and even death.
It is estimated that seven percent of Americans are affected by at least moderate sleep apnea. For those in middle age, this figure is higher, with as many as nine percent of women and 24 percent of men in this age group being affected, undiagnosed and untreated.
The costs of untreated sleep apnea reach further than just health issues. It is estimated that in the U.S. the average untreated patient's health care costs $1,336 more annually than an individual without sleep apnea. This may cause up to $3.4 billion/year in additional medical costs.
Treatments can include weight loss, upper airway surgeries, oral appliances, and continuous positive airway pressure (CPAP). However, while CPAP can be successful if used regularly, up to half of patients are unable to use it properly – largely due to discomfort with the mask and/or lack of desire to be tethered to a machine.
That's where a new device created at the University of Pittsburgh may help. Director of the UPMC Sleep Medicine Center, and lead author of the study, Dr Patrick Strollo, explains: "Inspire UAS therapy differs from other traditional sleep apnea devices and surgical procedures in that it targets muscle tone of the throat, rather than just the anatomy. Two thirds of patients using the device had successful control of their apneas, although even more reported improvement in snoring, daytime sleepiness and quality of life measures. Eighty-six percent of patients were still using the device every night at the one year mark, which compares very favourably to CPAP. The results of this trial show a huge potential for a new and effective treatment that can help millions of patients."
The device was fitted in three areas: a stimulation electrode was placed on the hypoglossal nerve, which provides innervation to the muscles of the tongue; a sensing lead was placed between rib muscles to detect breathing effort; and a neurostimulator was implanted in the upper right chest, just below the clavicle bone. Patients used a "controller" to turn on the device at night, so it was only used when the patient slept. The Inspire UAS therapy device was able to sense breathing patterns and to stimulate tongue muscles, thereby enlarging and stabilising the airway for improved breathing.
Kathy Gaberson, one of the study participants: "My short-term memory has improved significantly, and the surgery has made a huge difference in my quality of life. My apnea episodes went from 23 times an hour to just two."