In a world first, researchers at Sun Yat-sen University in Guangzhou, China, admit to having edited the genome of live human embryos to see the effect on a fatal blood disorder, thalassaemia.
The research is banned in Europe – but Chinese scientists have confirmed that they recently edited the DNA of human embryos for the very first time. Researchers at Sun Yat-sen University, led by Junjiu Huang, have tried to ease concerns by explaining that they used non-viable embryos, which cannot result in a successful live birth, that were obtained from local fertility clinics. Huang's team used a revolutionary new technique known as CRISPR/Cas9, discovered by scientists at MIT.
A total of 86 embryos were injected with the Cas9 protein and left for two days while the gene-editing process took place. Of these, 71 survived and subsequent tests revealed that 28 were successfully spliced, but only a fraction contained the genetic material needed to prevent the fatal blood disorder thalassaemia. Unexpected mutations were also noticed in the genes.
"I think that this is a significant departure from currently accepted research practice," said Shirley Hodgson, Professor of Cancer Genetics, St George's University of London. "Can we be certain that the embryos that the researchers were working on were indeed non-viable? Any proposal to do germline genetic manipulation should be very carefully considered by international regulatory bodies before it should be considered a serious research prospect."
"This news emphasises the need for an immediate global ban on the creation of GM designer babies," comments Dr David King, director of UK watchdog Human Genetics Alert. "It is critical that we avoid a eugenic future in which the rich can buy themselves a baby with built-in genetic advantages. It is entirely unnecessary since there are already many ethical ways to avoid thalassaemia. This research is a classic example of scientific careerism – assuring one's place in the history books even though the research is unnecessary and unethical."
"The study is a landmark, as well as a cautionary tale," says George Daley, a stem-cell biologist at Harvard Medical School in Boston. "Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes."
The research appears in the journal Protein and Cell after the prestigious journals Nature and Science refused to publish it on ethical grounds.
Following groundbreaking studies on mice, American scientists claim to have found a potential cause of Alzheimer's disease in the behaviour of immune cells, which it may be possible to target with drug treatments.
In a mouse model of Alzheimer's disease, immune cells called microglia (shown in the black stain) become active in areas of the brain involved in memory and consume an important amino acid, arginine. Credit: Carol Colton lab, Duke University
Increasingly, evidence supports the idea that the immune system, which protects our bodies from foreign invaders, plays a part in Alzheimer's disease. But the exact role of immunity in the disease is still a mystery. A new study in mice by researchers at Duke University in the USA suggests that in Alzheimer's disease, certain immune cells that normally protect the brain begin to abnormally consume a vital nutrient: arginine. Blocking this process with a small-molecule drug prevented the characteristic brain plaques and memory loss in a mouse model of the disease.
This new research – published on 15th April in the Journal of Neuroscience – not only points to a new potential cause of Alzheimer's, but may also eventually lead to a new treatment strategy.
"If indeed arginine consumption is so important to the disease process, maybe we could block it and reverse the disease," said Carol Colton, a professor of neurology at Duke University School of Medicine, and senior author of the paper.
The brains of people with Alzheimer's disease show two hallmarks – 'plaques' and 'tangles' – that researchers have been puzzling over for some time. Plaques are the build-up of sticky proteins called beta amyloid, and tangles are twisted strands of a protein called tau. In their study, the Duke team used a type of mouse, called CVN-AD, that they had created several years ago by swapping out a handful of important genes to make the animal's immune system more similar to a human's. Compared with other mice used in Alzheimer's research, the CVN-AD mouse has it all: plaques and tangles, behaviour changes, and neuron loss.
In addition, the gradual onset of these symptoms in the CVN-AD mouse gave researchers a chance to study its brain over time and to focus on how the disease begins. Looking for immune abnormalities throughout the lifespan of the mice, the group found that most immune system components stayed the same in number, but a type of brain-resident immune cells called microglia that are known first responders to infection begin to divide and change early in the disease.
The microglia express a molecule, CD11c, on their surface. Isolating these cells and analysing their patterns of gene activity, the scientists found heightened expression of genes associated with suppression of the immune system. They also found dampened expression of genes that work to ramp up the immune system.
"It's surprising, because [suppression of the immune system is] not what the field has been thinking is happening in AD," said co-author Matthew Kan, an MD/PhD student in Colton's lab. Instead, scientists had previously assumed the brain releases molecules involved in ramping up the immune system, that supposedly damage the brain.
The group did find CD11c microglia and arginase, an enzyme that breaks down arginine, are highly expressed in regions of the brain involved in memory, in the same regions where neurons had died. Blocking arginase using the small drug difluoromethylornithine (DFMO) before the start of symptoms in the mice, the scientists saw fewer CD11c microglia and plaques develop in their brains. These mice performed better on memory tests.
"All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect – the mouse, at least – from Alzheimer's disease," Kan said.
DFMO is being investigated in human clinical trials to treat some types of cancer, but it hasn't been tested as a potential therapy for Alzheimer's. In the new study, Colton's group administered it before the onset of symptoms; now they are investigating whether DFMO can treat features of Alzheimer's after they appear.
Does the study suggest that people should eat more arginine or take dietary supplements? The answer is no, Colton said, partly because a dense mesh of cells and blood vessels called the blood-brain barrier determines how much arginine will enter the brain. Eating more arginine may not help more get into the sites of the brain that need it. Besides, if the scientists' theory is correct, then the enzyme arginase, unless it's blocked, would still break down the arginine.
"The field has been driven by amyloid for the past 15, 20 years and we have to look at other things, because we still do not understand the mechanism of disease or how to develop effective therapeutics," Colton said. "We see this study opening the doors to thinking about Alzheimer's in a completely different way, to break the stalemate of ideas in AD."
Google has filed a patent application for a wearable medical device, able to use nanoparticles to detect and treat illnesses such as cancer.
For those wishing to protect their health and extend their lifespan, a futuristic medical device may become available in the next several years. Details of this wearable technology – known as a Nanoparticle Phoresis – have been published online by Google, via the World Intellectual Property Organisation.
The patent application describes a strap, or band, mounted on the lower arm. Similar in appearance to a wristwatch, it would "automatically modify or destroy one or more targets in the blood that have an adverse health effect." This would be achieved by beaming energy into blood vessels to stimulate cells and molecules, increasing their effectiveness at fighting diseases. It could even be used on synthetic nanoparticles. Millions of these tiny objects would be introduced into the wearer's bloodstream, then activated by magnets in the wristband and directed to specific locations.
In addition to its physical treatment abilities, the Nanoparticle Phoresis could generate vast amounts of data – not only helpful to the user, but also to researchers and doctors. It could accept inputs from the wearer regarding his or her health state, such as "feeling cold," "feeling tired," "pollen allergy symptoms today," "stressed," "feeling energetic," etc. According to the patent, these user inputs "may be used to complement any other physiological parameter data that the wearable device may collect and establish effective signal levels for and timing of modification of the target."
Analysts forecast that wearable technology will see huge growth in the coming years, with unit sales potentially reaching into the hundreds of millions. This new device from Google – if successfully developed – could become part of that rapidly evolving ecosystem. Initially aimed at patients who are seriously ill, this product (or its derivatives) could also be offered to mainstream consumers who aren't necessarily in bad health, but wish to monitor and improve their well-being.
For those with a needle phobia, injections might be possible using high-pressure jets. Although the patent itself makes no mention of this, we can speculate that such a procedure would eventually be incorporated into a wristwatch form factor. Similar to the "hypospray" on Star Trek, these jets would ensure that the skin is not punctured. High-pressure jet injection was covered on our blog in May 2012.
Looking further ahead, the prospects become even more exciting. Bill Maris – who helped form Google Calico – this month stated his belief that humans will live to be many centuries old in the future, while today's cancer treatments will seem "primitive" within just 20 years. His comments echo those of futurist and inventor Ray Kurzweil, also employed at Google and currently involved in AI research for the company. Kurzweil predicts that nanoparticles will be superseded by nanobots – small and compact enough to feature motors, sensors and other tools, allowing them to be controlled with extreme precision directly inside cells. If this idea sounds like science fiction, then consider this: a handheld smartphone today contains more processing power than a room-sized supercomputer of the 1980s. With ongoing advances in miniaturisation, together with new materials such as graphene, the future trend seems inevitable.
As humans become ever more dependent on technology, our bodies will gradually begin to incorporate these and similar devices on a permanent basis. Later in the 21st century, the line between man and machine could become blurred.
A new class of drugs known as "senolytics" has been shown to increase the healthy lifespan of mice. Not only that, but multiple different aspects of the aging process can be improved simultaneously.
In multicellular organisms, including humans, cell division is essential for growth, development and repair. The average person will experience approximately 10,000 trillion cell divisions in their lifetime. As we age, our cells become less capable of dividing. Like a VHS tape being copied over and over again, the process of bodily growth and renewal is less and less accurate. The resulting errors contribute to disease and ultimately death.
Cells that have stopped dividing are known as "senescent" cells. Over time, they accumulate inside us and cause aging. They are similar to cancer cells – in that they can resist apoptosis (programmed cell death). Normally, between 50 and 70 billion cells die each day in an adult. This form of cell suicide helps to maintain a healthy equilibrium, or homoeostasis, ensuring an appropriate number of cells in the body is maintained. With senescent cells, however, this balance is disrupted. The build-up of senescent cells results in side effects, including the production of harmful chemicals. The situation can worsen dramatically if a cell's DNA has been seriously damaged – leading to out-of-control cell growth and cancer, or neurodegenerative disorders.
This week, a study was published in the journal Aging Cell, by researchers from The Scripps Research Institute (TSRI) and Mayo Clinic. They describe a new class of drugs known as "senolytics", which can selectively kill senescent cells – potentially restoring the balance of cell numbers. Two compounds were identified as candidates for testing, both found in existing medications. In Petri dish cultures, they produced the following results:
Target location and result
Cancer drug, used mainly for leukaemia, and marketed under the name Sprycel.
Senescent human fat cell progenitors were eliminated.
A natural compound found in various fruits, vegetables, leaves and grains. Sold as a supplement that acts as an antihistamine and anti-inflammatory.
Senescent human endothelial cells (found on interior surface of blood vessels) were eliminated.
Individually, each compound was effective at removing the senescent cells in these locations, without damaging other cells. When combined together, however, the researchers observed even greater effects. Following the Petri dish experiments, a cocktail of both compounds was administered to mice in old age. The results were remarkable.
“In animal models, the compounds improved cardiovascular function and exercise endurance, reduced osteoporosis and frailty, and extended healthspan,” comments Laura Niedernhofer, PhD, in a press release from TSRI. “Remarkably, in some cases, these drugs did so with only a single course of treatment.”
FutureTimeline.net contacted the study authors to request more specific details. We received the following information regarding the mouse tests:
One leg of each mouse was irradiated with ionising radiation to lower their exercise endurance by 30-50%.
• Animals given a single dose of the senolytics recovered full exercise endurance within five days.
• Four months later, unmedicated mice were still 15% below normal endurance levels, while mice treated with senolytics retained their full exercise endurance.
This test looked at the heart function of normal aged mice equivalent to 65-year-old humans. For context, left ventricular ejection fraction (LVEF) is typically reduced when valves stiffen with age or the heart muscle is damaged.
• A single dose of senolytics increased LVEF by ~10%.
• A single dose of senolytics also improved how blood vessels in the old mice responded to vasodilators (drugs used for the treatment of hypertension) by 10-15%.
Mouse model of a human disease of accelerated aging
• Periodic treatment of the mice with senolytics led to a delay in the onset of age-related symptoms including unstable gait, hunched posture and trembling, for in some cases up to several weeks. Each week in the life of the progeroid mice is equivalent to 3-4 years in human life.
• Healthspan, the period of "healthy living", was extended by roughly 10%.
• Bone mineral density (a measure of osteoporosis) was improved by more than 15%.
• An index of vertebral health for avoiding lower back pain was improved by 20%.
• Brain and neurological dysfunction were also alleviated.
“We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders,” says Professor Paul Robbins, PhD, also from the Scripps Institute. “When senolytic agents, like the combination we identified, are used clinically, the results could be transformative.”
“The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with aging,” said Mayo Clinic Professor James Kirkland, MD, PhD, senior author of the new study. “It may eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group – instead of just one at a time.”
"Senescence is involved in a number of diseases and pathologies, so there could be any number of applications for these and similar compounds," concludes Professor Robbins. "Also, we anticipate that treatment with senolytic drugs to clear damaged cells would be infrequent, reducing the chance of side effects."
A new way of treating Alzheimer's disease with ultrasound has been demonstrated in mice, clearing the amyloid plaques in 75% of the animals.
Untreated Alzheimer's mouse (left) and treated with ultrasound (right)
Researchers at the Queensland Brain Institute (QBI), part of Australia's University of Queensland, have shown that non-invasive ultrasound technology can be used to treat Alzheimer's disease and restore memory in mice. This innovative, drug-free method breaks apart the neurotoxic amyloid plaques that result in memory loss and cognitive decline.
“The Government’s $9 million investment into this technology was to drive discoveries into clinics, and today’s announcement indicates that together with the Queensland Brain Institute, it was a worthwhile investment,” said Queensland Premier, Annastacia Palaszczuk. “I want my Government to encourage more of this type of innovative research. Our Advance Queensland initiative aims to increase research and discoveries like this and to put this state’s research at the forefront internationally by supporting local researchers and helping to keep them in Queensland. These exciting findings will hopefully be of benefit to all Australians in the future.”
Professor Jürgen Götz, study co-author, believes the new method could revolutionise Alzheimer’s treatment: “We’re extremely excited by this innovation of treating Alzheimer’s without using drug therapeutics. The ultrasound waves oscillate tremendously quickly, activating microglial cells that digest and remove the amyloid plaques that destroy brain synapses. The word ‘breakthrough’ is often mis-used, but in this case I think this really does fundamentally change our understanding of how to treat this disease, and I foresee a great future for this approach.”
There are now 343,000 people living with dementia in Australia, a number forecast to reach 900,000 by 2050. Worldwide, the figure today is 50 million, which is projected to hit 135 million by 2050, with Alzheimer’s among the leading causes. Over 7.7 million new cases are reported globally each year (equivalent to about one new case every four seconds) and the rate is accelerating as people live longer and their brains become more susceptible to this terrible condition. It will place enormous financial and other burdens on society in the future, unless new treatments can be developed.
Handheld brain scanning device of the 2050s. Credit: Štěpán Kápl / Dreamstime
“With an aging population placing an increasing burden on health systems, an important factor is cost. Other potential drug treatments using antibodies will be expensive,” explained Götz. “In contrast, this method uses relatively inexpensive ultrasound and microbubble technology, which is non-invasive and appears highly effective.”
The new treatment developed by QBI is able to temporarily open the blood-brain barrier – a layer that normally protects our brains from bacteria and other potential threats, but also blocks drugs from entering and therefore prohibits traditional medicine. By using ultrasound, microglial cells (which are basically a type of support cell for removing waste) were stimulated to engulf and clear toxic protein clumps, fully restoring memory functions in 75% of the mice. This was achieved without damaging brain tissue.
“With our approach, the blood-brain barrier’s opening is only temporary for a few hours, so it quickly restores its protective role,” Professor Götz added.
The next step will be to scale the treatment to higher animal models (sheep), followed by human clinical trials beginning in 2017.
Scientists have designed a radical new type of vaccine that could be the first ever for preventing genital herpes.
One of the most common sexually transmitted diseases, herpes affects some 500 million people worldwide. By using a counterintuitive approach, researchers at the Albert Einstein College of Medicine in New York City were able to prevent both active and latent infections caused by herpes simplex virus type 2 (HSV-2), which causes genital herpes. Findings from the research, conducted in mice, were published yesterday in the journal eLife.
"Developing a herpes vaccine is one of the holy grails of infectious disease research," said co-study leader William Jacobs Jr., Ph.D. "We decided to take an approach that runs counter to most of the tactics used by other scientists – and we seem to have cracked the code."
It was generally assumed that an effective HSV-2 vaccine must stimulate the body to produce neutralising antibodies – particularly against a viral surface protein called glycoprotein D (gD-2) that HSV-2 uses to enter human cells. A protein that triggers antibody production is called an antigen. For decades, researchers have focused on “subunit” herpes vaccines that rely primarily on gD-2 as the antigen to stimulate the body’s antibody response – but none has prevented HSV-2 infection in humans.
"This suggests we've been stimulating production of the wrong type of antibodies," said co-study leader Betsy Herold, M.D.
The researchers took a completely different approach in designing their “live” HSV-2 vaccine. Instead of using gD-2 to stimulate antibodies, they deleted the gene for gD-2 from the virus (and, consequently, the protein’s expression on the viral surface) – a manipulation that weakens the virus, rendering it unable to infect cells or cause disease. They hypothesise that this altered virus stimulates the body to produce different and more effective antibodies.
“We had a hunch that gD-2 might be masking other viral antigens, and that by removing this dominant protein we would expose those previously masked antigens to the immune system,” said Dr. Jacobs.
When the vaccine, dubbed “delta-gD-2” (“delta” is shorthand for a gene deletion) was given to mice, it provided complete protection against subsequent infection with normal (wildtype) HSV-2, whether animals were challenged intravaginally or through the skin. No virus was detected in vaginal or skin tissue of vaccinated mice or in neural tissue, where HSV-2 often hides in a latent form only to emerge later to cause disease. When unvaccinated mice were challenged with wildtype HSV-2, all showed evidence of the virus in the three tissue sites, and all succumbed to the disease.
The vaccinated mice showed low levels of neutralising antibodies, but high levels of antibodies associated with a different immune response called antibody-dependent cell-mediated cytotoxicity (ADCC). This and other experiments described in the paper – such as finding that blood serum from vaccinated mice was able to passively protect unvaccinated mice – conclusively demonstrated that ADCC antibodies were responsible for protecting against HSV-2.
“Our findings challenge the existing dogma that says an effective herpes vaccine must stimulate neutralising antibodies against gD-2,” said Dr. Jacobs. “It’s almost as if the virus evolved gD-2 specifically to hide the other antigens. gD-2 turns out to be a Trojan horse that misleads the immune system.”
The new vaccine also appears to be safe. The researchers calculated the number of wildtype viruses needed to kill mice – then administered 1,000 times that number of delta-g D-2 viruses to mice that lacked immune systems and so couldn’t ward off infections. The result: the mice survived and did not develop herpes. The Einstein team hopes to begin clinical trials on humans within a few years.
Initial tests suggest that the vaccine is also effective against HSV-1, oral herpes, although this needs to be further evaluated. In addition, the vaccine’s novel design may help in creating vaccines against other disease-causing microbes that invade the body through mucosal tissues, including HIV and the bacterium that causes tuberculosis.
“Genital herpes infections can not only be serious in and of themselves, but they also play a major role in fuelling the HIV epidemic,” said Dr. Herold. “People infected with HSV-2 are more likely to acquire and to transmit HIV – which further underscores the need to develop a safe and effective herpes vaccine.”
Albert Einstein College of Medicine has filed patent applications related to this research and is seeking licensing partners able to further develop and commercialise this technology.
A pioneering therapy using bone marrow stem cells to treat lung cancer patients has been announced in the UK.
A new combined cell-gene therapy for lung cancer will be tested on National Health Service (NHS) patients this year, after receiving £2m (US$3m) of funding from the Medical Research Council (MRC). Scientists at University College London (UCL) will conduct the world's first human clinical trials of a combined stem cell and gene therapy for the disease, which is notorious for its high incidence and low survival rates. In the UK, lung cancer is the second most common form of cancer, responsible for 34,000 deaths each year – while in the USA, it is the third most common form of cancer, killing 158,000. Globally, lung cancer is the single most common cause of cancer-related death in men and women, responsible for 1.6 million deaths in 2012. Five year survival rates are among the poorest of the 200 cancer types: only 9.5% in the UK and 17.5% in the USA. There has been slow progress in terms of improving these mortality figures, with only small incremental increases since the 1970s.
UCL's new experimental treatment could change that. Early tests have shown it can significantly reduce and in some cases eliminate tumours in mice. Researchers will now test the treatment in human volunteers – firstly to check that the treatment is safe, then in 56 lung cancer patients to see how effective the gene/cell therapy plus chemotherapy is compared with standard care.
Sam Janes, Professor of Respiratory Medicine at UCL and the study's leader: “Lung cancer is very difficult to treat, because the vast majority of patients are not diagnosed until the cancer has spread to other parts of the body. One therapy option for these patients is chemotherapy, but even if successful this treatment can normally only extend lives by a handful of months. Chemotherapy can also cause widespread toxic side-effects. We aim to improve prospects for lung cancer patients by using a highly targeted therapy using stem cells, which have an innate tendency to home in on tumours when they’re injected into the body. Once there, they switch on a ‘kill’ pathway in the cancer cells, leaving healthy surrounding cells untouched. If clinical trials are successful, our treatment could be transformative for the treatment of lung cancer, and possibly other types of tumour in future.”
In vitro tumour (red), seeded with stem cells (green), which burrow down through gel and into the tumour. The process shown here is 12 hours long.
Left video shows just the tumour; middle video shows just the stem cells; right video shows the green cells rushing into the tumour.
The new treatment works by genetically modifying bone marrow stem cells to express an anti-cancer gene called TRAIL. Being encased within a cell protects the genetic material from being degraded by the body, so that when it reaches the tumour it is able to trigger a signalling pathway that kills the cancer cells.
Each patient will receive almost a billion cells over three infusions, three weeks apart (injected one day after receiving chemotherapy). Over the next three years, 100 billion cells will be created at the Royal Free Hospital’s £2.1 million, state-of-the-art cell manufacturing lab. A key advantage of the treatment is that the cells can be used ‘off the shelf’ and do not need to be from a close relative or tissue match. This is because they have relatively few proteins on the surface and do not induce an immune response in the recipient.
“This will be the first cell therapy for lung cancer and the biggest manufacturing of cells of its kind,” said Professor Janes.
New research has predicted one in two people in the UK will develop cancer at some point in their lives – according to the most accurate forecast to date from Queen Mary University of London and Cancer Research UK.
With today marking World Cancer Day, a new study published in the British Journal of Cancer highlights the urgent need to bolster public health and cancer services, to cope with a growing and ageing population and the looming demands for better diagnostics, treatments, and earlier diagnosis. Prevention must also play an important role in the concerted effort required to reduce the impact of the disease in coming decades.
The UK’s cancer survival has doubled over the last 40 years and around half of patients now survive the disease for more than 10 years. But, as more people benefit from improved healthcare and longer life expectancy, the number of cancer cases is expected to rise. This new research estimating the lifetime risk finds that, from now on, one in two people will be diagnosed with the disease.
This new estimate replaces the previous figure, calculated using a different method, which predicted that more than one in three people would develop cancer at some point in their lives. Age is the biggest risk factor for most cancers, and the increase in lifetime risk is primarily because more people are surviving into old age, when cancer is more common.
Estimated cumulative risk for 1960 cohort. Credit: British Journal of Cancer.
Professor Peter Sasieni, who led the study at Queen Mary University of London, comments: “Cancer is primarily a disease of old age, with more than 60% of all cases diagnosed in people aged over 65. If people live long enough then most will get cancer at some point. But there’s a lot we can do to make it less likely – like giving up smoking, being more active, drinking less alcohol and maintaining a healthy weight. If we want to reduce the risk of developing the disease we must redouble our efforts and take action now to better prevent the disease for future generations.”
Harpal Kumar, Cancer Research UK’s chief executive, says: “We’re living longer and that means we’re more likely to develop a range of age-related health issues. We need to plan ahead to make sure the NHS is fit to cope. If the NHS doesn’t act and invest now, we will face a crisis in the future – with outcomes from cancer going backwards. But NHS investment isn’t the only answer. We need a concerted approach and a broader sense of how we can save lives and money by preventing more cancers. Growing older is the biggest risk factor for most cancers – and it’s something we can’t avoid. But more than four in ten cancers diagnosed each year in the UK could be prevented by changes in lifestyle – that’s something we can all aim for personally so we can stack the odds in our favour.”
Dr Emma King, Cancer Research UK head and neck surgeon: “We’re seeing more patients than ever before and the numbers are increasing year on year. But the resources for treating these people have stayed the same. If we’re going to give them the best possible chance of beating the disease then we’ll need greater investment and support now and in the future. Preventing more cancers and diagnosing the disease as early as possible, when treatment is more likely to be effective, could have a significant impact on survival. We also need the infrastructure to better tailor treatments to patients based on the molecular makeup underpinning their individual cancers.”
In a separate study, University College London has predicted that on current trends, by 2050, cancer will rarely kill anyone under the age of 80, due to ongoing advances in preventing and treating the disease. At present, a low dose of aspirin taken daily may be the single most effective action to protect against cancer for those aged between 50 and 65, according to UCL.
Researchers at Stanford University have demonstrated a fast and reliable method of extending the length of telomeres – the protective caps at the end of chromosomes that play a key role in aging.
As illustrated above, telomeres are regions of DNA at the ends of chromosomes. Like the plastic tips at the end of shoelaces, they protect chromosomes from unravelling and deteriorating, or mixing with other chromosomes. Over time, however, telomeres will begin to erode and shorten. When telomeres become critically short, the cell enters an inactive state, stops dividing and dies. More and more cells reacting in this way causes tissue degeneration, which gradually results in aging and disease. A young human starts with telomeres around 8,000-10,000 nucleotides long, with each cell division reducing this length, so a person in their 80s will average 4,000-6,000 nucleotides.
Researchers at Stanford University School of Medicine, in a study published this week by the FASEB Journal, have found a way to extend the length of human telomeres by up to 900 nucleotides – equivalent to over 10 years of additional lifespan. This was achieved with human muscle and skin cells in a Petri dish using modified messenger RNA (mRNA) containing TERT, a vital part of the telomerase complex. Telomerase is an enzyme that occurs naturally and is known to prevent the shortening of telomeres. It is common in stem cells, but most other cell types have very low levels.
The new technique developed at Stanford was designed in a clever way that managed to optimise the available treatment time – maximising the effects of TERT by preventing an immune response being triggered in the cell, while minimising the danger of cancer that might result from TERT staying too long and causing too many divisions. A balance was achieved whereby TERT was able to remain temporarily for about 48 hours, long enough to increase telomere lengths by 10%, before dissipating harmlessly. During this time, cells divided many more times in the culture dish than did untreated cells: about 28 more times for the skin cells, and about three more times for the muscle cells.
"We were surprised and pleased that modified TERT mRNA worked, because TERT is highly regulated and must bind to another component of telomerase," says co-author John Ramunas, PhD, in a press release. "Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase, which could be deleterious. In contrast, our technique is nonimmunogenic. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent."
"This new approach paves the way toward preventing or treating diseases of aging," says Helen Blau, PhD, a professor of microbiology and immunology at Stanford. "There are also highly debilitating genetic diseases associated with telomere shortening that could benefit from such a potential treatment.
"We're working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally useful. One day, it may be possible to target muscle stem cells in a patient with Duchenne muscular dystrophy, for example, to extend their telomeres. There are also implications for treating conditions of aging, such as diabetes and heart disease. This has really opened the doors to consider all types of potential uses of this therapy."
Scientists have managed to considerably prolong the lifespan of flies by activating a gene which destroys unhealthy cells. The results could also open new possibilities in human anti-aging research.
Immortality has long been a dream for humans. In many ancient mythologies, for example, immortality is one of the traits that distinguishes humans from the gods. More recently, biological research has tried to prolong human lifespan using model organisms such as mice or flies. Researchers at the Institute of Cell Biology from the University of Bern in Switzerland, led by Eduardo Moreno, have developed a new method to extend the lifespan of flies based on improved selection of the best cells within the body. Their work appears today in the journal Cell.
"Our bodies are composed of several trillion cells," explains Moreno, "and during aging, those cells accumulate random errors due to stress or external insults, like UV-light from the sun." But those errors do not affect all cells at the same time and with the same intensity: "Because some cells are more affected than others, we reasoned that selecting the less affected cells – and eliminating the damaged ones – could be a good strategy to maintain tissue health and therefore delay aging and prolong lifespan."
A cellular quality control mechanism
To test their hypothesis, the researchers used Drosophila melanogaster flies. The first challenge was to find out which cells within the organs of Drosophila were healthier. Moreno's team identified a gene which was activated in less healthy cells. They called the gene ahuizotl (azot) after a mythological Aztec creature selectively targeting fishing boats to protect the fish population of lakes, because the function of the gene was also to selectively target less healthy or less fit cells to protect the integrity and health of the organs like the brain or the gut.
Credit: Cell / Elsevier Inc. / Marisa M. Merino et al.
(CC BY 3.0)
Normally, there are two copies of this gene in each cell. By inserting a third copy, the researchers were able to select better cells more efficiently. The consequences of this improved cell quality control mechanism were, according to Moreno, "very exciting": The flies appeared to maintain tissue health better, aged slower and had longer lifespans. "Our flies had median lifespans 50 to 60 percent longer than normal flies," says Christa Rhiner, one of the study authors. For comparison, two previous fruit fly studies we reported on showed increases of 28% and 30%, respectively.
Could azot also slow down the human aging process?
However, the potential of the results goes beyond creating Methuselah flies, the researchers say: Because the gene azot is conserved in humans, this opens the possibility that selecting the healthier or fitter cells within organs could in the future be used as an anti-aging mechanism. For example, it could prevent neuro- and tissue degeneration produced in our bodies over time.
Researchers have developed a compound that causes the metabolism of mice to respond as if a meal has been eaten, so they burn fat to make room for new calories. Human trials could follow in the next few years.
Researchers from the Salk Institute for Biological Studies in California, USA, have developed a compound they describe as "an entirely new type" of pill that is able to prevent obesity in mice. Called fexaramine, it can stop weight gain, lower cholesterol and minimise inflammation.
Unlike most diet pills on the market, such as appetite suppressants or caffeine-based diet drugs, fexaramine won't dissolve into the blood. It remains within the intestines causing fewer side effects. It is so effective that researchers hope it can be fast-tracked for human trials within the next few years – perhaps by 2018, as predicted on our timeline.
“This pill is like an imaginary meal,” says Ronald Evans, director of Salk’s Gene Expression Laboratory and senior author of the study, which is published this week in Nature Medicine. “It sends out the same signals that normally happen when you eat a lot of food, so the body starts clearing out space to store it. But there are no calories and no change in appetite.”
Evans’ laboratory has spent nearly two decades studying the farensoid X receptor (FXR), a protein that plays a role in how the body releases bile acids from the liver, digests food and stores fats and sugars. The body turns on FXR at the beginning of a meal to prepare for an influx of food. FXR not only triggers the release of bile acids for digestion – but also changes blood sugar levels and causes the body to burn some fats in preparation for the incoming meal.
Pharmaceutical companies aiming to treat obesity, diabetes, liver disease and other metabolic conditions have developed systemic drugs that activate the FXR protein, turning on many pathways that it controls. But these drugs affect several organs and come with all kinds of side effects. Evans’ team has shown that switching on FXR only in the intestines – rather than the intestines, liver, kidneys and adrenal glands all at once – can have a very different outcome.
“The body’s response to a meal is like a relay race, and if you tell all the runners to go at the same time, you’ll never pass the baton,” says Evans. “We’ve learned how to trigger the first runner so that the rest of the events happen in a natural order.”
Scientists have mapped the bowhead whale genome and identified genes responsible for its 200-year lifespan, the longest of any mammal.
The bowhead whale is a 20 metre (65 ft) species of whale found in the waters of the Arctic and subarctic. It is believed to be the longest-lived mammal, with a recent study estimating they can live to at least 211 years of age, equivalent to a human born today reaching the year 2226. In a paper due for publication tomorrow in Cell Reports, a team from the Liverpool Centre for Genomics Research, UK – in collaboration with scientists in Alaska, Denmark, Ireland, Spain and South Korea – present the first complete bowhead whale genome and identify key differences compared to other mammals.
The researchers compared the bowhead's genes with those of a minke whale. The latter typically lives for only 30-50 years. As a result of their sequencing effort, they found that bowhead whales have unique mutations in two genes. These are the ERCC1 gene – which is believed to repair DNA, increase cancer resistance and slow aging – and the PCNA gene, which is also linked to DNA repair.
"Our understanding of species' differences in longevity is very poor – and thus our findings provide novel candidate genes for future studies," says the senior author, Dr. João Pedro de Magalhães, of the University of Liverpool, UK. "My view is that species evolved different 'tricks' to have a longer lifespan, and by discovering the 'tricks' used by the bowhead, we may be able to apply those findings to humans in order to fight age-related diseases."
The fact that large whales, with over 1,000 times more cells than humans, do not seem to have an increased risk of cancer suggests the existence of natural mechanisms that can suppress cancer more effectively than those of other animals. Dr. Magalhães now hopes to begin a project that will insert bowhead whales' genes into mice to observe the effects on health. If successful, human trials could follow, using drugs to activate the genes already inside the body, or by inserting the bowhead's genes into human cells before inserting them back into people.
The researchers also note that because the bowhead's genome is the first among large whales to be sequenced, the new information may help reveal physiological adaptations related to size. For example, whale cells have a much lower metabolic rate than those of smaller mammals, and the researchers found changes in one specific gene involved in thermoregulation (UCP1) that may be related to metabolic differences in whale cells.
Moscow State University has announced the creation of a DNA bank to store genetic samples from every living thing on Earth. This new facility, funded by the country's largest ever scientific grant, will be opened in 2018.
According to latest estimates, there are 8.7 million living species on Earth (excluding bacteria and other single-celled microorganisms). The total number may never be known for sure. New organisms are discovered while many others are disappearing on a regular basis – and most of those being lost are never scientifically documented. The first life, known as prokaryotes (simple cells), developed in ancient oceans 3.6 billion years ago. Since that time, it is believed that 99.9% of species have gone extinct. The rate of extinctions has accelerated dramatically in the last century, with experts now reporting a 1,000-fold increase compared to the natural "background" level seen in the fossil record. Up to half of presently existing plant and animal species may vanish by 2100, a disaster similar in scale to the K–Pg event that killed off the dinosaurs.
In order to preserve as much of what remains as possible, Russia intends to build a gigantic facility – 430km² (166mi²) in size – located at one of the central campuses of Moscow State University (MSU). Costing 1 billion rubles (US$18 million), this is funded by the country's largest ever scientific grant and will serve as a repository for millions of genetic samples. All of the university's departments will be involved in research and gathering of materials when the project begins from 2018 onwards. Collaboration with other facilities both in Russia and internationally is also being considered.
"I call the project 'Noah's Ark.' It will involve the creation of a depository – a databank for the storing of every living thing on Earth, including not only living but disappearing and extinct organisms. This is the challenge we have set for ourselves," says Viktor Sadivnichy, MSU rector. "It will enable us to cryogenically freeze and store various cellular materials, which can then reproduce. It will also contain information systems. Not everything needs to be kept in a petri dish."
Given the sheer numbers involved, it could be many decades before samples are retrieved from a significant majority of organisms – and even longer before a global rewilding effort takes shape – but this Noah's Ark of DNA is an important step towards that eventual long-term goal. Other countries have attempted similar projects in recent years, such as Norway's Global Seed Vault and Britain's Frozen Ark. Perhaps in a few centuries, these same efforts will be conducted on alien planets.
Research published online by JAMA Internal Medicine found that older people who felt three or more years younger than their chronological age had a lower death rate compared with those who felt their real age, or who felt more than one year older than their actual age.
Self-perceived age can reflect assessments of health, physical limitations and well-being in later life – and many older people feel younger than their actual age, according to background information in the report. Authors Isla Rippon, M.Sc., and Andrew Steptoe, D.Sc., of the University College London, examined the relationship between self-perceived age and mortality.
The authors used data from a study on aging, which included 6,500 individuals whose average chronological age was 65.8 years but whose average self-perceived age was 56.8 years. Most of the adults (69.6 percent) felt three or more years younger than their actual age, while 25.6 percent had a self-perceived age close to their real age and 4.8 percent felt more than a year older than their chronological age.
Mortality rates during an average follow-up period of 8 years were 14.3 percent in adults who felt younger, 18.5 percent in those who felt about their actual age and 24.6 percent in those adults who felt older, according to the study results. The correlation between self-perceived age and death from cardiovascular causes was strong, but there was no association between self-perceived age and cancer death. The study results remained the same even when factors like education, income, gender, ethnicity and previous illnesses were controlled.
"The mechanisms underlying these associations merit further investigation. Possibilities include a broader set of health behaviours than we measured (such as maintaining a healthy weight and adherence to medical advice), and greater resilience, sense of mastery and will to live among those who feel younger than their age. Self-perceived age has the potential to change, so interventions may be possible. Individuals who feel older than their actual age could be targeted with health messages promoting positive health behaviours and attitudes toward aging," the study concludes.
Regular doses of ibuprofen can extend the lifespan of yeast, worms and flies by 15 percent, it is reported.
A common, over-the-counter drug for treating pain and fever might also hold keys to a longer, healthier life. Regular doses of ibuprofen extended the lifespan of multiple species, according to research by Texas A&M AgriLife, published this week in the journal PLoS Genetics.
"We first used baker's yeast – which is an established aging model – and noticed that the yeast treated with ibuprofen lived longer," said AgriLife Research biochemist Dr. Michael Polymenis. "Then we tried the same process with worms and flies and saw the same extended lifespan. Plus, these organisms not only lived longer, but also appeared healthy."
The treatment, at doses comparable to that recommended for humans, added on average about 15% more to the species' lives. In humans, that would be equivalent to another 12 or so years of healthy living.
Ibuprofen is a relatively safe drug that was created in England during the 1960s. It was first made available by prescription, then after widespread use it became available over-the-counter around the world in the 1980s. The World Health Organisation (WHO) has included ibuprofen on their "List of Essential Medications" needed in a basic health system. It is described as a "nonsteroidal anti-inflammatory drug used for relieving pain, helping with fever and reducing inflammation."
Dr. Polymenis says the three-year project showed that ibuprofen interferes with the ability of yeast cells to pick up tryptophan – an amino acid found in every cell of every organism. Tryptophan is essential for humans, who get it from protein sources in the diet.
"We are not sure why this works, but it's worth exploring further. This study was a proof of principle to show that common, relatively safe drugs in humans can extend the lifespan of very diverse organisms. Therefore, it should be possible to find others like ibuprofen – with even better ability to extend lifespan – with the aim of adding healthy years of life in people."
"Dr. Polymenis approached me with this idea of seeing how his cell cycle analysis corresponded with our aging studies," said Dr. Brian Kennedy, CEO at the Buck Institute for Research on Aging in Novato, California. "He had identified some drugs that had some really unique properties, and we wanted to know if they might affect aging, so we did those studies in our lab. We're beginning to find not just ibuprofen, but other drugs that affect aging, so we're really excited about it.
"Our institute is interested in finding out why people get sick when they get old. We think that by understanding those processes, we can intervene and find ways to extend human health span, keeping people healthier longer and slowing down aging. That's our ultimate goal."
Chong He, a postdoctoral fellow at Buck Institute and lead author on the paper, said looking deeper into the common drugs that target individual diseases might shed light on understanding the aging process: "We have some preliminary data on worms that showed that this drug also extended the health span in worms. It made them live not just longer, but also more healthy. You can measure the thrashing of the worms. If they're healthy, they do have a tendency to thrash a lot, and also we can measure the pumping as they swallow, because if they're healthy, the pumping is faster. Ibuprofen is something that people have been taking for years, and no one actually knew that it can have some benefits for longevity and health span."
A Colorado man has become the first bilateral shoulder-level amputee to wear – and simultaneously control – two modular prosthetic limbs using his thoughts alone.
Image Credit: Johns Hopkins University Applied Physics Laboratory
A Colorado man has made history at the Johns Hopkins University Applied Physics Laboratory (APL), becoming the first bilateral shoulder-level amputee to wear and simultaneously control not one, but two Modular Prosthetic Limbs (MPL). Most importantly, Les Baugh – who lost both of his arms in an electrical accident forty years ago – was able to operate the system by simply thinking about moving his limbs, performing a variety of tasks during a short training period.
During two weeks of testing, Baugh took part in a research effort to further assess the usability of the MPL technology, developed over the past decade as part of the Revolutionising Prosthetics Program. Before putting the limb system through the paces, Baugh had to undergo a surgery at Johns Hopkins Hospital known as targeted muscle reinnervation.
“It’s a relatively new surgical procedure that reassigns nerves that once controlled the arm and the hand,” explained Johns Hopkins Trauma Surgeon Albert Chi, M.D. “By reassigning existing nerves, we can make it possible for people who have had upper-arm amputations to control their prosthetic devices by merely thinking about the action they want to perform.”
After recovery, Baugh visited the Laboratory for training on the use of the MPLs. First, he worked with researchers on the pattern recognition system.
Image Credit: Johns Hopkins University Applied Physics Laboratory
“We use pattern recognition algorithms to identify individual muscles that are contracting – how well they communicate with each other – and their amplitude and frequency,” Chi explained. “We take that information and translate that into actual movements within a prosthetic.”
Then Baugh was fitted for a custom socket for his torso and shoulders that supports the prosthetic limbs and also makes the neurological connections with the reinnervated nerves. While the socket got its finishing touches, the team had him work with the limb system through a Virtual Integration Environment (VIE) — a virtual-reality version of the MPL.
The VIE is completely interchangeable with the prosthetic limbs and through APL’s licensing process currently provides 19 groups in the research community with a low-cost means of testing brain–computer interfaces. It is used to test novel neural interface methods and study phantom limb pain, and serves as a portable training system.
By the time the socket was finished, Baugh said he was more than ready to get started. When he was fitted with the socket, and the prosthetic limbs were attached, he said “I just went into a whole different world.” He moved several objects, including an empty cup from a counter-shelf height to a higher shelf, a task that required him to coordinate the control of eight separate motions to complete.
Image Credit: Johns Hopkins University Applied Physics Laboratory
“This task simulated activities that may commonly be faced in a day-to-day environment at home,” said Courtney Moran, a prosthetist who worked with Baugh. “This was significant because this is not possible with currently available prostheses. He was able to do this with only 10 days of training, which demonstrates the intuitive nature of the control.”
Moran said the research team was floored by what Baugh was able to accomplish.
“We expected him to exceed performance compared to what he might achieve with conventional systems, but the speed with which he learned motions and the number of motions he was able to control in such a short period of time was far beyond expectation,” she explained. “What really was amazing – and was another major milestone with MPL control – was his ability to control a combination of motions across both arms at the same time. This was a first for simultaneous bimanual control.”
Principal Investigator Michael McLoughlin: “I think we are just getting started. It’s like the early days of the Internet. There is just a tremendous amount of potential ahead of us, and we’ve just started down this road. And I think the next five to 10 years are going to bring phenomenal advancement.”
The next step, McLoughlin said, is to send Baugh home with a pair of limb systems so that he can see how they integrate with his everyday life.
Baugh is looking forward to that day: “Maybe for once I’ll be able to put change in the pop machine and get pop out of it,” he said. He’s looking forward to doing “simple things that most people don’t think of. And it’s re-available to me.”
Researchers at Université Laval in Canada have developed "smart textiles" able to monitor and transmit wearers' biomedical information via wireless or cellular networks.
Credit: Stepan Gorgutsa, Université Laval
This technological breakthrough, described in the scientific journal Sensors, paves the way for a host of new developments for people suffering from chronic diseases, elderly people living alone, and even firemen and police officers. A team under the supervision of Professor Younès Messaddeq created the smart fabric by successfully superimposing multiple layers of copper, polymers, glass and silver.
"The fibre acts as both sensor and antenna," explains Professor Messaddeq, Canada Excellence Research Chair in Photonic Innovations. "It is durable but malleable, and can be woven with wool or cotton. And signal quality is comparable to commercial antennas." The surface of the fibre can also be adjusted to monitor a range of information such as glucose levels, heart rhythm, brain activity, movements and spatial coordinates.
The design is based on hollow-core polymer-clad silica fibres, featuring a thick polyimide polymer overcoat. This enables it to withstand high tensile and bending stresses, mechanical abrasion, extreme heat conditions (up to 350°C), humidity, water, detergent or acidic environments. A patent application has already been filed, though certain elements still need to be fine-tuned before the innovation is ready for commercialisation.
"Of course, the technology will have to be connected to a wireless network – and there is the issue of power supply to be solved," notes Messaddeq. "We have tested a number of solutions, and the results are promising."
A new study has provided evidence that a Mediterranean diet can increase longevity by preserving telomere lengths.
Eating a Mediterranean diet can extend your lifespan, suggests a study published in the British Medical Journal (BMJ) this week. The diet appears to be associated with longer telomere length – an established marker of slower ageing. In previous studies, a regular intake of Mediterranean food has been consistently linked with health benefits, including reduced mortality and reduced risk of chronic diseases, such as heart disease.
The diet is characterised by a high intake of vegetables, fruits, nuts, legumes (such as peas, beans and lentils), and (mainly unrefined) grains; a high intake of olive oil but a low intake of saturated fats; a moderately high intake of fish, a low intake of dairy products, meat and poultry; and regular but moderate intake of alcohol (specifically wine with meals).
Telomeres are located on the end of our chromosomes, like the plastic tips on the end of shoelaces, stopping them from fraying and scrambling the genetic codes they contain. In healthy people, telomeres shorten progressively throughout life, more than halving in length from infancy to adulthood, and halving again in the very elderly.
Shorter telomeres are thus associated with a lower life expectancy and greater risk of age-related diseases. Lifestyle factors, such as obesity, smoking and consumption of sugar sweetened drinks, have all been linked to people having shorter telomeres than typically occur in people of a similar age. Oxidative stress and inflammation have also been shown to speed up telomere shortening.
Given that fruits, vegetables and nuts – key components of the Mediterranean diet – have well-known antioxidant and anti-inflammatory effects, a team of US researchers led by Immaculata De Vivo, Associate Professor at Brigham and Women's Hospital and Harvard Medical School, set out to examine whether adherence to the Mediterranean diet was associated with longer telomere length. They analysed data on 4,700 healthy middle-aged women from the Nurses’ Health Study – an ongoing study tracking the health of more than 120,000 US nurses since 1976. Participants completed detailed food questionnaires and had a blood test to measure telomere length.
A diet score ranging from 0-9 points was calculated for each participant, with a higher score representing closer resemblance to a Mediterranean diet. The results, after adjusting for other factors, show that greater adherence to Mediterranean diets was significantly associated with longer telomeres. Each one point change in diet score corresponded on average to 1.5 years of telomere ageing.
However, none of the individual dietary components was associated with telomere lengths – underlining the importance of examining dietary patterns in relation to health, not just separate dietary factors such as intake of whole grains, say the authors.
“To our knowledge, this is the largest population-based study specifically addressing the association between Mediterranean diet adherence and telomere length in healthy, middle-aged women,” they write. “Our results further support the benefits of adherence to the Mediterranean diet for promoting health and longevity.”
A Mediterranean diet is the cornerstone of dietary advice in cardiovascular disease prevention, and the fact that it also links with a biomarker of slower ageing is reassuring, says Prof. Peter Nilsson from Lund University, Sweden in an accompanying editorial. He suggests that genetic background factors, reflecting ancestry, could probably explain some of the variation in association between dietary patterns and telomere length, and that future studies on this question “should take into account the possibility of interactions between genes, diet, and sex.”
Researchers at Queen Mary, University of London, have announced "a hugely exciting step forward" in treating advanced bladder cancer.
With almost 430,000 new cases each year, bladder cancer is the 9th leading cause of cancer in the world. A significant percentage of diagnoses are advanced (meaning the cancer has already spread to another part of the body), making it very difficult to treat, with chemotherapy the only option. Patients often choose to forgo chemotherapy due to its toxicity and limited survival benefit. As shown in the graph below, no major advances have occurred in treating bladder cancer during the past 30 years. That may be about to change, thanks to research by Queen Mary, University of London.
Published this week by the journal Nature, a new study examines an antibody (MPDL3280A) which blocks a protein (PD-L1) thought to help cancer cells evade immune detection. In a Phase one clinical trial, 68 patients with advanced bladder cancer (who had failed all other standard treatments such as chemotherapy) received a cancer immunotherapy medicine – MPDL3280A – which is being developed by Roche. In addition, the patients were all tested for the protein PD-L1 and 30 were identified as having PD-L1 positive tumours.
After six weeks of treatment, 43 per cent of PD-L1-positive patients found their tumour had shrunk. This rose to 52 per cent after 12 weeks of follow up. In two of these patients (7 per cent) radiological imaging found no evidence of the cancer at all following the treatment. Patients who had a positive response to treatment found the benefits were prolonged, and safety results were also encouraging, with few reported side effects. The early results of this drug are so promising that it has received a breakthrough therapy designation status by the U.S. FDA.
Dr Tom Powles, lead author and Consultant Medical Oncologist at Queen Mary University of London, says: "This study is a hugely exciting step forward in the search for alternative advanced bladder cancer treatment. For decades, chemotherapy has been the only option, with a poor outcome and many patients too ill to cope with it. Not only has this investigational drug had a striking response rate, we can target this therapy for patients by screening specific protein PD-L1.
"We now need larger trials to confirm our findings, and as this drug has been given breakthrough designation status by the FDA, we hope to fast track this process so we can begin to give hope to the thousands of people affected by advanced bladder cancer each year."
A vaccine to prevent Ebola has shown promising results in a Phase 1 human clinical trial. The current outbreak in West Africa has resulted in almost 16,000 cases and 6,000 deaths.
An experimental vaccine to halt the Ebola virus was well-tolerated and produced immune system responses in all 20 healthy adults who received it in a Phase 1 clinical trial conducted by researchers from the National Institutes of Health (NIH). The candidate vaccine, which was co-developed by the NIH's National Institute of Allergy and Infectious Diseases (NIAID) and GlaxoSmithKline (GSK), was tested at the NIH Clinical Centre in Bethesda, Maryland. These interim results are reported online in advance of print in the New England Journal of Medicine.
"The unprecedented scale of the current Ebola outbreak in West Africa has intensified efforts to develop safe and effective vaccines, which may play a role in bringing this epidemic to an end and undoubtedly will be critically important in preventing future large outbreaks," said NIAID Director Anthony S. Fauci, M.D. "Based on these positive results from the first human trial of this candidate vaccine, we are continuing our accelerated plan for larger trials to determine if the vaccine is efficacious in preventing Ebola infection."
The candidate vaccine contains segments of genetic material from two Ebola virus species – Sudan and Zaire. This material is delivered by a carrier virus (chimpanzee-derived adenovirus 3 or cAd 3) that causes a common cold in chimpanzees but causes no illness in humans. The candidate vaccine does not contain Ebola virus and cannot cause Ebola virus disease.
The trial enrolled volunteers between the ages of 18 and 50. Ten volunteers received an intramuscular injection of vaccine at a lower dose and 10 received the same vaccine at a higher dose. At two weeks and four weeks following vaccination, the researchers tested the volunteers' blood to determine if anti-Ebola antibodies were generated. All 20 volunteers developed such antibodies within four weeks of receiving the vaccine. Antibody levels were higher in those who received the higher dose vaccine.
A 39-year-old woman, the first participant enrolled in the trial, receives a dose of the Ebola vaccine at the
NIH Clinical Centre in Maryland.
Researchers also analysed the participants' blood to learn whether the vaccine prompted production of immune system cells called T cells. A recent study found that non-human primates inoculated with the candidate NIAID/GSK vaccine developed both antibody and T-cell responses, and that these were sufficient to protect vaccinated animals from disease when they were later exposed to high levels of the Ebola virus.
The experimental NIAID/GSK vaccine did induce a T-cell response in many of the volunteers – including production of CD8 T cells – which may be an important part of immune protection against Ebola viruses. Four weeks after vaccination, CD8 T cells were detected in two volunteers who had received the lower dose vaccine and in seven of those who had received the higher dose.
"We know from previous studies in non-human primates that CD8 T cells played a crucial role in protecting animals that had been vaccinated with this NIAID/GSK vaccine and then exposed to otherwise lethal amounts of Ebola virus," said Julie E. Ledgerwood, D.O., a VRC researcher and the trial's principal investigator. "The size and quality of the CD8 T cell response we saw in this trial are similar to that observed in non-human primates vaccinated with the candidate vaccine."
There were no serious adverse effects observed in any of the volunteers, although two people who received the higher dose vaccine did develop a briefly lasting fever within a day of vaccination.
The genomes from 17 of the oldest people have been published. Researchers were unable to find genes associated with extreme longevity.
Supercentenarians are the world's oldest people, living beyond 110 years of age. There are 74 alive worldwide, with 22 in the USA. The longest confirmed human lifespan on record is that of Jeanne Calment (1875–1997), a French woman who reached 122 years and 164 days. The oldest person alive today is Misao Okawa, a Japanese woman aged 116. She is the last living Japanese person to have been born during the 1800s.
In a study published yesterday by the journal PLOS ONE, whole-genome sequencing was performed on 17 supercentenarians to explore the genetic basis underlying extreme human longevity. The researchers – Hinco Gierman and colleagues from Stanford University – were unable to find any rare protein-altering variants significantly associated with extreme longevity compared to control genomes. However, they did find that one supercentenarian carries a variant associated with a heart condition, which had little or no effect on his/her health, as this person lived over 110 years. The authors say it is recommended by the American College of Medical Genetics and Genomics to report the results to this individual as an incidental finding.
Although the authors didn't find significant association with extreme longevity, they have publicly published the genomes, making them available as a resource for future studies on longevity.
Basic wound healing has been advanced with a synthetic platelet that accumulates at sites of injury, clots and stops bleeding three times faster. The synthetic platelets have realistic size, disk-shape, flexibility, and the same surface proteins as real platelets.
Artificial platelets made by the University of California and Case Western Reserve University have been shown to halt bleeding in mouse experiments much faster than nature can on its own. For the first time, they have been able to integratively mimic the shape, size, flexibility and surface chemistry of real blood platelets on albumin-based particle platforms. The researchers believe these four design factors together are vital for inducing clots to form faster at vascular injury sites while preventing harmful clots from forming elsewhere in the body.
The new technology, reported in the journal ACS Nano, is aimed at stemming bleeding in patients suffering from traumatic injury, undergoing surgeries or suffering clotting disorders from platelet defects or a lack of platelets. Further, it could be used to deliver drugs to target sites in patients suffering atherosclerosis, thrombosis or other platelet-involved pathologic conditions.
Anirban Sen Gupta, associate professor of biomedical engineering at Case Western Reserve, previously designed peptide-based surface chemistries that mimic the clot-relevant activities of real platelets. Building on this work, he now focuses on incorporating morphological and mechanical cues that are naturally present in platelets to further refine their design.
"Morphological and mechanical factors influence the margination of natural platelets to the blood vessel wall, and only when they are near the wall can the critical clot-promoting chemical interactions take place," he said.
These cues motivated Sen Gupta to team up with Samir Mitragotri, a professor of chemical engineering at the University of California. In his laboratory, Mitragotri has recently developed albumin-based technologies to mimic the geometry and mechanical properties of red blood cells and platelets. Together, the team has developed artificial platelet-like nanoparticles (PLNs) that combine morphological, mechanical and surface chemical properties of natural platelets.
The researchers believe this refined design can simulate natural platelet's ability to collide effectively with larger and softer red blood cells in systemic blood flow. The collisions cause "margination" – pushing the platelets out of the main flow and closer to the blood vessel wall – increasing the probability of them interacting with an injury site. The surface coatings enable the artificial platelets to anchor to injury-site-specific proteins, von Willebrand Factor and collagen, while inducing the natural and artificial platelets to aggregate faster at the injury site.
Testing in mouse models showed that injection of the artificial platelets formed clots at the site of injury three times faster than natural platelets alone in the control mice. The ability to interact selectively with injury site proteins, as well as remaining mechanically flexible like natural platelets, enables these artificial versions to safely ride through the smallest of blood vessels without causing damage.
Albumin, a protein found in blood serum and eggs, is already used in cancer drugs and considered a safe material. Artificial platelets that don't become involved in a clot and continue to circulate are metabolised within one to two days. The researchers believe their new artificial platelet design may be even more effective in larger volume flows where margination to the blood vessel wall is more prominent. They will soon begin testing that capability.
In addition to stemming bleeding, Sen Gupta believes this technology could also be useful in delivering clot-busting medicines directly to clots, to treat heart attack or stroke without having to systemically suspend the body's coagulation mechanism. The artificial platelets may also be used to deliver cancer medicines to metastatic tumours with high platelet interactions.
Scientists have found a possible way to halt one of the most common faults in many types of cancer, according to research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool today.
Molecular structure of KRAS, part of the Ras family of proteins. The 3 Ras genes (HRAS, KRAS, and NRAS) are the most common oncogenes in human cancer.
A team of scientists at the Max Planck Institute of Molecular Physiology in Germany has uncovered a new strategy and new potential drug to target an important signalling protein in cells called Ras, which is faulty in a third of cancers. When the Ras protein travels from the centre of a cell to the edge of the cell membrane, it becomes ‘switched on’ and sends signals which tell cells to grow and divide. Faulty versions of this protein cause too many of these signals to be produced – leading to cancer.
For decades, scientists have been attempting to target Ras, but with little success. The reason the protein is so difficult to target is because it lacks an obvious spot on its surface that potential drug molecules can fit into in order to switch it off, like a key closing a lock.
But now the researchers have shown that instead of directly targeting the faulty protein itself, they can stop it moving to the surface of the cell by blocking another protein which transports Ras – preventing it from triggering cancer in the first place. By targeting a link in the chain reaction that switches on the Ras protein, the scientists have opened opportunities to develop new treatments in the future.
Dr Herbert Waldmann at the Max Planck Institute of Molecular Physiology, said: “We’ve been scratching our heads for decades to find a solution to one of the oldest conundrums in cancer research. And we’re excited to discover that it’s actually possible to completely bypass this cancer-causing protein rather than attack it directly.
“We’re making new improvements on compounds for potential drugs, although the challenge still lies in developing a treatment that exploits this discovery without ruining the workings of healthy cells.”
Professor Matt Seymour, clinical research director at the NCRI: “This is an exciting approach to targeting one of the most common faults in cancer, which could lead to a new way of treating the disease. The research is still at a very early stage, and it will be years before it can benefit patients – but it is a key step forward in the field.”
Using stem cells from only 25 millilitres of blood, researchers have grown new blood vessels in just seven days – compared to a month for the same process using bone marrow.
Technology for making new tissues from stem cells has taken a huge leap forward. Two tablespoons of blood are all that is needed to grow a brand new blood vessel in just seven days. This breakthrough is reported from Sahlgrenska Academy and Sahlgrenska University Hospital in Gothenburg, Sweden and published in the journal EBioMedicine.
Three patients, all young children, were missing a vein that goes from the gastrointestinal tract to the liver. The procedure was planned and carried out by Suchitra Sumitran-Holgersson (Professor of Transplantation Biology at Sahlgrenska Academy), and Michael Olausson (Surgeon/Medical Director of the Transplant Centre and Professor at Sahlgrenska Academy).
"We used the stem cells of the patients to grow a new blood vessel that would permit the two organs to collaborate properly," says Michael Olausson.
In developing their new technique, however, they found a way to extract stem cells without taking them from the bone marrow.
"Drilling in the bone marrow is very painful," explains Professor Sumitran-Holgersson. "It occurred to me that there must be a way to obtain the cells from the blood instead."
Michael Olausson and Suchitra Sumitran-Holgersson. Credit: University of Gothenburg
The fact that the patients were so young fuelled her passion to look for a new approach. The method involved taking 25 millilitres (about 2 tablespoons) of blood, the minimum quantity needed to obtain enough stem cells. Sumitran-Holgersson's idea turned out to surpass her wildest expectations – the extraction procedure worked perfectly the very first time.
"Not only that, but the blood itself accelerated growth of the new vein," she says. "The entire process took only a week, as opposed to a month in the [case of bone marrow]. The blood contains substances that naturally promote growth."
Perhaps in the future, these substances might be exploited more fully, to reduce growth times even further.
So far, the team has treated three patients. Two of the three are still doing well and have veins that are functioning as they should. In the third case, the child is under medical surveillance and the outcome is more uncertain. The team is confident they can make further progress.
"We believe that this technological progress can lead to dissemination of the method for the benefit of additional groups of patients, such as those with varicose veins or myocardial infarction, who need new blood vessels," says Professor Holgersson. "Our dream is to be able to grow complete organs as a way of overcoming the current shortage from donors."
Scientists at Harvard have announced a new method of using toxic stem cells to fight brain tumours, without killing normal cells or themselves. This procedure could be ready for human clinical trials within five years.
Toxin-producing stem cells (blue) attacking brain tumour cells (green) in a mouse
Brain cancer has a five-year survival rate of only 35% (see "When will cancer be cured?"). Harvard Stem Cell Institute scientists at Massachusetts General Hospital have devised a new way to use stem cells in the fight against this disease. A team led by neuroscientist Khalid Shah, PhD, now has a way to genetically engineer stem cells able to produce tumour-killing toxins.
In the AlphaMed Press journal STEM CELLS, Shah’s team shows how the toxin-secreting stem cells can be used to eradicate cancer cells remaining in mouse brains after their main tumour has been removed. The stem cells are placed at the site encapsulated in a biodegradable gel. This method solves the delivery issue that probably led to the failure of recent clinical trials aimed at delivering purified cancer-killing toxins into patients’ brains. Shah and his team are currently pursuing FDA approval to bring this and other stem cell approaches developed by them to clinical trials.
“Cancer-killing toxins have been used with great success in a variety of blood cancers – but they don’t work as well in solid tumours, because the cancers aren’t as accessible and the toxins have a short half-life,” explains Shah. “A few years ago, we recognised that stem cells could be used to continuously deliver these therapeutic toxins to tumours in the brain, but first we needed to genetically engineer stem cells that could resist being killed themselves by the toxins. Now, we have toxin-resistant stem cells that can make and release cancer-killing drugs.”
Cytotoxins are deadly to all cells – but since the late 1990s, researchers have been able to “tag” toxins in such a way that they only enter cancer cells with specific surface molecules; making it possible to get a toxin into a cancer cell without posing a risk to normal cells. Once inside of a cell, the toxin disrupts the cell’s ability to make proteins and, within days, the cell starts to die.
Shah’s stem cells escape this fate because they are made with a mutation that doesn’t allow the toxin to act inside the cell. The toxin-resistant stem cells also have an extra bit of genetic code that allows them to make and secrete the toxins. Any cancer cells that these toxins encounter do not have this natural defense and therefore die. Shah and his team induced toxin resistance in human neural stem cells and subsequently engineered them to produce targeted toxins.
“We tested these stem cells in a clinically relevant mouse model of brain cancer, where you resect the tumours and then implant the stem cells encapsulated in a gel into the resection cavity,” he said. “After doing all of the molecular analysis and imaging to track the inhibition of protein synthesis within brain tumours, we do see the toxins kill the cancer cells and eventually prolonging the survival in animal models of resected brain tumours.”
Chris Mason, professor of regenerative medicine at University College London, says: "This is a clever study, which signals the beginning of the next wave of therapies. It shows you can attack solid tumours by putting 'mini pharmacies' inside the patient, which deliver the toxic payload direct to the tumour. Cells can do so much. This is the way the future is going to be."
Shah next plans to rationally combine the toxin-secreting stem cells with a number of different therapeutic stem cells developed by his team to further enhance their positive results in mouse models of glioblastoma, the most common brain tumour in human adults. Shah predicts that he will bring these therapies into clinical trials within the next five years.
Three cups of coffee a day can reduce the risk of abnormal liver enzyme levels by 25 percent, regardless of how much caffeine it contains.
If you're looking for ways to extend your lifespan, then coffee might be a good choice. Researchers at the National Cancer Institute report that it may significantly benefit liver health. Their study, published this month in Hepatology, shows that higher coffee consumption – regardless of how much caffeine it contains – results in lower levels of abnormal liver enzymes. This suggests that chemical compounds in coffee other than caffeine may help to protect the liver.
Coffee consumption is highly prevalent, with more than half of all Americans over 18 drinking on average three cups per day, according to a 2010 report from the National Coffee Association. Moreover, consumption has increased by between 1-2% each year since the 1980s. Previous studies have found that coffee may lower the risk of developing diabetes, cardiovascular disease, non-alcoholic fatty liver disease, cirrhosis and liver cancer.
"Prior research found that drinking coffee may have a possible protective effect on the liver," said lead author Dr. Qian Xiao. "However, the evidence is not clear if that benefit may extend to decaffeinated coffee."
For this study, researchers examined the coffee-drinking habits of 28,000 people, using data from a national health survey conducted from 1999-2010. 14,000 of the subjects drank coffee. Several markers were compared to determine liver function, including blood levels of four enzymes. After adjusting for age, sex, race, education, smoking, alcohol consumption and other factors, the researchers found that compared with people who drank no coffee, those who drank three cups a day were about 25 percent less likely to have abnormal liver enzyme levels. Among the 2,000 or so who drank only decaffeinated coffee, the results were similar.
Dr. Xiao concludes: "Our findings link total and decaffeinated coffee intake to lower liver enzyme levels. These data suggest that ingredients in coffee, other than caffeine, may promote liver health. Further studies are needed to identify these components."
In a related development, researchers last month sequenced the coffee genome.
Researchers at Harvard University have turned human embryonic stem cells into cells that produce insulin, a potentially major advance for sufferers of diabetes.
Harvard researchers have made a giant leap forward in the quest to find a truly effective treatment for type 1 diabetes, a condition that affects an estimated 22 million people worldwide. With human embryonic stem cells as a starting point, the scientists produced for the first time – in the kind of massive quantities needed for cell transplantation and pharmaceutical uses – human insulin-producing beta cells equivalent in most every way to normally functioning beta cells.
“We are now just one pre-clinical step away from the finish line,” says Prof. Douglas Melton, who led the work and has been researching the disease for nearly 25 years. “You never know for sure that something like this is going to work until you’ve tested it numerous ways. We’ve given these cells three separate challenges with glucose in mice and they’ve responded appropriately; that was really exciting. It was gratifying to know that we could do something that we always thought was possible, but many people felt it wouldn’t work. If we had shown this was not possible, then I would have had to give up on this whole approach. Now I’m really energised.”
Elaine Fuchs, a Professor at Rockefeller University, who is not involved in the research, hailed it as “one of the most important advances to date in the stem cell field, and I join the many people throughout the world in applauding my colleague for this remarkable achievement.”
“For decades, researchers have tried to generate human pancreatic beta cells that could be cultured and passaged long term under conditions where they produce insulin.” Fuchs continued. “Melton and his colleagues have now overcome this hurdle and opened the door for drug discovery and transplantation therapy in diabetes.”
Jose Oberholzer, Associate Professor at the University of Illinois at Chicago, said the work “will leave a dent in the history of diabetes. Doug Melton has put in a life-time of hard work in finding a way of generating human islet cells in vitro. He made it. This is a phenomenal accomplishment.”
Prof. Doug Melton, Harvard University
Type 1 diabetes is an autoimmune metabolic condition in which the body kills off all the pancreatic beta cells that produce the insulin needed for glucose regulation in the body. Thus, the final pre-clinical step in the development of a treatment involves protecting from immune system attack the approximately 150 million cells that would have to be transplanted into each patient being treated. Melton is collaborating with colleagues on the development of an implantation device to protect the cells. The device currently being tested has thus far protected beta cells implanted in mice from immune attack for many months. “They are still producing insulin,” Melton said.
Cell transplantation as a treatment for diabetes is still essentially experimental, uses cells from cadavers, requires the use of powerful immunosuppressive drugs, and has been available to only a very small number of patients.
Daniel G. Anderson from MIT, who is working with Melton on the implantation device, said the new work by Melton’s lab is “an incredibly important advance for diabetes. There is no question that ability to generate glucose-responsive, human beta cells through controlled differentiation of stem cells will accelerate the development of new therapeutics. In particular, this advance opens the doors to an essentially limitless supply of tissue for diabetic patients awaiting cell therapy.”
“There have been previous reports of other labs deriving beta cell types from stem cells,” said Melton. “No other group has produced mature beta cells as suitable for use in patients. The biggest hurdle has been to get to glucose sensing, insulin-secreting beta cells, and that’s what our group has done.”
Human transplantation trials using the cells are expected to start in the next few years. Melton's work was published yesterday in the journal Cell.
New research published in The Lancet suggests that, with sustained international efforts, the number of premature deaths could be reduced by 40% over the next two decades (2010-2030), halving under–50 mortality and preventing a third of the deaths at ages 50–69 years.
The Lancet reveals that, between 2000 and 2010, child deaths fell by one-third worldwide, helped by the fourth Millennium Development Goal (MDG) to reduce child deaths by two-thirds; and premature deaths among adults fell by one-sixth, helped by MDG 5 to reduce maternal mortality and MDG 6 to fight AIDS, malaria and other diseases. With expanded international efforts against a wider range of causes, these rates of decrease could accelerate, say the study authors.
The most striking change during 2000–2010 was a two-thirds reduction in childhood deaths from the diseases now controlled by vaccination (diphtheria, pertussis, tetanus, polio, and measles), highlighting what targeted international efforts can achieve.
“Death in old age is inevitable, but death before old age is not”, said co-author Richard Peto, Professor of medical statistics at the University of Oxford, UK. “In all major countries, except where the effects of HIV or political disturbances predominated, the risk of premature death has been decreasing in recent decades, and it will fall even faster over the next few decades if the new UN Sustainable Development Goals get the big causes of death taken even more seriously.”
The United Nations General Assembly has been discussing 17 Sustainable Development Goals for 2016–2030 to replace the MDGs that expire at the end of 2015. The new health goal is “Ensure healthy lives and promote well-being for all at all ages”. The group of 16 authors, writing in The Lancet, call for this new health goal to be accompanied by a specific target to avoid in each country 40% of all premature deaths (of the deaths that would occur in the 2030 population of that country, if its 2010 death rates continued).
The 40% reduction from 2010 to 2030 in deaths before age 70 would involve reductions of two-thirds in the causes already being targeted by the MDGs, and a one-third reduction in other causes of premature death, such as non-communicable diseases and injuries.
(A) Risk of death versus age for the world in 1970 and 2010
(B) and for country income groupings in 2010.
For historical comparison, the 1910 and 2010 risks for England and Wales are given.
Lead author Ole Norheim, Professor of global public health at the University of Bergen, Norway, explained, “Based on realistically moderate improvements in current trends, our proposed targets are a two-thirds reduction in child and maternal deaths and in HIV, tuberculosis, and malaria, and a one-third reduction in deaths from non-communicable diseases and injuries. For this, we are going to need improved healthcare, intensified international efforts to control communicable diseases, and more effective prevention and treatment of non-communicable diseases and injuries.”
“The most important cause of non-communicable disease is tobacco use – and one of the key determinants of smoking is the price of cigarettes”, says co-author Prabhat Jha, Director of the Centre for Global Health Research in St Michael’s Hospital, Toronto. “WHO is calling for a 30% reduction in smoking by 2025, and in many countries major increases in excise taxes that double the price of cigarettes are still possible. Such an increase would reduce smoking by about a third, but would increase the total Government tax yield from smoking by about a third.”
With political commitment and sustained efforts to improve health, the current rate of decline in premature death can be further accelerated. “We conclude that a 40% reduction in premature deaths is realistic in each country where mortality in 2030 is not dominated by new epidemics, political disturbances or disasters”, adds Professor Norheim.
Writing in a linked Comment, the Norwegian Ministers of Foreign Affairs and of Health and Care say, “[This] study shows what an important part science could play in the negotiations at the 69th Session of the UN General Assembly. We strongly urge the medical community to develop a common position that can enable the international community to arrive at a single health SDG with a limited number of simple, understandable and measurable targets.”
In another linked Comment, Professor Sir George Alleyne, Director Emeritus of the Pan American Health Organization (PAHO), Washington, DC, USA, and colleagues, write that, “The significant advance in this paper is to introduce quantification to the target-setting process, based on rigorous analysis of mortality trends by age as well as by disease category. The proposed targets focus on premature mortality and avoid more complex metrics which are much harder to measure and track over time. The authors stress the importance of countries adapting the targets to their own circumstances.”
This study was funded by the UK Medical Research Council, Norwegian Agency for Development Co-operation, University of Toronto Centre for Global Health Research, and Bill and Melinda Gates Foundation.
Doctors in Sweden have announced the first baby born to a mother with a womb transplant. This pioneering operation offers hope to thousands of couples who are unable to conceive children.
In 2013, researchers at the University of Gothenburg completed a series of nine womb transplants on women in Sweden. Among the patients was an unnamed 36-year-old with Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), a rare condition that prevents the uterus from developing. Her ovaries were intact, however, so she could ovulate. This female became the recipient of a uterus donation from her 61-year-old family friend, the latter having gone through the menopause around seven years earlier.
Drugs were needed to suppress the immune system, which otherwise would have resulted in the organ being rejected. Alongside this, IVF was used to produce 11 embryos, frozen and stored for later use. In January 2014, a year after the transplant, doctors successfully implanted one of these embryos into the patient, transferring it to her new womb. There were concerns over how well a transplanted uterus would cope with the strains of pregnancy, during which it swells greatly in size. The procedure had been attempted by scientists in the past – but in each case, it led to either a miscarriage or organ failure caused by disease.
On this occasion, however, the operation was successful. There were problems in the 31st week of pregnancy – as the mother developed a condition known as pre-eclampsia (characterised by high blood pressure) – but a caesarean section delivered a healthy baby boy weighing 3.9 pounds (1.8 kg); normal for that stage of pregnancy. British medical journal The Lancet has released a photo below and is due to publish a report on the case shortly.
Credit: The Lancet
This milestone in reproductive medicine – the culmination of more than 10 years' research and surgical training – offers hope to thousands of couples who are unable to conceive children. The doctor who led the work, Prof. Mats Brännström, has issued a note of caution, however. In an interview he stated it will be "many, many years" before this operation becomes routine. This is partly because of the extremely high cost, but also because it remains a new and somewhat experimental procedure, only performed by certain specialist surgeons in select centres and requiring various further studies.
Dr Allan Pacey, of the British Fertility Society says: "I think it is brilliant and revolutionary, and opens the door to many infertile women. The scale of it feels a bit like IVF. It feels like a step change. The question is can it be done repeatedly, reliably and safely."
"He’s no different from any other child – but he will have a good story to tell," the father says. "One day, he can look at the newspaper articles about how he was born and know that he was the first in the world to be born this way."
A new drug for advanced breast cancer extends patients' lives by nearly 16 months, a 38 per cent improvement on current therapies.
Pharmaceutical giant Roche has announced the final results of its Phase III clinical trials on Perjeta. This drug – when combined with existing treatments – offers "unprecedented" improvements in survival rates, according to the study of 808 people. Those patients with previously untreated HER2-positive metastatic breast cancer (an advanced form of the disease) who received Perjeta, Herceptin and docetaxel chemotherapy lived a median of 56.5 months compared to 40.8 months for patients who received only Herceptin and chemotherapy.
Breast cancer cells produce a gene known as HER2. This makes a protein called the HER2 receptor, which acts like a broadcast antenna, promoting the growth and spread of more cancer cells. Perjeta is designed to prevent these receptors from pairing with each other on cell surfaces, a mechanism that is complementary to Herceptin. Used together, they can provide a more comprehensive blockade of HER signalling pathways.
"Adding Perjeta to treatment with Herceptin and chemotherapy resulted in the longest survival observed to date in a clinical study of people with HER2-positive metastatic breast cancer," said Sandra Horning, M.D., Roche’s Chief Medical Officer and Head of Global Product Development.
"These results are impressive," said Professor David Miles, who led the study for Roche. "They show a magnitude of survival benefit which we have never seen before in advanced breast cancer, let alone this particular type, previously regarded as having a poor prognosis and being difficult to treat."
In the US, approximately 230,000 people are diagnosed with breast cancer each year and 30% of those will eventually develop advanced (metastatic) forms of the disease. Perjeta in combination with Herceptin and chemotherapy is approved in the United States and the EU. It has also been granted accelerated approval as a neoadjuvant treatment (use before surgery) for early breast cancer by the U.S. Food and Drug Administration (FDA).
A mathematical model that replicates Ebola outbreaks can no longer be used to ascertain the eventual scale of the current epidemic, finds a study conducted by the University of Warwick.
Credit: Leopoldo Martin R [CC-BY-SA-3.0]
Dr Thomas House, of the University’s Warwick Mathematics Institute, developed a model that incorporated data from past outbreaks that successfully replicated their eventual scale. The research, titled Epidemiological Dynamics of Ebola Outbreaks and published by eLife, shows that when applying the available data from the ongoing 2014 outbreak to the model that it is, according to Dr House, “out of all proportion and on an unprecedented scale when compared to previous outbreaks”.
Dr House commented: “If we analyse the data from past outbreaks, we are able to design a model that works for the recorded cases of the virus spreading and can successfully replicate their eventual size. The current outbreak does not fit this previous pattern and, as a result, we are not in a position to provide an accurate prediction of the current outbreak”.
Chance events, he argues, are an essential factor in the spread of Ebola and many other contagious diseases: “If we look at past Ebola outbreaks, there is an identifiable way of predicting their overall size based on modelling chance events that are known to be important when the numbers of cases of infection are small and the spread is close to being controlled”.
Chance events can include a person’s location when they are most infectious, whether they are alone when ill, the travel patterns of those with whom they come into contact or whether they are close to adequate medical assistance. The Warwick model successfully replicated the eventual scale of these past outbreaks by analysing two key chance events: the initial number of people and the level of infectiousness once an epidemic is underway.
“With the current situation, we are seeing something that defies this previous pattern of outbreak severity,” says Dr House. “As the current outbreak becomes more severe, it is less and less likely that it is a chance event – and more likely that something more fundamental has changed”.
Discussing possible causes for the unprecedented nature of the current outbreak, Dr House argues that there could be a range of factors that lead it to be on a different scale to previous cases: “This could be as a result of a number of different factors: mutation of virus, changes in social contact patterns or some combination of these with other factors. It is implausible to explain the current situation solely through a particularly severe outbreak within the previously observed pattern”.
In light of the research findings and the United Nations calling for a further $1bn USD to tackle the current outbreak, Dr House says that “Since we are not in a position to quantify the eventful scale of this unprecedented outbreak, the conclusion from this study is not to be complacent but to mobilise resources to combat the disease.”
This image was captured in Monrovia, Liberia's capital city, during the 2014 West African Ebola outbreak that has affected
not only Liberia, but Sierra Leone, Guinea, and Nigeria as well. Credit: Athalia Christie, courtesy CDC
The coffee genome has been published, with more than 25,000 genes identified. This reveals that coffee plants make caffeine using a different set of genes from those found in tea, cacao and other such plants. The new findings could help to improve coffee production in the future.
Researchers have published the genome of Coffea canephora, a plant which accounts for about 30 percent of the world's coffee production. By comparing the sequences and positions of genes in coffee, tea and cacao (chocolate) plants, they have shown how enzymes involved in producing caffeine likely evolved independently in each of these three organisms. In other words, coffee did not inherit caffeine-linked genes from a shared common ancestor – but instead developed the genes on its own.
Compared to several other plant species – including the grape and tomato – coffee has larger families of genes that relate to the production of alkaloid and flavonoid compounds, which contribute to qualities such as aroma and bitterness. Coffee also has an expanded collection of N-methyltransferases, enzymes that are involved in making caffeine.
Upon taking a closer look, the researchers found that coffee's caffeine enzymes are more closely related to other genes within the coffee plant than to caffeine enzymes in tea and chocolate. This provides evidence that caffeine production emerged independently in coffee. If this trait had been inherited from a shared common ancestor, the enzymes would have been more similar between species.
There are several possible reasons why caffeine is so important in nature. The chemical may help to deter pests, as well as nearby competitors by stunting their growth when coffee leaves fall on the soil. It may also facilitate pollination. One recent paper showed that – like humans – certain insects can develop caffeine addiction. Bees visiting caffeine-producing plants often returned to get another taste.
Worldwide, over 2.2 billion cups of coffee are consumed daily. It is the principal agricultural product of many tropical countries. According to estimates by the International Coffee Organisation, more than 8.7 million tons of coffee is produced each year from 110,000 sq km (42,500 sq mi) of land – an area equivalent in size to the U.S. state of Pennsylvania. Annual export revenue is $15.4 billion and the sector employs 26 million people in 52 countries.
Philippe Lashermes, at the French Institute of Research for Development: "Coffee is as important to everyday early risers as it is to the global economy. Accordingly, a genome sequence could be a significant step toward improving coffee."
In addition to new and exotic flavours, these improvements may include better resistance to drought and disease. Leaf rust, for example, is currently affecting about half the plants in Central America, in the worst outbreak since 1976. Scientists could also engineer the plants to grow faster and increase their output of coffee beans. Such genetic enhancements may prove vital in the future – a study in 2012 estimated that climate change alone will lead to the extinction of wild Arabica coffee (Coffea arabica) by the 2080s.
Biologists have identified a gene that can slow the aging process throughout the entire body when activated "remotely" in key organ systems.
Working with fruit flies, scientists at the University of California, Los Angeles (UCLA), activated a gene known as AMPK. This gene is a key energy sensor within cells; it gets activated when cellular energy levels are low. Increasing the amount of AMPK in fruit flies' intestines boosted their lifespans by 30% – to eight weeks from the typical six – and the flies stayed healthier for longer as well. This is equivalent to extending the average human lifespan for OECD countries from 80 to 104.
The research, published in the journal Cell Reports, could have important implications for delaying aging and disease in humans, explains David Walker, associate professor of integrative biology and physiology at UCLA and senior author of the study.
“We have shown that when we activate the gene in the intestine or the nervous system, we see the aging process is slowed beyond the organ system in which the gene is activated,” Walker said.
These findings are important because extending the healthy life of humans would presumably require protecting many of the body’s organ systems from the ravages of aging – but delivering anti-aging treatments to the brain or other key organs could prove technically difficult. This study suggests that activating AMPK in a more accessible organ such as the intestine, for example, could ultimately slow the aging process throughout the entire body, including the brain.
Humans have AMPK, but it is usually not activated at a high level, Walker explained: “Instead of studying the diseases of aging – Parkinson’s disease, Alzheimer's disease, cancer, stroke, cardiovascular disease, diabetes – one by one, we believe it may be possible to intervene in the aging process and delay the onset of many of these diseases. We are not there yet, and it could, of course, take many years, but that is our goal and we think it is realistic. The ultimate aim of our research is to promote healthy aging in people.”
The fruit fly, Drosophila melanogaster, is an excellent model for studying aging in humans, because scientists have identified all of the fruit fly’s genes and know how to switch individual genes on and off. The biologists studied approximately 100,000 of them over the course of the study.
Co-author Matthew Ulgherait, who conducted the research in Walker’s laboratory as a doctoral student, focused on a cellular process called autophagy, which enables cells to degrade and discard old, damaged cellular components. By getting rid of that “cellular garbage” before it damages cells, autophagy protects against aging, and AMPK has been shown previously to activate this process. Ulgherait studied whether activating AMPK in the flies led to autophagy occurring at a greater rate than usual.
“A really interesting finding was when Matt activated AMPK in the nervous system,” said Walker. “He saw evidence of increased levels of autophagy in not only the brain – but also in the intestine. And vice versa: activating AMPK in the intestine produced increased levels of autophagy in the brain and perhaps elsewhere, too.”
Many neurodegenerative diseases, including both Alzheimer’s and Parkinson’s, are associated with the accumulation of protein aggregates, a type of cellular garbage, in the brain, Walker noted.
“Matt moved beyond correlation and established causality,” he said. “He showed that the activation of autophagy was both necessary to see the anti-aging effects and sufficient; that he could bypass AMPK and directly target autophagy.”
AMPK is thought to be a key target of metformin – a drug used to treat Type 2 diabetes – and metformin is believed to activate AMPK. In research published in May 2013, Walker and his colleagues identified another gene, called parkin, which delayed the onset of aging and extended the life span of fruit flies by 28%.
Last year, Google announced Calico, a spin-off company with the specific aim of developing treatments for age-related diseases. In its first major step since that launch, Calico has now formed a partnership with AbbVie, another biotech firm. Together, they will collaborate to accelerate the discovery, development and commercialisation of new therapies.
The companies will co-invest up to $1.5 billion to create a world-class R&D facility in the San Francisco Bay Area. This will combine Calico's discovery and early development capabilities with AbbVie's broad research, development and commercial expertise, with a focus on aging and age-related diseases including neurodegeneration and cancer.
Art Levinson, CEO and founder of Calico, says in a press release: “Our relationship with AbbVie is a pivotal event for Calico, whose mission is to develop life-enhancing therapies for people with age-related diseases. It will greatly accelerate our efforts to understand the science of aging, advance our clinical work, and help bring important therapies to patients everywhere.”