The new issue of Guru came out at the beginning of the month, but I’ve been so busy I haven’t had time to promote it here until now. You can read issue 11 online or download it in various formats from the Guru website.
This month also saw the launch of the Guru app, so now you can never miss an issue on your Android or iPhone. There were some compatability issues on launch, but these seem to have been cleared up now. It works fine for me and the app itself is a model of functional simplicity and style, so get downloading and give it the rating it deserves!
My news column this issue includes two pages of developments in cancer research, including a new hope for the future of treatment. Also how to frighten the fearless, and earth-like planets in our backyard.
It didn’t turn out quite how I’d intended though, so I’m reproducing it here. Enjoy!
Swinging 60s puts chest over breast: Research published in Annals of Oncology this Feb predicts lung cancer will overtake breast cancer as the bigger killer of European women by 2015, based on World Health Organisation mortality data. This is already true in the UK and Poland, the two EU countries with the highest lung cancer death rates. Although overall cancer deaths have fallen by 6% in men and 4% in women since 2009, lung cancer deaths have risen by 7% in women in that time, while breast cancer rates have fallen. The fall in breast cancer is due to advances in early diagnosis and treatment of that disease, while the increase in lung cancer probably reflects changing cultural attitudes in the 60s and 70s leading to more women smoking. Fewer young European women are smoking now however, so lung cancer should start to level off around 2020.
Virus Vs. Cancer: Meanwhile, scientists are busily studying what they hope might turn out to be a revolution in cancer treatment. The past few years has seen a surge of interest in oncolytic viruses.
A virus reproduces by hi-jacking a host cell to make copies of itself, which then go on to invade other cells, destroying the host cell in the process. Oncolytic viruses attack cancer cells, so the approach is known as “viral therapy”. Naturally occurring oncolytics were discovered over half a century ago, but they didn’t really do the trick – either because they were harmful, or our immune system dealt with them better than they dealt with cancer. But thanks to modern genetic engineering techniques scientists are now custom-building viruses to attack cancer. They can be tweaked to target specific types of cancer cells, to be less vulnerable to immune suppression, or to produce cancer-suppressing genes. The first of these to be approved for use was Oncorine in China in 2005, and a treatment derived from the Herpes simplex virus, OncoVEX GM-CSF, has shown promise in clinical trials.
Now, a genetically-engineered form of vaccinia virus, JX-594, has been shown to prolong the lives of people with terminal liver cancer. Of 30 patients, 14 on a low dose survived for 6.7 months on average, whereas 16 on a high dose survived for 14.1 months. The trial, published in Nature Medicine in February, also found both doses decreased blood flow to tumours and reduced their size. As well as replicating inside cancer cells and destroying them directly, the virus caused the body’s immune system to attack the cancer, providing a two-pronged assault. The only side-effects tended to be a day or two of flu-like symptoms, which is trivial compared to other forms of therapy. A larger follow-up trial is already underway and the virus is being tested on other types of cancer.
Although that work involved injecting tumours directly, many of the same researchers have previously shown that JX-594 can be administered intravenously. In a trial published in 2011, a single infusion was shown to infect the tumours – without harming healthy tissue – of 23 people whose cancer had spread to several organs. This is crucial, not only because tumours anywhere in the body can be treated this way, but also, once tumours start spreading to other organs and tissue – something called metastasis (see: Metastasis Matters) – they become virtually incurable by existing methods. Viral therapy can be especially effective against such metastatic cancers, but blood-borne viruses are easily mopped up by antibodies, so avoiding the immune system until the virus has done its job is probably the biggest obstacle to developing a full-blown oncolytic cure for cancer.
Metastasis matters: Metastasis is what ultimately kills most people with cancer, but scientists don’t completely understand how it happens. Epithelial tissue is one of four tissue types (the others being connective, nerve and muscle), and epithelial cells form the surface of many structures in the body, including the lungs, liver, and breasts. They bind tightly together in stable tissue layers however, so how the cancerous versions migrate around the body has been something of a puzzle. A paper published in Science this January however, provided the best evidence yet supporting a strong theory of metastasis, which is that it involves something called “epithelial-mesenchymal transition”. Mesenchymal cells don’t bind to each other and can move more freely, so it was thought epithelial tumour cells might become more like mesenchymal cells to enable them to enter the bloodstream and circulate. There was some support for this theory from animal studies, but this recent study used a set of markers the researchers developed to identify circulating tumour cells (CTCs) allowing them to track and genetically analyse them in 11 women with breast cancer. They found that when the tumours were responding to chemotherapy, the proportion of CTCs with mesenchymal properties fell, but rose when therapy failed. Many had features of both epithelial and mesenchymal cells however, suggesting the real enemy may be an intermediate cell type. The work paves the way for researchers to more easily track how cancer spreads, and could provide a range of new targets for drug developers.
Other attempts to tackle this problem include using reovirus – a naturally occurring oncolytic that “piggybacks” on blood cells to avoid the immune system, and a study which hid an engineered adenovirus inside white blood cells to deliver it to prostate cancer in mice. This technique uses the immune system itself – spurred into action by chemotherapy or radiotherapy – to deliver a viral payload which “completely eradicates” tumours, but it is yet to be tested in humans.
How to frighten the fearless: A woman who has been extensively studied because she was thought to be unable to experience fear was terrified by an experiment in which she inhaled carbon dioxide. The woman, known as SM, has a rare genetic condition called Urbach-Wiethe disease, which has left a part of her brain called the amygdala severely damaged. This ancient brain structure is thought to be important for generating fear responses and SM had not shown fear since childhood, either in real-life threat situations, or in response to the scary films, spiders, snakes, etc., presented to her by previous researchers.
One way of provoking fear is to have people breathe carbon dioxide as this builds up rapidly in the body when a person can’t breathe and so is detected as a suffocation threat. Some of the same researchers had previously shown that the amygdala directly detects carbon dioxide to generate fear in mice. So when they tested SM, two other patients with the condition, and 12 healthy participants, by having them inhale 35% carbon dioxide (850 times that in normal air), they only expected to see panic in the healthy participants. They saw almost the exact opposite. All three patients reported intense fear – a novel experience for them – whereas only a few healthy participants experienced panic. The study, published in Nature Neuroscience, proves the amygdala is not essential for generating fear responses and suggests there are different pathways involved in responding to external and internal threats. The brainstem and insular cortex – a part of the brain involved in bodily awareness – are likely candidate parts of an internal threat system.
Near-Earth neighbours: Astronomers at the Harvard-Smithsonian Centre for Astrophysics announced in February that the nearest Earth-like planet could be a stone’s throw away in astronomical terms – orbiting a red dwarf just 13 light years away.
NASA’s Kepler space telescope spots planets outside our solar system by watching for dips in a star’s brightness as a planet “transits” between us and the star. Most of Kepler’s targets are Sun-like, but red dwarfs are dimmer and smaller, so an Earth-sized planet produces a bigger dip, making it easier to see. They’re also cooler so a planet must be closer to be in the habitable “Goldilocks” zone where liquid water is possible. This makes it more likely the planet will pass directly between us and the star.
The astronomers first re-analysed all the red dwarfs in the Kepler catalog of 158,000 stars, and found most were smaller and cooler than previously thought, implying transiting planets must also be smaller to account for the same signal. They then identified 95 candidate planets orbiting red dwarfs, and calculated that around 90% of red dwarfs should therefore host planets between half and four times Earth’s size. Only two in the habitable zone were Earth-sized however, so, statistically, around 15% of red dwarfs should host Earth-like planets. The paper was submitted to the Astrophysical Journal.
Around three quarters of the roughly 100 billion stars in the Milky Way are red dwarfs, meaning around 4.5 billion such planets should be littered throughout the galaxy. That’s a lot of places to look for life, and, given the distribution of red dwarfs, the nearest could be right next door. In fact, a more recent paper has reduced the estimate to 6.5-7 light years, using updated definitions of habitable zones.