tag:blogger.com,1999:blog-90529373077175625612024-03-12T20:02:59.038-07:00Recovering Scientistscience writing, commentaryAnonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.comBlogger24125tag:blogger.com,1999:blog-9052937307717562561.post-70197072868861025902013-11-15T05:45:00.001-08:002013-11-15T05:46:01.466-08:00Placebo and nocebo: conscious thought not required<div dir="ltr" style="text-align: left;" trbidi="on">
<span style="font-size: large;">I went to a fascinating New Scientist Live event earlier this week. They're launching a new <a href="http://www.newscientist.com/special/nothingness">book</a> literally about Nothing -- from the number zero to the state of mental nothingness induced by anaesthetic. Helen Pilcher was there talking about the nocebo effect, the "evil twin" of the placebo effect. Most of you are undoubtedly familiar with the placebo effect. This effect, also known as homeopathy (in my humble opinion), is when sick people actually do get better by taking pills containing no medicinal ingredients. It's a fascinating effect and seems to happen to about 1/5 of people in any given trial. For years I thought of the placebo effect as a 'mind over matter' type thing, where positive feelings cause the release of neurotransmitters that subsequently make the person actually feel better. My favourite fact about the placebo effect, though, is that even people who know the pills they're taking contain nothing but sugar still feel better when taking them. Mind over matter has nothing to do with it. Disappointing, really-- I've always had a soft spot for the idea of a positive attitude enabling us to overcome anything. Science once again fails to bend to my will.</span><br />
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<span style="font-size: large;">The nocebo effect is the placebo effect inverted. People experiencing the nocebo effect have deteriorating health because they're told they're going to get sick. Helen spoke about witch doctors placing curses, about patients in clinical trials overdosing on sugar pills, and about the reluctance of surgeons to operate on people who think they're going to die during surgery. An unusually large number of those who think they're going to die during surgery indeed do, ruining our poor surgeon's statistics. So is the nocebo effect, unlike the placebo effect, actually a 'mind over matter' phenomenon?</span><br />
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<span style="font-size: large;">Some fascinating <a href="http://www.ncbi.nlm.nih.gov/pubmed/23019380">work</a> from researchers in Boston suggests that consciousness isn't required for the nocebo effect either. Fist, volunteers were conditioned to associate high and low pain with two different faces. When patients were shown face 1, they were simultaneously given a painful heat stimulus. When they were shown face 2, they were simultaneously given a mild heat stimulus. Then they were shown those same faces while an intermediate level of heat was applied, and as you'd expect, the volunteers reported feeling more pain while they were looking at face 1. Now comes the interesting part. The experimenters then showed the faces so quickly that the volunteers were unable to consciously recognise them. Again, face 1 elicited more pain than face 2, despite identical heat stimuli.</span><br />
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<span style="font-size: large;">So much for the conscious mind over matter there, too. There's something much more primal going on to cause these two effects. Perhaps patients who are genuinely at an increased risk of dying during surgery can somehow feel that something is just a bit off. I don't think, as Helen does, that these patients die not from the disease, but from believing that the disease will kill them. There's something else going on here. Belief has nothing to do with it.</span></div>
Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-16490150820941614322012-10-16T04:45:00.000-07:002012-10-16T04:45:59.939-07:00Pushing boundaries<div dir="ltr" style="text-align: left;" trbidi="on">
<span style="font-family: inherit;"><span style="font-size: large;">I have a soft spot for men who are willing to throw themselves out of balloons (I professed my undying love for Joseph Kittinger in my <a href="http://recoveringscientist.blogspot.co.uk/2011/02/day-at-science-museum.html">Day at the Science Museum</a> post). There were a couple of things that impressed me most about the recent Baumgartner records:</span></span><br />
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<span style="font-family: inherit;"><span style="font-size: large;">1. He found himself in an out-of-control spin and pulled himself out of it. What amazing presence of mind and calmness under pressure. </span></span><br />
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<span style="font-family: inherit;"><span style="font-size: large;">2. He broke the sound barrier and highest freefall records. Definitely cool.</span></span><br />
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<span style="font-family: inherit;"><span style="font-size: large;">3. He didn't hit a bird. At least none that we know of.</span></span><br />
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<span style="font-family: inherit;"><span style="font-size: large;">4. He captured the imagination of the entire world. Eight million people watched his stream on youtube.</span></span><br />
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<span style="font-family: inherit;"><span style="font-size: large;">We can't help it, we all love people who push boundaries. Have you looked at the <a href="http://www.xprize.org/">X prizes</a> lately? They're super cool. The X prizes are a series of multi-million dollar competitions designed to push boundaries. They have prizes for putting robots on the moon (governments need not apply), sequencing genomes with incredible speed and accuracy, and cleaning up disatrous oil spills in oceans and seas. They try to identify "Grand Challenges" and design prizes to spur innovation and development in these areas. Go on, take a look. Maybe you should enter!</span></span></div>
Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-13514895576043956402012-09-17T08:04:00.000-07:002012-09-18T01:55:29.903-07:00The Old Man and the G (G to A transistion, that is)<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="font-size: large;">When I was a kid, my dad used to make the same joke every time my mom's birthday came around. "Twenty-nine again, eh?" he'd say. We'd laugh a bit at my mom's expense, but at that age I didn't really understand why adults, particularly women, cared so much about their age. Women dye their hair and buy "rejuvenating" creams. Female models over 30 are relegated to Dove ads. Men, on the other hand, compare themselves to fine wines. The Bernie Ecclestones of the world outnumber the Duchesses of Alba.</span></div>
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<span style="font-size: large;">Much of this underscores the importance of maternal age on fetal health. Pregnant women over the age of 35 are routinely screened for chromosomal abnormalities in their fetuses. Meiosis, the process through which oocytes (eggs) and sperm are generated, is very different in men and women. Men produce sperm on-the-go from germ cells with a virtually unlimited production capacity. Those germ cells spring into action whenever they're needed, and men can produce viable sperm from puberty 'til death. Women's germ cells are already half-way to being oocytes (eggs) by the time they're born. Women don't have an unlimited capacity to produce oocytes because their germ cells don't self-renew. Biology can be a bit quirky, and oogenesis is a particularly odd example. The partially mature oocytes in a newborn baby girl are stuck half-way through a cell division, with their chromosomes aligned in the centre of the cell. One of the problems with this is that large chromosomal abnormalities, such as those seen in Down syndrome, can occur more easily when the DNA is coiled and lined up side-by-side for a long time. The only place I can think of where this happens is in oocytes. The longer the cells remain with their DNA lined up ready for division, the greater the chance that things will go wrong when meiosis resumes. Hence the routine screening for women over 35. When things go wrong they go really wrong, with big chunks of one chromosome getting stuck on another chromosome. You don't need to look very closely at the DNA to see the abnormalities. You need a microscope, but not a DNA sequencer.</span></div>
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<span style="font-size: large;">So women have all their oocytes with them when they're born and they don't produce any more. But sperm production is ongoing, and it relies on continued cell division in the adult. Each cell division carries its own risks. DNA must be reliably copied, checked for mutations, packaged and sent off to make a new cell. </span><span style="font-size: large;">Since most mutations occur during DNA replication</span><span style="font-size: large;">, every cell division presents an opportunity for mutations to arise. Sperm are no exception. Recent <a href="http://www.nature.com/nature/journal/v488/n7412/full/nature11396.html">work</a> on Icelandic parent-offspring trios (mom, dad, baby) shows that the number of new mutations in a baby is strongly correlated with the age of the father at the time of conception. The age of the mother has no detectable impact. The child of a 20-year-old father has an average of 25 mutations, while the child of a 40-year-old father has about 65. </span><span style="font-size: large;">That translates to about 2 additional mutations for each year of paternal age. </span><span style="font-size: large;">The number of mutations doubles every 16.5 years, and is surprisingly linear. Many mutations have no obvious consequences, but others can give rise to diseases ranging from autism to cancer predisposition syndromes. Many diseases, particularly those associated with impaired brain function such as </span><span style="font-size: large;"><a href="http://archpedi.jamanetwork.com/article.aspx?articleid=570033">autism</a></span><span style="font-size: large;">, </span><span style="font-size: large;"><a href="http://schizophreniabulletin.oxfordjournals.org/content/27/3/379.abstract">schizophrenia</a></span><span style="font-size: large;">, dyslexia and reduced intelligence are caused by multiple mutations working together and are <a href="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000040">associated</a> with paternal age. Increased paternal age increases the probability of having enough mutations to make a difference in a child's overall health.</span></div>
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<span style="font-size: large;">A French teacher of mine had an amusing way to remember the gender of disaster words. Un probleme, c'est masculine. To really make a mess you need the feminine: une catastrophe. The same idea seems to apply to DNA. Massive damage to the DNA comes from ageing mothers, while ageing fathers provide multiple smaller problems. Catastrophic DNA damage rarely makes it into viable babies; they don't usually make it past the first few weeks of a pregnancy. A fetus with a collection of DNA "problems" is much more likely to make it through gestation. So next time your charming partner makes a crack about your age, you can do what my mom used to do and tell him to put a cork in it. Even fine wine ages poorly without one. And you might need to double your order of hair dye.</span></div>
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Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-78105332025212459192012-06-12T07:22:00.002-07:002012-06-12T07:22:15.967-07:00The rise of scientific activism<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="font-size: large;">A couple of weeks ago I heard Mark Henderson speak about his new book, the Geek Manifesto. He has recently been appointed Head of Communications at the Wellcome Trust, but was previously the science editor for the Times. Henderson's central thesis is that science should play a bigger role in politics, and that those of us who are scientifically-minded should become more political to ensure this. We should be writing to our MPs to push the scientific agenda. Scientific process should be used to determine policy. The scientific consensus should be presented as "expert evidence", and ill-informed and incorrect science should not. He proposes the establishment of an Office for Scientific Responsibility, an independent body which would hold MPs to account for their assurances of scientific evidence in the House of Commons.</span></div>
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<span style="font-size: large;">I've never written a letter to an MP. Even after hearing Mark speak I don't plan to. I think there are better ways to push a scientific agenda, many of which have been growing in the last decade. Henderson complains that only 1 in 650 MPs has a scientific background. But what he doesn't mention is that the House of Lords is a different story. Of the 825 peers, about 700 are there because of their achievements outside the House. This includes accomplished medics and scientists along with the expected</span><span style="font-size: large;"> collection of lawyers, politicians and business-people. Many Lords are crossbenchers, and therefore do not expressly support any political party. The Lords, like the House of Commons, has a <a href="http://www.parliament.uk/business/committees/committees-a-z/lords-select/science-and-technology-committee/">Science and Technology Committee</a>. Unlike the House of Commons committee the Lords committee contains distinguished lecturers and scientific minds, including John Krebs (a zoologist), Alec Broers (an engineer), </span><span style="font-size: large;">Narendra Patel (an obstetrician),</span><span style="font-size: large;"> and Martin John Rees (president of the Royal Society). I'm against Lords reform for precisely this reason. I want people like this to look at every bill and decide if it passes muster before being passed into law. MPs are often chest-thumping, highly politicized line-toers, but the Lords are not. They are the measured voice of reason. The Lords is full of smart people who have genuine political power. Let's keep it that way.</span></div>
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<span style="font-size: large;">The government also gets scientific advice from independent science advisers. Last week Radio 4 had an <a href="http://www.bbc.co.uk/radio/player/b01jgll3">interview</a> with Robert May, the Chief Scientific Adviser to the UK government from 1995-2000. He's exactly the kind of person we, as scientists, want to have an influence on politics. I've written about some of his work in a <a href="http://recoveringscientist.blogspot.co.uk/2011/03/shark-tank.html">previous post</a>, but his contributions to the fields of ecology, mathematics, and theoretical physics are outstanding. His job as Chief Scientific Adviser was, in his own words, to "speak truth to power". He advised the government through the first death from variant CJD, the human disease caused by the prions found in cows with BSE. He then advised the government through the public uprising against genetically modified foods. Since the GM debate took off shortly after the first CJD death, I don't think GM ever had much of a chance in the UK. People were just too worried that their food was going to kill them. But during his time there he set up a protocol for giving scientific advice to the government. When something important comes along, the government should seek the best scientists in that field to give advice. They should deliberately include dissenting voices. They should do it in the open, and they should emphasize the uncertainties. That protocol was excellent advice from an outstanding scientist. By the way, he's also a Lord.</span></div>
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<span style="font-size: large;">Perhaps due to issues such as BSE and GM crops, scientific activism and public engagement in science is on the rise. The "lay summary" required by virtually all granting bodies is becoming more and more important. In the last month, scientists protested against the "<a href="http://www.bbc.co.uk/news/science-environment-18063913">death of British science</a>" in a rather over-the-top and uncharacteristically childish march to Downing Street. I don't think it was particularly productive and I don't support these types of protests, but I do think it's a sign that scientists are getting more political. More importantly, anti-science protesters who were trying to dig up an important GM research site at Rothamsted were stopped by a bunch of pro-science protectors. The Rothamsted site is purely a research site, not a commercial site. It has been measuring the effects of agriculture since 1843, and is therefore one of the longest running agricultural and environmental experiments in existence. The scientists' <a href="http://www.youtube.com/watch?v=I9scGtf5E3I">appeal to the protesters</a> on youtube has over 30,000 hits. Organizations like <a href="http://www.senseaboutscience.org/">Sense about Science</a>, which provides scientific advice to anyone who's looking for it, are one of our best tools in the pro-scientific movement. They are independent and respected, and look for ways to expand public understanding through targeted campaigns as well as by answering individual questions. Scientists should support them. They provide a means for us to promote <a href="http://www.libelreform.org/">libel reform</a>, engage with protesters in a productive way, and ensure our voices get heard. Organizations with strong public support such as the Royal Society, the Medical Research Council, and the Wellcome Trust should follow their example. And we should all get behind them.</span></div>
</div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-45052576018774684952012-05-18T03:36:00.001-07:002012-05-18T03:36:28.355-07:00The mind-robot connection<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="font-size: large;">I admit it, I cry sometimes when I watch movies. But this is the first time a movie in the supplemental figures of a paper has brought tears to my eyes. This video shows a tetraplegic woman using a robotic arm controlled by an implant in her brain to lift her coffee and take a sip for the first time in 15 years. The smile on her face at the end is amazing. </span></div>
<span style="font-size: large;"><span style="font-family: inherit;">It's an outstanding medical achievement, too. The researchers implanted microelectrodes in the motor cortex of two patients rendered tetraplegic and anarthric (could not speak) as a result of a brainstem stroke. They then asked the patients to imagine moving objects, and looked to see which motor cortex cells were activated. This information was used in the next trial, where the patients controlled a robotic arm with their minds and used it to grasp balls in 3-dimensional space. That was an immense achievement, and is the focus of the paper. But what really got me was the idea of giving this woman, who has been unable to physically control her environment for 15 years, a touch of independence. What an accomplishment for the researchers and their subject alike.</span></span><div style="font-family: inherit;">
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<span style="font-size: large;">http://www.nature.com/nature/journal/v485/n7398/extref/nature11076-s5.mov</span></div>
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<span style="font-size: large;">For those of you without Nature subscriptions, you can watch a shortened version of it here:</span></div>
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<span style="font-size: large;">http://www.nature.com/news/mind-controlled-robot-arms-show-promise-1.10652</span></div>
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</div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-25249554917197897852012-04-20T02:48:00.001-07:002012-10-16T04:46:52.238-07:00How we hear<div dir="ltr" style="text-align: left;" trbidi="on">
<span style="font-family: inherit;"><span style="font-size: large;">More stories for Cosmos- how turning your head can cause you to lose "streams" of sounds (like conversations). http://www.cosmosmagazine.com/news/5527/hearing-readjusts-after-head-movements</span></span></div>
Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-60947045691392093652012-04-13T08:30:00.002-07:002012-04-13T08:38:48.114-07:00Let them eat mud<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="font-size: large;">The hygiene hypothesis has always appealed to me. I like
dirt. I like playing in dirt. I’ll believe just about anything that gives me a
good reason to do something that feels a bit naughty. I love the concept of
“good fat”. I’m sure ice cream is full of it (although I make a point of never
checking).</span></div>
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<span style="font-size: large;">The <a href="http://en.wikipedia.org/wiki/Hygiene_hypothesis">hygiene
hypothesis</a> states that children need exposure to infectious agents early in
life to ensure the normal development of their immune systems, and that without
this exposure they will become atopic. Atopy refers to the inappropriate
activation of the immune system that can cause allergies, eczema, and asthma. The
hygiene hypothesis was originally proposed to explain why children from larger
families have fewer allergies. The theory is that children from large families
are exposed to more infectious agents through their siblings, and these good and
necessary immune stimulations prevent the bad and unneccesary immune
stimulations later in life known as allergies. It’s as though the immune system
gets bored if it has nothing to do and starts attacking anything it can get its
dirty little hands on. Get a few more colds as a kid and you won’t have
allergies. Let your kids play in the dirt. Sounds like a good idea. Given my
partner’s family history of allergies and my daughter’s infantile eczema and
milk sensitivities, I particularly liked the idea of pro-actively preventing
future allergies in my children. I’ve never actually looked into the science of
it, and it’s about time.</span></div>
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<span style="font-size: large;">The immune system is fascinating and dynamic. It is
comprised of T cells, B cells, macrophages and a few others. The B cells
produce antibodies. The macrophages eat things like parasites, bacteria and
viruses. The T cells just help. They recognize the infection and can either
help the macrophages (in what’s known as a Th1 response) or the B cells (Th2
response). Allergies are all Th2 since they involve the production of IgE from
B cells, which then causes histamine release from mast cells (mast cells fall
into my broad category of “other” immune cells). </span></div>
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<span style="font-size: large;">Evidence for the hygiene hypothesis comes from 2 sources:
epidemiology and mouse experiments. There are a number of interesting mouse
models of atopic diseases. A few weeks ago, a <a href="http://www.sciencemag.org/content/early/2012/03/21/science.1219328.abstract?sid=ef69ed6e-cbad-48ba-b304-99c86192d14e">paper</a>
in Science argued that mice raised in a germ-free environment were more prone
to allergic asthma. Exposure to germs as a newborn could reverse this, while
exposure during adulthood did little. The mouse evidence is quite nice, and
definitely supports the hygiene hypothesis.</span></div>
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<span style="font-size: large;">Epidemiology doesn’t establish causes, but it’s about the
only way to find correlations in human populations. Epidemiology showed us the
correlation between smoking and lung cancer. It can produce powerful
information. The epidemiological data supporting the hygiene hypothesis are as
follows:</span></div>
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<span style="font-size: large;">1. Children from large families are less likely to have hay
fever and eczema</span></div>
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<span style="font-size: large;">2. Allergies and asthma have been increasing dramatically in
developed countries in recent decades, where hygiene standards have also been
improving</span></div>
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<span style="font-size: large;">There are a couple of glaring <a href="http://ije.oxfordjournals.org/content/37/3/570.full">issues</a> with the
epidemiological data. Asthma can have a variety of underlying pathologies and
is more like a bunch of different diseases which all look the same. Some types
of asthma are immune-related, some are not. It’s about a 50:50 split. Changes
in the incidence of asthma are therefore inaccurate indicators of atopy.
Furthermore, the incidence of asthma in the developed world is now on the
decline (with the notable exception of inner-city African Americans). Despite
the popularity of the hygiene hypothesis, I don’t think we’re any dirtier than
we were 10 years ago. Given the number of handbag-sized hand sanitizers on
offer at my local drugstore, it might be the opposite. A recent world-wide <a href="http://erj.ersjournals.com/content/35/2/279.full">WHO study</a> showed a
U-shaped relationship between GDP and asthma, further undermining the hygiene
hypothesis as an explanation for increasing asthma in developed countries. The
poorest and the richest countries tend to have more asthma and wheezing than
those in the middle. Even if we take asthma out of the picture altogether, the
evidence for increasing atopy of any kind in the developed world is unclear.
Some countries are experiencing declines, others are not. The epidemiological
evidence for the hygiene hypothesis is sketchy at best, even though the
hypothesis originated there.</span></div>
<div class="MsoNormal" style="font-family: "Helvetica Neue",Arial,Helvetica,sans-serif;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: "Helvetica Neue",Arial,Helvetica,sans-serif;">
<span style="font-size: large;">In its original form the hygiene hypothesis argued that Th1
responses early in life (the macrophage-stimulating ones) could prevent
subsequent inappropriate Th2 responses (the antibody-producing ones). But
there’s a bit of an adaptation of that original hypothesis that seems to hold
more weight. It’s not as much about exposure to infectious agents as it is
about repeated, low-dose exposure to the allergens themselves. It’s more about inducing
tolerance than it is about immune-skewing. Epidemiology can help here, too.
Farming and early exposure to pets are associated with lower incidences of
allergies and asthma, and that data is relatively robust. Recent
allergy-prevention strategies involve low-dose shots of allergen in an attempt
to induce immune tolerance. They don’t cause disease and they don’t induce
immune responses.</span></div>
<div class="MsoNormal" style="font-family: "Helvetica Neue",Arial,Helvetica,sans-serif;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: "Helvetica Neue",Arial,Helvetica,sans-serif;">
<span style="font-size: large;">Perhaps the hygiene hypothesis should be renamed. I’m not
convinced that my kids need to come into contact with every infectious agent
that causes the outpouring of fluids from noses, mouths and bums, but I’m glad
to see that there is some evidence that letting them play in the mud and pet
strange dogs might help them avoid future allergies. And if current
allergy-prevention strategies are a good indicator, perhaps low-dose exposures
even as an adult can induce tolerance. Yay for dirt.</span></div>
<div class="MsoNormal" style="font-family: "Helvetica Neue",Arial,Helvetica,sans-serif;">
<span style="font-size: large;"><br /></span></div>
</div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com1tag:blogger.com,1999:blog-9052937307717562561.post-74636356954555859872012-02-28T07:30:00.001-08:002012-04-13T08:34:27.044-07:00<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="font-family: "Helvetica Neue",Arial,Helvetica,sans-serif;">
<span style="font-size: large;">Will the Y chromosome disappear completely? Take a look at my recent article for Cosmos magazine:
http://www.cosmosmagazine.com/news/5328/extinction-men-put-hold</span></div>
</div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-73385896815817738822012-02-13T03:07:00.001-08:002012-04-13T08:31:35.731-07:00Go on, take a shot<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="font-family: inherit;">
<span style="font-size: large;">
</span>
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<span style="font-size: large;">A mathematical model suggests NBA
players should be shooting earlier</span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span></div>
<div class="MsoNormal" style="font-family: inherit; text-align: justify;">
<span style="font-size: large;"><br /></span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span></div>
<div class="MsoNormal" style="font-family: inherit; text-align: justify;">
<span style="font-size: large;"> Depending
on which side of the Atlantic you call home, basketball is either riveting or
coma-inducing. Basketball players are both athletes and actors. For sports enthusiasts,
much of the excitement comes from waiting for the right scoring opportunity to
arise. But a recent study suggests that NBA players may be waiting too long
before shooting, and that shooting earlier could add about 4.5 points per game.</span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span></div>
<div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;">
<span style="font-size: large;">For mathematicians,
the high scores and frequent shots found on basketball scoresheets give robust
data sets. With only 5 players per team and a limited playbook, the
interactions between players can be examined using classic models such as game
theory. Most sports require quick decisions, and the results of those choices
determine the score at the end of the game. </span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span></div>
<div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;">
<span style="font-size: large;">Shot-selection
in basketball falls under the broad category of “optimal stopping problems”,
the most famous of which is the so-called secretary problem. In the secretary
problem, an administrator wishes to hire the best secretary out of<i> n</i> applicants. The applicants are
interviewed one-by-one, in random order, and the outcome of the interview is
determined immediately. Each applicant can therefore only be ranked relative to
those already interviewed. How can the administrator maximize the probability
of selecting the best candidate? The secretary problem has a surprisingly
simple solution. The best strategy is to interview about 1/3 of the candidates
(<i>n/e</i>, to be more precise), reject all
of them and then offer the job to the first applicant after that who is better
than the unlucky 1/3.</span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span></div>
<div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;">
<span style="font-size: large;">Deciding when
to shoot the basketball presents a similar problem, but the solution is more
complicated. By shooting early, a team forfeits any shots that would have
arisen later in that possession. On the other hand, teams waiting too long pass
up opportunities and instead take low-percentage shots in the dying seconds.
Brian Skinner of the University of Minnesota constructed a model of the “shoot
or pass up the shot” decision. In his model, the optimum time to shoot depends
on three factors: the probability that a shot will go in, the distribution of
shot quality that the offense will generate in the future, and the time remaining
(the NBA allows each team 24 seconds before they have to either take a shot or
surrender the ball). The resulting model states, unsurprisingly, that only
high-quality shots should be taken early, and that the cut-off for shot quality
decreases as the clock ticks down. But NBA players seem to take this too far;
with 15 seconds left on the clock, the optimal model predicts about 3 times
more shots than are actually taken. NBA players prefer to shoot in the dying
seconds.</span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span></div>
<div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;">
<span style="font-size: large;">The model
makes a number of assumptions, the most controversial of which is that shot
opportunities arise randomly in time. It takes time for a team to set up its
offence. Break-away plays may not use the same decision-making process, so
shots from the first 7 seconds of ball possession were discounted. After 7
seconds, a team’s offence should be in place. In support of the assumption,
there was little correlation in the NBA data between average shot time and the
probability that a shot would score.</span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span></div>
<div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;">
<span style="font-size: large;">Under-shooting
could be a sign of over-confidence. Players may be unwilling to take
moderate-quality shots early in their possession, believing they’ll generate
better scoring opportunities in the near future. They may also be
underestimating the probability of a turnover and therefore overestimating the
time remaining. This model advises ‘ballers to do less acting and more
shooting. After all, smug grins are best worn by winning teams.</span></div>
<div style="font-family: inherit;">
<span style="font-size: large;">
</span>
</div>
</div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-76120285694965400752011-12-12T05:33:00.000-08:002012-02-13T03:09:23.417-08:00Saving the pharmaceutical industry<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="font-size: large;">Sometimes I feel sorry for the big pharmaceutical companies.
In popular culture they’re part of an axis of evil that includes other
satan-worshipers like oil companies and banks. Have you seen The Constant
Gardener? Not a particularly sympathetic portrayal of the industry.
</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;">Things have not been looking good for the pharmaceutical
industry lately. The health of each company depends on how many drugs they have
under patent, and the size of the market for each of those drugs. In 2005, the 9
largest pharma companies had 9 new molecular entities (drugs, vaccines, etc)
approved by the FDA. In 2010, they had 2. Many of them face expiring patents
with little to fill the gap. Lipitor, Pfizer’s blockbuster cholesterol-lowering
drug, lost its patent protection at the end of November. This drug alone
accounts for 1/6 of Pfizer’s income, and they are in a battle to hold market
share against their new generic competitors. While consumers, the NHS, and
other health insurers around the world are ecstatic, we should be cautious
about the graves we dance on. Pharmaceutical companies have discovered and
developed drugs to treat a myriad of human diseases. Sales fund research. After
years of increases, R&D spending fell by almost 3% last year. In 2011 both Novartis
and Pfizer closed their major UK R&D sites. Big pharma isn’t finding new
treatments and time is running short.</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;">What’s going wrong? Drug discovery is a long and expensive
process (see my human genome post). It takes an average of 13 years for a drug
to reach the clinic and can cost upwards of $1bn to develop. A much bigger
problem is the attrition from drug target identification to FDA approval. After
preclinical development, a drug goes through clinical trials (phase I, II and
III), gets registered with the FDA and finally becomes an approved drug. For
every approved drug there are 24 drugs in preclinical development. Drugs fail
at every stage of development, but the biggest drop is after phase II clinical
trials. Phase I clinical trials aim to find the best dose, phase II trials
examine the efficacy of the drug, and phase III trials compare the new drug
with existing treatment regimens. Approximately half of the phase II trial
failures are because the drug doesn’t work.</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span><br />
<span style="font-size: large;">Pharmaceutical companies have responded by making significant strategic and
structural changes. Many of them have cut early-stage in-house research in
favour of mining biotechs and academia for drugs and drug targets. Many have
fostered increased cooperation between industry and academia. These changes are
probably a good thing both for pharma and for drug development in general.
Pharma companies get to outsource the risky early stages of drug development,
and budding biotechs have someone to sell their product to. Academics can
publish their results in interesting journals even if they don’t have obvious
and immediate therapeutic value. Increased competition amongst the biotechs
should foster creativity. </span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span><br />
<span style="font-size: large;">There is, of course, a caveat to all of this. Industry experts have always
known that results are not always reproducible from one lab to another. It’s generally
thought that about half of drug targets don't validate. It turns out that this
is may be a dramatic underestimation of the problem. In fact Bayer scientists
could only validate about a quarter of drug targets found in the academic literature.
According to Reuters, drugs that originate in-house are 20% more likely to make
it to the market. What R&D budgets have saved on in-house programs they'll
have to spend on target validation and intellectual property acquisition.</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;">This strategic change may be good for a different reason.
While half of phase II trials fail due to inefficacy of the drug, 29% failed
for "strategic reasons" (one common translation: Pharma B has a
better drug that Pharma A's drug can't compete with). Stage II trials are time-consuming
and costly, and overlap is not particularly constructive. Decreased reliance on
in-house programs should make the early stages of drug development more open.
Small biotech companies with good products will peddle their wares to multiple
different pharmas, so even if Pharma A doesn't buy a given drug they still know
that the drug exists and is being developed by Pharma B.</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;">GlaxoSmithKline had a different approach. Three years ago
they separated their R&D into Discovery Performance Units, each of which
should each perform as an independent biotech. Drugs coming out of these units
should be as reliable as previous in-house drugs. GSK will be at a distinct
advantage: they will have reliable drugs and access to information from
biotechs, but won’t have to share information on their own drug development
program. Not necessarily good for the industry, but good for GSK.</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;">Strategic changes can help the industry, but they cannot
save it. Over half of phase II trials still fail because the drug doesn’t work.
They need to find a way to choose better targets. A recent Nature Chemical
Biology paper by Mark Bunnage, a Pfizer medicinal chemist, outlined a number of
ways in which target selection can be improved. He encourages target selection
based on a number of hallmarks of target quality, including human genetic data
and the existence of robust endpoints. </span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;">In my mind, the purpose of the pharmaceutical industry is to
find new cures to diseases. In reality, big pharmas spend twice as much on
marketing as they do on R&D. Biotech companies spend about 70% of their
revenues on R&D, pharmas spend about 13%. Different companies, different
priorities. And different outputs. I’m not saying the pharmaceutical industry
is full of saints, but the research that has happened on their dime has
improved the lives of millions. I hope they find a way to continue finding
drugs to sell.</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br /></span></div>
</div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-83549960642491330722011-08-30T09:16:00.001-07:002012-02-13T03:09:11.557-08:00The human genome: we’re just getting started<div dir="ltr" style="text-align: left;" trbidi="on">
<span style="font-size: large;"><span style="font-family: inherit;">When the human genome was sequenced over a decade ago, it was a momentous scientific breakthrough. The human genome is enormous. The genome is about 3 billion DNA bases lined up one after the other along chromosomes (which are conveniently broken up into 23 parts). It contains all our genes as well as all the information about when those genes should be switched on and off. Many diseases are caused by genetic changes, so by comparing your or my genome to the average we should be able to see what diseases await us. It was as though a crystal ball had been dropped into our laps. All we had to do was look into it and see everything from our next colds to our eventual deaths. Really, by now there should be an iPhone App for it. So what happened?</span></span> <span style="font-size: large;"><br style="font-family: inherit;" /><br style="font-family: inherit;" /><span style="font-family: inherit;">As with many scientific discoveries, the sequencing of the human genome was over-hyped. It was a scientific breakthrough, but not a medical one. It takes a long time for scientific discoveries to become medicines that affect the lives of patients. A decade or more usually passes from the time a treatment is thought up to the time the first patient is treated, and most drugs don’t work and therefore never make it into patients at all. One of the most important things that scientists have used the genome data for is genome-wide association studies. In these studies the genomes of healthy people are compared with the genomes of people with diseases like heart disease, diabetes, cancer and autoimmunity. Scientists have found a number of mutations in people with those diseases, but knowing that a mutation is there is only the first step. The next steps are to see what that mutation does, try to develop drugs to fix the problem, and then see if those drugs are safe. These discoveries will take time. But without the genome data there in the first place, we wouldn’t even have a starting point. There are over 500 genetic diseases from cystic fibrosis to hemophilia. We can test for most of these. Now we need to develop ways to treat them.</span></span> <span style="font-size: large;"><span style="font-family: inherit;"> </span></span><br />
<br />
<span style="font-size: large;"><span style="font-family: inherit;">Another important change has occurred over the last ten years. DNA sequencing has become cheaper and faster. Since most genomes differ by 1-3%, we need to have a better idea of what “normal” is. The only way to do this is to collect a bunch of normal samples and see how they differ from one another. The Human Genome Project, the publicly-funded effort to sequence the human genome, cost about £1.5 billion and took 11 years to complete. Sequencing the genome now would cost closer to £15,000 and take a couple of months. The X-prize Foundation currently has a $10 million prize for anyone who can sequence 100 human genomes in 10 days for less than $10,000 per genome. We’re not there yet, but we’re not far off. The competitive spirit has been part of sequencers’ ethos since the very beginning. The race to publish the genome itself was nail-biting, including a photofinish between the Human Genome Project and a splinter biotech company founded by a maverick scientist out to show us all how it should be done. Who says scientists are boring?</span></span> <span style="font-size: large;"><br style="font-family: inherit;" /><span style="font-family: inherit;"> </span></span><br />
<span style="font-size: large;"><span style="font-family: inherit;">Anyone with internet access and a penchant for staring at repetitive things can look at the human genome for themselves (</span></span> <span style="font-size: large;"><a href="http://genome.ucsc.edu/" style="font-family: inherit;">http://genome.ucsc.edu/</a><span style="font-family: inherit;"> has a good browser for this). The Human Genome Project and the scientific journals have been instrumental in ensuring that all the data is publically available. Before the human genome it was difficult to convince another scientist to show you his data unless you showed her yours. Anyone with little to show was left in the dark. Having easy access to data means that scientific discoveries happen faster. Genomes are being sequenced faster and faster, and that data is available to anyone who wants it. DIY biologists are starting up companies in their garages. Making DNA is becoming faster and cheaper. Bacteria with synthetic genomes have been created. Biology is accelerating.</span><br style="font-family: inherit;" /><span style="font-family: inherit;"> </span></span><br />
<span style="font-size: large;"><span style="font-family: inherit;">As Isaac Newton once said, “If I have seen further it is only by standing on the shoulders of giants”. The sequencing of the first human genome was a gigantic accomplishment. It will take some time before we can use this information to improve our health, but as discoveries start happening faster and faster it’s only a matter of time before the era of genetic medicine is upon us. These are exciting times, and they will yield exciting results. One day we will be able to sequence a person’s genome, know what diseases they’re likely to get, and then prevent those diseases from happening. It will, however, take time. Patience, patients. </span></span></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-56696658657060160822011-08-09T06:59:00.000-07:002011-09-05T09:34:37.385-07:00Higgs vs Jupiter: a modern-day David vs Goliath<div dir="ltr" style="text-align: left;" trbidi="on">
<div style="font-family: inherit; margin: 0.1pt 0cm;">
<span style="font-size: large;">Physics is about extremes. Even by Newton's time we had figured out the rules governing most things we can see with our eyes, so physicists for the last 200 or so years have been left with the task of investigating things that are either too small, too far away, or too hard to detect with our meagre five senses. The first half of the 20th century was devoted to small things. Thomson discovered electrons, Rutherford discovered atoms, Marie Curie discovered radioactivity, nuclear bombs were made. Bohr's and Schrodinger's atomic models remain largely unchanged today. Nuclear physics was born, space exploration was still a fantasy. It was all about the small guys.</span></div>
<div style="font-family: inherit; margin: 0.1pt 0cm;">
<span style="font-size: large;"><br />
</span></div>
<div style="font-family: inherit; margin: 0.1pt 0cm;">
<span style="font-size: large;">Tides turned when the Cold War started. The space race captured the imagination of big and little kids everywhere. Astronauts became the coolest people on the planet. Men went into space and walked on the moon. Space stations orbited the earth. When we were little, my dad made a set of bookshelves for my brother where the endpieces were shaped like rocketships launching into space. Go figure, my brother grew up to be a space physicist and spends his time launching things into space (although not bookshelves). NASA and its counterparts in Japan (JAXA) and Europe (ESA) have successfully sent probes to every planet, some of their moons, and a handful of meteors, meteorites and dwarf planets. There's still a lot more to be learned about these bodies, but the tides have turned once again.</span></div>
<div style="font-family: inherit; margin: 0.1pt 0cm;">
<span style="font-size: large;"><br />
</span></div>
<div style="font-family: inherit; margin: 0.1pt 0cm;">
<span style="font-size: large;">On July 21, NASA's space shuttle program came to a controlled stop at the end of the Kennedy Space Center's runway. As the Atlantis landed for the last time, the reins of human space flight were turned over to the likes of Richard Branson and friends until the International Space Centre de-orbits in 2020 and humans come back to earth. Since its first manned flight in 1958, NASA has spent $470 billion, at an average of 1.2% of the US annual budget. That's a serious commitment to looking at big, far-away things. The knock-on effects of NASA spending were huge and impossible to quantify, but it unquestionably inspired two generations of scientists, engineers and other dreamers in the US and beyond. NASA really did boldly go where no man had gone before. NASA's most recent mission, the Juno probe's trip to Jupiter, successfully launched last Friday. The Juno probe will take a polar orbit to look at the biggest planet in our solar system, a huge gas planet that resembles the sun except for the obvious lack of fire. An interesting mission, but we are entering the post-astronaut era. The "wow" factor has waned. Although they strapped a couple of smiling Lego people to the probe in an attempt to attract a younger audience, Lego people are simply too big. Our imaginations have moved on.</span></div>
<div style="font-family: inherit; margin: 0.1pt 0cm;">
<span style="font-size: large;"><br />
</span></div>
<div style="font-family: inherit; margin: 0.1pt 0cm;">
<span style="font-size: large;">On the other end of the size spectrum, the Higgs boson and other particles currently being sought by the large Hadron collider (LHC) have attracted an astounding amount of media attention since the accelerator was turned on in September 2008. Even on the subatomic front there has been considerable rivalry between the big guys and the small guys. There’s more than one way to look for subatomic particles. Colliders such as the LHC make atoms move really really fast and then crash them into each other, hoping that not only does the hubcap pop off, but that the seat leather comes off too. These theoretical, subatomic particles should also exist in space, and probes outside the earth’s atmosphere can look at waves from distant objects that would be destroyed by the time they reach the earth. So we should also be able to detect Higgs in space, as Miss Piggy has known from the start. NASA’s FERMI satellite is currently doing just that. The race is on. Even people who traditionally focus on big things are investigating subatomic structure. The coming decades will push the limits of our understanding of all things small. I’d better start building some atomic structure bookshelves.</span></div>
<div class="MsoNormal" style="font-family: inherit;">
<span style="font-size: large;"><br />
</span></div>
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Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-64131227148725720262011-08-05T07:17:00.000-07:002011-08-30T15:24:01.271-07:00The problem with science careers is sample size<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><style>
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</style> </div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">Science is an attractive career for many reasons. On the surface, academics have no real boss, flexible working hours, and job-for-life stability. They spend their time poking around, collecting tidbits of data on whatever catches their eye, and self-aggrandizing to passers-by in the hallways. Sounds like a pretty enjoyable career. An undergraduate science student looking to extend her jean-wearing, coffee-guzzling days into retirement could be easily fooled into thinking this was for her (that’s right, over half the undergraduate science students at most universities are female).</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">As you might guess from the title of this blog, the reality is very different. In fact, the statistics are rather appalling. One in ten biologists has a professor/assistant professor position 10 years after completing her PhD. Admittedly, some of those have left science of their own volition, but many more have been driven out by a lack of opportunity. Theoretically, if everyone wants a to become an academic, a 10% success rate should mean that the best 10% of scientists get positions while the rest do something else, which isn't that different from a lot of other careers. Surely we want the best scientists to lead their own research programs. That’s the problem. I’ve seen people in that top 10% get academic jobs, and I’ve seen people in that top 10% leave science altogether. Same for the other 90%. It all comes down to a problem of iterations.</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">Let’s say a person can get an academic job if she publishes in one Holy Trinity journal (Cell, Science, Nature- make sure to cross yourself as you say these) during her PhD/post-doc. If a young scientist publishes a total of 4 first author papers during this time, she’s done well. The papers that make it into the Holy Trinity are there because they’re interesting. And they’re interesting because they’ve asked timely questions and gotten useful and sometimes unexpected results. Some of this comes down to outstanding experimental design and skillful execution, but in equal measures it comes down to luck. Even outstanding scientists don’t publish exclusively in the Holy Trinity. Some great ideas simply don’t pan out, or the answer to a key question was “no” rather than “yes”. Biology can’t be bent to the experimenter’s desires. The answer doesn’t change the quality of the work, but it changes the interest factor and therefore the impact factor of the resulting paper. That “yes” or “no” answer often comes at the end of a body of work, when the scientist has already invested 2-3 years in the project, is running out of time and money and needs to publish or perish. Out of 10 great ideas, perhaps 1 or 2 will result in a Holy Trinity paper. Ensuring that 1 in 4 early-career papers gets into a Holy Trinity journal is as much luck as it is skill. In order to gauge scientific ability instead of luckiness scientists need to have more iterations before having their CVs scrutinized. If a paper took 6 months of full-time work, an early-stage scientist could put out at least 10 before applying for independent funding. Three-month projects would give her 20. Then there would be enough data points to assess the quality of the candidate. The more data points there are, factors such as luck will play a smaller and smaller role. As scientists and statisticians, we should know this better than anyone.</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">Unfortunately, I can’t imagine science moving in that direction. Today’s papers have much more information in them than papers from 10 years ago. A knock-out mouse model used to be a paper in itself; now it’s Figure 1a. The amount of time it takes to do the experiments, however, has remained unchanged. A PhD still produces 1-2 papers, same for a post-doc. Time seems to be constant.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com4tag:blogger.com,1999:blog-9052937307717562561.post-60937773094582705222011-06-21T06:48:00.000-07:002011-08-30T15:24:21.545-07:00Everyone loves stem cells<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><style>
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</style> </div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">Stem cells have been THE hot topic for a number of years now. In theory, stem cells can be turned into any other cell type and could therefore be used to repopulate a damaged organ with healthy, normal cells. Sounds cool. "Stem cell" refers to a number of different cell types, some can become any cell in the body and some can become only a small subset of cells. Bone marrow, which contains blood stem cells, has been successfully used to repopulate blood after chemotherapy since the 1950s. Half a century later, some recent papers suggest that stem cells could also be used to repopulate damaged hearts and livers, but there have also been some troubling reports about the nature of stem cells, particularly induced pluripotent stem cells.</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">Stem cells come in three flavours: embryonic stem cells (ES cells), induced pluripotent stem cells (iPSCs), and resident stem cells. ES cells are more of a research tool than a potential therapeutic tool. They can be used to study the normal processes which turn a stem cell into all the different cells in the body. They have their much-debated ethical pitfalls, and ES research continues to be plagued by government restrictions and the threat thereof. The advantage of ES cells is that they can be turned into literally any cell, whereas iPSCs and resident stem cells are more restricted. An iPSC cell might become a heart or liver cell, but not a brain cell. The downfall of ES cells is immune incompatibility. When foreign cells are injected into a patient, the patient's immune system will recognize them as foreign and attack them. Bone marrow and other organ donations are matched as closely as possible to the patient, but even then most patients are on immunosuppressant drugs to prevent rejection. ES cells, since the embryo is destroyed in order to get the cells, will never be genetically identical to a prospective patient and immune incompatibility will always be an issue.</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">iPSCs, on the other hand, are made from the patient's own cells so shouldn't be rejected. Cells taken from a person's skin (for example) are grown in dishes and turned into iPSCs through a variety of different protocols including genetic modification or drug treatment. Recently, cells from a mouse's tail have been turned into iPSCs and used to repopulate its damaged liver. iPSCs have their own problems: most iPSCs have multiple, large mutations. Putting mutant cells into someone is not exactly the best idea; not only would they be unlikely to work properly they'd also potentially form cancers. The second major problem is that iPSCs are also rejected by the host's immune system. This was quite unexpected, since iPSCs are theoretically genetically identical to their host. Changes to the cells that occur during their transformation into iPSCs seem to be recognized by the immune system, and the iPSCs are rejected. So the iPSC field now has two enormous hurdles to overcome; they must find cells that are both genetically stable and not rejected by the host's immune system. The two might have a similar solution but iPSCs are a long way from the clinic. The tail-becoming-liver experiment is still promising, but it used genetic modification with some nasty genes in order to perform its feat. No tumours were found in the mice after 2 months, but the long-term effects remain to be determined.</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">Resident stem cells are perhaps the best prospect for stem cell therapies. Many of our organs have the capacity to regenerate themselves, at least partially. A person can have a big chunk of their liver removed and the resident stem cells will help it to grow back. Bone marrow repopulates blood. Resident stem cells are specific to each organ but are already present in the body. The question is how to get them to grow when needed. Livers and blood regenerate themselves without needing to be stimulated, hearts and brains don't. Interestingly, a recent paper shows that resident stem cells in the mouse heart can grow and repopulate a damaged heart when the mouse is injected with a growth factor cocktail. The key to using resident stem cells will be finding the right cocktail for each organ. Some organs may not have stem cell populations that are inducible. It will take a lot of trial and error to find the right mix. The possibility of stimulating a population that's already in place is attractive since it circumvents the problems that arise when the cells are grown outside the body or genetically modified. Repopulating an organ from resident stem cells is a new idea and there will undoubtedly be problems along the way. Therapeutically it could only be used with partially damaged organs, since organs which are heavily damaged or removed completely wouldn't have the necessary stem cells. Some organs may not have resident stem cell populations, or those populations may not respond to growth cocktails. Neurons, for example, are particularly difficult to make. Things that work in mice don't always work in humans. And of course putting molecules into a human which stimulate growth could theoretically cause other inappropriate growth related diseases (ie cancers).</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit; margin: 0.1pt 0cm;"><span style="font-size: large;">Few topics in biology have been as over-hyped as stem cells. They are a potentially powerful tool. Let's see what resident stem cell researchers come up with in the next few years.</span></div><div class="MsoNormal" style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-37018443383847236482011-06-05T14:19:00.000-07:002011-08-30T15:24:53.905-07:00Sorry, it's been a while...<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">Yes, it's been almost a month since my last post. And I have to make one small correction- there was technically a meltdown at the Fukushima Daiichi plant. But I still stand by what I said.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">I'm going to do a bit of recycling right now, so here's a little tidbit on oil droplets I wrote about a year ago. I thought you might find it interesting. For some more of my thoughts over the last month, check out:</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">http://www.economist.com/blogs/babbage/2011/05/controlling_illegal_fishing</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">In the meantime, enjoy this bit about oil drops.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
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</style> </div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: large;"><b><u>Like lipids through a maze</u></b></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: large;"><br />
</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: large;"><b>Oil droplets may be used to solve complex network problems (from 05.06.10)</b></span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify;"><span style="font-size: large;"><br />
</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;"><span style="font-size: large;">The maze is a long-standing test of problem-solving and learning skills. From rats looking for cheese to children running through a labyrinth, finding the end usually requires a trial and error approach. The successful maze solver must correct a few wrong turns along the way, staying focused enough on the end goal to not get disoriented and distracted licking one’s own paws.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;"><span style="font-size: large;">Now it seems that lipid droplets laced with acid have moved into the ranks of successful maze navigators. Bartosz Grzybowski and colleagues at Northwestern University found that lipid droplets can successfully navigate mazes, and can even turn back when they encounter dead ends. In this case the “cheese” is an acid which diffuses through the maze to create a pH gradient. Since the laced droplets themselves slowly release acid, the side of the droplet facing the exit becomes more acidic while the side facing the start of the maze becomes more basic. This difference in acidity creates surface tension on the droplet, which propels the droplet towards the finish line.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;"><span style="font-size: large;">Two types of acid-laced droplets were used, based either on mineral oil or on dichloromethane, an organic solvent. Dichloromethane releases the acid faster than mineral oil, and the two lipids displayed different properties. The mineral oil always chose the shortest possible route. More interestingly, the faster-moving dichloromethane behaved like a cab driver encountering unexpected roadworks; it didn’t always choose the shortest route but was able to correct itself when it found a dead end. In some situations this required the droplet to backtrack for a period of time before resuming its path. When two droplets were simultaneously introduced into the maze, they rarely got in each other’s way.</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;"><span style="font-size: large;">This system could be useful in a number of ways. On a practical level, the movement of acid-laced droplets could be used as a micropump in equipment such as medical diagnostic tools or DNA microchips. If the system is scalable, the maze could also be used to solve more complex network problems. Tracing the paths of different droplets attracted to different targets may serve as a model for the flow of traffic through roads or websites. Robotics and plant and facility layouts could also be modeled using oil drops. The dichloromethane drop’s ability to correct errors could show what happens when slower-moving regions are introduced into the system. At what point will the drop change from a slower but more direct route to a longer but faster route?</span></div><div class="MsoNormal" style="font-family: inherit; text-align: justify; text-indent: 36pt;"><span style="font-size: large;">There are two types of maze-solving experiments, testing spatial navigation or learning respectively. The oil drop experiment examines spatial navigation, where the maze-runner has no previous knowledge of the maze. To examine learning, the maze runner is placed in the same maze repeatedly; the time needed to complete the maze decreases as the runner learns. Lipid droplets can navigate, but living organisms still seem to have the edge on learning.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-84228155872373386522011-05-03T05:06:00.000-07:002011-08-30T15:25:18.405-07:00Go nuclear<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">Energy will always be a politically-charged topic. Growing up in a white-collar town dominated by oil companies, I understand what impact energy has on the economy. In Calgary everyone drives Porches when oil prices are high and they trade those Porches for Fords when times are tough. The rest of the world does precisely the opposite; when oil prices are high it costs us more to drive, heat our homes, and manufacture goods. Inflation goes up. Food is more expensive. The difference between countries that produce their own energy and those that don't is stark.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">I was living in the UK in 2009 when the Russians and the Ukranians starting spitting at each other and the Russians turned off the natural gas pipeline. The knock-on effects (both real and potential) were felt throughout Europe, with 18 European countries reporting major drops or complete cuts in their gas supplies. It was a bit of a wake-up call for me; I'd never really understood the importance of energy self-sufficiency before. Last winter, during the most bitter of the cold spell, Norway (which supplies an ever increasing fraction of UK's gas) had to shut down one of its gas processing centres, leaving the UK with only 7 days worth of gas. Not exactly reassuring.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">The UK produces energy from a number of sources. Approximately 40% of the UK's power comes from gas, 33% from coal, 20% from nuclear and 7% from renewables (mainly wind). Coal is dirty, and many of the coal plants are scheduled to be shut down in accordance with EU objectives. The UK aims to have 20% of its power come from renewable sources by 2015, so renewables are certainly not poised to produce the majority of the UK's electricity in the next decade. That leaves us with nuclear power and gas to make up the rest of the 80% once the coal-powered stations are shut down.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">When the double-punch earthquake and tsunami hit Japan on 11 March, it was a once in a lifetime test for the nuclear community. The forty-year-old Fukushima power station was the 15th largest nuclear power station in the world</span><span style="font-size: large;">. What shocked me was that there wasn't a melt-down. The footage of the greenhouses being flattened or of the enormous ships being pushed around like toys highlights the power of water. The Fukushima station did not escape unscathed, but there was no mushroom cloud either. Japan is in a seismically active region. The largest nuclear power station in the world, the </span><span style="font-size: large;">Kashiwazaki-Kariwa Nuclear Power Plant, was shut down in 2007 after a nearby earthquake shook the power plant more than it should have. Fortunately no radiation leaked that time, and the plant re-started 21 months later. The Fukushima station was not as lucky, and radiation has certainly left the site. It will be years before we can assess the impact on the health of those living near the site, but nearby residents showed no immediate signs of radiation poisoning. The Fukushima power station shows that a nuclear power station can withstand a severe beating and not melt down. Well-done.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">The problems of waste disposal and storage still exist. But I hope the UK will continue to recognize the importance of nuclear power as a source for safe, green electricity. </span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-63191817979225927852011-04-28T07:25:00.000-07:002011-08-30T15:25:43.725-07:00The age-old question: should I have my genome sequenced?<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><style>
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</style> </div><div class="MsoNormal" style="font-family: inherit; text-indent: 36pt;"><span style="font-size: large;">In the early days of the post-genomic era, some scientists were predicting a boom in individuals having their genomes sequenced. For about £1000, you too can have the coding portion of your genome (about 1-2%) sequenced. Fewer people have been willing to fork out for this information than many scientists had thought. We all know we shouldn’t smoke or drink too much and that we should get regular exercise. With few exceptions, knowing the precise sequence of your DNA won’t give you many more insights than that. Having your genome sequenced can only bring bad news: you’re more likely than most to get disease A, B or C. Perhaps we should look at the genomes of people who have lived extraordinarily long and disease-free lives. If I thought that having my genome sequenced would give me license to eat chocolate with impunity, I might consider it.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-82245376028994697682011-04-12T13:51:00.000-07:002011-08-30T15:26:09.033-07:00Seeing is believing<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">Biology is beautiful. Living organisms have symmetries, colours and shapes that are aesthetically pleasing. Our eyes can only appreciate this at centimeter or millimeter resolutions, but the same is true on much smaller scales. It's an obvious thing to say, but computers (and increasingly inexpensive data storage) have changed the way we can see biological events. Videos containing gigabites of high-resolution data are easy to generate, and can give us a four-dimensional view of development and other cellular processes. Erik Sahai's lab always showed beautiful videos of migrating cells during their seminars and it made me want to study migration. If you're a Youtube junkie like me, here are a couple of videos that are worth watching:</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Dividing cells:</span></div><div style="font-family: inherit;"><span style="font-size: large;">http://www.youtube.com/watch?v=m73i1Zk8EA0&feature=channel_video_title</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">From a textbook publisher with some great videos including audio explanations of what you're seeing:</span></div><div style="font-family: inherit;"><span style="font-size: large;">http://www.youtube.com/user/garlandscience#p/a (check out the zebrafish development video)</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">The development of the eye itself is a complex and multi-step process. It starts as a big ball of cells that then gets flattened into a bilayer called the optic cup. This bilayer is like taking the air out of a volleyball or soccer ball and pushing in one side until it's folded in half. The lens of the eye then sits at the opening of this bilayer. A fascinating new publication from Yoshiki Sasai's lab shows that these first few stages of eye development can happen in mouse embryonic stem cells growing ex vivo (i.e. in a dish). Naturally, there are also great videos of this process.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Differentiation of organs ex vivo is both a goal and a tool for developmental biologists. If organs such as the retina could be grown in dishes it would reduce the need for organ donations where demand always outstrips supply. It would also allow for custom organs to be grown, making organ rejection less likely. Growing organs ex vivo also marks an important point in our understanding of how that organ develops. A mouse (or any other organism) starts out as a single cell and ends up with many different kinds of cells including heart cells, lung cells, and muscle cells. Two identical cells side-by-side will grow and divide and change into very different cells by the time development is complete. Numerous signals from neighbouring cells and the rest of a cell's environment help to ensure that each cell chooses the correct fate for its time and place. To recapitulate this in a dish is no small feat. Luckily for early eye development, the requirements for differentiation are minimal and the optic cup develops spontaneously from balls of cells. Most organs will probably need a precisely engineered environment that will be defined over many years through trial and error, but the optic cup system is a good start.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-52792259524138435882011-03-01T09:45:00.000-08:002011-09-20T22:40:22.080-07:00The Shark Tank<div dir="ltr" style="text-align: left;" trbidi="on">
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<span style="font-size: large;">Some papers feel like they were written over drinks at the pub one night. So it is for a recent <i>Nature</i> paper co-authored by an Oxford ecologist and a Bank of England economist (doi:10.1038/nature09659). What these two were doing at the same pub remains unclear, but the result is an interesting analysis of the banking system's inherent fragility using established food web models.</span></div>
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<span style="font-size: large;">Increased globalization of the banking system in recent decades has resulted in significant interdependency. As much as two-thirds of the growth in banks' balance sheets is accounted for by banks lending to banks and to other financial institutions. The collapse of Lehman Brothers in the autumn of 2008 caused a global financial crisis as waves of banks, each dependent on banks in the preceeding wave, found themselves in financial trouble.</span></div>
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<span style="font-size: large;">Interdependency is a common theme in ecology. Species interactions range from relationships which benefit both species (mutualistic interactions) to those in which one species eats the other (predatory interactions), but all depend on the population dynamics of interacting species. Predator and prey population sizes depend on each other. If rabbit food is scarce, rabbit populations decrease, and fox populations follow closely behind. Similarly, if bank #1 fails, then bank #2 which lent bank #1 money now has debts that won't be repaid, and if bank #2 fails then bank #3 which lent money to bank #2 now has the same problem. These "financial ecosystems" can be modelled with banks replacing species in standard food web interaction models. In this model each bank has assets (interbank loans and external assets such as mortgages or bonds) and liabilities (interbank borrowing and deposits from customers). The difference between these two must be positive or the bank fails. Each bank must also keep a fraction of its money as a reserve. This reserve insulates banks from shocks. If the bank's customers decide they want to take their money out, the bank has a reserve of money so that the customers can be paid immediately. If those reserves aren't big enough the bank then has to find money in other ways, either through selling off its assets or by borrowing money from another bank. If a fraction of the bank's assets are wiped out by a shock, the bank fails if it does not have sufficient capital reserves. This paper looks at how an initial failure is propagated through the financial ecosystem, and how the size of the reserve affects this propagation.</span></div>
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<span style="font-size: large;">Three types of shocks were examined, and each had a different outcome. When a single shock hits a single bank, all other banks are affected only by their interbank loans. Increased connectivity attenuates risk. Fewer banks fail in the second wave. In a second situation, a generalized decrease in market prices causes bank #1 to fail. In this situation, bank #2 now has two problems: a generalized decrease in market prices and outstanding loans to bank #1 which won't be repaid. The shock amplifies as more and more banks fail, and connectivity propagates risk. The third situation attempts to describe the most recent financial crisis; intrabank loans decrease following an initial shock, and affected banks follow suit. This liquidity-hoarding shock does not attenuate as the second and third generation of banks are affected.</span></div>
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<span style="font-size: large;">Some interesting observations emerge. If all banks do the same thing and hold a similar mix of assets, each bank individually is less likely to fail if the value of one of those assets decreases. The system as a whole, however, is much more volatile, since it behaves like a single bank. One big shock could wipe out the whole banking system. If regulators want to decrease systemic risk, they should encourage diversification. They should also encourage modularity, so that failures from one type of financial activity do not contaminate banks engaged in unrelated activities. The United States has already proposed the Volcker rule to do precisely that.</span></div>
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<span style="font-size: large;">As the authors point out, the banking system is not quite as simple as the model they used. One major difference is that in reality there tends to be a few large, well-connected banks and many more smaller banks. The smaller banks are especially well-connected to the big banks, since the big banks have a proportionally big share of the banking market. The spread of infections uses a model similar to food webs. In the epidemiology of infectious diseases, people with lots of interpersonal connections (ie big banks) are known as "super-spreaders", and a web with super-spreaders maximizes the number of infected individuals. Regulations aimed at reducing systemic risk, as opposed to bank-by-bank risk, should require super-spreader banks to have larger reserves than other banks.</span></div>
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<span style="font-size: large;">This is not the first time the financial world has turned to science to find answers. The Black-Scholes model used for pricing derivatives is, at its core, a heat dispersion equation. Perhaps interbanking webs will be better than these much-scapegoated derivatives at identifying and reducing systemic risk.</span></div>
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Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-27879626373301539222011-02-15T08:44:00.000-08:002011-08-30T15:26:55.955-07:00A day at the science museum<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">A couple of weeks ago we took our little girls to the Science Museum. It was absolutely rejuvenating. My almost-two-year-old fell in love with the rockets. I explained to her how rockets launch things into space and then fall back to earth. She then ran around pointing at them, and kept telling me "rockets fall down"! She looked at the models with such intensity; she was truly amazed. Her excitement was contagious, and when we later saw the Apollo 10 landing capsule and a 1 million volt particle accelerator from the 1930s, I felt amazed too. I love that feeling. Lately we make lots of play-doh rockets, probably because I want to remind us both what awe feels like.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">A friend of mine was recently accused of being a geek for wondering how much a person's head weighed. I don't think geek is the right word. The accused is one of the best scientists I know, probably because she spends her spare time wondering about things like the weight of her head. Scientists must be inherently curious people, as scientific discovery doesn't take a straight path and discoveries are often fortuitous. One of my favourite examples is restriction enzymes. Restriction enzymes are used in the lab to cut pieces of DNA and glue them back together in a different order. They are the cornerstone of the molecular biologist's toolkit. They weren't discovered by someone looking to cut DNA into pieces, but rather by a scientist studying the effects of radiation on bacteria. He received the Nobel Prize for this discovery. In his autobiography he writes, "When I started investigations on the mechanisms of host-controlled modification, I did not of course imagine that this sidetrack would keep my interest for many years. Otherwise I might not have felt justified to engage in this work because of its lack of direct relevance to radiation research." There's a message somewhere in there for those who fund scientists. Luckily for the rest of us his curiosity was piqued by this mechanism.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">If you're ever looking for inspiration and don't have easy access to the Apollo 10 landing capsule, check out </span><span style="font-size: large;"><span class="long-title" dir="ltr" id="eow-title" title="First Man in Space - Skydiving From The Edge Of The World">First Man in Space - Skydiving From The Edge Of The World on youtube. It's a video from Joseph Kettinger skydiving out of a helium balloon from 100,000 feet. As a reference, trans-Atlantic flight paths are around 35,000 feet. Performed in 1960, Kettinger's dive pushed our understanding and our expectations of human knowledge. There aren't many people with enough courage to get into a helium balloon in a space suit and wave goodbye, but I'm certainly glad those people exist. Since there's no atmosphere up there, he fell so fast he exceeded the speed of sound. Amazing.</span></span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Lately I've been lulled into routine and into the mundane. Maybe it's winter. Spring is on its way though, and I want to be amazed. Since I'm too much of a chicken to skydive from 100,000 feet, I'm going to go try to weigh my head.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-52729262531348240002011-01-19T06:00:00.000-08:002011-08-30T15:27:15.926-07:00Uncertainty is everywhere<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">It is impossible to determine whether or not my six-month-old is asleep in her cot without altering her state of wakefulness. The Heisenberg uncertainty principle is everywhere.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-25274624496975306472011-01-18T08:09:00.000-08:002011-08-30T15:27:38.838-07:00The MMR vaccine and the motivational powers of fear<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">Last week the scientific community once more denounced the work of Andrew Wakefield, the lead author of the now infamous Lancet paper which falsely linked the measles, mumps and rubella (MMR) vaccine to autism. Previous investigations into his work demonstrated unethical behaviour in his data collection; in the most distasteful example he was passing out £5 bills at a kids' birthday party in exchange for blood samples. There were also substantial and unreported conflicts of interest. While investigating the possible link between the MMR vaccine and autism he was paid as an expert witness by lawyers preparing a case against the manufacturers of the vaccine itself. If he had found no link, Dr. Wakefield wouldn't have been a particularly useful witness. Moreover, he had filed for patents for individual vaccinations. Individual vaccinations would have been an obvious choice if the triple vaccine was unsafe.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">So we knew that Dr. Wakefield employed questionable practices and was motivated by questionable and undisclosed funding. He behaved unethically. But the more important question is, was he right? Is there a link between the MMR vaccine and autism?</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Subsequent work from numerous labs has failed to reproduce his data. It is important to note that he was drawing his conclusions from a patient sample of 12. Statistical anomalies happen, especially with small sample sizes. A confidence interval of 95% is generally acceptable for the publication of an association between two medical conditions. This means that 95% of the time, the two conditions are associated. The converse is that 5% of the time the two medical observations are simply a coincidence. Theoretically, he could have observed the association and reported it, not knowing that he saw these conditions merely by chance. Was Dr. Wakefield the unfortunate victim of coincidence? Was his reputation sullied by fate?</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Part of me had hoped that to be true. With great power comes great responsibility. Those in positions of authority, from politicians to medical professionals, have a great responsibility to promote the public interest. Dr Wakefield broke that trust. He fabricated data to fulfill his predictions. He was a liar. Of the twelve cases reported in his original paper, eleven of them were irreconcilable with the hospital's health records. The Lancet paper describes twelve children who were developmentally normal until they received the MMR vaccination, and then developed autism. According to the hospital records only one child actually had regressive autism, and five of them were developmentally abnormal before receiving the MMR jab. Dr. Wakefield was not the victim of coincidence, he was a fraud.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Why did his findings have such an enormous impact on public health, and how can the damage be repaired? Insurance companies can tell you the answer. Horrible but unlikely events are such stuff as nightmares are made on. It's terrifying to think that vaccinating your infant could cause him to become autistic, and correspondingly immunization rates in the UK fell below 80% in the early naughties. This has now caused another horrible and increasingly likely event; a fatal outbreak of measles, mumps or rubella. The fatality rate from measles for otherwise healthy people in developed countries is 3 deaths per thousand cases. In the last two years outbreaks of measles have occurred in Wales, New York, San Diego, France, and Germany. It is only a matter of time before an unvaccinated child dies from measles, and parents start rushing back to their GPs to have their children vaccinated. Fear is a powerful motivator.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-86528979515479428242011-01-11T08:41:00.000-08:002011-08-30T15:28:08.912-07:00If immune systems could talk<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">Throughout our lives, we are exposed to a variety of pathogens. These exposures result in immune memory. A one-year-old gets every cold that comes her way; her parents are likely to be immune to many of these viruses and will therefore not get sick every time. Disorders of the immune system from allergies to multiple sclerosis occur when the immune system misidentifies something normal as being abnormal and therefore attacks it. Each immune disorder should theoretically each have a set of diagnostic antibodies, antibodies which recognize the thing that they shouldn't. </span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Many other diseases, such as cancers and neurodegenerative diseases, cause physiological changes that are recognized by the immune system. Alzheimer's disease, while not a disease of the immune system, is associated with the accumulation of antibodies which recognize the brain damage. These diseases should also have a set of diagnostic antibodies. Recently, a group in Florida has described a new way to look for antibodies in patient blood samples. They were able to find antibodies in both human Alzheimer's disease and in a mouse model of multiple sclerosis that were abnormal and therefore potentially diagnostic.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Using antibodies to detect these diseases could be very useful. Often, the detection and diagnosis of neurodegenerative diseases is difficult. MRI scans are expensive. Taking blood is not. Diagnosis of these diseases through antibody screening of blood samples could provide a cheap and reliable alternative to MRI scans. For diseases such as cancers, early detection is the key to prevention. If antibodies can be detected early enough, many cancers could be treated early enough to prevent them from spreading.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Wisdom comes with experience. Many of our experiences have been witnessed by our wizened immune systems. Perhaps we now have a way to let them talk.</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com0tag:blogger.com,1999:blog-9052937307717562561.post-8541018001106899442011-01-06T13:44:00.000-08:002011-08-30T15:28:30.512-07:00Me in a nutshell<div dir="ltr" style="text-align: left;" trbidi="on"><div style="font-family: inherit;"><span style="font-size: large;">Welcome!</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Let me start with a brief introduction. My name is Megan, and I have a problem. </span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Two years ago, I was enjoying my postdoc in a cancer research institute in London. My days consisted mainly of staring at unconscious flies under a microscope, pipetting dilute solutions of nasty chemicals from one tube to another, and learning French swear words from my benchmate. I had the standard plans to start my own lab and live happily ever after within the Ivory Tower. Then something terrible happened. I came to the realization that I didn't actually want to be a scientist when I grew up. A career in science is kind of like a career in acting. It's great if you're Angelina Jolie, but waiting tables in Hollywood while being recognized as "that girl in the Colgate ad" isn't very satisfying. Unfortunately, I'm no Angelina. And I'm a lousy waiter. So I threw in the proverbial pipetteman and chose a new path.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Do I miss being at the bench doing experiments? No. Not a bit. Okay, sometimes I do. But not too much, and not for too long. I miss the "woo hoo!" moment. Anyone who's had one knows what I'm talking about. It's the bubbling excitement you get when you're first looking at the results of an experiment that really tests your theory, and everything is clean and clear and the answer is staring back at you from the film as you pull it out of the developer. At that moment, there's nothing to say other than "woo hoo!". Unfortunately, in the decade I spent doing research I can count my "woo hoo!"s on one hand. Were those moments worth all the time and effort? Did my work change our fundamental understanding about health and disease, or even our understanding of a single subset of a single disease? If the answers were yes, I'd probably still be slugging away.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Science, however, is a bit addictive. I don't miss pipetting. What I really miss is reading about and discussing new ideas. Here's where the blog comes in. A blog is the perfect way for me to get my fix, without having to devote my entire life to a lab. So come and check out my posts for some ideas and discussions about discoveries, politics, and a few quirks and quarks. Comments are always very welcome.</span></div><div style="font-family: inherit;"><span style="font-size: large;"><br />
</span></div><div style="font-family: inherit;"><span style="font-size: large;">Enjoy!</span></div></div>Anonymoushttp://www.blogger.com/profile/11171338829684087595noreply@blogger.com1