Go nuclear

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.

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.

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.

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. 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 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.

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.

The age-old question: should I have my genome sequenced?

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.

Seeing is believing

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:

Dividing cells:

http://www.youtube.com/watch?v=m73i1Zk8EA0&feature=channel_video_title

From a textbook publisher with some great videos including audio explanations of what you're seeing:

http://www.youtube.com/user/garlandscience#p/a (check out the zebrafish development video)

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.

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.

The Shark Tank

Some papers feel like they were written over drinks at the pub one night. So it is for a recent Nature 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.

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.

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.

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.

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.

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.

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.

A day at the science museum

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.

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.

If you're ever looking for inspiration and don't have easy access to the Apollo 10 landing capsule, check out 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.

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.

Uncertainty is everywhere

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.

The MMR vaccine and the motivational powers of fear

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.

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?

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?

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.

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.

If immune systems could talk

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.

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.

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.

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.

Me in a nutshell

Welcome!

Let me start with a brief introduction. My name is Megan, and I have a problem.

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.

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.

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.

Enjoy!