Wednesday, 19 January 2011

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.

Tuesday, 18 January 2011

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.

Tuesday, 11 January 2011

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.

Thursday, 6 January 2011

Me in a nutshell


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.