MMR and Statistical Manipulation

Measles virus

When I was still at high school, way back in the late 1970s, there was a health scare that got a lot of media attention. Apparently, there was a perceived risk that the whooping cough vaccine could cause brain damage. The fall off in vaccination for this disease is claimed to have led to the widespread outbreaks of whooping cough in 1979 and 1982, there having previously been almost zero annual cases. At the peak there were some 60,000 cases.

Fast forward to the near present and you will recall similar scare stories about the combined measles-mumps-rubella vaccine, the MMR, and claims by researcher Andrew Wakefield (Lancet, 1998) that MMR could cause autism in some children. It’s a topic guest blogger Michael Marshall covered on Sciencebase in November 2004. It seemed that, at the time, the debate was pretty much over. However, despite repeated demonstrations of the apparent inadequacies of the original research into a link between MMR and autism, the issue is resurrected on a regular basis. Most recently in a cover story in The Observer, which drew much flack, but also left the chattering classes once more in a flap.

Right now, I’m looking at an article from the print edition of The Times offering an answer to the Question of the Week – “Measles or vaccine?” – the article talks of how measles has reappeared and it is apparently all down to many parents’ reluctance to have their children vaccinated with the MMR jab. The article talks of “herd immunity” and how enough children have had a double dose of MMR which should stave off an epidemic. The emergence of herd immunity, of course, will be little comfort for a parent whose child experience any of the potentially severe side-effects of vaccination.

In the article, pictured alongside a blow-up of the measles virus and an image of a nasty-looking hypodermic needle, are two charts, one showing the number of cases of measles in the UK from 1940 to the present day and the other showing the number of deaths over the same period. Incidence of the disease ebbed and flowed during the period up to the early 1970s whereupon cases began to fall rapidly from a peak of 800,000 a year in the early 1960s to just one or two hundred a year by the mid-1970s.

The MMR vaccine was introduced in the US in 1971 and later in the UK, thereafter incidence of measles has pretty much fallen to levels close to zero. It seems that the pre-vaccine drop had another cause, presumably reduced overcrowding, improved nutrition, better hygiene and healthcare. No one knows at what point this fall would have reached a plateau.

In contrast, the second chart of death rates shows an exponential decline in measles deaths since the 1940s, by about 1970 measles deaths were also close to zero. The risk of getting measles is about one in three, assuming no vaccination coverage at all. The risk of serious consequences to this disease, which personally I had in 1972 or thereabouts, is somewhere between 1 in 5000 and 1 in 15,000. Compare that to the risk of death in a road accident. According to Transport2000 , the UK’s national environmental transport body, each of us has a 1 in 17 chance of being killed or seriously injured in a road crash during our lives. Such figures damn the disease statistics somewhat. Of course, vaccination does come with some risks, but adverse reactions, such as seizures with an associated risk of brain damage, exist at the 1 in 10,000 level.

There has been one UK death from measles since 1992 (as opposed to the several hundred each year during the 1940s). The unfortunate victim was apparently suffering an underlying lung disease for which he required long-term immunosuppressant drugs. He was very unfortunate to be exposed to the measles virus, and when he contracted the disease he was very unlikely to have recovered. This is one fatal case. Even with near 100% vaccination, there would still be a finite risk of any random member of the population contracting the disease. Unfortunate, but true. The statistics would not lie surely?

Intellectual genetics

Tug of war

Two worthy legal moratoria – the Agreement on the Trade-Related Aspects of Intellectual Property Rights (TRIPS)
and the Convention on Biological Diversity (CBD) – are potentially in direct conflict when it comes to plant genetic resources and intellectual property rights, at least that is the conclusion of legal expert Megan Bowman. However, potential conflicts could be reconciled in this context by applying the common sense notion of remaining true to the over-arching principle of global welfare-maximisation in TRIPS and by utilising patent exemptions in appropriate circumstances. This, Bowman claims, will allow TRIPS and CBD to operate in a way that achieves both their objectives equally well so that intellectual property rights can be appropriately recognised and biodiversity can be sustained.

Writing in the International Journal of Intellectual Property Management (2007, Vol. 1, pp 277-292), who is a trained barrister and a lecturer in the Law School and Centre of Strategic Economic Studies, at Victoria University, Melbourne, Australia, points out that international recognition of intellectual property rights has grown, particular in the biotech arena, as biodiversity levels have fallen across the globe. Bowman points out that these two trends have become related since the creation of TRIPS and CBD in 1993 whose spheres of operation overlap significantly, particularly in relation to plant genetic resources and intellectual property rights. Bowman states that this is because biological diversity, at both genetic and physical levels, is being exploited as the key ingredient for lucrative biotech and pharmaceutical industrial creation. Patent protection of that creation raises questions about biodiversity sustainability and also access to the resultant benefits and technologies derived from use of a raw product ‘owned’ by source countries or communities.

Currently we are experiencing global biodiversity degradation and decimation due to causes such as global warming that may result in the extinction of nearly half the current lifeforms by 2050. Bowman comments: ‘Apart from the intrinsic value of biological diversity, without healthy and diverse ecological systems on this planet there is no quality of life for humans — no fresh air or water, no arable land or edible food, and exposure to devastating storms, floods and droughts. But at the same time, humans are evolutionary creatures and we see that clearly with technological innovation. We are also wed to the dollar and we see that, in the context of this discussion, in the jealous guarding of rent for patents, specifically in the growing sector of biotechnology and pharmaceuticals based on plant genetic resources. So the question is how do we marry these components in a way that honours each of them? I look at this question from a purely legal standpoint. Undoubtedly any solution is complex, multi-faceted and multi-disciplined. Nonetheless, the legal principles embedded in the key international treaties on protection of biodiversity and protection of intellectual property rights in plant genetic resources share a commitment to global welfare enhancement. So it becomes clear that the legal foundations exist for cooperation between these two sectors. This knowledge paves the way for productive dialogue and action in boardrooms, patent offices and parliaments around the world.’

Related article from the Sciencebase archives on corporate academia: Will publicly funded research become mired in patent protection and intellectual property rights or remain purely altruistic?

(Updated: August 21, 2007)

Mice and a slice

Raman brain sliceA new methodology for fibre-optic Raman mapping and FTIR imaging of secondary cancer cells, metastases, and detecting tumour cells has been developed by researchers in Germany. The technique facilitates imaging of samples thicker than 50 micrometres and could be used in detecting cancer cells, as a tool for molecular histopathology, in metabolic fingerprinting, general disease diagnostics.

Team member Christoph Krafft is currently in the Department of Materials and Natural Resources, at the University of Trieste, Italy, but will be returning to Dresden University of Technology with a new research grant in September. I spoke to him about the research and he told me that, “This fibre-optic Raman method will allow detecting tumour cells and tumour tissue in vivo and enable studies of tumor development.” You can read more details in the latest issue of SpectroscopyNOW.com in the Raman ezine.

Master AND commander

Master commanderAn fMRI scan of the upper echelons of the human brain, reveals that there are apparently two commanders at the helm, according to US neuroscientists; it is as if Russell Crowe were joined by his twin brother to captain the ship. The work may suggest new insights into behavioural problems that occur following brain injury.

Neuroscientist Steven Petersen and his team at Washington University School of Medicine in St. Louis also found that these two captains at a single helm do not consult each other in the control of voluntary, goal-oriented behaviour. Such behaviour encompasses a vast range of activities from reading and surfing the net to singing a song or even sailing a ship. In contrast, involuntary behaviour, such as pulse rate, breathing, and digestion are not controlled in this way.

You can read the full story in my SpectroscopyNOW column in the MRI channel.

Ragworm Ragtime

RagwormWhen I was a youngster I used to do a spot of sea fishing on the freezing cold north east coast. It wasn’t so much a hobby as an obsession at one point. Key to success was a plentiful supply of lugworm which could be dug from the wet golden sand at lowtide and stored ready for the next angling venture, while ragworm, which have a nasty bite, came from the local fishing bait supplier. Never would it have occurred to my 11-year old self that these lowly creatures could harbour the secrets of our own evolution.

However, apparently it does. Detlev Arendt of the European Molecular Biology Laboratory has been studying the multifunctional neurones that sense the environment and release hormones in vertebrates (including ourselves), flies, and worms. The last common ancestor of all of these creatures must provide the evolutionary basis of our modern brains that endow us with the skills to varying degrees of success to dig up ragworm, take part in fishing trips, and ponder our origins.

Hormones control growth, metabolism, reproduction and other biological processes. In humans, as indeed in all vertebrates, the chemical signals are produced by the hypothalamus and other specialist brain centres and secreted into the blood for circulation around the body. This signalling system is not, it turns out, the preserve of those creatures with a backbone. Arendt and his colleagues now believe that the hypothalamus and its hormones have their evolutionary origins in an ancient worm-like creature that lived hundreds of millions of years ago and is the common ancestor of vertebrates, flies, and worms.

Hormones work slowly, on the whole, and have body-wide effects. Insects and nematode worms use hormones, but the specific molecules they use are very different from their vertebrate counterparts.

“This suggested that hormone-secreting brain centres arose after the evolution of vertebrates and invertebrates had split,” explains Arendt, “But then found vertebrate—type hormones in annelid worms and molluscs, indicating that these centres might be much older than expected.” Comparisons of two types of hormone-secreting nerve cells from zebrafish, a vertebrate, and the annelid worm Platynereis dumerilii, in Arendt’s lab have now revealed some stunning similarities that point to a shared and ancient ancestry for our hormonal systems.

“These findings revolutionise the way we see the brain,” says Kristin Tessmar-Raible who carried out the comparison, “So far we have always understood it as a processing unit, a bit like a computer that integrates and interprets incoming sensory information. Now we know that the brain is itself a sensory organ and has been so since very ancient times.” The research appears in detail in the journal Cell.

Bewildering to think that I used to skewer these little creatures on a barbed hook and cast them into the sea to catch scaly marine creatures. It almost makes no sense.

DNA Network

DNA Network logoSciencebase was recently invited to join the excellent DNA Network and as such our genetics news feed is now being pulled by the network’s feed system. If I had been a little slower off the mark, I could have been site number twenty in the list, but when I joined I think I jumped in at #18. There are, at the time of writing, nineteen members, no DNAying it.

So, here is a quick random selection of fellow network members. The links will take you to the individual RSS feed for each site whereby you can subscribe (for free) and get some great and timely information on DNA and the latest happenings and business news in genetics and DNA research.

VentureBeat Life Sciences

Discovering Biology in a Digital World

DNA Direct Talk

Epidemix

The Daily Transcript

henry: the human evolution news relay (genetics)

Mary Meets Dolly

Genetics News

Microarray and Bioinformatics

Gene Sherpas: Personalized Medicine and You

The Personal Genome

All excellent newsfeeds, all focused on one thing, DNA. You can find links to the others, including Eye on DNA, the owner of which led me to the DNA Network in the first place, via DNA Network. I’ll do another round-up of the remaining members later.

Genetic Research Hits Pay Dirt

DNAThe budget for the Human Genome Project and all that post-genomic, proteomic, metabonomic, immunomic…research was almost on a par with defense spending; it was almost c-omical really. Well, maybe not quite, but it stretches out with a lot of zeros nevertheless. At the time the grants were written and the funding given, we, as a society, were promised all kinds of medical miracles from gene therapies and new treatments to cure all those nasties – cystic fibrosis, sickle cell, thalassemia, cancer, heart disease and more.

We were promised personal medicine courtesy of pharmacogenomics. This would allow your doctor to profile your genome and tailor your medication to the particular set of enzymes running in your liver and whether or not you were likely to respond positively, suffer adverse effects, or simply not respond at all. We have even seen, this last few days, the sequencing of James Watson’s genome; an effort that cost less than $1m and took under four months. But do any of these promises add up to very much beyond myriad PhD theses and thousands of biotech startups many of which have already crashed?

Hopefully, the answer is yes. In the next few years, gene science will hit pay dirt as genes finally give up their real secrets and the true meaning of so-called junk DNA will become clear. Our understanding and ability to treat a wide range of disease from breast cancer and obesity to hypertension and bipolar disorder will come of age and perhaps finally succumb to all this genetic scrutiny and manipulation.

Nature, Science and the Wellcome Trust provided a useful summary of the genetic state of the art for a recent Times report by Mark Henderson on our genetic future. In the summary Henderson highlighted the latest “in press” results, most of which are now online, so I am providing here the hyperlinked executive summary:

Breast cancer – Three papers published in Nature and Nature Genetics at the end of May reported four new genes and one genomic region associated with increased risk. 10.1038/nature05887, 10.1038/ng2075, 10.1038/ng2064

Obesity – An obesity gene, the FTO gene, was published in Science in April and reported in Sciencebase at the time.

Diabetes – Again in Science (and 10.1126/science.1142382 and 10.1126/science.1142358, three common genes for increased diabetes type 2 risk were reported, bringing the total known genes associated with diabetes to nine.

Alzheimer’s disease – New results also published this week in Neuron discuss an Alzheimer’s gene

Data that were still under press embargo at the time Henderson’s feature appeared in The Times, however, meaning he could only hint at the true potential of human genome results were revealed today.

The largest ever study of genetics of common diseases in which almost 10 billion pieces of genetic information were analysed were published just one minute ago, so I can now outline the findings in a little detail. The new study compared 2000 cases each of seven common diseases with 3000 shared control patients, and reveals new genetic associations with these disorders. A pair of related papers in Nature Genetics (a and b) offer further insights into two of the seven diseases investigated.

In the Nature article, scientists from the Wellcome Trust Case Control Consortium report genetic variants associated with the development of bipolar disorder, Crohn’s disease, coronary heart disease, type 1 and type 2 diabetes, rheumatoid arthritis and hypertension. This is the first study from this large scope and it, the scientists found one genetic region newly associated with bipolar disorder, and another with coronary artery disease. A separate group of three markers have been found to be associated with rheumatoid arthritis. The researchers also identify nine new genetic associations for Crohn’s disease and ten chromosome regions that contain genes related to diabetes.

These new results would suggest a medical revolution is at hand and that the Human Genome Project and its spinoff -omics really are about to hit pay dirt. But, are we really on the verge of a new era in medicine, or are the various genetic revelations simply more grant-baiting hyperbole?

Combined effort makes for glowing report

Hybrid ramanOne of the most powerful techniques available to analytical scientists is Raman spectroscopy. Unfortunately, it is not easy to distinguish the low-intensity signals it produces when studying fluorescent species in cells because they are swamped by the much brighter glow from various cell components. Now, Dutch researchers have overcome this incompatibility to hybridize Raman with fluorescence microscopy by exploiting the optical properties of semiconductor fluorescent quantum dots (QDs). They have demonstrated hybrid Raman fluorescence spectral imaging in studies of single cells.

Biophysical engineers Henk-Jan van Manen and Cees Otto of the University of Twente, The Netherlands, have used fluorescent nanoparticles to broaden the scope of single-cell microscopy by combining it with intracellular chemical analysis based on Raman. The researchers explain that quantum dots allows weak Raman signals from DNA to shine through the ubiquitous glow from proteins and lipids.

You can read the full story in my SpectroscopyNOW column this week.

Possums, horses, and pigs do it

Brushtail possums, photo by wollombi http://www.flickr.com/photos/wollombi/I just received an early publication alert from the Australian research organisation CSIRO announcing the imminent publication of volume 19 of their journal on reproductive science, fascinating I thought as I opened the attachment.

First up in the list of contents was a paper that sounded rather intriguing from FC Molinia and colleagues entitled: “Uterine and vaginal insemination optimised in brushtail possums (Trichosurus vulpecula) superovulated with pregnant mare serum gonadotrophin and porcine luteinising hormone”.

So, let us just dissect what that convoluted title actually means. Basically, they stimulated brushtail possums with hormones from a horse and a pig to make it produce more eggs than normal and then artificially inseminated the females, with brushtail possum sperm, obviously. I am pretty sure it is all standard procedure for getting those little brushtails up the duff, and it is not so odd that they used horse hormones in the process, after all, one form of human hormone replacement therapy uses equine estrogen.

Something worries me a lot about this particular EarlyAlert. The abstract says that artificial insemination of brushtail possums (Trichosurus vulpecula) is being developed as an assisted breeding model for endangered marsupials, as well as a bioassay for testing fertility control vaccines to manage overabundant populations.

Hmmm…humans do not have a strong record on “assisting” animals in this way, and particularly not in Australia, I am thinking rabbits and mixomatosis, feral camels, and the infamous cane toad, to name but three. Why is it that we feel we can intervene and manage ecosystems in this way? The end results are usually disastrous and given the purportedly fragile nature of Australia’s ecosystems, should we not leave well alone?

The full paper can be accessed here.

Cervical fluids and boron nitride

Two more reports of general interest from my SpectroscopyNOW column. The first is on a new informatics approach to understanding cervical vaginal fluids and the second on a new study of boron nitride the technological wonder material of the future
Screening for premature problems
The application of multiple protein identification algorithms to an analysis of cervical vaginal fluid (CVF) can provide a detailed map of biological markers to help researchers understand the course of human pregnancy and the problems that can arise. Preliminary tests suggest it could be used to determine the likelihood of a premature birth.

Inelastic boron nitride
The results of inelastic X-ray scattering and other techniques have been combined with ab initio calculations to characterise and explain the behaviour of the superficially simple binary material boron nitride. Insights from the research could lead to new ways to exploit the electronic and mechanical properties of hexagonal boron nitride.