Are You Ready For This?!!

The one thing almost everyone knows about cancers is that early detection is the best start to dealing with them. I make no apologies for repeatedly stressing this both in Betrayed by Nature and in these articles, most recently in Seeing the Invisible: A Cancer Early Warning System. Putting my cards on the table, if I had a bank balance resembling that of Mr. Bill Gates and wanted to go down in history as the guy who did most to reduce the major cancers to manageable conditions, I’d open a research centre dedicated to identifying biomarkers – i.e. molecules in circulating blood – that appear as the earliest sign of something abnormal.

Crikey, you might think. If he does financial fantasy on that scale maybe he just makes up the science too! Undeterred, and seeing as I’ve started, I’ll reveal that the first thing I’d do to staff my own institute would be to get on the phone to a fellow by the name of Johannes Kettunen in Helsinki. Reason: he’s one of the lead authors of a quite astonishing paper that came out last week.

Thinking outside the box

Those of us who live in more gentle climates occasionally wonder what the Finns and their fellow far north dwellers get up to in the long winter nights (ah! those Scandinavian fantasies!). Well, this paper told us nothing remotely titillating (how did it get by the reviewers?!) but instead revealed that, presumably cloistered in their sauna having exhausted all the interesting possibilities, Kettunen & Co came up with a cracker. “I know” someone said “let’s screen a huge number of blood samples for biomarkers that predict the risk of death amongst the general population.” Wow! Gasps all round. “Why didn’t I think of that – far more fun than all this naked cavorting and birching.”

A bit of discussion showed that all they needed was a nuclear magnetic resonance (NMR) machine (to measure the amount of each biomarker molecule) and a vast number of blood samples from a random group of people. They had both to hand: NMR machine? No prob courtesy of the University of Helsinki and by collaborating with friends just across the Baltic they could combine the extensive store of blood samples and health records that Finland has built up over many years with a corresponding Estonian collection.

So that was the gig: they picked 106 candidate biomarkers, quantitated each in blood samples from 17,345 people and looked to see if any correlated with what happened to the donors in the following five years – i.e. whether they died. Almost incredibly, the levels of four biomarkers appeared to predict with great accuracy the risk of death within this short period. Perhaps equally surprising, the marker molecules weren’t remotely exotic. There were a couple of proteins (albumin – the most abundant protein in blood sometimes called a molecular ‘taxi’ as it carries all sorts of things around the circulation) and alpha-1-acid glycoprotein (which also operates a blood taxi service), a cluster of proteins (very-low-density lipoprotein (VLDL) that carries fats and cholesterol around the bloodstream – the size of the particle being the ‘marker’) and citrate (a metabolite involved in turning food into chemical energy in the form of ATP).

So there you have it: the levels of four very drab molecules floating around in us can indicate whether otherwise healthy people are at short-term risk of dying. They cover all the major causes of death – heart disease, cancer and other illnesses – and what’s more, this biological tarot mularkey seems to work just as well in men as in women and at any age.

As one of Kettunen’s pals put it:“It was a pretty amazing result. First of all we didn’t really believe it. It was astonishing that these biomarkers appeared to actually predict mortality independent of disease. These were all apparently healthy people but to our surprise it appears these biomarkers show an undetected frailty which people did not know they had.”

Anyone for biological tarot?

Anyone for biological tarot?

So where does that leave us?

Well, first with all the usual reservations them scientists tend to attach to their utterances. Need to study a larger group, maybe these markers only apply to Finns and Estonians – no offence northern relatives but there can be differences between ethnic groups, need to screen more markers as there may be even better ones lurking in our system – and the markers themselves tell us nothing about underlying causes. And then, of course, would you take a death test when, however accurate the results, we can’t do anything about it?

But it certainly makes you think a bit doesn’t it – and whatever your thoughts, the finding that the same four biomarkers are associated with a short-term risk of death from a variety of diseases is quite mind-boggling and, who knows, maybe these very ordinary molecules will eventually lead us to causes that can be stopped or slowed.

So, next time you’ve worked your way through the Kama Sutra trying to fill in the winter nights, think laterally, try and come up with something utterly tedious that takes enormous effort and is almost certain to come up with nothing interesting or useful. Then be prepared to be amazed!

Reference

Fischer K, Kettunen J, Würtz P, Haller T, Havulinna AS, et al. (2014) Biomarker Profiling by Nuclear Magnetic Resonance Spectroscopy for the Prediction of All-Cause Mortality: An Observational Study of 17,345 Persons. PLoS Med 11(2): e1001606. doi:10.1371/journal.pmed.1001606.

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001606

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Policing DNA

In A Sinister Side to Sequencing we noted that, wondrous though the advances in sequencing DNA have been, every silver lining …, so to speak. This was in the context of our now being able to determine whether babies will be born with genetic defects, raising the prospect that parents may opt not to have afflicted children. Because we feel that the avoidance of politics has such beneficial effects on the tone of these pieces, we did not mention another problem raised by the ready availability and sophistication of current DNA analysis methods, namely use of the data by police forces, specifically by the procedure usually called DNA fingerprinting. But, needs must …

First of all, what’s DNA fingerprinting?

DNA profiling (or fingerprinting) methods, pioneered by Sir Alec Jeffreys at the University of Leicester, have undergone substantial refinement since they were first used as a police forensic test in 1986 to identify the rapist and killer of two teenagers. Regardless of detail, the essential point is that that the genetic code of individuals is compared using DNA that can be extracted from most tissues or body fluids (e.g., blood, semen, cheek cells, etc.). From the samples to be compared short lengths of DNA are generated and separated by size in a gel, stained so that the DNA fragments show up as bands. Each of us has a unique pattern. In the picture the pattern from suspect 2 is identical to that of DNA taken from the crime scene – so he dunnit!

DNA patterns

 

 

 

Short lengths of DNA samples obtained from a crime scene and from the tissues of three suspects separated in a gel and stained to show as black bands

 

 

 

 

Why is it in the news?

The Supreme Court of the United States has just ruled that the police should be permitted to take DNA samples from an arrested individual, as Maryland officers had done from a character who’d been waving a shotgun only to find that he’d committed an unsolved rape case in 2003 from which they were still holding a DNA sample. An excellent result, you might think. Perhaps, but the ruling has nevertheless got the liberals up in arms, as represented by Antonin Scalia, an Associate Justice of the Supreme Court. Put briefly, his point is that DNA sampling is following the path of fingerprinting, things will go headlong downhill and before long we’ll have to submit to it if we want to get on a plane or play for a school sports team. This would clearly be an unacceptable invasion and so, inevitably, The Fourth Amendment to the United States Constitution is invoked – for outsiders that’s the thing purporting to protect citizens from ‘unreasonable’ actions by the powers that be, whatever that means to any administration that happens to be in charge.

No one sane is arguing that the police should not be permitted to use DNA in the pursuit of villains. The problem is how to keep the lid on Pandora’s box. So, without for a moment implying that the good denizens of the US of A might be a touch parochial, let’s take the drastic step of casting a glance beyond the limits of sea to shining sea.

In the rest of the world?

What better place to start than with the mother of modern democracy and what was the land of the free before the US of A was invented? Shock horror: it emerges that little old England has more DNA samples per head of population in the hands of its police than any other country for which information is available! How can this have come about? Well, the Police and Criminal Evidence Act of 1984 permitted the police to take fingerprints and body samples without consent from people charged with, or convicted of, a recordable offence (these include begging, being drunk and disorderly and taking part in an illegal demonstration – ‘illegal’ having been interpreted somewhat flexibly in recent times). However, those powers were extended in 2004 to permit samples being taken from anyone arrested on suspicion of any recordable offence. You will recall that this was during the Premiership of Mr. Blair, a chap with little interest in civil liberties and none at all in parliamentary democracy.

Back in 1949, when a parliamentary democracy seemed an immovable feature of British life, the United Kingdom (UK) became a founder member of something called The Council of Europe – designed to promote cooperation over matters relating to the law and human rights. Bear in mind that this is quite distinct from the European Union (EU) – the organization that lives in decadent style in Brussels to which the mother of parliaments has for some time ceded control of its affairs. EU members include Poland, Hungary and Estonia and it’s largely run by the Germans and the French. Funny how things turn out. Shock horror number 2 is that the UK is the only Council of Europe member that allows retention of biological samples from people who have been acquitted of charges or against whom criminal charges have been dropped. The Council of Europe has a sort of sub-body called The European Court of Human Rights before which was recently brought a UK case about whether the retention of DNA and fingerprints from innocent people is consistent with human rights law. In short, they don’t think it is and it’s worth quoting a key phrase in their conclusions: “… retention … constitutes a disproportionate interference with the applicants’ right to respect for private life and cannot be regarded as necessary in a democratic society.

So, what’s happened?

Well, for once let us rejoice in being interfered with by those pesky Europeans because, as of May 2012, the UK now has a Protection of Freedoms Act covering the operation of the UK Police National DNA Database. A critical feature is that DNA and fingerprint records of over a million innocent individuals will be deleted and the DNA samples destroyed. It should be added that seemingly Maryland law also requires destruction of DNA samples taken in cases that do not lead to conviction.

What will be done?

The problem with protecting freedoms is that laws are OK but someone needs to do the protecting. No one who has reviewed the activities of the British police that have come to public attention over the last twenty years would have any confidence either in their morality or their competence, never mind their inclination to police themselves. The fact that, according to GeneWatch UK, companies have been permitted to use the police DNA Database for research purposes without, of course, individual consent would confirm your doubts.

Re-crossing the Atlantic it would also seem sensible to ensure first that reasonable legal safeguards are in place across all states to control police activity  but after that to keep Mr. Scalia’s concerns in mind and remain vigilant in ensuring that those provisions are adhered to.

Finally, all that having been said and with due regard to the seriousness of this matter, one might observe that countries prone to promoting themselves as models of human rights that nevertheless pass laws permitting indefinite detention of citizens without trial and are not averse to the use of torture have somewhat weightier matters to resolve than what the fuzz do with a few cheek swabs.

References

https://cancerforall.wordpress.com/2012/07/01/a-sinister-side-to-sequencing/

http://www.thedailybeast.com/articles/2013/06/04/big-brother-invades-your-genes.html

http://www.genewatch.org/sub-539478

National Defense Authorization Act, 2012.