The answer to … everything is …

42, as all fans of Douglas Adams and The Hitchhiker’s Guide to the Galaxy will instantly tell you. In the years before he produced his best-seller, a chance contact with Footlights had drawn me into spending many merry evenings with Douglas in The Baron of Beef public house, more or less opposite St John’s College, where he was studying – sporadically, he would doubtless have said – English.

Had a piece of work that’s just come out in The British Medical Journal been published 40-odd years earlier I suspect I would have mentioned it at one of those gatherings – early on before rational thought took alcohol-fuelled flight. It’s interesting because it says we can put off dying from the things that kill most of us (heart failure and cancer) by what Jason Gill, Carlos Celis-Morales and their pals in the University of Glasgow call ‘active commuting’. By that they mean cycling to work is good. Physical inactivity (e.g., spending happy evenings in the pub) is bad.

Had I mentioned it, rather than coming up with an entirely whimsical response to the “ultimate question of life”, Douglas would have spotted that the key to hanging on to life is “on your bike”. Just think: if Jason & Chums had got a move on, history would have been changed. Pondering all their evidence over several pints of The Baron’s best, it’s hard to imagine Douglas coming up with any title other than The Biker’s Guide to the Galaxy.

But hang on: isn’t this just another pretty useless survey?

Maybe – but for several reasons it’s hard to write it off.

First, there have been quite a few studies over the years showing that cycling is good for you.

Second, this is one was huge – so more likely to be meaningful. Using the UK Biobank data it looked for links between death and the way in which more than a quarter of a million people got to work.

Third, and the thing that really caught my eye: the key finding stuck out like the proverbial sore thumb. Usually in surveys of things that might affect our health any trends are difficult to spot: eating X makes you live 10% longer or be 5% less likely to get Y … bla, bla, bla. But here you didn’t need to peer: cycling (a ‘long distance’) to work makes you 40% less likely to die – from anything!

Below is just one bit of their data: I’ve re-drawn it with the cycling result in red but it hardly needs that to highlight the difference between it, walking (blues) and the ‘non-actives’ (green: car or public transport). It’s true, a bit of biking can help (orange: mixed mode cycling) but the really clear benefit comes from cycling (lots) – though they don’t actually say how many miles per day counts as ‘long-distance cycling.’ Modes of transport and distances were self-reported and the latter just divided into ‘long’ and ‘short’.

How you get to work impacts your life expectancy. The figure shows the risk of death from all causes as hazard ratios (ratio of the hazard rates of death): the reference (hazard ratio 1) is travel by car or public transport (green). (From Celis-Morales, C. et al., 2017).

So what of heart failure and cancer?

Perhaps not surprisingly then, commuting by cycling was also associated with a markedly lower risk both of getting heart disease or cancer and of dying therefrom. To give one specific figure: cycling to work lowers the chance of developing cancer by 45%.

It can’t be the lycra

These are horrible studies to undertake, partly because they rely on human beings telling the truth but also because of what are called ‘confounding factors.’ For example, if someone plays a lot of sport and eats sensibly, you might guess they’d be relatively healthy, regardless of how they get to work. Conversely for smoking. However, Celis-Morales & Co did their best to allow for such things and therefore to come up with results that mean something.

But, if you take their findings at face value there remains a key question that the authors do not mention: what is it about biking that’s such a life-saver (assuming you don’t get knocked-off and squashed)? It’s a real puzzle because walking is generally held to be very good for you whilst cycling is the most energy-efficient means of transport devised by man. Both activities use nearly all of your muscles, albeit that biking really works out your glutes and quadriceps, but because bikes are so efficient you use less energy.

Counting the calories

You can do the sums – i.e. work out how many calories used walking, running or cycling on Wolfram Alfra. It’s just confirmed that my daily bike commute does indeed use about half the number of calories required for the same walk.

If you take your commute as training you would suppose that expending more energy (i.e. walking rather than biking) would strengthen your heart and cardiovascular system – and indeed this study shows commuters who did more than 6 miles a week at ‘typical walking pace of three miles an hour’ slightly lowered their risk of cardiovascular disease. But cycling was far more beneficial.

As to cancer, beyond the simplistic notion that fitness = strengthening your immune system and hence capacity resist abnormal cell growth, it’s hard to see a mechanism for biking being so much better than anything else.

So, never mind the science …

Away with Ford Prefect and latter-day variants, automotive  or otherwise! On your bike!! And if you can do it with a friend on a tandem, so much the better!!! Though if you’re going to do it à deux, it might be worth recalling that the Jatravartids had the wisdom to invent the aerosol deodorant before the wheel.

Reference

Celis-Morales, C. et al. (2017). Association between active commuting and incident cardiovascular disease, cancer, and mortality: prospective cohort study. British Medical Journal 357 doi: https://doi.org/10.1136/bmj.j1456

Transparently Obvious

 

Scientists have a well-earned reputation for doing odd things – by which I mean coming up with a ‘finding’ that leaves me, at least, wondering how, in the name of all things wonderful, they ever got money to do their study. To be fair, it’s the ‘social scientists’ – rather than the ‘real’ lot – that excel in this field. An example? Take your pick. They crop up pretty well weekly in the press. I liked the one on how something called ‘personal congruence’ affects marriage survival. The more congruence you and your partner have the better your chances: if, over time, your congruence goes down the tubes, your relationship will surely follow. But what on earth is congruence? Seemingly it’s a ‘state of agreeing.’ Lots of it equals harmony, loss of it = discord. So, it is what you remember from school geometry: it means more or less equal. Wow! Now I’ve grasped the upshot of this ‘study’: agreeably happy couples tend to make it: pairings based on whacking each other with frying pans tend to end in tears. Why didn’t they tell us earlier!!

Axolotl

   Axolotl

Fortunately, in my world, even the weirdies usually turn out to be quite sensible, once you know what’s going on. Many moons ago a girl-friend asked me if I’d like to see her collection of axolotls. Not having a clue what she was on about I gave it an excited ‘yes please’. Whilst it mayn’t have been what I was hoping for (I was very young back then), I immediately fell in love with these wonderful amphibians that I’d never heard of as she explained what I should have known: these ‘Mexican walking fish’ have very large embryos which makes them particularly useful for studying development. These sensational salamanders really are amazing, not least because they can regenerate entire limbs after they’ve been chopped off.

More recently there’s been another unlikely recruit to the scientific armoury: the zebrafish – a tropical freshwater fish from the Himalayas. This mighty minnow was the first vertebrate to be cloned which led to its being genetically modified to give a transparent variety. That’s all good fun but what on earth is the point of a see-through fish? Well, in Betrayed by Nature we pointed out that you can actually watch tumours growing in transparent zebrafish and we got so excited by that we even included a photo – kindly provided by Richard White of the Dana Farber Cancer Institute in Boston. The cancer was a melanoma which had grown into a black mass about 1 cm in diameter in the fish’s body after a small number of tumour cells had been injected a couple of weeks earlier.

And the driver is …

Nearly 15 years ago, just as the first complete sequence of human DNA was being unveiled, Mike Stratton and his colleagues at the Sanger Centre in Cambridge discovered a mutation that arises in about two-thirds of all malignant melanomas. It’s in a gene called BRAF. The protein made by the gene is an enzyme that’s part of a signalling pathway that pushes cells to divide. The mutation changes the shape of BRAF protein so it works 24/7 as an enzyme: the pathway is no longer controlled by a message from the world beyond the cell. It’s a ‘molecular switch’ that’s been flipped by mutation to act as a cancer ‘driver.’

Richard White and his colleagues showed that the same mutation drove melanoma development in zebrafish and that when it did so something remarkable happened. As the tumours got going they turned on a gene that is normally only required during the first 72 hours after fertilization. The gene’s called crestin – because it’s switched on in a tissue called the neural crest where crestin protein helps to form the bony support for the gills. After that it’s switched off and crestin protein never appears again. Except in the pigment-containing cells called melanocytes when they are turning into a tumour.

Seeing the problem

In a great example of how science can work, Charles Kaufman, Leonard Zon and colleagues in Boston and other centres took this finding and made another transgenic variant of the transparent zebrafish. They cut out the stretch of DNA that controls whether the crestin gene is ‘on’ or ‘off’ and hooked it up to a gene that makes a green fluorescent protein (GFP). Result: when the machinery of a cell turns crestin on, GFP is also made – and the cell glows green under the appropriate light. Hence you would expect to see a glowing neural crest early in development but thereafter a non-glowing fish. Unless it has a melanoma. And Zon & Co saw exactly that. Because green fluorescent protein glows so brightly, a single cell shows up and it turned out that whenever one green cell was detected it always went on to expand and grow into a large melanoma tumour.

1 cell to mel

Tracking a single cell turning into a tumour over 6, 9, 11.5 and 17 weeks. The green fluorescence marks an early developmental gene (crestin) being re-activated in a melanoma tumour (from Kaufman et al., 2016).

But why might it be useful to ‘see’ single cells?

Since the original finding by Stratton & Co more detailed studies have confirmed that mutated BRAF is indeed an important ‘driver’ in about two-thirds of malignant melanoma. But here’s the odd thing: lots of melanocytes (the cells that can turn into melanomas) have mutated BRAF – but they don’t become cancerous. Why not? And there’s something else: it’s well-known that ultraviolet radiation in sunlight causes many melanomas and they do indeed often arise on exposed skin – but they can also crop up in places where, as they say, the sun doesn’t shine. So clearly, important though mutated BRAF and sunlight are, there’s something else that’s critical for malignant melanoma.

The Kaufman experiment was remarkable, not least because it offers a way of getting at this key question of what happens in a cell to kick it off as a tumour, by comparison with a near neighbour that remains ‘normal.’

The tumour cells used in this model carry mutated BRAF and another gene, P53, was knocked out. This gives two major genetic drivers and it may be that further genetic changes aren’t needed. If that’s the case, then the decisive push must come either from epigenetic changes (that affect gene expression without change in DNA sequence) or from adaptations of the tumour microenvironment to provide an optimal niche for expansion. At the moment we don’t know very much about these critical areas of cancer biology. Being able to follow single cells may lead us to the answers.

Keep your eye on the transparent minnows!

Reference

Kaufman, C.K., Zon, L.I. et al. (2016). A zebrafish melanoma model reveals emergence of neural crest identity during melanoma initiation. Science 351, Issue 6272, pp. DOI: 10.1126/science.aad2197

 

Heir of the Dog

I’ve probably in the past owned up to causing generations of students to do that raised eyebrow thing, familiar to all parents of teenagers, that, far more pointedly than words, says ‘The old boy’s finally lost it.’ Indeed I may well have a bit of a causative repertoire but one that unfailingly works is revealing that, even after a life in science, I still get ‘Wow’ moments every couple of months or so when I read or hear of some new discovery, method or insight that brings home yet again the wonder of Nature – or has you asking ‘Why didn’t I think of that?’ (The response to that one’s easy, by the way, so please don’t write in).

A common question

The most recent of these jaw-dropping events relates to a question often asked about cancer: ‘Can you catch it from someone else?’ In other words, can cancers be passed from one person to another by infection, much as happens with ’flu? The answer’s ‘No’ but, as usual in this field, even the firmest statement can do with a little explanation. The first point is that the ‘No’ is true even for 20% or so of cancers that are actually started by microbial infection – what you might call ‘bugs’ – bacteria, fungi, and viruses. One such, the bacterium Helicobacter pylori, can cause stomach ulcers that may lead to cancer. Those even smaller bugbears, viruses (typically one one-hundredth the size of a bacterium), are responsible for much of the cervical and liver cancer burden world-wide. Oh, and there’s a little, single-cell parasite (Trichomonas vaginalis), the most common non-viral, sexually transmitted infection in the world that, in men, can cause prostate cancer. But these infections are not cancers even though they may be an underlying cause – bacteria through prolonged inflammation and effects on the immune system and viruses by making proteins that affect how cells behave. Only when these perturbations cause genetic damage – i.e. DNA mutations – do you have a cancer. Which is why the answer to the original question is ‘No.’

There’s always one

Well, two in this case – and, given that we’re talking about cancer, you won’t be surprised that there are some oddities. They’re not exceptions to the ‘No’ answer because they occur in other animals – not in humans – but, in each, tumour cells are directly transferred from one creature to another – so it is cancer by infection. One such contagious tumour occurs in the Tasmanian devil. It’s transmitted by biting, an activity popular with these little chaps, and it gives rise to a particularly virulent facial tumor, eventually fatal because it prevents eating. To counter the probability that Tasmanian devils will become extinct in their native habitat, a number of Australian sanctuaries have breeding programmes aimed at setting up a disease-free colony on Kangaroo Island, South Australia.

TDs

Tas D

 

 

 

 

 

Tasmanian devils – cancer-free – Lone Pine Koala Sanctuary, Brisbane

A very similar condition in dogs known as canine transmissible venereal tumour (CTVT: also called Sticker’s sarcoma), mainly affects the external genitalia. First spotted in the nineteenth century by a Russian vet, it too is spread either by licking or biting and also through coitus. Dogs with CTVT can now be found on five continents and, from DNA analysis, we’ve known for some time that – remarkably – all their cancers are descended from a single, original tumour cell that appeared many years ago. They’re like one of those cell lines grown in labs all over the world, except they’ve been going far longer than any lab – with man’s best friend doing the cultivating.

So what is new?

Elizabeth Murchison and colleagues at The Wellcome Trust Sanger Institute, Cambridge have just produced the first whole-genome sequences of two of these tumours – from Australia and Brazil (an Aboriginal camp dog and a purebred American cocker spaniel). These confirmed that all CTVTs descend from a single ancestor who, they estimated, was trotting around about 11,000 years ago. The last common relative of the two dogs whose tumours were sequenced lived about 500 years ago, before his descendants went walkies to different continents.

And the ‘Wow’?

We already had a pretty good idea of how CTVTs have been handed down. In this paper the really amazing bit came in the detail. The authors estimated roughly how many mutations were present in each tumour. Answer: a staggering 1.9 million. And it’s staggering partly because it’s only slightly less than a change every 1,000 units (bases) in dog DNA but it’s truly awesome when you note that it’s several hundred times more than you find in most human cancers. We’re getting used to the idea of thousands or tens of thousands of mutations turning up in human cancer cells with associated gross disruptions of individual chromosomes. But these canine cancers display genetic mayhem on a massive scale – perhaps best visualized by comparing their chromosomes with those of a normal dog using a method that labels each with a different colour. A glance at the two pictures tells the story: all the cancer chromosomes from one of the tumour-bearing dogs (on the right) have been shuffled as if in some molecular card game. The full range of colours can still be seen, but of the normal pattern of 39 pairs of identical segments of DNA (left) there is no sign.

Two dogs chromos

Dog chromosomes. Left: normal; right: CTVT

(from Murchison, E.P. et al. (2014) Science 343, 437-440)

It seems incredible that cells can survive such a shattering of their genetic material – a state called ‘genetic instability’ because, once DNA damage sets in, mutations usually continue to accumulate. These cancers are uniquely bizarre, however, because although their genomes have been blown to smithereens, not only do the cells survive but they’ve continued suspended in this surreal state for centuries. They’re genetically stable – it really is the cellular equivalent of balancing an elephant on a pin.

‘Wow’ Indeed – but so what?

So like me you’ve been blown away by these discoveries but you may be asking, apart from the excitement, what’s in it for us humans? Well, there’s one other very strange thing about these dog cancers. Infected animals do indeed develop the most unpleasant, large tumours – but most of them are eventually rejected by the host dog. That is, its immune system gets to work to eliminate them – and after that the dog is immune to further infection. We are only just beginning to find ways of boosting the human immune system so that it can attack cancers and maybe, just maybe, we can extract from the stable chaos of the CTVT genome the secret of how they provoke rejection – and maybe that will guide human treatments.

Reference

Murchison, E.P. et al. (2014). Transmissible Dog Cancer Genome Reveals the Origin and History of an Ancient Cell Lineage. Science 343, 437-440.

A Small Helping For Australia

There’s an awful lot of very good things in Australia. Australians for a start. They’re just so kind, open, welcoming and accommodating it makes touring round this vast land a joy. Not merely do they cheerfully find a way to fix anything you want but they’re so polite that no one’s drawn attention to my resemblance to a scientific version of those reconstructed geriatric pop groups (viz the Rolling Stones or whatever) staggering round the place on their Zimmer frames. And they say wonderful things about my talks – that’s how charming they are!!

Greater bilgy

Greater bilby

Of course, you could say of Australia what someone once said of America and Britain: two nations divided by a common language. In the case of Oz you could also add ‘and by a ferociously competitive obsession with sport.’ So it’s wonderfully not home. Even Easter’s different in that here you get chocolate Easter bilbies rather than rabbits. Bilbies, by the way, are a sort of marsupial desert rat related to bandicoots. The lesser version died out in the 1950s so only the greater bilby is left (up to 20 inches long + tail half as long again) and you have to go to the arid deserts to find those. Not the choccy versions obviously: they don’t do too well in the deserts but they’re all over Melbourne:

Easter bilby

Easter bilby

shops full of ’em – and a lot bigger than the real thing. So, together with the egg avalanche, there’s no limit to the number of calories you can consume in celebrating the resurrection of Christ. Coupled with the glorious fact that there’s scarcely any mention of wretched soccer, all these novelties mean you’re never going to be lulled into thinking you’re still in dear old Blighty (or back in the old country as they delightfully put it here).

Hors D’Oeuvres

Even so there are some marked similarities to make you feel at home. One of the least striking is that most people are overweight. That is, I scarcely notice it, coming from what I regard as the global fat capital, i.e. Cambridge. The stats say that that’s not true, of course. The USA does these things better than the UK. Of course it does. But there’s not much in it. More than two-thirds of American adults are overweight and one person in three is obese. For the UK the prediction is that one in three will be obese by 2020. Currently in Australia 63% of the adult population is overweight, a figure that includes 28% who are obese.

The essential point is that there’s stuff all difference between those countries and the really critical thing is that the rates go on soaring. In the U.S. between 1980 and 2000 obesity rates doubled among adults and since 1980 the number of overweight adolescents has tripled. By 2025 one Australian child in three will be in the overweight/obese category.

Main course

The meat in this piece is provided by a report written by a bunch of Australian heavyweights – all Profs from Sydney or wherever. It has the droll title ‘No Time To Weight’ – do I need to explain that or shall I merely apologise for the syntax? ‘Oh c’mon!’ I hear our Aussie readers protest. ‘We’re going to hell in a handcart and you’re wittering about grammar. Typical b***** academic.’ Quite so. Priorities and all that. So the boffins’ idea is to wake everyone up to obesity and get policy-makers and parliamentarians to do something effective.No Time to Weight report

Why is this so important? Probably unnecessary to explain but obesity causes a variety of disorders (diabetes, heart disease, age-related degenerative disease, sleep apnea, gallstones, etc.) but in particular it’s linked to a range of cancers. Avid followers of this BbN blog will recall obesity cropping up umpteen times already in our cancer-themed story (Rasher Than I Thought?/Biting the bitter bullet/Wake up at the back/Twenty winks/Obesity and Cancer/Isn’t Science Wonderful? Obesity Talks to Cancer) and that’s because it significantly promotes cancers of the bowel, kidney, liver, esophagus, pancreas, endometrium, gallbladder, ovaries and breast. The estimate is that if we all had a body mass index (BMI) of less than 25 (the overweight threshold) there would be 12,000 fewer UK cancers per year. Mostly the evidence is of the smoking gun variety: overweight/obese people get these cancers a lot more often than lesser folk but in Obesity Talks to Cancer we looked at recent evidence of a molecular link between obesity and breast cancer.

Entrée (à la French cuisine not North American as in Main course)

Or, as you might say, a side dish of genetics. The obvious question about obesity is ‘What causes it?’ The answer is both complicated and simple. The complexity comes from the gradual accumulation of evidence that there is a substantial genetic (i.e. inherited) component. Many people will have heard of the hormone leptin, a critical regulator of energy balance and therefore of body weight. Mutations in the leptin gene that reduce the level of the hormone cause a constant desire to eat with the predictable consequence. But only a very small number of families have been found who carry leptin mutations and, although other mutations can drive carriers to overeating, they are even rarer.

However, aside from mutations, everyone’s DNA is subtly different (see Policing DNA) – about 1 in every 1000 of the units (bases) that make up our genetic code differs between individuals. All told the guess is that in  90% of the population this type of genetic variation can contribute to their being overweight/obese.

Things are made more complicated by the fact that diet can cause changes in the DNA of pregnant mothers (what’s called an epigenetic effect). In short, if a pregnant woman is obese, diabetic, or consumes too many calories, the obesity trait is passed to her offspring. This DNA ‘imprinting’ activates hormone signaling to increase hunger and inhibit satiety, thereby passing the problem on to the child.Preg Ob

So the genetics is quite complex. But what is simple is the fact that since 1985 the proportion of obese Australians has gone up by over 10-fold. That’s not due to genes misbehaving. As David Katz, the director of Yale University’s Prevention Research Center puts it: ‘What has changed while obesity has gone from rare to pandemic is not within, but all around us. We are drowning in calories engineered to be irresistible.’

Desserts

We might hope that everyone gets theirs but for obesity that’s not the way it works. The boffos’ report estimates that in 2008 obesity and all its works cost Australia a staggering $58.2 billion. Which means, of course, that every man, woman and child is paying a small fortune as the epidemic continues on its unchecked way. The report talks formulaically of promoting ‘Australia-wide action to harmonise and complement efforts in prevention’ and of supporting treatment. It’s also keen that Australia should follow the American Medical Association’s 2013 decision to class obesity as a disease, the idea being that this will help ‘reduce the stigma associated with obesity i.e. that it is not purely a lifestyle choice as a result of eating habits or levels of physical activity.’ Unfortunately this very p.c. stance ignores that fact that obesity is very largely the result of eating habits coupled to levels of physical activity. The best way to lose weight is to eat less, eat more wisely and exercise more.

In 2008 Australian government sources forked out $932.7 million over 9 years for preventative health initiatives, including obesity. This latest report represents another effort in this drive. Everyone should read it but, clear and well written though it is, it looks like a government report, runs to 34 pages and almost no one will give it the time of day.

The problem is that in Australia, as in the UK and the USA, all the well-intentioned propaganda simply isn’t working. As with tobacco, car seat belts and alcohol driving limits, the only solution is legislation, vastly unpopular though that always is – until most folk see sense. Start with the two most obvious targets: ban the sale of foods with excessive sugar levels (especially soft drinks) and make everyone have a BMI measurement at regular intervals, say biannually. Then fine anyone over 25 in successive tests who isn’t receiving some sort of medical treatment.

Amuse bouche

I know: I’ll never get in on that manifesto. But two cheers for ‘No Time To Weight’ and I trust the luminaries who complied it appreciate my puny helping hand from Cambridge. In the meantime, not anticipating any progress on a national front, I’m going to start my own campaign – it’s going to be a bit labour-intensive, one target at a time, but here goes!

The other evening I had dinner in a splendid Italian restaurant (The Yak in Melbourne: very good!). And delightful it would have been had I not shared with two local girls at the next table. One was your archetypal tall, slender, blonde, 25-ish Aussie female – the sort you almost feel could do with a square meal. Her companion of similar age was one of the dirigible models. (You’ll understand I wasn’t looking at them at all: I was with my life’s companion so no chance of that – but I do have very good peripheral vision. Comes from playing a lot of rugby). Each had one of the splendid pasta dishes on offer – but, bizarrely, they also ordered a very large bowl of chips. No prizes for guessing who ate all the fries. Miss Slim didn’t have one – not a single one! (OK, by now I was counting). Her outsize friend had the lot. How could she do that with a shining example of gastronomic sanity sitting opposite?

So c’mon Miss Aussie Airship: you know who you are. Let’s have no more of it. Obesity is not a personal ‘issue.’ Regardless of your calorie intake in one meal, your disgraceful behavior ruined a delightful dining experience for me, and quite possibly several other folk within eyeshot, upset the charming waitress and insulted The Yak’s excellent chef. Just think in future: there’s a place in life for chips – but it’s not with everything.

Reference

“Obesity: A National Epidemic and its Impact on Australia”

Genetic Roulette in a New World

In 2003 it was a sensation. No really – it’s probably true that in medicine only the first human heart transplant operation back in 1967 has generated as much publicity. That was in the pre-web dark age but, nevertheless, the South African surgeon Christiaan Barnard was immortalized as a global hero: even the patient’s name was on everyone’s lips (Louis Washkansky if you’re struggling to recall) and you can re-live the whole event at the Groote Schuur Hospital museum in Capetown. But, although 2003 was just a decade ago, in today’s world sensations fade almost with the following dawn, whether they are pop groups or life-changing scientific advances.

So if now you mention “The Human Genome Project” to a man on the Clapham omnibus you are likely to elicit only a puzzled look. What happened in 2003 was of course that the genetic code – that is the sequence of bases in DNA – was revealed for the entire human genome. And an astonishing triumph it was, not least because, in contrast to almost everything else in history with a major British component, it was completed within schedule and under cost.

The feat was deservedly greeted with a fanfare of public interest unprecedented for any scientific project short of the early space missions. President Clinton in the White House was hooked-up live to whoever was living in No. 10 at the time, the leading British scientists in this amazing project dropped in for tea and Mike Dexter, then Chairman of The Wellcome Trust and a restrained and conservative fellow – being a scientist – described it somewhat inelegantly as “… the outstanding achievement not only of our lifetime, but in terms of human history.”

The Sanger Centre, Cambridge

The Genome Analysis Centre, Norwich

The Genome Institute at Washington University

However, even more remarkable is what happened next. The ensuing decade has brought technical advances so breathtaking as to almost overshadow the original human genome project itself. This quite staggering revolution has seen the introduction of fully automated, high throughput flow cells that simultaneously carry out hundreds of millions of separate sequencing reactions – just say that slowly. In the jargon it’s called ‘massively parallel sequencing’. The upshot of this stunning technology is that sequencing speed has gone up by 100 million times whilst, almost unbelievably, the cost has dropped by a factor of 10,000. Even computing science can’t match that progress!

One consequence of this incredible, though relatively unpublicised, revolution is that genomes can be now be sequenced on an industrial scale and in the years to come that is going to impact on every facet of mankind’s existence. Thus far the field of cancer has been the foremost recipient of this technological broadside with thousands of tumour genomes now sequenced. This has unveiled the almost incomprehensible panoply of genetic changes that cells can sustain and yet emerge still capable of proliferating. One of the first cancer genomes to be sequenced was that of a female who had died from leukemia. The work was carried out by The Genome Institute at Washington University in St. Louis, Missouri and since then, under its Director Richard Wilson, this group has continued to be a world leader in genomics and in particular in unravelling the extraordinary complexity of the group of cancers collectively called leukemias.

Wilson and his colleagues know, of course, that they are at the forefront of the most extraordinary transformation in medicine – because eventually it will affect everyone –though Rick Wilson himself is as improbable a revolutionary as you could imagine: a gentle, soft-spoken American, he’s what on this side of the pond would be called a thoroughly nice chap.

However, if they had any doubts about the direction in which their science was leading the world, these would have been dispelled when one of their own community, Lukas Wartman, was diagnosed with a very rare form of leukemia. This had first appeared ten years ago when Lukas was a student completing his medical degree at Washington University, and at that time it had been treated with chemotherapy and a bone-marrow transplant.

In the following years, Dr. Wartman had pursued his career goal of becoming a practicing oncologist specializing in leukemia until, in July 2011 the disease returned and he went into relapse. As his condition deteriorated rapidly and only one outcome seemed possible, those treating him turned in desperation from conventional approaches to local expertise. They applied genomic analysis to his cancer cells. From the vast number of disruptions identified, one in particular stood out: an abnormally expressed gene that had previously been associated with other types of leukemia but is very rare in the form Wartman had developed.

By an unlikely chance there is a drug available that can knock out the activity of the protein made by that gene. Its effect was phenomenal, restoring the normal blood count and achieving complete remission. This wonderful outcome does not mean that Dr. Wartman is cured for life – but for now he is alive and well – and a co-author of the group’s latest paper – on leukemia.

He had been a desperately unlucky in that the genetic roulette that is life generated in him a hand of mutations that drove the development of a rare and almost invariably lethal form of leukemia. But life also smiled on Lukas Wartman in that circumstances found him at the heart of the genomics revolution that is ushering in a new world of medicine. His isn’t the first life to be saved through the use of this fabulous technology but he is one of the first few who will, in years to come, be followed by many as these marvellous methods for diagnosis and the design of treatment come into widespread use.