From Trickle Down Genomics to the Virtuous Circle

In the spaces between the scientist’s bench and the patient’s bedside, practitioners of translational medicine concern themselves with the conversion of basic research into real world medical applications.

The field of translational research is evolving from its trickle down, bench-to-bedside roots into something which approaches an ongoing dialog between scientists and clinicians. From the NIH translational research site:

Scientists are increasingly aware that this bench-to-bedside approach to translational research is really a two-way street. Basic scientists provide clinicians with new tools for use in patients [sic] and for assessment of their impact, and clinical researchers make novel observations about the nature and progression of disease that often stimulate basic investigations.

The silent partner in translational research has always been the patient, who is presumably in bed, supine.

The Virtuous Circle
The field of personal genomics is on course to evolve the model of translational research one step further. Trickle down, bench-to-bedside genomics; two-way streets between researchers and clinicians…to finally, the virtuous circle, where individuals, at their desktops, are equal partners in what is bound to be an exhilarating group exploration of science, medicine, and our shared humanity:


An recent editorial in the journal Nature Genetics signifies this mindshift is indeed underway:

Giving individuals their own genotype is not so much premature as truly disruptive. The individual gains a personal stake in the ongoing research effort and a huge incentive to find out more. A personal stake in finding out something that was not previously known is the key to getting students into research and may well be a powerful tool to educate and interest members of the public in the details of their own health and functioning. This boon was anticipated two years ago by George Church…at the launch of the ‘collaborative research endeavor’ called the Personal Genome Projects (…

…It is right to be skeptical of unknowns, but it would be wrong to underestimate the motivational potential inherent in handing people their genomes and asking them to participate in finding out more about their variation and phenotypes…

…In the meantime, individual genomics will have informed thousands participating in one of the most exciting areas of biomedical research, and it may recruit participants in prospective
studies that they will have funded partially from their own pockets. That being said, they are co-investigators, not patients, and the experiment will be conducted on their own terms!

Hurrah! I’m breathless.

Editorial. Positively Disruptive. Nature Genetics. 40(2): 119. February 2008.

Note to readers: The cast of characters in the graphic design above (aren’t they great?), were kindly provided by Ricardo Vidal. I can’t tell you how convenient it is to have a file folder containing a physician, a scientist, and red-headed woman in a blue dress. Thanks Ricardo! BTW, Ricardo is supplementing his grad school tuition with graphic design work for hire!

Free Personal Genome Activism goes International

Today GTO pointed to a new website advocating the $0 Genome Project. A WhoIs look-up shows the administrative contact for the various websites associated with this project to be the Korean Bioinformation Center (KOBIC).

The last major bid for a free genome project was made from California in September of 2004 under the banner of the CUVIGS Initiative, or Californians for Universal Voluntary Individual Genome Sequencing.

Without surprise, CUVIGS supporters looked to George Church for feedback (interview still available here). Snip from their news release:

Professor Church believes that the emergence of Californians for Universal Voluntary Individual Genomic Sequencing, which is trying to place an initiative on the California ballot that would provide public funding to increase the availability and lower the unit cost of doing individual genomic sequencing, “sounds like a wonderful initiative, very visionary of California to think of such a thing….If the people spoke out like that, it would be a historic moment.” He added that “it needs to be phased in carefully with lots of oversight.” He also supported competition between Massachusetts and California to see who could pass such an initiative first.

Now, it seems, we can add South Korea to the competition for free personal genomes.

If they were to exist, “free genomes” would be more equivalent to “free kittens” than “free beer” in terms of the responsibility needed. Free beer requires very little commitment, there are virtually no instructions for its proper use and it can just be poured down the sink if it is doesn’t meet expectations. George’s recommendation for careful oversight of any such project, would be essential.

Figures from History, Redux 1: Gregor Mendel


This is the first installment in a new series called Figures from History, Redux. I’ll be asking scholars and historians of science, medicine, and technology to provide a voice for long-departed historical figures, so that they too might weigh-in on current issues.

For this installment, I asked Simon Mawer, biologist and author of Mendel’s Dwarf, to speak-up for Gregor Mendel, the beloved lover of peas.

Question: If Gregor Mendel were alive today, do you think he would be part of the early adopter crowd anxious to have a peek at his personal genome sequence? Might he even eschew privacy and put it on the web for others to see and use?

I am certain - as certain as one can be about such things - that Mendel would have been delighted with a whole genome project and the idea of having his own sequenced. It would have appealed to the mathematician in him, and the chess-player. ‘And after all, what do I have to hide?’ he’d have said. And then, on consideration, he would have added, ‘But what will it really show? The cause of my baldness, probably. My overweight - damned overweight! - and poor eyesight, possibly. But my love of plants? My love of nature? My ideas about garden peas? My love of teaching? My sense of humour? Surely none of those! There’s more to man than mere machinery!’

He was a man of meticulous curiosity and a fine mathematician. The thought that you can, in some sense, reduce a living organism to a kind of algebra would have amused him no end, not least because he would have seen that it is not, and indeed cannot be, the whole story. Indeed, how can a sequence of As Gs Cs and Ts in any real sense be one of his garden peas, or one of his beloved fuchsias? What is the code for beauty? However, the medical applications of genome sequencing would have appealed to him although I suspect he would have been cautious. Molecular genetics seems all the time to promise more than it actually yields and he would have been quick to point that out. But he was very much a man of the future and an enthusiast for progress. Obfuscation and ignorance appalled him. So, yes, bring on the sequences, but accept that we are merely opening the hidden door by reading our genes; it is barely possible to see any detail of the garden beyond.

-Simon Mawer

Big thanks to Simon for participating in the inaugural entry of the Redux series!

Simon Mawer’s homepage

See also the Field Museum’s exhibit called:
Gregor Mendel: Planting the Seeds of Genetics

50 million personal genome sequences by 2015?

Just how quickly will the market for personal genome sequences grow? My back-of-the-napkin calculation pegs it at 50 million sequences obtained by 2015, give or take. While this is far from a scientifically derived calculation, my rationale is simply to assume that the trend line for the personal genome sequencing market might look a lot like the one experienced in the personal computer market.

Welcome to 1980
The personal computer industry grew from several thousand units sold in 1975 to 50 million units in 1995. If the personal genome sequencing market follows suit, we might say that 2007 for personal genome sequences was like 1979 for personal computers, and we’ve just turned the corner into 1980 where units sold remains sub 1 million, but growth is noticeable. If growth continues apace, we’ll hit 50 million sequences obtained somewhere around 2015-2020.

PCs 1980-1995: sparkline
pDNA 2007-2015: sparkline


Deus ex machina
A difficulty with predicting the future is human agency, or choice. How quickly will people warm to the idea of surfing their personal genome sequence? Although we’re in the early days, personal genome sequencing evangelists are starting to appear in unexpected places. Enter Christopher Hitchens. In a recent interview about his newest book on the Hoover Institute’s show Uncommon Knowledge, he paused and said: “As it happens, I’ve had my DNA sequenced recently. You can get yours done too. And you should, by the way…”. Here is the clip (you can skip the 8 min point):


History, on repeat
How else might the personal genome sequencing market resemble the personal computing industry? For some ideas, witness this absolutely brilliant piece of video from Britain in 1969 — a year when computers were not yet “personal” computers, but they were clearly heading that direction:

Part 2, and Part 3

The interviews with people on the street are amazing. When asked, “So what do you think of computers?”, responses range from the aloof “What are computers?” to the utopian “a revolution like we’ve never seen” to the dismissive “yeah, they’re great, but I don’t know what all the fuss is about” to the completely dystopian “the government will use them to control us”.

At the close of the video, renowned professor Donald Michie (University of Edinburgh) had this to say:

“[Computers are] bringing about the greatest revolution the human race has ever known…This revolution could lead to terrible consequences, or it could lead to the greatest advances ever for the human race. Which of these things are to happen, is up to us.”

Fools Game
Attaching a number to a 10 year forecast is a fools game. The timescale may be off-base in either direction. The point of writing this post though is to help set expectations about a near-term future where many millions of people have obtained personal genome sequences (including partial sequences). This point still escapes many people who work in and around the genetics field.

Flashback 1995: Epidemiology faces its limits

“With epidemiology you can tell a little thing from a big thing. What’s very hard to do is to tell a little thing from nothing at all”…journals today are full of studies suggesting that a little risk is not nothing at all. The findings are often touted in press releases by the journals that publish them or by the researchers’ institutions, and newspapers and other media often report the claims uncritically…And so the anxiety pendulum swings at an ever more dizzying rate. “We are fast becoming a nuisance to society,” says [Dimitrios] Trichopoulos. “People don’t take us seriously anymore, and when they do take us seriously, we may unintentionally do more harm than good.” As a solution, epidemiologists interviewed by Science could suggest only that the press become more skeptical of epidemiologic findings, that epidemiologists become more skeptical about their own findings–or both.”

From, Gary Taubes, Epidemiology Faces Its Limits. Science. 269(5221):164-169. July 14, 1995. (sorry subscribers only, but here is decent pdf)

Rarely does a journal article have me hanging on every word. On occasion they do. This 1995 article is one to get excited about. I suspect the field of personal genomics has a lot to learn from this article, especially as it relates sober-faced communication of research findings. The personal genome enthusiasts who are interested in drinking from the firehose of new genomic associations would do well to take the advice for vigilant skepticism of the newest findings. But skepticism alone seems like a rather weak antidote, new tools are definitely needed for organizing a publicly available scoreboard for genomic associations.

Happy New Year

At the start of every trip around the sun, I like to spend some time getting my bearings. This quote from Unweaving the Rainbow sure did it for me this year:

“We are going to die, and that makes us the lucky ones. Most people are never going to die because they are never going to be born. The potential people who could have been here in my place but who will in fact never see the light of day outnumber the sand grains of Sahara. Certainly those unborn ghosts include greater poets than Keats, scientists greater than Newton. We know this because the set of possible people allowed by our DNA so massively outnumbers the set of actual people. In the teeth of these stupefying odds it is you and I, in our ordinariness, that are here.”

May all of the ordinary ones have an extraordinary year. Happy New Year!

P.S. In an interview last year, Richard Dawkins mentioned that he has set aside this passage and asked for it to be read at his funeral.