10 year old human genome feels the weight of false expectations

DNA birthday cake. Image credit: Bigthink.com

It’s annoying when people pick on the human genome. Especially since this June marks its 10th birthday (scientists unveiled its first draft 1o years ago), and we should be throwing the genome birthday bashes, not bashing it up. And particularly because the genome critics are two rather prominent members of the media who get a lot of bylines by writing about genome-related medical advances and who should know better than to rough up the poor genome because it hasn’t coughed up causes and cures for human diseases — all of them — in 10 years.

A Decade Later, Genetic Map Yields Few New Cures,” lamented Nicholas Wade in the NYTimes earlier this week.

Why our decade of genome sequencing should end,” exposited Sharon Begley in a 2010 Newsweek essay not too long ago.

It’s true that 10 years have passed and $3 billion spent to sequence the human genome (completed in 2003) since the Human Genome Project (HGP) was initiated with the goal of finding the genetic causes of common diseases and ways of curing them.

Mr. Wade’s right; it hasn’t done these things. But then again, it wasn’t expected to, at least not by scientists, in that timeframe. Expecting the decoding of the genome to solve humanity’s health problems in 10 years is absurd. It’s like asking astrophysicists and NASA, “Well, we’ve been throwing billions of dollars into outer space for more than half a century now. Where is E.T? Or the colonies on the moon? And Mars – are we there yet?”

Aside from the absurdity, that sort of expectation after only a 10 year investment and exploration of the genome is also dangerous. It’s the kind of idea that falsely leads and encourages the public to confuse science with science fiction and to remain ignorant of the realities of the former while lapping up the fantasies of the latter.

Mr. Wade anchors his case on statements made by President Clinton and NIH director Francis Collins at the inaugural press conference 10 years ago. According to him,

“At a news conference, Francis Collins, then the director of the genome agency at the National Institutes of Health, said that genetic diagnosis of diseases would be accomplished in 10 years and that treatments would start to roll out perhaps five years after that.”

Actually, what Collins said was that by 2010 (excerpted from his 31 March article in Nature), he expected the following:

  • Predictive genetic tests will be available for a dozen conditions
  • Interventions to reduce risk will be available for several of these
  • Many primary-care providers will begin to practise genetic medicine
  • Preimplantation genetic diagnosis will be widely available, and its limits will be fiercely debated
  • A ban on genetic discrimination will be in place in the United States
  • Access to genetic medicine will remain inequitable, especially in the developing world

These were the actual bullet-pointed statements that he showed on a slide.

In the last 10 years, this is almost exactly what has been achieved and no scientist associated with the HGP has ever claimed otherwise. So it’s unfair and unfortunate for the Times article to assert so in an article that’s filed as a news report, not an opinion piece.

I have so many other quibbles about this piece, which has some pretty awful errors in explaining some basic ideas and concepts about the genome  (especially about what it teaches us about evolution), but to list them all would turn this blog post into a book chapter. (But Mr. Wade should know at least by now that chromatin is not “the complex protein machinery that both packages the DNA of the genome and controls access to it,” as he puts it. It’s actually a complex of DNA and proteins. But I should stop being petty.)

Ms. Begley does better, but not by that much. Her focus isn’t on the human genome project but on the broader issue of genome sequencing of multiple organisms. Her beef is that we’ve spent too much time and effort sequencing genomes and not enough resources on figuring out how most of genes and sequences within the genomes function.

There are 1,129 organisms whose genomes have been sequenced already, she points out. And so, no mas! After getting a press release about a paper that reports on the genome sequence of the cucumber, she’s had enough, she says, and so “stop them (sequencers) before they start again!”  she pleads.

Although she does a nice job of spelling out the value of sequencing multiple genomes with some good examples, she back-tracks and wonders whether scientists are going after genome sequencing and not after genome annotation (figuring out functions for every bit of the genome) because sequencing is easier, or as she puts it, “low-hanging fruit.”

Yes, sequencing is easier and faster and getting ridiculously cheaper, and that’s why there are more and more people doing it. But they’re not generating sequence information at the expense of functionally analyzing this information, as Ms. Begley contends. Every talk that I’ve ever heard by a genome sequencer—and I’ve heard dozens of them in the last couple of years—always ends with a “here’s what we’re doing next to figure out what this sequence information means” segment.

I also fear that Ms. Begley has overlooked an important new development in the genome sequencing field that renders her “stop sequencing, speed up analyzing” mantra, well, meaningless. A majority of the sequencing effort today to understand which genes cause disease and how, is spearheaded by researchers studying “disease genomes” – i.e, sequencing the genomes of individuals with different types of cancer, for example, to understand why cancers metastasize in some people and not others, or why some people respond to a drug but not others. These are questions that can be answered much faster by directly sequencing each patient’s genome and comparing it with others’ rather than trying to infer answers from the few other genomes (mostly healthy ones) sequenced to date.

Anyway, let me stop here by saying that it’s too bad that these usually good, fair and widely-read writers are barking up the wrong tree. Or maybe I shouldn’t be too suprised that such weakly argued criticism exists. As Collins points out in his Nature piece,

“Those who somehow expected dramatic results overnight may be disappointed, but should remember that genomics obeys the First Law of Technology: we invariably overestimate the short-term impacts of new technologies and underestimate their longer-term effects”

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