DNA: A winding string of achievements (continued)

Additional stories examining 60 years of scientific progress since the discovery of DNA...and looking forward

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What is DNA? 
There was a time, not that long ago, when a news item in thelay press would explain that DNA was deoxyribonucleic acid, the long, twistedmolecule that provided the blueprint of life. Those days are no longer, as DNAhas entered the standard lexicon of the average citizen.
To test this, we briefly surveyed people with the simplequestion: What does DNA mean to you?
For most, the answer was quite succinct:
String of life.
Others took a more scientific approach (thank you, CSI):
Personal identification markers.
But for a few, the answer was more poignant and personal:
"It's part of how I explain to my six-year-old that her Momand I are to blame for her sore muscles and asthma."
"Since I'm adopted and I have absolutely no health history,it means I finally know what to be on guard for. Plus, through the 23-and-mewebsite, I've found blood relatives, which to someone who has not been relatedto anyone for 50 years, is quite a feeling."

James Watson's speechat the Nobel Banquet in Stockholm, Dec. 10, 1962
Your majesties, your royal highnesses, your excellencies,ladies and gentlemen.
Francis Crick and Maurice Wilkins have asked me to reply forall three of us. But as it is difficult to convey the personal feeling ofothers, I must speak for myself. This evening is certainly the second mostwonderful moment in my life. The first was our discovery of the structure ofDNA. At that time, we knew that a new world had been opened and that an oldworld which seemed rather mystical was gone. Our discovery was done using themethods of physics and chemistry to understand biology. 
I am a biologist, while my friends Maurice and Francis arephysicists. I am very much the junior one, and my contribution to this workcould have only happened with the help of Maurice and Francis. At that time,some biologists were not very sympathetic with us because we wanted to solve abiological truth by physical means. But fortunately, some physicists thoughtthat through using the techniques of physics and chemistry, a real contributionto biology could be made. The wisdom of these men in encouraging us wastremendously important in our success. Prof. Bragg, our director at theCavendish, and Prof. Niels Bohr often expressed their belief that physics wouldbe a help in biology. The fact that these great men believed in this approachmade it much easier for us to go forward.
The last thing I would like to say is that good science, asa way of life, is sometimes difficult. It often is hard to have confidence thatyou really know where the future lies. We must thus believe strongly in ourideas, often to point where they may seem tiresome and bothersome and evenarrogant to our colleagues.
I knew many people, at least when I was young, who thought Iwas quite unbearable. Some also thought Maurice was very strange, and others,including myself, thought that Francis was at times difficult. Fortunately, wewere working among wise and tolerant people who understood the spirit ofscientific discovery and the conditions necessary for its generation. I feelthat it is very important, especially for us so singularly honored, to rememberthat science does not stand by itself, but is the creation of very humanpeople.
We must continue to work in the humane spirit in which wewere fortunate to grow up. If so, we shall help ensure that our sciencecontinues and that our civilization will prevail.
Thank you very much for this very deep honor. 

Gazing into the next 60 years
Even after so much progress, there's still more about DNA wedon't understand than we do 
By Jeffrey Bouley
Fifty or 60 years ago, if you were reading Popular Mechanics or visiting theTomorrowland part of Disneyland, it was pretty clear we'd have flying cars,personal jetpacks and robotic kitchens before the year 2000. Well, we're morethan a decade into the 21st century and they still haven't arrived.Humph!
However, when Watson and Crick described the structure ofDNA 1953, what wasn't nearly as much in the public imagination—perhaps not eventhe scientific imagination—that we'd one day be able to read the very blueprintof our genetics and have technology with the ability to add or remove genes andto turn them on and off individually.
Yet here we are—and only 10 years past the completion of theHuman Genome Project, too. But as with so many things, the more you know, themore that you realize that you don'tknow.
"While we're overwhelmingly impressed with what's transpiredin the past 10 years in terms of the technology for sequencing DNA andcompletely changing the face of genomics research with incredible increases inspeed and declines in cost, I don't think we're near the end of that road byany means yet," says Dr. Eric D. Green, director of the National Human GenomeResearch Institute of the U.S. National Institutes of Health. "Even over thenext 10 to 20 years I think we'll continue to see better, faster and cheaperways of sequencing DNA and with that, continue to bring seismic changes to thegenomic landscape."
Even though the cost of sequencing has come down so much andso fast that the race to achieve the $1,000 genome has already given way totalk of perhaps a $100 genome one day, there is still a lot of expense toconsider. Just ask Dr. Laszlo Nagy, the head of the new multidisciplinaryresearch program at Sanford-Burnham Medical Research Institute.
"We're still in an expensive period because we have more andmore data to interpret and store. It's not just someone's genome, but also allthe other 'omics data pouring in. Also, there's more than one genome toconsider in even just one person because of things like the microbiome or geneexpression of tumors," he says. "What I think we will see more and more overthe next years and decades will be more streamlined ways of looking at data andintegrating it, and more people looking at existing data and finding newinsights into it."
Dr. Gustavo Stolovitzky, manager of functional genomics andsystems biology at the IBM Computational Biology Center, who is involved withsuch potential technological breakthroughs as nanopore DNA sequencing, sees atime soon—within the next five to 10 years—when DNA sequencing will becommonplace enough that the devices to do it will be desktop-sized like so manyother molecular biology tools. However, as he cautions, the question will be:What can we learn from that sequenced data?
"Sixty years ago, we learned the structure of DNA. I thinkthe next 60 years will largely see us trying to learn the function of it,"Stolovitzky says. "But like everything else, first we need the technologybreakthroughs. There was a time before we even knew how to read DNA at all, andeven with what relatively little knowledge we have, we can do a lot. I like toimagine it's like we are kids learning how to read. At first you read withdifficulty and try to make sense of a lot of confusing material. We are not sofluent yet in reading DNA. Soon enough as the decades move on, we will becomefluent, and that is when much of what we don't understand now will make sense.
"There is a phrase from Groucho Marx that I like very much,and it goes something like, 'Outside of a dog, a book is a man's best friend.Inside of a dog, it is too dark to read.' And that it the challenge we haveright now," Stolovitzky continues. "Inside of cells, DNA is being read all thetime and the body is doing something with that information, but it's too dark inthere for us to read it ourselves. That is something that will probably take usseveral decades to really understand."
In the relatively short run of the next decade or two, Greensays that one of the next big things will be to find out how to read very longstretches of DNA, whether through nanopore technology or something else.
"We still can't sequence across the human centromere," Greennotes. "We look at the centromere and we say, 'that's just horribly repetitive'and that's just a kind of 'feel-good' conclusion we come to in the short runbecause we can't properly read or interpret that part of the genome. But aswith so-called 'junk DNA,' which turned out to be functional, there is noreason to think that the seemingly repetitive information in the centromereisn't biologically relevant. It's just that it's so hard to read and so boringto read with current technology that we cannot decipher it."
We should marvel at how far we've come in the past 60 years,Green says, he but adds that it would be naïve to think that 60 years from now,we won't look back and marvel to a much greater degree how our understandinghas multiplied.
"I'm very optimistic with respect to the next 60 years,"says Stolovitzky. "If you look at 10 years ago, the gene expression array racewas big. But if we didn't know about the human genome, we wouldn't have beenable to do gene expression arrays at all. Now we're moving on areas likeRNA-seq and proteomics technology and such. All of these technologies and morewill create a huge amount of data that, as we learn how to analyze it, will seeour knowledge grow exponentially. We're at the verge of that area now, thanksto Watson and Crick 60 years ago." 

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