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DNA: A winding string of achievements (continued)
June 2013
by Randall Willis  |  Email the author

(To return to the main article on "60 years of DNA," click here)

What is DNA?
There was a time, not that long ago, when a news item in the lay press would explain that DNA was deoxyribonucleic acid, the long, twisted molecule that provided the blueprint of life. Those days are no longer, as DNA has entered the standard lexicon of the average citizen.  
To test this, we briefly surveyed people with the simple question: 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 Mom and I are to blame for her sore muscles and asthma."   —M.F.  
"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-me website, I've found blood relatives, which to someone who has not been related to anyone for 50 years, is quite a feeling."   —M.M.    

James Watson's speech at 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 for all three of us. But as it is difficult to convey the personal feeling of others, I must speak for myself. This evening is certainly the second most wonderful moment in my life. The first was our discovery of the structure of DNA. At that time, we knew that a new world had been opened and that an old world which seemed rather mystical was gone. Our discovery was done using the methods of physics and chemistry to understand biology.
I am a biologist, while my friends Maurice and Francis are physicists. I am very much the junior one, and my contribution to this work could 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 a biological truth by physical means. But fortunately, some physicists thought that through using the techniques of physics and chemistry, a real contribution to biology could be made. The wisdom of these men in encouraging us was tremendously important in our success. Prof. Bragg, our director at the Cavendish, and Prof. Niels Bohr often expressed their belief that physics would be a help in biology. The fact that these great men believed in this approach made it much easier for us to go forward.  
The last thing I would like to say is that good science, as a way of life, is sometimes difficult. It often is hard to have confidence that you really know where the future lies. We must thus believe strongly in our ideas, often to point where they may seem tiresome and bothersome and even arrogant to our colleagues.  
I knew many people, at least when I was young, who thought I was quite unbearable. Some also thought Maurice was very strange, and others, including myself, thought that Francis was at times difficult. Fortunately, we were working among wise and tolerant people who understood the spirit of scientific discovery and the conditions necessary for its generation. I feel that it is very important, especially for us so singularly honored, to remember that science does not stand by itself, but is the creation of very human people.  
We must continue to work in the humane spirit in which we were fortunate to grow up. If so, we shall help ensure that our science continues 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 we don't understand than we do
By Jeffrey Bouley  
Fifty or 60 years ago, if you were reading Popular Mechanics or visiting the Tomorrowland part of Disneyland, it was pretty clear we'd have flying cars, personal jetpacks and robotic kitchens before the year 2000. Well, we're more than a decade into the 21st century and they still haven't arrived. Humph!  
However, when Watson and Crick described the structure of DNA 1953, what wasn't nearly as much in the public imagination—perhaps not even the scientific imagination—that we'd one day be able to read the very blueprint of our genetics and have technology with the ability to add or remove genes and to turn them on and off individually.  
Yet here we are—and only 10 years past the completion of the Human Genome Project, too. But as with so many things, the more you know, the more that you realize that you don't know.  
"While we're overwhelmingly impressed with what's transpired in the past 10 years in terms of the technology for sequencing DNA and completely changing the face of genomics research with incredible increases in speed and declines in cost, I don 't think we're near the end of that road by any means yet," says Dr. Eric D. Green, director of the National Human Genome Research Institute of the U.S. National Institutes of Health. "Even over the next 10 to 20 years I think we'll continue to see better, faster and cheaper ways of sequencing DNA and with that, continue to bring seismic changes to the genomic landscape."  
Even though the cost of sequencing has come down so much and so fast that the race to achieve the $1,000 genome has already given way to talk of perhaps a $100 genome one day, there is still a lot of expense to consider. Just ask Dr. Laszlo Nagy, the head of the new multidisciplinary research program at Sanford-Burnham Medical Research Institute.  
"We're still in an expensive period because we have more and more data to interpret and store. It's not just someone's genome, but also all the other 'omics data pouring in. Also, there's more than one genome to consider in even just one person because of things like the microbiome or gene expression of tumors," he says. "What I think we will see more and more over the next years and decades will be more streamlined ways of looking at data and integrating it, and more people looking at existing data and finding new insights into it."  
Dr. Gustavo Stolovitzky, manager of functional genomics and systems biology at the IBM Computational Biology Center, who is involved with such potential technological breakthroughs as nanopore DNA sequencing, sees a time soon—within the next five to 10 years—when DNA sequencing will be commonplace enough that the devices to do it will be desktop-sized like so many other 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 think the next 60 years will largely see us trying to learn the function of it," Stolovitzky says. "But like everything else, first we need the technology breakthroughs. There was a time before we even knew how to read DNA at all, and even with what relatively little knowledge we have, we can do a lot. I like to imagine it's like we are kids learning how to read. At first you read with difficulty and try to make sense of a lot of confusing material. We are not so fluent yet in reading DNA. Soon enough as the decades move on, we will become fluent, 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 have right now," Stolovitzky continues. "Inside of cells, DNA is being read all the time and the body is doing something with that information, but it's too dark in there for us to read it ourselves. That is something that will probably take us several decades to really understand."
In the relatively short run of the next decade or two, Green says that one of the next big things will be to find out how to read very long stretches of DNA, whether through nanopore technology or something else.   "We still can't sequence across the human centromere," Green notes. "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 run because we can't properly read or interpret that part of the genome. But as with so-called 'junk DNA,' which turned out to be functional, there is no reason to think that the seemingly repetitive information in the centromere isn't biologically relevant. It's just that it's so hard to read and so boring to 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 understanding has 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 race was big. But if we didn't know about the human genome, we wouldn't have been able to do gene expression arrays at all. Now we're moving on areas like RNA-seq and proteomics technology and such. All of these technologies and more will create a huge amount of data that, as we learn how to analyze it, will see our knowledge grow exponentially. We're at the verge of that area now, thanks to Watson and Crick 60 years ago." 

(To return to the main article on "60 years of DNA," click here)



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