Issue link: https://tmcpulse.uberflip.com/i/375565
t m c » p u l s e | s e p t e m b e r 2 0 1 4 13 TMC SPOTLiGhT Q | Tell us a little bit about your formative years. A | I was born in rural, Southern Australia. I went to college in Melbourne and was immediately enamored with biology and biophysics. Serendipitously, I came to the United States to work here in the Texas Medical Center with Dr. Thomas Caskey, at a time when we knew almost nothing about the structure of DNA changes that lead to genetic disease. But it was at a time when the technology was beginning to evolve and the human genome project was just a 'twinkle in the eye' of some key leaders. But this was a wave of excitement that began at that time. Q | Where were the epicenters of discovery at that time? A | The early genomics groups were widely distrib- uted at that time. There were many groups that were involved at the genesis of the human genome project. There was a period of discussion in the late 1980s and a realization internationally that this might be a good thing—even though we didn't really quite know what the 'it' would be. It was similar to the Mars mission now. For a while we talked about the 'moonshot of biology,' but really because there are so many challenges, it is more like today's view of the Mars journey. That was the mood for the early thoughts of the human genome project. Not even having a clue about what the good way to get there was. So there were probably about 20 groups that were seriously engaged in the project internationally. And of course, there were model organisms that were also tackled because they were simpler problems. So there was a period then, towards the late 80s, when things began to ferment. That was before the project really hit the ground in the very beginning of the 90s. It began with trying to improve the technology, a long way from being able to sequence the first human genome. The methods were really very crude by today's standards. Then there was a collapsing down of the number of groups that were involved. This reduction in the num- ber of participants was partly because of the focus of the funding agencies. But also there was a realization by the participants that completing a human genome was a full time, long-term commitment. It wasn't some- thing one could do part time! You really had to want to get this task done. So the struggle to get the methods to high enough efficiency continued on through the mid 90s, then there was just about the moment that we saw the light at the end of the tunnel, a fierce competition with a private group emerged. That really kicked the public groups into action. Because all those involved in the human genome community were committed to the idea that these data should be freely available to all researchers. The idea there was that we didn't want a private group to sequence the genome and exercise DNA patents—like a 'land grab'. We wanted to stimulate research, not hide information away and lock it up into early patents. So we fought that battle and won. We got the data out there into the public domains by the early 2000s. That was the whole 13-year project from 1990 to 2003- 2004. It was originally supposed to be a 15-year project with a $3 billion dollar budget. We did it a little faster and cheaper. Q | I've heard people describe early genome sequencing as being like a New York City phonebook. There is a lot of information in there, and it's hard to know what to do with it all. A | Great analogy—except at that time we did not even how many telephones are in New York or how to organize them! That would be the better analogy. So it wasn't just taking existing phonebooks and stacking them in a pile. It was really figuring out what a phone- book might look like. There are very basic principles of biological research that were forged during that period. Those are some of the unrealized contributions of the human genome project, and more subtle transi- tions that occurred during that period, which people are really feeling the ramifications of now. So what are those things? There is digitalization. Biology was completely an analog science up until then. That's really critical because with the digitization you have a precision and an operability that you don't have otherwise. Comprehensiveness was empha- sized—the idea that you don't just nibble at the side of a problem. Instead you slice it, you dissect it fully and then you completely describe it. That's really a funda- mental principle that's practiced widely now. Free and open data release was also a product of the project. Historically, scientists are very secretive about their data, right up until they publish it. We changed that principle. We developed a model where data can go straight from a machine, into the pub- lic view. That's a huge contribution and one that is echoed in many projects now. In fact now, if you do a large project in biology, it's very difficult to get trac- tion and support unless you are supportive of free data release and free sharing. Those principles really have been transitional. Another one worth mentioning is simply scale. Biologists historically have been small thinkers. I really mean focused thinkers. They look down and practice reductionism to figure out problems. But the human genome project challenged that. I am not sure that is recognized. Now, when big projects come along, like Google mapping the world, people will often say 'Well we can map the entire planet and have a click on view of every room in the world.' You think that's pretty amazing, but biology really got that going. Let's take something as vast as the human genome and have a comprehensive complete view of it. So those principles really came out of the human genome project. Q | Talk about the cost of sequencing a genome today, as compared to the past. A | The advances are astounding. It was three billion dollars for the first half genome. We have two copies in each of us, so we only sequenced one for the reference. It was also a mosaic of many people's DNA, and that's what you see in the reference database now. If you get a new sequence, you compare it to that reference. The reference is pretty refined, but it's still only a half copy and it costs three billion or so dollars to produce. Now, we have tremendous advances in the DNA technologies. These are all technologies that were around at that time, but took this long to do the engineering required to support them. But now, we are talking realistically about the $1,000 genome. Today it costs anywhere from $5,000 to $8,000 for a genome sequence, but we're really heading to a point where a $1,000 genome is realistic. Now we've also got meth- ods were we can look at just the interpretable part of the genome, the one percent that contains the genes. That cost today is now about $600, and we're thinking we can get that down to under $100. So that's very affordable. This is really key because when you think about general use, where a genome sequence becomes as accessible as an X-ray, that's the order of cost that you need. Q | With this technology coming faster and being less expensive than it has been in the past, what should we envision in the next five to ten years rela- tive to genomic data? A | I think it depends on how far you want to project, but in the five to ten year time frame, it's almost certain that genome sequencing will be a routine part of your medical workup. That is, unless you have some personal objection. But from the medical point of view, there's not rational reason to object. So because this is inexpensive and comprehensive, there are issues that can be discovered within that data that may be critical ricHArd A. GiBBS, pH.d., Director of the human Genome SequencinG center at Baylor colleGe of meDicine, Sat Down with texaS meDical center executive vice preSiDent anD chief StrateGy anD operatinG officer william f. mckeon to DiScuSS the value of inteGratinG Genetic Data, anD a future where Genomic SequencinG can leaD to perSonalizeD patient care anD treatment.