SUSAN DENTZER: Now, both in terms of when the working draft is completed and what is accomplished hopefully by 2003, just to make this very concrete, what will a good geneticist sitting out there in the heartland be able to do with this information? Specifically, what can that person now accomplish that was not, could not be accomplished before?
FRANCIS COLLINS: So, there are several uses of the sequence that people are already plunging into with great abandon and having a wonderful time moving progress forward. A particular kind of problem is to try to find a gene that is involved in disease. That is basically what my own research has been for the last 15 years.
FRANCIS COLLINS: The way you do that is first you study families, where the disease is occurring, and you sample various parts of the genome looking for a place that seems to correlate with who has the disease. And when you find that, you get very excited but you still have a very large region to work with. You want to get down to the precise letter that is responsible. To do that without the sequence is a very slow, tedious process. It would take you years.
With the sequence in front of you, you can now telescope that down into a matter of weeks. And, in fact, as one looks at what has happened in the last year, that kind of disease gene discovery has accelerated to a dramatic degree because of the availability of working draft sequence.
So, we're going to see that paying off in a tremendous way.
SUSAN DENTZER: And in essence, what this geneticist looking for a particular gene would be doing, would be comparing a sequence that he or she had found in this particular family or this particular individual and using a computer program to compare it against what was known of the entire human genome. That is what we're talking about here.
FRANCIS COLLINS: Right. If you are looking for a needle in a haystack, and somebody has already cataloged all the straw in the haystack, when you get to that needle you will recognize it's different than what was supposed to be there based on all that computerized haystack information that had been predetermined for you.
So, it speeds up that process. You don't feel like you suddenly fell into new territory that nobody had ever looked at before. Somebody got there ahead of you and laid it all out about what it ought to look like and then you can focus on that tiny difference between your patient who has diabetes and what was supposed to be in that region.
SUSAN DENTZER: Now, as you said a moment ago, just in recent months, a dozen new disease genes have been identified this way. Let's talk about those.
FRANCIS COLLINS: So, it's a wide range of genes that have already been found by this process. Three or four of them are involved in cancer; one in breast cancer, others in somewhat rarer kinds of cancer, a skin cancer, a kidney cancer. There are two of these that just came out that are involved in a particular kind of kidney disease that leads to end-stage renal failure and dialysis.
In both instances, those were conditions that most people did not think were strongly genetic. They thought that these might well be environmental toxins of some sort. With this set of tools in two different circumstances, they are able to go in and find a specific gene that has a misspelling that is the reason why these young folks are coming down with renal failure out of the blue.
That's very exciting to see that kick in, in a category of disease where people thought, well, you know, maybe genetics isn't going to be that relevant there. The tools are getting very powerful.
Now, another thing you can do which you can really only do once you have the majority of the genome in front of you, let's say 90 percent, is to ask the question, what's there in a global sense? And what's not there? What genes would you expected to have found that haven't turned up? And you can start to ask how are we different from fruit flies or round worms or mice, where, in fact, a lot of other information has been accumulated about those genomes as well.
So, we are already in the circumstance where people who are interested in particular gene families can say, well, how many members of that family are present in the human genome? How many tryosine kinases do we really have ? And what do you suppose they are all doing?
This allows you to build sort of a global picture of the set of genes that we, as humans, need in order to carry out biological functions which we have never had the chance to do before. We just had little snapshots of bits and pieces. Now, we have a chance to look at the whole thing.
SUSAN DENTZER: For all of the wonderful things that could come out of knowing one's genetic makeup in terms of being able to identify diseases in the future and perhaps new therapies for them, obviously many people remain concerned that their genetic material will be used against them.
FRANCIS COLLINS: Yes. So, I think we all have a sense that genetics can be pretty powerful stuff. Powerful in a good way in the sense that we could use this approach to unravel mysteries of diseases and come up with cures for conditions that we currently don't really quite know how to treat. But potentially powerful in a more frightening way, where this kind of information might get used against you to discriminate, to take away your health insurance or your job, or perhaps used in other ways that violate privacy or in some way begin to lessen what it means to be human in the full sense of the word by moving us in the direction where everything about us is viewed as being hard-wired as part of our DNA, taking away all of the wonderful aspects of who we are as human beings.
A case in point is genetic discrimination. Every expert that has looked at this has said, it is not just, and it's not workable to have my glitches or yours used as a reason to take away our health insurance or our jobs because we're all at risk and this is something that just ought to be off the table.
That is agreed to in most political circles and, in fact, has been the subject of quite a number of bills that have been introduced into the U.S. Congress and a number that have passed in now more than two dozen States. But we still aren't quite there yet. We lack sort of that final, over-the-finish-line success of saying, this just will not happen; it is prohibited.
Can we, as a force of our national will, take care of that before there are hundreds of thousands of people who have been injured in some way by discriminatory practices? That is the question of the moment. I hope, with every fiber, that this is the year where we're going to take care of that.
SUSAN DENTZER: What can, in fact, and what should, in fact, be protected through intellectual property mechanisms, so that the private sector can move forward and advance some of the therapies that are already under development?
FRANCIS COLLINS: Well, the whole area of intellectual property and gene sequences continues to be one where reasonable people can disagree and I'm glad to see there's a lot of public interest right now and a lot of debate about where the appropriate line ought to be drawn. And actually my sense is that this is beginning to coalesce into a consensus that is pretty broadly shared amongst public enterprise and in the private sector.
The basic outlines are if you have a DNA sequence that is directly tied to a product, that you can see developing based on that sequence, that that meets the standards of utility that Benjamin Franklin had in mind when patent laws were written way back when. On the other hand, if you have a DNA sequence that you don't know anything about, you don't know what its function is, that's probably not an appropriate item for you to claim intellectual property ownership on.
There are obviously debates about where between those extremes the line ought to be drawn. But basically everybody has kind of come to the conclusion that those two extremes ought to be handled in a way that makes sense.
Ultimately, it will be 10 years, I think, before we know whether the patenting process was handled in a way that benefitted the public, which is really the question, or whether we were too liberal in granting patents or too stringent. And the courts are going to have their say on this pretty soon, as well.
But it actually is reassuring to see that this is something that's very much out in the public as far as the discussion of this and that what had been very polarized views for a while seem to be coming together into a pretty good consensus with some disagreement remaining about precisely where the dividing line ought to be drawn.
SUSAN DENTZER: And part of that consensus does appear to be that information about the entire genome should be public.
FRANCIS COLLINS: So, I think everybody agrees that the raw fundamental genome sequence of us folks, ought not to be the subject of constraints on its accessibility and, so, it ought to be in the public domain and it ought to not be patented.
When it comes to a gene that has a function then, in fact, patenting makes a lot more sense. But the raw fundamental information, the stuff that we're putting on the Internet every 24 hours really just ought to be out there because the public is only going to benefit if scientists put their best energies to figuring out what it all means. And that will most likely happen if there are no constraints on their ability to do.