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Ten years ago on Saturday, Francis Collins and Craig Venter walked onto the White House lawn with Bill Clinton, to announce the completion of the first draft of the human genome. I had the opportunity to sit down this week with Dr Collins, who's been visiting the UK ahead of the anniversary, and my interview with him appears in the paper today.
+ X% H7 O) z8 f. H+ }0 g( u My piece has focused on Collins's prediction that most of us, at least in the developed world, will probably have had our complete genetic codes sequenced by the time the reference genome is 20 years old. But we spoke about much more than that, and I've included some of the highlights of our conversation here.
- i' L- o* A2 L! s Perhaps of greatest current interest, given the FDA's current clampdown on direct-to-consumer genomics companies, were his thoughts on how this fledgling industry should properly be regulated. He accepts that there is a case for some regulation, which should focus on risk and accurate test results. But he is very wary of over-zealous regulation that might stifle innovation, or unreasonably restrict individuals' access to the contents of their DNA. And he doesn't think such access needs always to be mediated by a doctor.4 |. J a6 f$ J- }: y+ g
% V( ^+ B7 b8 [# J/ } The direct quotes follow after the jump...
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1 e+ [" O7 s( _/ a) |& EOn regulation- M% ]! k- P# l$ | C+ i9 N, E' z
0 U% o, T9 f, d( c$ w I started by asking Collins what he thought of FDA's intervention on DTC genomics. He said: "The FDA is being fairly reasonable about their approach, in the sense that I think they are sensitive in not wanting to shut down a set of scientific advances that are potentially going to become a valuable commercial enterprise.
1 l9 j: n1 G- g( V/ n "I think the approach they're going to take is to focus on those kinds of test that are associated with risk, and have a risk-based oversight system rather than a knee-jerk system of 'oh, it's a genetic test, we need to review it no matter what'. That's clearly what's needed, and some groups have been arguing for that for 10 years.+ Q7 Y$ N0 C. b7 u" I
"I do think the time has come, when you look at some of things that are out there on the web that are quite unsubstantiated scientifically, to pay some attention to that. Peggy [Hamburg, the FDA Commissioner] and Josh Sharpstein [Hamburg's deputy] are aware of the need to do this on a rational basis and not to slam the door. But I do think the public is increasingly concerned about whether this occurring in a completely unregulated way is going to be of benefit to them.
0 s$ i5 ]0 Q4 N "I'm not sure exactly where this will go over the next year or two, or what the implications will be for access to genetic information. I am both a strong proponent of the need for quality of what's offered, but I also believe in patient empowerment, and the opportunity to find out something about themselves if they want it seems like something we should be reluctant to get in the way of, so long as the information is scientifically valid.
* m& s# A/ `% f; f1 C! G "Regulators have a tough job. They need to be sensitive to not stifling innovation, but they also need to protect the public against really unscrupulous use of new technologies. And in that regard, by preventing the real misuse of technology, they're certainly protecting the innovators from seeing a complete meltdown and a distrust of technology that might persist for years to come./ \+ ]3 G, V u
"So in many ways the regulators are also the guardians of science, in the sense that they keep it from slipping into snake oil, which ultimately does a lot of damage to science. But there is a tough balance, which is one of the reasons the FDA has had such a hard time figuring out how to regulate genetic technology. I give Peggy and Josh a lot of credit for being willing to take this on and do something."5 a2 E$ I3 ^3 u* @
Collins has himself been tested by several of the DTC genomics companies, and I asked how his experience as a consumer had influenced his thoughts on regulation:
' x5 R$ K/ h# n$ g7 S "My own experience with this did inspire me to take some action which I probably should have taken anyway. No-one should generalise from your own personal experience to make federal policy, but there's plenty of other data to show that when individuals are given predictive information about the future, at least some of them do find that useful and do modify their health behaviours, and are able to understand that these are not yes-no black-white answers, but risk factors they might want to pay attention to, just as they pay attention to their cholesterol." t/ t) H4 V+ n" N
Medical supervision of DTC genetic tests
1 m4 q6 a9 S, v$ c; m5 B4 Q Next we moved onto the sometimes vexed issue of medical supervision. Should genetic testing always be conducted in concert with a doctor or genetic counsellor? Collins said:
( \: k; \5 Y" H/ u "That of course is one of the hot potatoes. Even within the field of medical genetics there are strong differences. The American Society of Human Genetics thinks that having a medical professional involved is not required. The American College of Medical Genetics thinks that oh yes, there are great dangers if a medical professional is not involved.
~. y; ~4 `6 F; ^ "I think my view is that people are in many instances capable of absorbing this educational information without the need for a professional to walk them through, but if they want that they should have access to it quite easily, and should not be hit with information without a medical professional to assist them.
) {) x) J) i3 @3 W* e B( H+ Y "I've been impressed by the way in which the direct-to-consumer companies have worked pretty hard at this, in terms of providing information and what it does and doesn't mean. But there is probably no substitute for having the opportunity to ask questions of someone who is an expert in the field after you have begun to absorb your own results, and I think people ought to have a chance to do that if they want to.
0 j& {& b' q& B0 S3 l" i. P "I would be very uncomfortable with a system that says no, we know better than you do, you won't understand this information so we're not going to let you have it. There's something that doesn't feel right about that." ( j" c6 b! A' G( V' I8 V
7 B3 l( P3 p) H9 `Validity and utility
, d3 \2 S7 j" M; k8 h To what extent should test be regulated for scientific validity and clinical utility? Collins said:; I. D U! I: s% E9 e; `7 _3 L
"A lot of this debate relates to what you call clinical utility. If you're going to have a test that's marketed to the public, it should have analytical validity, that is the lab should be able to prove that they can do a DNA test and get the sequence right. And it should have clinical validity, that is the test if it says it means something, that should be clearly true. If it says your risk for this SNP goes up for diabetes, then there ought to be evidence to back that up.
: w8 V% d8 u, t# Z5 [" j* J% z "But what about clinical utility? That's so much in the mind of the beholder. I mean you may say knowing your Alzheimer's risk from APOE has no clinical validity because you can do nothing to change your risk by changing your diet or taking drugs or doing Sudoku or whatever. But for somebody who wants to know that information for purposes of planning, and that was shown very clearly by Bob Green's REVEAL study, that is useful to them. So don't tell these people this is not clinically useful. It is clinically useful from their perspective, and we shouldn't be paternalistic about it.") _# }* t! H/ `# l0 f5 z
So, I asked, is a light touch what's called for? Collins replied:
% _; D, o; [3 [; i& a9 u "A light touch but a touch that is also focused on risk. For instance, if a lab is offering individuals BRCA1 testing, to individuals with a strong family history of breast cancer, with no pre-test or post-test counselling, that's a problem. If you're talking about highly penetrant conditions where the test result has high medical significance, that's probably not something you should get at Walgreens. For example.". b. F0 a g( A7 O7 z! ?2 X
' e& m v8 e) L- gAlso important, he said, are the interpretation services that are offered:5 P8 | K$ p% G' V; }4 u# W
"I gather Ozzy Osbourne has had his genome sequenced. Ozzy's probably going to need a little help figuring out what this means."
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a. ^3 r. T" Z% @4 pCancer genomics9 @& t5 R! T4 i
Like many observers, Collins feels that cancer will be a standard-bearer for genomic medicine:- z+ j6 J6 v9 l, x d9 t
“Cancer is I think going to be right out in front here. And I think we would all expect that within the next decade every cancer identified, at least in countries that have the resources, a full enumeration of what is going wrong in that tumour, and then an ability to match that up with the available therapeutics so you are doing the best possible job of throwing smart bombs, instead of the carpet bombing of traditional chemotherapy.”% v+ C: W; }6 e( j; Y
"The question is will that be helpful because we have a nice menu of therapies, and we'll be able to pick just one or two that are going tobe active against that patient's malignancy. We have a lot of work to do. ! g2 ^, T) D/ t5 ?; T! m6 ?( `
"Could I tell you that in ten years most patients will have both a complete genomic analysis and a choice of compounds that should be clinically active? I don't know, I would hope we will be pretty close to that, and certainly well beyond the menu we have now of targeted therapeutics, which is still a pretty short list. It's going to grow."/ @, m9 D2 N6 N' M$ [# \1 H
3 J, h& @- k6 W5 cPharmacogenomics as a driver of widespread sequencing! k6 Y. d1 Y" j6 e; a
Collins was clear that he thought the potential of pharmacogenomics would be the main driver of widespread sequencing.
$ p; L, o; l* g$ [9 Q "I think it's another great payoff over the fairly near future, and certainly over the next decade. 10 per cent of FDA approved drugs have a label saying something about genetics and its ability to predict a side effect, or something about whether that person is going to respond or have a dose adjustment.
7 w" k x* q7 V, S/ C0 R/ G "The problem with pharmacogenomics now, in terms of real mainstream application, is in a certain way logistic. We already know enough variations that could be used in dose adjustments, in terms of the CYP genes, but most of the time the physician doesn't know that much about the science anyway, and there's the problem of sending off the drug sample know, and where do I send it to, and I want the sample now. But, how's it going to change?* k h/ E( E6 p+ N8 V) c" ?" V$ x
"Well, when the sequencing of your genome or mine really does drop into the affordable range of less than 1,000 dollars, it will become very compelling for pharmacogenomics in particular to do it just once, to do it right, to get it into the medical record. There would be no need to take more blood samples, it’s just a click of your mouse to know whether that drug dose ought to be adjusted, or whether there’s a risk of a nasty side-effect you want to avoid. That will be a moment when a lot of the barriers to pharmacogenomics go down."
0 g3 o* k$ R; U6 U7 ?: \' s* I "When you see the cost of sequencing dropping much faster than Moore's law for computers, we're now down to about $10,000 for a reasonably complete sequence. I can't believe it won't drop to less than 1000 within five years. Will that become the moment then, where at least to people in some kinds of health plans, when it becomes compelling to do it? Good heavens, we spend a lot more than that on all sorts of unnecessary scans.
# r4 D6 }( J% ^ "Why not just make the case for each of us that this is information that will only gain in value over time, and if it's possible to do it accurately it would be cost-effective, both in terms of prevention and pharmacogenomics and so on? I think that will get pretty compelling.5 t- x$ [! @8 R$ K. s4 U
"What will the timetable be from when it's possible to when it actually happens? That's the key question. A lot will depend on reimbursement and who's going to pay for it? Will third parties see it as a key investment? Where's the capacity going to come from to do all these genomes? Will we have that kind of throughput abilities? I don't know.6 W& Y' G# G5 u9 k7 I3 u7 i; v8 x q6 R
"But certainly within ten years I will be very surprised and very disappointed if most people in the developed world will not have their genomes sequenced as part of their medical record, and I would hope it will come even sooner."
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; s6 _. w3 d \! o, X7 cComplex disease and the missing heritability
W* d. g) u* {' \7 c# K7 L How confident, I asked, was Collins that the "missing heritability" of complex, common diseases would be unlocked over the coming years? He said:# r7 R: K0 r& T
"Nobody knew what the structure would be of genetic variation that contributes to heritability until we started to look for it. But there's certainly a lot more there hiding in the dark matter of the genome. Presumably, that will start to come to light as we are able to look for less common variants with sequencing of lots and lots of genomes from lots and lots of studies. I'm not despondent about that at all. It's just that the structure is not what we thought it might be.4 L* v. h- k* j2 T& a
"It doesn't seem we were wrong about heritability and its contribution to diabetes and heart disease, all of those common diseases, it looks as if heritability is about 50 per cent, which means it's somewhere in there. We just need a finer lens to discover it. That probably means that within the next decade, our ability to make finer predictions about disease risk are going to get pretty good. Then it will be I think increasingly compelling to use programmes for prevention. It's something you can do right now, so long as you're aware you're not dealing with all the information that's lurking in the genome."6 l8 h" V7 s' T* [) Q& s' V
6 R& Z' x2 t8 m1 ASequencing children
^1 ]% m& }7 s' {; r! b. g In April, I broke the story that the children of the Solexa entrepreneur John West, Anne and Paul, had become the first minors to be sequenced for non medical reasons. I asked Collins how he felt about that:) i& W* u1 _5 W" e
"Frankly, that one did make me a little bit uneasy, because here were two kids who were promoting the idea that they were glad to have this, but you have to wonder how could they say otherwise when their dad was the company founder. There are statements out there in the literature, that genetic data on minors should not be obtained unless the data needs to be known, but those may start to look a little dated.5 [1 s( |8 K8 o& S+ X6 n
"This leads us to the question about newborn screening, because we do after all already determine a fair amount of genetic information about every newborn. Newborn screening is recommended in the US for 29 diseases. The time will come when it's cheaper to do that by sequencing than by 29 different tests, and at that point wouldn't it make more sense just to do it, and then to have a plan to release that information in a graded fashion as it becomes actionable. I do think we need to preserve the right not to know. That's a substantial component of our resonsibilities. If every newborn is being sequenced, those newborns should have the opportunity to say at 18: 'the rest of that sequence, forget about it.'" |
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发表于 2010-7-8 16:49
