WHOSE GENES? Patenting the Human Genome

Thursday, July 13, 2000

Over the past several years, biotechnology companies, in a race to find possible new drugs, have deluged the U.S. Patent Office with tens of thousands of requests for patents on pieces of human DNA. Are gene patents being granted inappropriately, before gene functions are fully understood? Are gene patents encouraging or hindering the progress of medicine and the development of new drugs? Some critics have a broader objection to gene patents, arguing that it is inappropriate to give a company the exclusive right to genetic material that is inside us all. Are gene patents, as they suggest, patents on life?

Recorded on Thursday, July 13, 2000

Peter Robinson: Welcome to Uncommon Knowledge. I'm Peter Robinson. Our show today, Patenting the Human Genome. Here I am a human being, flesh and bone, and here I am a human being or rather a representation of a teeny, tiny part of me in the form of a DNA molecule.

In recent years, biotechnology companies have deluged the U.S. patent office with tens of thousands of requests for patents on genes. Pieces of information inside the DNA molecule. Why? Drugs or rather drug money. It turns out that genes are very valuable in developing new drugs. Now, there are a couple of problems here. One is, should we be granting patent rights in pieces of information that reside inside every human being? Another, at what stage during the research process should patents be granted? Some companies have applied for patents on genes before they understood quite what the genes did. Human genome sciences, for example, patented a gene called CCR5. Later, other researchers discovered that CCR5 is useful in the treatment of AIDS. Human genome science has responded by demanding licensing agreements and royalties from researchers wishing to use CCR5.

With us today, three guests. Hugh Rienhoff is Chief Executive Officer of DNA Sciences. John Barton is a Professor of Law at Stanford University and Seth Shulman is author of the book, Owning the Future.

When he was asked about patenting the polio vaccine, Dr. Jonas Salk is said to have remarked, "Can you patent the sun?" Well not the sun but what about the human genome?

Title: A Sea of Trouble

Peter Robinson: A professor of molecular biology at MIT named Jonathan King has said this, "The notion that some company has a monopoly on my genes is like claiming ownership of the sea." Is patenting genes like claiming ownership of the sea? Hugh?

Hugh Rienhoff: No, it's not.

Peter Robinson: Nothing like it?

Hugh Rienhoff: No, I don't-I don't believe so.

Peter Robinson: John?

John Barton: No.

Peter Robinson: Seth?

Seth Shulman: Well I don't know if it's like claiming ownership of the sea but I think it might share some-some similarities. I've…

Peter Robinson: What are the similarities?

Seth Shulman: I think one that maybe Jonathan King is-is going to is the fact that a gene is something that exists out of nature, in a certain sense, the way the sea does. And so to consider it an invention is stretching this-the patent system a fair bit. So that's-that's one part.

Peter Robinson: Okay. We'll come to that. Hugh, what is a gene?

Hugh Rienhoff: A gene is-is somewhat controversial to define but operationally, it is the stretch of DNA that codes for a protein.

Peter Robinson: And proteins are important to human beings for what reason?

Hugh Rienhoff: Proteins are the little operators in the cell that do things like repair the cell, help it to divide and grow, etc., etc., all the-what you might call the-the executors. If-if software is the-is the DNA, than the hardware is what proteins are.

Peter Robinson: Okay. And would you grant this is really the exciting place to be working in medicine and biotechnology today?

Hugh Rienhoff: It is the beginning of the transformation of medicine and I think, in ten years, medicine will be dictated a lot by what your genetic make-up is.

Peter Robinson: John, what is a patent?

John Barton: Patent is the right to keep somebody else from doing something, from using a technology. So you keep-you get to be the only person that uses the technology.

Peter Robinson: So it's the creation of a property right and a particular technology?

John Barton: Yes.

Peter Robinson: Got it. And the Patent & Trademark Office is…

John Barton: That's the place that grants the patents. If you come in and tell them how to do the technology and show that it's new, that it's not obvious, and that it's useful.

Peter Robinson: Useful, non-obvious and new or novel. Those are three cri-criteria. All right. Seth, we have genes. We know they're important. We have patents which create property right in genes or genetic research, bits and pieces of genes. Where does the problem lie?

Seth Shulman: Well the problem is, the way I see it anyway, that you're using something of an outmoded system to-to apportion property rights to-to something that's really quite new. The genome as-as Hugh's just talked about is-is a resource of information that medical science is going to need to return to, time and again, for the next century or more. And, in that sense, I like to liken it more to the Rosetta Stone which you might remember is the stone that helped decipher hieroglyphics in Egypt. If you had taken the Rosetta Stone and carved it up into lots of little pieces and allowed different people to have an exclusive right over them, you never would have gotten all the-the excitement of-of deciphering hieroglyphics. Essentially we're sort of trying to decipher a lot of things about how the body works.

Peter Robinson: John, can I just ask this point that Seth made earlier actually about the gene occurring in nature. Could you just clear how-Thomas Edison invents the light bulb. It is an object. It didn't exist until he put together light and filaments and elec-so on. But the gene exists. The gene exi-how is it that a gene can be patented?

John Barton: What we actually patent when we patent a gene is, in most cases, the right to use the protein that the gene codes for. And a whole variety of subsidiary claims that give me the right to use the particular sequence to put it into an organism to make more quantities of the protein. I strongly support that kind of patent.

Peter Robinson: What is the standing in law though for-for patenting a natural process or a natural-naturally occurring substance or entity such as a gene?

John Barton: I-I see your point. What we-what we say as a matter of law is, it was never found in adequate purity in nature. So that if I take the tissue-plasminogen Activase that's-I assume some is in my body, I am not infringing Genentech's patents because those patents on that same protein purified to a significantly higher level than ever found in my body. Otherwise, the patent would lack novelty. The patent wouldn't be new.

Peter Robinson: So-so-so the same thing that happened with, for example, a naturally occurring substance such as penicillin where it is isolated, purified, all this by the hand of man, put in a form in which it can be used and deployed in a way in which it was never deployed or used in nature, that creates standing for a patent?

John Barton: Exactly.

Peter Robinson: And the work that's done on genes, at least in legal theory, is analogous. It creates the same sort of legal standing for a patent?

John Barton: Well I think there's a real question in the law where they're simply sequencing the genome…

Peter Robinson: Right.

John Barton: …is enough work…

Peter Robinson: Hugh?

Hugh Rienhoff: Yeah, that-that's the issue really, is how much discovery or novelty is incorporated in the process of simply determining its sequence. Now, to be fair…

Peter Robinson: Next topic, what's at stake if gene patents are a problem?

Title: Survival of the Fattest

Peter Robinson: What are the things that will or could go wrong? One point you've already made is that information that should be broadly available will be limited, sliced and diced and given away under so many different-and that's one problem.

Seth Shulman: The biggest problem is the problem of stifling innovation, exactly the opposite of what the patent system's intended to do. If you give patents on information that's-that's too-that's-that's needed by everyone in the field to-to create new treatments and drugs, then essentially what you do is provide a disincentive for new people to go in because someone controls that part-that piece of turf.

Hugh Rienhoff: But I would argue actually that the human genome will be fully available to all researchers and-and actually any good research that comes out of the genome will be published. So I think what you're-the-the…

Seth Shulman: That's right. I don't disagree with that.

Hugh Rienhoff: …the heart of the issue is really, do researchers who add value to our knowledge of the genome get to reap those benefits. That's really what the issue is.

Peter Robinson: How does your business work? How do you make money? How do you make a profit on this new research?

Hugh Rienhoff: What we…

Peter Robinson: For example?

Hugh Rienhoff: What we do is we do very large scale genetic studies and try to understand what utility variations in the genome are responsible for. So, for example, what-what are the genes that are involved in diabetes? And that is completely unknown. And by looking at the genome, you can't tell. You actually have to do a study and so, by virtue of having discovered something through that, you know, genetic study process, the law will, in principle, allow us to patent those-those results.

Peter Robinson: You're patenting findings so-you're patenting pure information. Not a process, not an object or an entity but pure information?

Hugh Rienhoff: That's correct. It's a litt-the-to use…

Peter Robinson: That's patentable counselor?

John Barton: At least under the most recent Court of Appeals for the Federal Circuit decisions, yeah.

Peter Robinson: It is?

Hugh Rienhoff: Yes, absolutely. I mean, it-it's a little bit like saying we discovered penicillin and you could, in principle, and I don't know whether this was done, say this is useful for anti-for anti-infectives. And it's not useful for heart disease. That piece of information was-was-had to have been discovered and that piece of information is patentable.

Peter Robinson: I see. What about moral questions? Jeremy Rifkin, "Like the anti-slavery abolitionists of the nineteenth century, a new generation of genetic activists is beginning to challenge the very concept of patenting life," patenting life, Hugh, "arguing that life is imbued with intrinsic value and therefore, can never be legitimately reduced to commercial, intellectual property." Does this concern you at a moral level?

John Barton: I guess it concerns me at a moral level if we don't come out the opposite way. Because I think it's absolutely crucial that we need some kind of intellectual property right, some kind of exclusivity on those final proteins and the therapeutic products that you make from them. Now I get worried as it gets closer to information. And I understand…

Peter Robinson: So there's a little something in what Rifkin says?

John Barton: I don't see anything wrong with owning certain kinds of rights vis-à-vis technologies that relate to medicine and derive from human beings.

Peter Robinson: So we're not-this-this-the way that he's framed it, that we're owning life…

John Barton: I don't think we're really owning life in any…

[Talking at same time]

Peter Robinson: Hugh, does this bother you at all? Does this bother you?

Hugh Rienhoff: I mean, I-to-to some extent, it does because I think my biggest concern about patenting the genome is patenting it without knowing how to use it and to the-this issue of patenting information really boils down to how do you use the information? That's the critical thing that you're trying to patent, not so much the fact that a certain, particular variant correlates with the presence or absence of a disease because you want that to be ubiquitous information.

Peter Robinson: Hold that thought. Does this moral stuff bother you?

Seth Shulman: Well I suppose of the panel it probably bothers me the most. I mean, I think you can't leave out the public perceptions and the public concerns. And I think-I think that's…

Peter Robinson: That's true. Now you two guys, this is a democracy. If there's a political head of steam that gathers behind this argument, you'll find yourselves at…

Seth Shulman: It's not-it's not just that. I think that the public realizes that we're moving into terrain that's a little unfamiliar. And I think it's right to be-to-to treat it differently and I-I…

Peter Robinson: Let's examine a case that brings out some of the problems with gene patenting.

Title: Finders Keepers

Peter Robinson: Earlier this year a company called Human Genome Sciences or HGS was granted a patent on a gene that other researchers later discovered plays a role in AIDS. HGS, initial innovator, is now claiming a royalty on the use of its gene, even though it was later, other researchers, who figured out what it was useful for. That's exactly what bothers all three of you. Is that the case?

Seth Shulman: I think that's…

[Talking at same time]

Seth Shulman: …that bothers me.

Hugh Rienhoff: That bothers me although I have to be fair and say I haven't read the claims in the patent and the-they might have made…

Seth Shulman: I-I have. You probably have too.

Hugh Rienhoff: ..and they might have made claims…

Peter Robinson: I don't mean to blame HGS but the question is, the patent office granted them the patent.

Seth Shulman: No I actually read that patent and that patent mentions nothing about HIV, nothing about AIDS.

John Barton: What that comes from is traditional chemical patenting. I find a chemical that has a wonderful therapeutic application, spend the money to get it on the market, get a patent on it. You come along five years later and discover this has another application that I didn't know anything about. You can't proceed without permission from me under traditional chemical patenting. It's…

Peter Robinson: The trouble arises when…

[Talking at same time]

John Barton: …the system has to practically work.

Seth Shulman: The-the trouble arises back to the-brings us back to the kind of the Rosetta Stone problem. That this-to-all this information is going to have multi-layered kinds of use. We don't even know all the kinds of-but it-but we do know that people have to return, time and again, to a fairly finite, limited human genome, big as it is. It's-it's-it's already pretty much out there. A lot of what the debate is, is how much do you have to know about what this particular sequence of information does in the human body before you can get some kind of claim on it. And I-I think…

[Talking at same time]

Peter Robinson: Hugh?

Hugh Rienhoff: I-I would argue that-that that burden should be very high because, to be honest with you, the cost of actually determining the chemical sequence of the gene is probably a hundred times cheaper than it is to figure out what it actually does in the kind of studies that we do. And that's really the issue. If we discover that-that a gene or gene variant, I should say, is responsible for diabetes, we would like to be able to develop a test. If somebody had already patented that particular gene variant without knowing what it did, then we would be precluded from doing that and that's why…

Peter Robinson: You would have to pay them a royalty?

[Talking at same time]

Hugh Rienhoff: If they grant it. It's-it's possible that they could exclude us from doing that if they-if they wanted to. I mean, they could say…

[Talking at same time]

Hugh Rienhoff: I mean, there's nothing in the law that says they couldn't…

[Talking at same time]

Seth Shulman: And-and can I just fill in one thing?

Peter Robinson: Hold on. Hold on. I want to get to John.

John Barton: I just want to pick up the same points. I think it's really crucial. If I-if my company gets a lot of little rights on pieces of genes that we don't understand about and your company wants to use them in some way, you have to come to me for permission. And if my real contribution to the science was very minimal which today I think the basic, producing the sequence is. It's fairly cheap and easy. Your contribution has to be for a much more expensive field test and trial. We need to decide in that situation, should I have these patent rights that essentially amount to a hold-up, right, against you or should I not have those patent rights and you'll be free to proceed your technology and then patent something that's going to be the basis for reimbursing your substantial research…

[Talking at same time]

Seth Shulman: And there's tremendous uncertainty…

Peter Robinson: Now that we've laid out the problems with gene patents, let's look at a few possible reforms.

Title: A Code to Live By

Peter Robinson: We have here a legal expert in this field and John Barton has written an article in which he has proposed three reforms. We'll go through them. I'm not a lawyer, John, so you're dealing with somebody truly ignorant. John will explain his reforms, the two of you will comment. At the end of it all, we'll send the tape to the patent office and get them to change the way they do business. Barton reform number one: I quote from your article, "Raise the standards for patentability." What do you mean by that John?

John Barton: I mean, for example, make sure that what is non-obvious by statutory standards really is non-obvious in terms of applying that standard to a particular invention. Arguably today, it is obvious what the sequence of the gene is, or what the sequence of the genome is because I can learn it very quickly and…

Peter Robinson: Just running stuff through a computer…

John Barton: Exactly.

Peter Robinson: And that ought not to be…

John Barton: Computers…

Peter Robinson: You go for that?

Hugh Rienhoff: I totally agree with that. In fact, I would have it such that simply running it through a computer to find out that it's related to something else and then you guess the function should not be allowed.

Seth Shulman: No question that the-what the lawyers like to call the threshold of utility should be higher. I think most-most people agree with that. The-the question is how high?

Peter Robinson: And the answer is…pretty damn hard to figure out, isn't it?

Seth Shulman: Well I-no actually I don't think it's that hard to figure out. I mean, I-you know, one thing that Hugh said that-that I think's kind of important is that one the one hand, because of this private/public partnership that we've had, the fact of the matter is the-the bulk of the human genome will be out there on the internet. It will be publicly available.

Peter Robinson: Right.

Seth Shulman: The question is what you can do with that. And my proposal for what it's worth or at least one…

Peter Robinson: No, put it on the table…

[Talking at same time]

Seth Shulman: I'd like to hear what-especially what John-is-is to codify that into law. To say that the-the raw sequence data should be considered something akin to what we-what we do with land ownership in a national park, make it what I call an IPT free zone essentially. To say…

Peter Robinson: IP free, IP…

Seth Shulman: Intellectual Property Free. Nobody can own this and the reason that I think that's worth doing even though it's sort of defacto, done already, is it's going to start a process us to sort of proactively determine what kinds of information shouldn't be ownable.

Peter Robinson: That puts a legal cloud over every step of it…

Seth Shulman: Well may-well maybe…

Peter Robinson: …of business that you undertake.

Seth Shulman: Well no, I don't think...

Peter Robinson: because…

Seth Shulman: Hugh sort of agrees with that.

Peter Robinson: If a-if a genome is-is, by statute, free to everyone then which piece of…

Seth Shulman: The raw-the raw sequence data…

Peter Robinson: …if he comes up with something that can be used in treating diabetes, you can-can believe me the diabetic lobby will…

Seth Shulman: But he…

Peter Robinson: …spring up and want to meet that.

Seth Shulman: … he's not trying to own the raw sequence data.

Peter Robinson: Hugh, what do you say to this one?

Hugh Rienhoff: I-I think that it's-it's difficult simply because the raw sequence will always be improved upon and it's-it-there's even some debate about what the raw sequence is. And-and the-the-the problem is that there's so many variations in the sequence and you get into those arguments. So…

Seth Shulman: Well that's true too and…

Hugh Rienhoff: …to be quite honest with you, I think the-the major force that's-that is going to stand behind the patenting of the chemical code itself are the pharmaceutical companies that have-have a vested interest in keeping the patent system the way it is because of the legacy of chemical patents.

Peter Robinson: Okay.

Peter Robinson: Onto John Barton's next patent reform.

Title: To Helix and Back

Peter Robinson: Barton reform number two: It is crucial to balance incentives to initial innovators to follow-on innovators. Experience suggests that this balance is currently weighted too much in favor of the initial innovator.

John Barton: Almost all innovation today, we're building on the shoulders of other people's work. One person sequences the genome, another person finds some differences, another person finds that those are related to diabetes. Another person finds out how to use that as a…

Peter Robinson: There's a long stream of discoveries…

John Barton: Right.

Peter Robinson: …before you get something to the marketplace and make money on it.

John Barton: Exactly. Exactly. And there's only one place that the money's all made and that's when the product is sold to the consumer.

Peter Robinson: Right.

John Barton: And all rights that we give for people early on have to come out as pieces of that money.

Peter Robinson: Right.

John Barton: And if we give too many rights for people early on the people that assemble the final package and serve the consumer won't be able to deal with all the licenses and costs and legal complications.

Peter Robinson: We've gone through reform number one. Now we have before us reform number two and in a moment we'll come to Barton reform number three. And my question is, how would you affect these reforms? Is this simple matter, not that it's simple but is it a matter of getting congress to pass a piece of legislation, the president signs it and, from that point forward, the patent office must act on it. Is that the way it happens?

John Barton: That's one way it…

Peter Robinson: …ordinary political undertaking to change a law in congress?

John Barton: That's one way to do it. The other way's the standard, essentially, you know, led-litigated process of trying to bring briefs before the Court of Appeals to the Federal Circuit or get the Supreme Court to tell the Federal Circuit that they should change their doctrines. The question is whether or not the courts will do so themselves or whether or not congress has to push them or whether or not…

[Talking at same time]

Peter Robinson: What's the best way? What's the best and cleanest way in this democracy to get these changes affected?

John Barton: I, in a sense, it's congressional, of course, because we then get broader public participation. One of the interesting points though is if you go to congress, everything gets grandfathered.

Peter Robinson: Right. Right.

John Barton: If you go to courts, things do not get grandfathered. So one of the interesting questions is, the transition and that's a very important question, any kind of reform effort.

Peter Robinson: So what would you want? What's your preferred …

John Barton: I think I would prefer not to grandfather things because I think we've made too much of a mess with some of the patents we have.

Peter Robinson: So you would like to…

Hugh Rienhoff: And I would agree with that.

Peter Robinson: …see a couple of juicy lawsuits?

Hugh Rienhoff: Mostly because the-the sequence is a finite thing. And it's not like there's more sequence out there to-to-to work with.

Peter Robinson: Last topic, John Barton's final reform.

Title: Lawyers, Start Your Lawsuits

Peter Robinson: Barton reform number three: Ease legal attack on invalid patents. You want to make legal attacks easier?

John Barton: Yes. I guess I would like to make it easier to attack the patent rather than have to spend the rest of your lifetime negotiating with the person who holds the patent when you don't think the patent's been properly issued.

Peter Robinson: And the obstacles to attacking a patent today are?

John Barton: That the patent comes with the presumption of validity. We assume that the patent office doesn't make mistakes. I-I'm overstating that of course.

Peter Robinson: And you would make a change in the…

John Barton: I would make……

Peter Robinson: …the law?

John Barton: …it easier to te-test whether or not the patent office applied the legal standards correctly.

Peter Robinson: All right now, Hugh, what's your view on this?

Hugh Rienhoff: I-I-I think he has an excellent point because the-really the issue is a-a lot of these patents are prosecuted in a highly variable way from one examiner to the next and it's very difficult to set standards. And the problem is that the-there are many patent applications to which, I would say, are almost fraudulent in the sense that they make claims that-that what they're doing is novel or not obvious.

Peter Robinson: The patent office does a bad job of ferreting those out?

Hugh Rienhoff: I-I don't-I'm not going to say uniformly but I think it's highly variable and, in some cases, it's patently obvious to people who are really in the field, who really understand what's going on, that-that there was prior art, for example, or that things were obvious.

Peter Robinson: Prior art means?

Hugh Rienhoff: That before the patent application was filed that there was-that discovery was made in-in whole or part before.

Peter Robinson: Which would make the patent invalid?

Hugh Rienhoff: In principle, yeah.

Peter Robinson: Then it's not novel. Gotcha! Okay. You like Barton reform number three?

Seth Shulman: I think they're all very sensible reforms. I…

Peter Robinson: Do they go far enough for you?

Seth Shulman: Well they don't-they-they don't necessarily go far enough and I also think that it's-it's…

Peter Robinson: Are they a good starting place?

Seth Shulman: Absolutely. I mean, I think-I think…

Peter Robinson: It's unanimous. They carry…

Seth Shulman: It's unanimous. Yeah, they carry, absolutely. Let's have them carry. I-I do differ. I think congress needs to step in. I-I think, in this case, you could adopt legislation…

Peter Robinson: Neither political party that I've been able to discover has taken a stand on this.

[Talking at same time]

Seth Shulman: Actually…

John Barton: But there have been proposals for hearings on the genomic patenting.

Seth Shulman: Actually I-I…

Peter Robinson: And that's good news for you?

Seth Shulman: And I actually think the companies themselves realize this variability that Hugh was talking about in the way that the patent offices handle this causes uncertainty for everybody. Everyone knows that the-this kind of capricious verdict that might come about ownership of one thing or another, that works against everybody. What you need is rules of the road that people…

Peter Robinson: Now it has taken the space of only one television show to hammer out consensus on the need for the three Barton reforms and why hasn't it happened?

John Barton: I think the key obstacle is that most people in the system really like the system the way it is. They don't ask outside policy questions about it. They tend to view it in terms of very technical legal standards and…

[Talking at same time]

Peter Robinson: …the people…

[Talking at same time]

Peter Robinson: …the people in the patent office?

John Barton: I'm talking about in the patent office and the Court of Appeals for the Federal Circuit and in the patent bar.

Peter Robinson: This is complicated stuff and they figured it out.

John Barton: Yeah, yeah…

[Talking at same time]

John Barton: …concerns come from the economists, the scientists and now, which is new, to some extent, the business people.

Peter Robinson: Last question, it is television after all. It's now 2005, five years from now, this is a question about the state of play of politics and the law. Will John Barton's reforms, at a minimum John's reforms, have been acted upon five years from now? Seth?

Seth Shulman: Well fives years is actually a fairly short window but I think there's a fair chance.

Peter Robinson: Things are moving fast in this world?

Seth Shulman: I-I think there's a fair chance of seeing reforms in this area. I think especially as the public comes in, they-the key thing is I think to begin to see it more as a public policy matter and not, I mean, he-now I'm talking about the-the lawyers are one obstacle, in some sense, the big scientific players are an obstacle too.

Peter Robinson: Will you get your reforms in five years?

John Barton: I think I'll get some swing towards them because I think this is partly a pendulum swing. We took intellectual property not seriously right after World War II. We began taking it more and more seriously particularly during the beginning of the Reagan administration. I think that pendulum is now beginning to swing back the other way.

Peter Robinson: Hugh, will you have reforms to your liking within five years?

Hugh Rienhoff: When citizens of this country see what the genome is doing for them or if there are examples where they are actually denied access to therapeutics or diagnostics that come out of the human genome project, that's going to make the difference.

Peter Robinson: It'll become politically interesting…

Hugh Rienhoff: And I think-I think consumers recognize that money has to go in so whoever put that money in it has to go back to them so they're not totally against commercialization of this. And if-if commercialization of it speeds or if-if-if it's done in a business environment, the commercialization of this research gets to consumers sooner, they're going to be in favor of that. And-and I think the-there will be fewer reforms.

Peter Robinson: Hugh, John and Seth, thank you very much.

Peter Robinson: Our guests tend to agree. Whether the patent process will be reformed or not depends on whether it works or not. Either it'll produce better and cheaper drugs or it'll get fixed. I'm Peter Robinson. Thanks for joining us. I wonder whether there's a gene in her for hosting TV shows.

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