Edited transcript of a 11/18/04 Leonard Lopate show on WNYC radio on the ethical challenges posed by the rapid advances in biotechnology.
LEONARD LOPATE: I'm Leonard Lopate. This is WNYC, 93.9, AM 820. We are online at wnyc.org.
Thanks to advances in science, we have cured diseases, developed treatments for depression, extended the human lifespan, and even created faster and stronger athletes. But as positive as they may seem, those developments have some people concerned. Are the leaps in biotechnology changing what it means to be a human being?
Today on our "Underreported" feature we'll look into bioethical issues. I am joined by Arthur Caplan from the Department of Medical Ethics at the University of Pennsylvania and Julian Savulescu of the Centre for Practical Ethics at Oxford University. Welcome.
ARTHUR CAPLAN: Thanks for having us.
LEONARD LOPATE: Arthur, you gave a talk yesterday called "What Is So Sacred About Human Nature?" Have you come to a conclusion?
ARTHUR CAPLAN: Yes. I'll shock our listeners by saying that philosophers come to a conclusion. I think there isn't much sacred. My view would be that if you looked at our evolution, sort of how we came to be, the kind of creatures we are, with our lifespans, our reproductive capacities, our cognitive abilities, we are the end result of a long biological evolutionary process upon which has been layered a cultural evolution. That is useful to understand and know, it tells us kind of who we are, but it doesn't really tell us much about what we should be or become. That is, it is hard to read what we might choose to engineer into ourselves just from our past.
LEONARD LOPATE: But isn't even the concept of human nature something that constantly changes?
ARTHUR CAPLAN: Well, it has certainly been a fact of our evolution that our nature has changed. One of the things that anthropologists like to fight about is when does humanity emerge?
LEONARD LOPATE: With tools, with the first agriculture.
ARTHUR CAPLAN: Yes. Is it fire? Is it metal? Is it speaking? Is it standing up? So we get into these battles about the properties that define us. Even if we go back, though, very simply, to say 10,000-12,000 years ago to our agriculturally using ancestors, if they were to see us today, living seventy-eighty years of age, riding around in cars, flying in the air, computing, talking through the airwaves like we're doing right now, they would think we were divine.
LEONARD LOPATE: Go ahead, Julian.
JULIAN SAVULESCU: I would like to say something about what I think human nature is. What distinguishes us as human beings from all other animals is not our sexual practices or our social relationships; all animals share similar things in common. What distinguishes us is our minds and our capacity to make decisions based on reason and for what we judge to be better.
Arthur is very correct that nature delivers up, or evolution delivers up, human beings who are capable of reproducing and then die fairly soon after that. That is just what we are as evolutionary beings.
Recently, medicine has sought to change evolution. It tries to enable us to have healthier lives. I think we are about to take a much bigger step, and that is to choose our evolution not just to be healthier beings but to be better beings, to be beings who can have a greater opportunity of having a better life.
LEONARD LOPATE: Well, I'm not sure I understand how that is done. I do understand how we can extend lifespan, although I'm not sure everyone wants to live to be 150, which is another matter.
ARTHUR CAPLAN: Keep pondering the possibilities.
LEONARD LOPATE: But as we come to this point, a lot of people have gotten upset. Some scientists, bioethicists, even Leon Kass [chairman of the President's Council on Bioethics] of the Bush Administration, feel that something about human nature is being threatened. What are their problems?
JULIAN SAVULESCU: Well, what we can do now is we can improve people's mood through the use of alcohol or through the use of caffeine or Prozac; we can improve people's sexual performance by using Viagra; we can improve their sporting performance by using growth hormone or human erythropoietin. So we are able to change people's lives, not in the ways of preventing disease, but by enabling them to lead better lives. Now, the question is: will we go any further and allow them to manipulate their own biology in order to have those sorts of opportunities?
LEONARD LOPATE: But also we welcome some of those things and we reject others. For example, sports right now is going through serious problems dealing with those growth hormones, with the steroids, with other performance-enhancement drugs. Why is that all that different than developing Viagra to enhance performance?
ARTHUR CAPLAN: Well, I'm not sure it is all that different. I think if you looked at the critics, the toughest critics, say Kass and the President's Council on Bioethics, which have been pretty adamant that it is very dangerous and disturbing to tamper with human nature, their view might be that natural competitions without any drugs, without any technology, reveal facts about human beings—what they can do, what they can achieve—that we should celebrate, and that's great. My view might be: look, that is a kind of activity that one can engage in, but there's nothing wrong with upgrading your pole vault from a bamboo pole to a synthetic composite pole and jumping higher.
LEONARD LOPATE: Golf clubs, tennis rackets, have all been improved.
ARTHUR CAPLAN: There's nothing wrong with nutrition and training. There's nothing wrong with learning to lift weights, which athletes didn't use to do, and being stronger. There may be nothing wrong with having a competition where someone uses interventions that are pharmacologic, if they are safe — I mean certainly when you get into the dangerous ones, that's another story. But let's say we had a safe steroid.
I don't agree that there is inherently one way to compete, one way to be, and that's the only one we can celebrate or favor.
LEONARD LOPATE: So Barry Bonds' MVP award [Most Valuable Player] is safe as far as you are concerned?
ARTHUR CAPLAN: As far as I'm concerned.
JULIAN SAVULESCU: Some people say the use of performance enhancement is against the spirit of sport, and it is from one view of sport. I mean if sport is just like a horse rate, where you line up the horses and you flog them and the one with the greatest biological capacity is the one that wins, yes, taking drugs, performance enhancement, is against the spirit of sport.
But we talked about human nature. If it is human nature to want to be better, to develop tools not just to affect the environment but to affect ourselves, I think it is in the spirit of sport to allow athletes to modify not just their training but their underlying biology. As long as it is safe, I don't see the problem.
And there are safe performance enhancers. EPO [the blood booster erythropoetin] can push up the red cell level, and provided you don't use too much, there's no problem with using a bit to improve performance. So really we're picking and choosing.
LEONARD LOPATE: I have a friend whose daughter probably would be dead if modern science hadn't been able to intervene, and now she is ten years old. And nobody would have suggested, "Well, we just let her suffer when she was an infant because it would be unnatural." But we pick and choose those things.
ARTHUR CAPLAN: We do. And you are getting, Leonard, to something I think is very important. One fear, aside from tampering with the natural, which I think we probably have beaten into the ground.
LEONARD LOPATE: Well, if we were supposed to fly, we would have been given wings.
ARTHUR CAPLAN: Correct. It always strikes me as odd that the people who have been tough in the Bush Administration against intervention and change fly to the meetings and put their views on television and all kinds of other technological means to assist the promulgation of their opinion and don't worry about it. The biological seems to trouble them, but not the social, so to speak, engineering.
But put that aside. Something else bothers people, and that is: are you going to be forced or coerced or made to be better? I mean you said we choose, and I think that is an important principle.
You know, not far from where I live in Philadelphia there is a large population of Amish people, and they don't ride cars and they don't use electricity and they don't in fact use zippers; many of them button their clothes. It's not a lifestyle I choose, but you have to make room, if we are going to get involved in improvement, betterment, and enhancement, to let people decide to do it, not force them to do it.
LEONARD LOPATE: But it's not the same thing as choosing to have a cell phone when you decide whether you should encourage the development of cloning. And there are certain words, like cloning, that do upset people. Stem cell research has been a divisive issue in this country—and not in Britain, as I gather. But has the debate gone on in Britain as well?
JULIAN SAVULESCU: Well, there's always a debate around stem cell research and cloning that hinges around the moral status of the early human embryo, and that's not a debate that we are going to get consensus on. Some people believe that human life begins in a morally significant sense at the moment of conception. That view is inconsistent with abortion, with the use of the morning-after pill, IUDs, vast areas of social practice that most other people accept. So I think that there will always be controversy because people hold fundamentally different views about what it is to be human.
The question is: how far will we allow science to go ahead and potentially develop treatments that will be available to all of us? Here I think the views of a minority should never cost human life.
LEONARD LOPATE: So are we on a threshold right now? Are we at a point where technology is developing faster than it was in the past and many more things are opening to us?
ARTHUR CAPLAN: I'll answer that with a yes. I think that we have just seen the mapping of the human genome. That's a marvelous accomplishment. We have figured out the location and placement of all of our genes that sit on our chromosomes. The next mission is, however, to figure out what they correlate with, what they control, what they contribute to, what they cause. That's an explosion of new understanding of the genetic or hereditary contribution to all of our traits and properties. We are going to see that available both to test ourselves, test our embryos, test our children, and say: are these traits or these behaviors going to develop or not? And, ultimately, we will be able to engineer them to actually try and genetically change them. So that is an unprecedented explosion of knowledge.
LEONARD LOPATE: Haven't we seen something like this backfire in China, where people chose to have sons and now China is faced with a future of a lot more males than females as a result?
JULIAN SAVULESCU: Well, China was facing extinction from overpopulation.
LEONARD LOPATE: But they didn't enforce equal abortions or whatever, a One Child Rule that only, whatever your first child is, is what you have. They actually allowed people to pick and choose, and now they have many too many males as a result.
JULIAN SAVULESCU: I think you will see in China once things are liberalized that the pendulum will come back. Yes, sometimes there are momentary abuses of freedom, but generally we do much better to allow people the freedom to choose and make reproductive decisions. When we don't, we end up with a situation like in Nazi Germany, where people were forcibly sterilized and the state made decisions about what the correct constitution of society is. I don't want the state deciding what a correct sex ratio is and forcing that on people. I'd much prefer to leave it to individual families to make that decision for themselves.
ARTHUR CAPLAN: That's why I'm so strong about this idea that a principle to guide the future of bioengineering, the explosion of genetic knowledge, is that individuals have to be free to choose. We know from the 20th century history, both in China and Germany and elsewhere, that government-imposed mandates, coercion, the violent imposition of public policy has been disastrous. So you've got to make sure that, wherever we head in public policy, we leave room to let people choose what they want to do.
I'll put it another way, Leonard. I'm not worried about sex selection if we use genetic information to let people pick the sex of their children. What I worry about is sexism. You have to try and make people choose wisely.
We have to take a little break. We'll come back to these issues.
Before we went into that break, I got the feeling that you were saying that anything should be allowed to go in science; it doesn't matter. There is a man named Joe Rosen, also known as "Dr. Daedalus," [PDF 1.89 MB] who is a radical plastic surgeon who would be willing to make people wings and horns if they wanted to alter their appearance. I think that would upset most people, wouldn't it?
ARTHUR CAPLAN: I think it would. I am not here in favor of carte blanche when it comes to where biotechnology/bioengineering might take us. What I'd argue is the critics worry more about, in principle, reasons never to go anywhere. I don't think those arguments hold up. But case by case, let's look at the consequences, let's think about whether these things are likely to enhance somebody's capacities and abilities or limit them, what's the impact on children, what does it mean in terms of cost and access. Great, let's debate that. But let's not say, in principle, "our nature is what it is; we shouldn't touch it."
LEONARD LOPATE: Well, there have been any number of drugs developed to change the way people behave. For example, Ritalin for kids. Some people say it actually helps the kids; others say it just simply calms the kids down so the parents can have better lives. We see the same thing with the drugs that are aimed at people with more serious problems like bipolar, problems of depression, schizophrenia. Most of those people will tell you that they hate those drugs, that those drugs don't really put them back into balance, they just simply dull them and keep them under control. So is that something that we should consider a positive or a negative?
JULIAN SAVULESCU: I think it's a difficult decision whether a drug or an enhancement is actually in somebody's interests. There is a recent study that showed that you can take monkeys that are naturally lazy and introduce the gene from the reward center into their brain and they become very hard-working.
LEONARD LOPATE: It sounds like Aldous Huxley.
ARTHUR CAPLAN: It sounds like Microsoft.
JULIAN SAVULESCU: Well, the question was are we going to engineer hard-working children? It's not clear to me that that would be in the child's interest. But there are others.
LEONARD LOPATE: But some parents might want that, the parents who push their kids to get only A's.
JULIAN SAVULESCU: Well, that's right. But the question is whether it's in the child's interest. We were talking about principles, and I think the fundamental principle has to be: is this modification in the individual's interest?
There are other cases like impulse control. Impulse control, our ability to control our temper and our impulses, is strongly correlated with socioeconomic success and staying out of prison. We all know people with a hot temper, but even to a milder degree the ability to control your impulses will determine whether you stay in or out of prison to some degree. Now, if somebody has a very hot temper, I don't see the problem with offering that person or their parents the opportunity to calm that down. After all, we laud parents who try to educate their children to control their tempers. Why not do it biologically?
LEONARD LOPATE: But isn't there also a tradeoff usually, and the tradeoffs are side effects, sometimes loss of other ability? There may be impulse control on the one hand, but then this person is also a writer who finds out that he can't write anymore because something seems to have been lost.
JULIAN SAVULESCU: We have to guard against hubris or excessive pride and arrogance in this area and a belief that we know what is best, and we ought to be very admitting of various different ways of living our lives, and I think we should be reluctant to use these things. But in the end we have to make a judgment based on a balance of the costs and the benefits.
The point that Arthur is making is exactly correct; we can't just say because there are risks, there are side effects, we should never consider this. We have to as rational beings make a judgment about what's best for us and our children.
LEONARD LOPATE: What are the decisions being made in the White House? What is Leon R. Kass, the Chair of President Bush's Council on Bioethics, telling scientists?
ARTHUR CAPLAN: He's telling scientists:
- "Watch out, we have an eye on you. Our ethics board, if you will, is being made very nervous about directions you're heading in. We don't like the idea of your getting involved in embryonic research because we think it is not respectful; it involves destruction of potential human life.
- Watch out, we're made nervous by things like cloning, even for research, because we think there's a slippery slope, or we don't trust you to have the character and the moral judgment to control those technologies and not get involved in reproduction.
- Watch out, we're made nervous about enhancement, about calls to change or modify human nature or our children. We think that that is going to fall into the hands of people who would degrade and make us subhuman if we do these things."
So it's a message that I think is part of the general moral values that we heard about so much in the election. They are on display pretty clearly in the Council of Kass and his committee.
LEONARD LOPATE: Well, if scientists won't draw the line, shouldn't someone, a lawmaker or someone in tune with the cultural sensibilities of the time, be able to draw that line?
JULIAN SAVULESCU: No, no. The line is drawn at the well-being of people. You've got to remember that if we don't do the research people will die prematurely, they'll develop Alzheimer's disease and cancer. Moral values are wonderful things, and I'm all for respecting everyone's moral values, but people should never suffer harm as a result of moral values. And unfortunately, it seems to me, we have a situation here where moral values are costing people's lives and harming people.
LEONARD LOPATE: But weren't scientists sent a message by the public, at least some of the voters,who said in the last election, that opposition to stem cell research was one of the reasons they chose certain candidates?
JULIAN SAVULESCU: If the public really understood that their life or their child's life was the consequence of respecting these values, I think their views would change. The choice is not that obvious to them, it's not that stark. We're all in favor of human dignity, equality, and various moral values. They sound wonderful. They're motherhood and apple pie. But we have to remember that sometimes respecting these values has consequences. I don't want to see ten-year-old children dying of leukemia.
ARTHUR CAPLAN: You know, it's interesting. I might read the election slightly differently. For the most part, I think messages were sent about abortion, I think messages were being sent very clearly about gay marriage. But in the stem cell area California voted overwhelmingly to allow it. States like Illinois, Massachusetts, New Jersey, have been moving fast also.
LEONARD LOPATE: But they're all states that are called Blue states.
ARTHUR CAPLAN: Yes, those are Blue states. But if you look at the actual leanings in Congress, they shifted in the Republican Senate from "we're absolutely opposed to this" to almost fifty-seven senators now in the newly constituted Senate in favor. So education, discussion of the issue, did make a difference here. People began to say, "Wait a minute. If we have embryos and we're going to destroy them anyway at infertility clinics, then what are we talking about?" So it's possible to change their views.
LEONARD LOPATE: Well, doesn't it also matter whether it affects you personally? I don't know what Nancy Reagan's position was on stem cell research before her husband developed Alzheimer's, and for example, there's Senator Burton, who's very involved with autism issues because his grandson is autistic.
ARTHUR CAPLAN: In American politics nothing gets you moving like having an issue touch you. So Strom Thurmond, of all people, came out in favor of stem cell research because he had people in his family with diabetes. Yes, celebrity does make a difference. If Michael J. Fox and Christopher Reeve come onboard, in our society, media-driven as it is, that can swing the politics.
On the other hand, part of the reason I think that it's important to move away from some of what the Kass Committee has done is that they are using rhetoric to describe some of the things that people propose to do that isn't appropriate. Remember, there's no one in the United States who really is interested in reproductive cloning. But that forms a big part of this debate because it's a scare tactic relative to other issues like abortion.
LEONARD LOPATE: Like late-term abortion, which is very rare but has become a big issue in the abortion debate.
ARTHUR CAPLAN: Right, and a symbol of that.
LEONARD LOPATE: I understand that you're here to participate in a conference on bioethics?
JULIAN SAVULESCU: Yes. It's a conference looking at the possibilities of human enhancement in the future. I think probably the greatest ethical issue that we will face in the next ten or twenty years is how far can we radically modify the kinds of beings that we are. We have just seen the tip of the iceberg with Prozac and Viagra, but we are going to see many more opportunities to change fundamentally the way we are. The question is: how far should we go?
LEONARD LOPATE: Well, one of the talks yesterday was called "Do Civil Liberties Presuppose Roughly Equal Mental Ability?" How does that apply to what we're talking about?
ARTHUR CAPLAN: Well, if you're going to engineer people and give them different traits and properties, one of the things that people worry about is would you create an intellectual elite. It's like the old Aldous Huxley story.
LEONARD LOPATE: Brave New World.
ARTHUR CAPLAN: The Elois live up in the heavens and the workers are down in the caves. [Reference to The Time Machine by H.G.Wells.] Would everybody still retain their rights if we really got to serious engineering of biologically embedded differences? It's a real challenge. I think the answer has to be: yes, we must, or we better not go there.
You asked me earlier if I would give carte blanche. No. If people such as those with disabilities, or people who choose not to be engineered, can't have their rights guaranteed to vote and participate in civic society, because the geniuses, so to speak, would see them as unfit, that might be a reason to say, "Sorry, you can intellectually engineer 5 or 10 percent but we're not going to double, triple, quadruple that. It's going to be unmanageable for the kind of polity we want."
LEONARD LOPATE: But to what extent should we adjust our ethics and views on truth and morality to what's happening in science? Are we forced to change our ethical standards as science changes?
JULIAN SAVULESCU: Look, I'll give you an example. What scientists want to do in one area is take a skin cell from a cancer patient and take the genetic material from that and introduce it into a rabbit egg with its genetic material removed. That will go on and produce stem cells for the study of cancer and the testing of new anti-cancer drugs.
Now, this is therapeutic cloning. It involves nuclear transport, the cloning process. The living entity that you produce by mixing human genetic material with a rabbit egg will not produce the Easter Bunny or some kind of chimera or hybrid; it just produces cells and tissues. In no sense is it an embryo. So science now delivers up a new life form that challenges us to think about how we should view this entity and this kind of research. I think we should do it.
LEONARD LOPATE: But that would be called cell cloning, wouldn't it, as opposed to animal cloning?
ARTHUR CAPLAN: It would. What both the Kass Commission and a bill just put in by Senator Brownback of Kansas would call it is illegal. That is, you can't make any transgenic cell constructs mixing animal and human materials. I think, as Julian correctly points out, that's crazy because this isn't anything that can develop into anything other than interesting cells to study. But we have a lot of misunderstanding and fear-mongering about this.
LEONARD LOPATE: But this same Congress would support the biological engineering of crops. So is the bioengineering different in one or the other?
JULIAN SAVULESCU: It's worse than that. They support the development of bioweapons that will exterminate humanity. It seems to me crazy that scientists can't look into curing cancer but meanwhile we're engineering weapons of mass destruction.
I mean, push this case further. Science can also tell you that you can remove the remaining rabbit's genetic material and introduce human mitochondrial DNA so the cells will only have human DNA. So for a transient period they had some animal DNA but you could remove that. What's the problem with that? Yet, as Art said, that will still be illegal. We've got a crazy situation where our ethics has just been left behind by science.
ARTHUR CAPLAN: I was going to respond to your question about the plants. It's very interesting. Most of the critics of human engineering, human change, bioengineering of cells in dishes or of us as people, pay no attention in the U.S. context to the bioengineering going on in the plant world and the food world. There are some critics, but there are none in this Bush Council, none within the Administration, and very few in the Senate. Everybody is on-board for using genetic knowledge to make more money, more crops, better food.
I think what we're looking at is almost an implicit religious claim, that we are different from nature; we are sacred, but that other stuff is not.
LEONARD LOPATE: Could we make humans more ethical and moral through technology?
JULIAN SAVULESCU: There are certainly traits that contribute to the kind of people that we are that are going to have a significant genetic contribution. There is a recent study of voles, which are a kind of rat that live in the wild. The meadow vole is monogamous; the male only has one partner. The prairie vole, which is closely related to it, is polygamous; the male has many partners. If you introduce the gene from one part of the brain of the meadow vole into the prairie vole, it becomes monogamous.
LEONARD LOPATE: This could cause a lot of changes in southern Utah, for instance.
ARTHUR CAPLAN: Maybe the voles reflect the local population. We don't know.
JULIAN SAVULESCU: Now, some people might have a view on whether it's better to be monogamous or polygamous—I don't—but there will be characteristics that are quite complex, like our mating procedures, that will have a genetic contribution we can change.
LEONARD LOPATE: What about the economics of all of this? Are all of these developments reserved for people with the money to be able to afford them?
ARTHUR CAPLAN: I think that's a real issue. It's not an issue, however, about enhancement or improvement; it's a question about what's fair. You know, we send people off to special colleges; parents compete in Manhattan to get their kids into the best nursery schools. These are ways to improve our kids' cognitive performance that aren't fair. We haven't prohibited them yet. We can argue about whether we should.
But I think it may be important for society now to say, "Look, if we're moving into such fundamental things as enhancing intelligence or changing personality or modifying our memory, maybe that should be available to everyone as a guarantee of equal opportunity. I have no problem saying that. Do I believe that is going to happen? No. Do I think that we're going to be in a period where the rich have more than the poor? Yes. Was it ever thus? Yes.
LEONARD LOPATE: But it could even open a larger gap between the haves and have-nots.
ARTHUR CAPLAN: It could.
LEONARD LOPATE: And we mentioned Aldous Huxley earlier. We could have a situation in which the rich have engineered their children. They already have certain advantages. They could engineer them even further.
JULIAN SAVULESCU: It might well. But it's important to remember that nature does not deliver equality. We're all born with different genetic "haves" at birth. It may be that biological manipulations can correct that natural inequality.
If you look at a tangible example such as performance enhancement in sport, the use of human erythropoietin, or EPO, is very cheap, but it's illegal. However, the use of oxygen tents or hypoxic air tests costs around $10,000. American athletes can push up their red blood cell level using legal means which are very expensive, but other athletes from poorer countries can't use very cheap biological manipulations.
LEONARD LOPATE: They can even train in high-altitude situations and afford to go and live in those places for a long period of time, whereas others have to show up the day of the race.
ARTHUR CAPLAN: Again, I think the equity issue—two class standards, increasing disparity—is a real and immediate problem. I'm not even as worried about it in the U.K. or the United States as I am when we think about what's going on between us and Burundi and Malawi and places like that. I wouldn't be surprised to see attempts made by international treaty or convention, or perhaps even by threat of trade and so forth, to say, "You've got to make that technology available to us. It isn't right that you are having better children."
And we see it already. You know where we see it a bit now? It's in things like the demand to give us AIDS medicines and the demand to provide us with things that we just can't afford to battle malaria. We're starting to see those pressures. They're not biological engineering of our nature, but they are, if you will, biological supplements for therapy.
LEONARD LOPATE: Although the government just said, "Let's slow down on all of this because we're really not ready." I'm not sure whether we are or not, but the money definitely is not in place. And this is all very expensive, isn't it?
ARTHUR CAPLAN: Some is, some not.
JULIAN SAVULESCU: It may be cheaper. Look, I think to be human is to be better. Whether we can afford that is another question. But it's a question that applies to education, it applies to health care, and it applies to biological manipulation. There is no reason to single out for discrimination this area of scientific research, which is what is happening now.
ARTHUR CAPLAN: I'll give you an example where it may not be costly but it's a lot better. If you take vaccination for flu shots or against diphtheria, we are boosting our immune system from what it is naturally to something more. Is it expensive? Not really. It's actually pretty cheap. Have we organized ourselves enough to get it done? No. But the very idea here—laser surgery at the mall? Relatively affordable. You can improve your vision a lot. Not everything has to turn out to be expensive, although it usually expensive is. But it may be politically beyond us to get it done.
LEONARD LOPATE: We have to leave it there. I want to thank you both so much for participating in this part of our series of underreported stories. It has been a real pleasure.