STEM CELL WARS will be in U.S. bookstores on September 19, 2006. It will be released in the UK, Europe and Australia in January 2007. Preorder today on Amazon.com or Amazon.co.uk.
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Question: Can you explain embryonic stem cell research in basic terms? Why it is important?
EH: There’s a vast range of diseases and conditions that involve the degeneration and death of cells in the body. For example, in diabetes, the insulin-producing cells of the pancreas are lost, and in Parkinson’s disease, the brain loses the specialized cells that make dopamine. There are about 200 cell types in the human body, and all of them are vulnerable to disease or injury. The idea behind stem cell research is to be able to replace the cells that are being lost to a disease or even a traumatic injury like a spinal cord injury or a stroke.
This research is really critical because, for most of the diseases that stem cell research has the potential to treat, there currently is no cure. Most of these diseases are chronic, degenerative conditions, many of them fatal, that doctors try to manage. These include heart disease, diabetes, ALS, multiple sclerosis, cancer, Alzheimer’s, Parkinson’s disease, lung, liver and kidney disease, and many more. These conditions all have something in common—they involve the loss of some specialized cell type that the body simply can’t replace. If we could replace sick and dying cells with healthy news ones, we could stop the disease in its tracks. This is where stem cell treatments could bring about a medical revolution—by replacing the actual cells and permanently curing the disease.
Question: Why isn’t it possible for adult stem cells to replace the need for a certain number of embryos, at least for the time being?
EH: As everyone knows by now, the field has been riddled with controversy over which types of stem cells should be used in research. There are political and religious groups who have been saying that adult stem cells, taken from the human body, can do everything that embryonic stem cells, taken from a very early-stage embryo can do. This is simply not backed up by science. There has been a lot of research on adult stem cells, and rightly so, because they do seem to have some healing potential. And they’ve been very successful at treating some blood diseases. The problem is that they’re quite limited compared to embryonic stem cells. So far, scientists have found that adult stem cells can give rise to only a limited number of other cell types. On the other hand, embryonic stem cells are the “master” cells of the human body. They are pluripotent, meaning that can give rise to any of the body’s 200 cell types, so they can treat many more diseases. And embryonic stem cells are much easier to identify, cultivate and grow in the lab—you can produce huge numbers of them from one embryo. It’s very hard to isolate and grow enough adult stem cells to make a dent in an advanced disease.
Question: What about all the talk about taking adult cells and “reprogramming” them or converting them into embryonic cells?
EH: This is a very active area of research. To try to put an end to the controversy over using early-stage embryos in research, many scientists are trying to find a way to return adult cells, taken from a patient’s body, and return them to a pluripotent state. So far, no one has found a way to “reprogram” adult cells and come up with normal cells, except through the use of therapeutic cloning. The irony is that groups opposing embryonic stem cell research want to have their cake and eat it, too. They want to ban embryonic stem cell research and at the same time find ways to return adult cells to an embryonic state. Yet to figure out how to do that, scientists have to go to the source of pluripotentcy—to embryos—to find out what conditions make a cell pluripotent in the first place. Another very important reason to do embryonic stem cell research is because these cells contain a treasure trove of information about developmental biology, and about how diseases develop from their very beginnings.
Question: How much information reaching the American public about stem cell research is actually misinformation? Where is the misinformation coming from, and what is the most outlandishly false myth about stem cell research that has been accepted as truth?
EH: There is a tremendous amount of misinformation, coming mainly from right-wing, social conservative groups like the Family Research Council, Concerned Women for America, The U.S. Council of Catholic Bishops, and right-to-life groups like the American Life League. The most outlandish myth that they’ve been able to plant in people’s minds is that embryonic stem cell research is predicated on abortion, that it actually requires abortions so that scientists can conduct experiments on late-stage fetuses. They use over-the-top language like “fetus farming,” and “growing fetuses so scientists can harvest and use their body parts.” This is outrageous. It’s science fiction. Embryonic stem cells don’t come from aborted fetuses—they come from microscopic eggs that have been fertilized in a lab dish. There’s no pregnancy, no fetus, no baby, just cells in a dish. The fact that these early-stage embryos, in their first few days of cellular division, will never be implanted into a womb means that their chance of developing into a baby is zero. People have a right to object to the research if it troubles them, but it is inaccurate to link embryonic stem cell research with abortion.
Question: What about people who consider themselves pro-life? Can they still be in favor of embryonic stem cell research?
EH: I think that saving lives by curing disease is about as pro-life as you can get. And also, many people who are strongly pro-life are in favor of embryonic stem cell research, because they know it could proceed full speed ahead without there ever being another abortion. Another irony here in the U.S. is that our federal government funds fetal tissue research, yet it has imposed crippling restrictions on funding to do research with left-over IVF embryos that are just going to be thrown away as medical waste. The knowledge that could be gained from using those embryos in research could help save millions of lives, but our current policy is that it’s more acceptable to discard them than to use them in research.
Question: It is estimated that 3,000 Americans die each day from conditions that stem cell research might end up curing. Why isn’t this enough to persuade George W. Bush to allow American scientists to proceed with their stem cell research?
EH: I can’t say what goes on in the president’s mind, but I do know he is beholden to the social-conservative groups that helped elect him. If you look at his approval ratings right now, and the fact that moderate Republicans seem to be distancing themselves from him, you might guess that his extreme right-wing base is more critical to him than ever. This is even more evident when you consider that the recent stem cell research bill that the president vetoed had the support of not only Democrats, but many prominent Republicans as well. By vetoing the bill, which would have allowed research on additional frozen embryos that were already slated for destruction, the president came down on the side of the most far-right extremists. What the president was really saying through his veto was that it’s better to throw excess embryos away than to use them in life-saving research. President Bush claims that he is pro-life, but he has consistently placed the importance of microscopic cells in a lab dish far above any consideration of the millions of real, suffering patients.
Question: In STEM CELL WARS you say that stem cell research has been hijacked by the politics of abortion. What do you mean by that?
EH: Human embryonic stem cells were first isolated in 1998, when the right-to-life movement was at a critical juncture. Groups that wanted to ban abortion had had a lot of success in restricting abortions, but with the makeup of the Supreme Court at that time, they knew they couldn’t overturn Roe vs. Wade outright. Despite all their incremental successes, their ultimate goal has always been a 100% ban on abortions. So they’ve also had a long-term strategy: to focus on defining the fetus at any stage as a person. Obviously, taking the life of a person is considered murder, and if the fetus could be legally defined as a person, abortion would have to become illegal. At the same time, new technologies were pushing the envelope. The RU 486 pill, which came along in the late 1980s, could terminate a very early pregnancy, so anti-abortion groups adapted their language to include protection of the embryo.
Meanwhile, the emergence of in-vitro fertilization threw everyone a curve ball. All of a sudden you had embryos existing outside of a woman’s body, where no pregnancy could be said to exist. But right-to-life groups had already become entrenched with an absolutist view of the embryo—that it is just as fully human, and has exactly the same rights, as you or me. Soon right-to-life groups started saying that fertilized eggs in a lab dish are “human beings.” I think they took this position partly because they had to in order to be consistent, and partly in order to strengthen their hand, to bring about a ban on abortion from the moment of conception onward.
Question: Why has this particular form of medical research gotten caught up in the conflict of science vs. culture?
EH: Opposition to embryonic stem cell research is not just about people confusing it with abortion. There is a lot of unease these days about how fast science is moving into uncharted territories. Powerful new technologies, such as stem cell research, genetic modification and nanotechnology, which are coming within our grasp, could profoundly impact human life. People are concerned about the dangers of unintended consequences, and also about the possible misuse of new technologies. This is a legitimate concern, and is why scientists themselves are calling for more U.S. government funding for embryonic stem cell research. With government funding comes a whole package of rules and regulations that are designed to prevent a wide range of possible abuses. I think everyone agrees that we are dealing with a field that has special sensitivities, and like every other technology ever invented, it has the capacity to be misused. But we shouldn’t let our fears over some hypothetical “what ifs” overshadow an intelligent, ethically sensitive exploration of life-saving science. In my view, ignoring the science that could potentially save millions of lives and radically improve millions of others would be truly unethical.
Question: Stem cell research will play a major role in the November elections. What effect will President Bush’s July 2006 veto of the Stem Cell Research Enhancement Act have on the political campaigns from both parties? Are there any states with stem cell proposals on the ballot this November?
EH: One thing is for sure: President Bush didn’t do Republicans any favors by thumbing his nose at the 70% of Americans who wanted to see the Act become law. Democrats have become really energized around this issue, and they are bringing it to the foreground in several House and Senate races. In Wisconsin, Governor Jim Doyle, who is very pro-stem cell research, is using the issue as a major part of his platform in his bid for reelection. The issue is also going to be prominent in the Governor’s race for Maryland. All over the country, pro-research Democrats and moderate Republicans are holding their anti-research opponents’ feet to the fire on this issue, because they know the people want to see it go forward. In Missouri, there will be a line item on the state ballot giving voters a chance to choose whether they want their state to fund all types of stem cell research. There’s no doubt that stem cell research will play a very prominent role in the November elections.
Question: What do you think is the long-term effect of the president’s veto?
EH: I think the summer of 2006 and the presidential veto of the Stem Cell Research Enhancement Act marked a turning point when politicians could no longer ignore the fact that the vast majority of Americans want this research to go forward. There is a rising groundswell of support for the research, and for the millions of patients who could benefit from it. In the past, patients have had very little representation in the stem cell debate. For a while they had no one to connect them with what was happening in the research labs of academia and in the halls of Congress and the Senate, to make sure that their needs were paramount. But there are over 100 million chronically ill people in the U.S., and they are very angry about their plight having essentially been ignored in all the policy-making of the last six years. Now we have a few organizations, and the Genetics Policy Institute is one of them, to help bring these patients together into a movement. We call it the pro-cures movement. You wouldn’t think that Americans would have to fight so hard for something as basic as their right to benefit from the most advanced research in the world today, but they do. It’s a sad commentary on today’s political landscape.
Question: You traveled to Seoul, Korea for the opening of the World Stem Cell Hub and met with Dr. Woo Suk Hwang, who was then the world’s foremost cloning expert. While you were there you walked though his labs and witnessed some of their research projects. What did you learn about cloning while you were there?
EH: First of all, I was amazed to see what a superstar Dr. Hwang was in his own country. It’s impossible for us Americans to imagine a research scientist having such celebrity status. But in Korea, Dr. Hwang was like having Michael Jackson, Bill Gates, Einstein and Elvis all rolled up into one person. He became a national icon, a symbol for Korea’s future as a world leader in biotechnology. The whole country was enthralled by his supposed accomplishments, and this unbridled fame no doubt contributed to his downfall.
One thing I did learn from touring his lab is that the Koreans really were making strides in cloning technology, or at least were well positioned to do so. Their claimed specialty in the way of gently removing the nucleus from an egg cell, which is less damaging than earlier methods, was real. I saw this being done in front of my eyes (on a magnified video monitor) in Dr. Hwang’s lab, when a researcher took an egg cell, poked a hole into its outer membrane, and then gently squeezed it until the nucleus popped out. Before this method was developed, researchers would suction the nucleus out, which inevitably removed some of the cell’s cytoplasm, or the material floating around outside of the nucleus. There’s a reason for that cytoplasm to be there, and keeping as much of it intact as possible probably contributed to the lab’s great success in cloning animals.
Question: What is the difference between cloning and stem cell research?
EH: This is another area where there’s a lot of confusion and unfortunately, a lot of misinformation. When most people use the word “cloning,” they mean making an entire copy of an animal or a person. This is what scientists call reproductive cloning. In the last few years, quite a few animals have been cloned, including sheep, cows, cats, mice and even a horse. But no reputable scientist is interested in reproductively cloning human beings, and this not the kind of cloning that stem cell scientists are interested in. The kind of cloning that is relevant to stem cell research is therapeutic cloning, sometimes referred to as nuclear transfer.
Question: What is therapeutic cloning?
EH: Any time you transplant cells into a patient’s body, they have to be genetically matched, just as transplanted organs do. Otherwise, there is a risk of rejection. Therapeutic cloning is the only way known to create embryonic stem cells that are a sure match for the patient. It involves taking an egg and removing its nucleus, as I described before, and then fusing the egg with an adult cell, usually a skin cell taken from a patient. The nucleus of the skin cell, which contains the patient’s DNA, then becomes the nucleus of the egg cell. The egg is activated to begin dividing and as it does so, it creates embryonic stem cells that carry the patient’s DNA. This means that brand new, pluripotent, “master” stem cells are being created that are the best possible match for that patient. Genetically speaking, they are “his” cells, returned to an embryonic state. From these master cells, scientists should be able to create any kind of cell the patient needs to cure his disease, with very little chance of rejection. It’s like making more of your own cells—your own personalized “cellular pharmacy” to replace those that a disease has destroyed.
Question: You returned to Korea when Dr. Woo Suk Hwang was faced with scandal over his research practices. How had things changed in Korea since your last visit?
EH: The change in the atmosphere from when I had been in Korea for the opening of the World Stem Cell Hub was dramatic. Not only that, the emotional tenor kept changing on a day-to-day basis, as the Koreans started to understand that they had a serious problem on their hands. The mood at the opening of the Hub was one of tremendous elation. The Koreans were so proud of the strides they were making in therapeutic cloning research that you couldn’t help but be swept up in their optimism. Everyone believed that Dr. Hwang and his research team were going to make Korea the world leader in stem cell research and hence, a leader in biotechnology.
But on my second trip, which was right after allegations were made of improprieties in obtaining human eggs for research, it was as though someone had flipped a switch and all the scientists were plunged into a state of severe anxiety. There was also a considerable amount of confusion on the part of some of Dr. Hwang’s colleagues at Seoul National University and SNU Hospital. Apparently, most people were taken completely by surprise. The international press were all over the story, and the Koreans were in such a state of confusion that they had no plan for how to handle the crisis. Many of the scientists on Dr. Hwang’s research team seemed especially troubled. There was a terrible sense of foreboding, and it was only later that it all made perfect sense. At one point, I sat down with Dr. Hwang and asked him about the egg donations and the accusations that they had been made improperly, about who did what, when. He gave me a trajectory of events that made it sound as though his only mistake was not coming forward sooner and admitting that some of his own researchers had donated eggs. But one couldn’t help noticing that Dr. Hwang, throughout the investigations, was strangely silent and distant. About a week later, he did his first press conference on the issue. I’ve never seen such a mob of reporters in my life, all crammed into a room at Seoul National University Hospital. Dr. Hwang made essentially the same statement he had given me, but at the same time, without explicitly saying so, he seemed to be confessing to some guilt and apologizing for a much greater crime than he had admitted to. He alluded to a “great shame” that he had brought on himself, but it didn’t seem justified just by not admitting sooner that some of his own researchers had donated eggs. I was sitting in a room full of scientists and employees from the World Stem Cell Hub watching it on a live broadcast. People were so devastated to see their hero in that situation that they wept.
Question: What was it like being inside Dr. Hwang’s labs after the press conference?
EH: Immediately after his puzzling confession, Dr. Hwang simply disappeared. The hospital announced that he had gone to a Buddhist monastery to meditate and cleanse himself spiritually. But then it was like another switch was thrown, and the mood at the university and the hospital became very dark. The hospital attorneys took control of the situation, and there was suddenly a circle-the-wagons, bunker-like mentality. In fact it was because of this, and because of the intimidation of certain investigators, that I began to suspect that there really was a much bigger problem than anything Dr. Hwang had explicitly admitted. When I thought about it, there was only one logical conclusion to explain the way these officials were acting—that there was something wrong with Dr. Hwang’s scientific data, and in his claims of having created the world’s first therapeutically cloned stem cells. After I left Korea, I stayed in touch with a fellow investigator there as the rest of the story unfolded. Some of the things she told me in confidence contrasted starkly with some of the news reports, and only confirmed that, from that time on, Dr. Hwang was taking part in a carefully choreographed charade to hide the real truth.
Question: How did the accusations against Dr. Hwang affect stem cell research across the globe?
EH: As shocked as the world was over Dr. Hwang’s fabrications, I don’t think that in the long run it has hurt the field in a big way. Other researchers are now striving to be the world’s first to clone human stem cells. But it does mean that the enormous breakthroughs that Dr. Hwang claimed, in creating patient-specific embryonic stem cells, have not been made. It’s a sad thing for all the patients who got their hopes up that there would be cures coming sooner rather than later. And it was a very sad thing for Koreans. There are many honest, extremely hardworking scientists in Korea, and it is to their credit that they’re the ones who really exposed the fraud, by examining Dr. Hwang’s published data. I still have a lot of affection for the Korean people and admire their industriousness. I think their scientific community will recover, but they have learned some hard lessons.
Question: Where does the United States rank in terms of stem cell research advancement when compared to other countries?
EH: The U.S. has been in a political quagmire over the issue of embryonic stem cell research. Unfortunately, for the duration of the Bush administration politics has trumped the need for legitimate, life-saving research. During the past six years, scientists have been leaving the country to go to Britain, Singapore, and other countries where they can get funding to do the research. Since the end of WWII, the U.S. has been the world leader in biomedical research, but with the current policy, that is rapidly changing. The number of scientific papers being published by American scientists in this field is going down, while in several other countries, the number is going up. In addition to that, there’s evidence that many the brightest foreign students in science are no longer being drawn to American universities. They naturally want to go to countries where they can do the most cutting-edge research, where they can get government grants to do it, and where there’s a career awaiting them. The U.S. is falling behind on so many levels, but the upshot is that American patients will have to wait longer to receive the cures derived from embryonic stem cell research than the patients in countries where the first treatments are developed. And in a worst-case scenario, some treatments (those based on therapeutic cloning) may not become available to American patients for a very long time because of political opposition.
Question: What does this mean for the future of medical research in the United States?
EH: I think it’s a dangerous precedent when you take decisions about what research should be done out of the hands of scientists and place it in the hands of politicians and religious extremists. This is a radical turnaround from the way the United States has always handled research. Many people are unaware that the U.S. government funds the vast majority of research in this country, and this is why we’re the world leader. But scientists don’t work in a vacuum, they are part of a scientific community that does a pretty good job of policing itself. In addition to that, our government and our universities have evolved some very sophisticated ways of overseeing research. This system has worked very well. It has brought us quite a few life-saving breakthroughs. It’s disturbing that some politicians want to return us to an age when scientific advancements were suppressed because they didn’t agree with some people’s religious views.
Question: What about those who claim that there are some “rogue scientists” out there who only want to clone people?
EH: The way our system works, if there are any rogue scientists out there who want to do that, they will be working completely outside of the system anyway. Passing laws to restrict legitimate research, as some groups want to do, will not affect any “outlaw” scientists at all—it will only hurt legitimate scientists who are simply trying to find cures for disease.
Question: Do you see this as part of an anti-science trend in the U.S.?
EH: There’s no question that a majority of Americans are very supportive of biomedical research. But there is now an increasingly vocal minority that is very alarmist and unnecessarily suspicious of scientific advances in general. I’m disturbed by what I see as a real backlash against science in this country, among some politicians and some highly outspoken political groups. There’s outrageous rhetoric on the floor of the U.S. Congress and the Senate that blatantly demonizes scientists. This is unfair to the vast majority of research scientists, who are engaged in some of the most humanitarian work one could choose—to help cure humanity of terrible diseases. Furthermore, the United States has evolved an elaborate system of regulation and oversight that comes along with the federal funding of research. It isn’t perfect, but so far it has been very effective. Essentially what we say to scientists is, in order for the government to fund your research, you have to play by certain rules. You have to meet certain standards. And because the vast majority of scientists depend heavily on federal funding, they have a huge incentive to play by the rules. One of the greatest ironies of the Bush policy is that he has driven most of the stem cell research into the private sector, and outside of government oversight, where it truly could be abused.
Question: Can you explain the concept behind “bankruptcy by disease”? What effect will the stem cell debate have on the future of disease in this country?
EH: This is one of the shameful secrets of the American health care system—that despite insurance, a health crisis can easily send a family into bankruptcy. There was a shocking study done by a group at Harvard in 2005 showing that more than half of all bankruptcies are caused by high medical bills that people are unable to pay. This situation doesn’t exist in any other industrialized country—because every other industrialized country has nationalized healthcare. The American system is seriously broken. Americans pay far more per capita for their health care than patients in any other country, yet our population is less healthy than the populations of many other countries. And I’m talking about the people who have insurance. Millions of Americans are underinsured, which means that if they have a true health crisis, they can be stuck with enormous bills, and at least 45 million Americans have no insurance at all. They just have to live with their illness, until they reach the crisis stage and end up at the emergency room. By then the cost of helping them is often dramatically higher than it would have been if they had had early medical intervention. The cost of treating these patients is then passed on to all of us. It’s incomprehensible to me that there isn’t a massive effort going on to reform the American health care system before the baby boomers reach old age. As it is, with the current rates of chronic disease and disability growing by the day, our lack of ability to institute a more humane, effective and cost-efficient system of health care is incredible.
Question: How does this tie in to stem cell research?
EH: It’s the economic side of why cutting-edge medical research like stem cell research is so critical. Because with the aging of the population, the rates of disease are now threatening to drain the economy like never before. There are a lot of promising areas of research going on now, but none of them have the paradigm-shifting potential of stem cell research, because stem cell research can apply to such a huge number of diseases. The benefits of coming up with cures for many of our most devastating conditions seems to me an economic imperative as well as a humanitarian one.
All too often, something critical is left out of the endless discussions about whether a clump of cells in a Petri dish is a person. And that’s the fact that there are millions and millions of real, living people who are sick, who are suffering, and they need our help. They need to be cured, and current medicine isn’t able to do that for them. In my view, the need is urgent. Millions of people are dying each year who perhaps don’t have to die, and millions more are disabled who might be living better, more productive lives. I have a chapter in the book about this, which I call Health Care and Hypocrisy, because we have a lot of politicians who claim to care about sick people, yet they’ve voted against the most promising biomedical research of our lifetime.
Question: You’ve outlined seven questions every woman should ask herself before going forward with any type of IVF treatment. What are those questions and why are they so important?
EH: Many people don’t realize that once they’ve completed the IVF process—either had all the children they want or given up on the process—that there are likely to be embryos left over. This means that the woman or couple must make some critical decisions about what to do with these remaining embryos.
There are four possible choices for what can be done with leftover embryos: they could be donated to other couples who are trying to have a child; they could remain frozen indefinitely; they can be disposed of as medical waste; or, they could be donated for research. President Bush has very obviously supported the first option—donating embryos to other couples who will become surrogate parents to them. Everyone is in favor of this, but there’s a huge problem—very few people want to donate their embryos to other couples, and very few couples want to “adopt” other people’s embryos, especially when they can have their own genetic children. To give you an idea of the scale of the problem, there are approximately 400,000 frozen embryos sitting in IVF clinics, and only about 100 so far have been “adopted.” Meanwhile, thousands of these embryos have been donated to research, but they aren’t being used in that way because U.S. scientists are forbidden the funding to work with them. Nevertheless, any woman or couple entering into the in-vitro fertilization process should ask themselves the following questions:
“If I donate my embryos to another couple, how would I feel about having someone else raise my genetic child?”; “Am I comfortable with the idea of disposing of my unused eggs or embryos?”; “How would I feel about having my eggs or embryos used in medical research?”; “Can I afford to maintain them in their frozen state (about $2,000 per year) while I make up my mind?”; “What would I do if one of my embryos was found to have a genetic defect?”; and last but not least, “What would I want to happen if my partner and I separate before using all of our embryos?” It’s a lot to think about.
Question: Many people are afraid about advancements in stem cell research because they are worried that stem cell science can possibly be abused. Do you have a message for them?
EH: My message to them is that they are right to be concerned and to be vigilant. Science is indeed crossing frontiers that we couldn’t even imagine a generation ago. Regenerative medicine, including stem cell research, is likely to dramatically extend our life spans. How will society cope with people living 15 – 20 years longer than they do today? How can we make sure that the benefits of cutting-edge research reach all the people who need them, worldwide? And how can we make sure that no women are exploited for their eggs, or that gene-based cures that wipe out a certain disease don’t introduce other problems? There are no guarantees in science just as there are no guarantees in life. But to try to put a stop to medical progress because we can’t foresee each and every possible outcome in advance is not only irrational, it is in my view unethical. We are faced with the problem of millions, perhaps billions, of people worldwide who are sick and suffering. We have a moral imperative to face up to the challenges, to do the work, to tackle the ethical issues. But above all, we can’t shirk our duty to try to improve the state of human health just because some of the issues are unprecedented. There have always been unprecedented issues in science, and their always will be. It’s inherent in the very nature of progress.
And last, if you think about it, just about any technology can be abused. People can use cars to run over people, but we haven’t banned cars. People have used airplanes to fly into buildings and commit mass murder, but we haven’t banned airplanes as a result. Because most of the time when a technology is abused, the problem is with the people, not with the technology. Now if you could cure the human conditions that cause people to do such things, then you really would have accomplished something.
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