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</o:shapelayout></xml><![endif]--></head><body lang=EN-US link=blue vlink=purple><div class=WordSection1><p class=MsoNormal>An introductory overview:<o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p class=MsoNormal><a href="http://hplusmagazine.com/2011/05/31/open-cures-an-initiative-to-speed-clinical-development-of-longevity-science/">http://hplusmagazine.com/2011/05/31/open-cures-an-initiative-to-speed-clinical-development-of-longevity-science/</a><o:p></o:p></p><p class=MsoNormal><o:p> </o:p></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>You may recognize me as the author-slash-editor of</span><span class=apple-converted-space><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'> </span></span><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><a href="http://www.fightaging.org/" target="_blank"><b><span style='color:#C96905'>Fight Aging!</span></b></a>, a long-running news and advocacy site focused on progress towards reversal of aging and engineering longer human lives. There is more to progress in the general sense than just the underlying science, however, and with that in mind I recently announced the launch of</span><span class=apple-converted-space><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'> </span></span><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><a href="https://www.opencures.org/" target="_blank"><b><span style='color:#C96905'>Open Cures</span></b></a>, a volunteer initiative with the aim of greatly speeding up the development of clinical applications of longevity science. Participation is open to anyone who can help with the goals listed in the</span><span class=apple-converted-space><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'> </span></span><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><a href="https://www.opencures.org/roadmap" target="_blank"><b><span style='color:#C96905'>Open Cures roadmap</span></b></a>: for example, we’re presently looking for life science writers and people familiar with the medical tourism industry, amongst others.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>But why, in this age of biotechnology and accelerating progress, it is even necessary to build an organization to help speed matters along? What is the roadblock that stands in the way of the clinical development of longevity-enhancing biotechnology?<o:p></o:p></span></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The Biotechnologies of Longevity, Undeveloped</span></strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>When we look at work on aging and longevity in the laboratory, we can see that more than a dozen ways to use biotechnology to extend the lifespan of mice have been demonstrated over the past decade. About half of those methods appear to lack serious side-effects, delivering only longer lives, lower cancer risk, improved health and vigor, and little else. Similarly, a range of laboratory demonstrations conducted since the turn of the century have reversed specific, measurable biological changes that occur with age in mice: damaged mitochondrial DNA replaced throughout the body, the function of cellular garbage collection mechanisms restored to youthful levels in liver tissue, and so on. We live in an era of rapidly improving biotechnology – and it is delivering the goods, in the laboratory at least.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>But there is one common theme to all of these advances: none are undergoing further development for clinical use in healthy humans for the purpose of slowing or reversing degenerative aging, and thereby extending healthy life span. Why is this? You would imagine, given the size of the market for medicine, that a hundred start-up biotech companies would be leaping upon these opportunities, giving rise to an era in which “anti-aging” fakes and frauds finally start to fade away in favor of a market built upon true rejuvenation science. This is not happening, however, as there is a gargantuan roadblock that stands in the way.<o:p></o:p></span></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The Nature of the Roadblock</span></strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>In the US, where much of the research most directly relevant to engineered longevity takes place, this roadblock is called the FDA: the Food and Drug Administration. Appointed FDA bureaucrats have absolute control over the commercial deployment of medical technology in the US: only those technologies formally approved by the FDA can be sold for clinical use. Further, the FDA only approves a new medical technology for narrow usage in treating a specific, defined disease in a specific, defined way. Obtaining even this narrow approval is a staggeringly expensive process. For one, that list of diseases changes only very slowly, and an entire industry of lobbyists exists solely to try to add new medical conditions to that list – burning money that would better used for research and development.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Consider sarcopenia, for example, the characteristic age-related loss of muscle mass and strength. Sarcopenia was first named as a distinct condition a decade ago or so, and expensive efforts have been ongoing for some years to convince the FDA to add it to the approved list of diseases. There seems little prospect of this happening any time soon, however, and so the lobbying efforts continue. There are potential therapies for sarcopenia, or at the least the scientific basis for potential therapies that might prove useful in humans, but little to no private funding to further develop these leads – as there is no market on which to sell any resulting treatments. Even if a storybook industrial philanthropist turned up tomorrow to devote his entire net worth to pushing through development of a therapy for sarcopenia, it would still be illegal to offer the resulting medical technology for human use in the US.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Aging itself as a medical condition is in the same boat. Aging is not a disease, per the FDA – and therefore, no one is legally permitted to treat aging in humans with biotechnology in the US. The present state of the lobbying game, as illustrated by the situation for sarcopenia, is that it will take years and millions of dollars in to carve off one tiny component of aging and have FDA bureaucrats grudgingly allow commercial development to proceed. Thus what comparatively little development of longevity science does take place – such as work on sirtuins and other possible calorie restriction mimetics – sees applications of the underlying research shoehorned into treatments for late-stage diseases of aging, whether it fits or not. Even if successful, the resulting therapies will not be legally available for use by healthy or younger people for the purposes of treating aging itself.<o:p></o:p></span></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The Mirage of Reform<o:p></o:p></span></strong></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><o:p> </o:p></span></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Numerous organizations and advocates (such as</span><span class=apple-converted-space><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'> </span></span><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><a href="http://www.fastercures.org/"><b><span style='color:#C96905'>FasterCures</span></b></a>, for example) have been trying for years to reform the FDA, or at least make it less obstructionist – to try to make it possible for new therapies to emerge without the stifling costs in years and hundreds of millions of dollars, or to emerge at all where they are not recognized by the FDA. These initiatives are all failing: over the course of time that they have been active, and despite the funds and efforts poured into them, the FDA has only become worse, approving fewer and fewer new technologies, and continually raising the bar and the cost for approval. The fundamental incentives that shape the actions of FDA political appointees are these: they suffer very few problems due to medical technologies that are suppressed or denied approval, but take a great risk to their career in approving any new application of medicine or biotechnology. The rest of this undesirable state of affairs unfolds from that basis – bureaucrats will follow their incentives, regardless of the harm it causes.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Meanwhile, the years pass, funds are consumed by political processes rather than being spent on actual research, and we’re all getting older – our bodies slowly sabotaged by the processes of aging.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>All in all, working with the FDA is not a game that we win by playing. A system so entrenched and badly broken cannot be reformed through existing channels, and efforts to change it by playing within the rules do little but provide the FDA with additional legitimacy. The only way to win here is to refuse to play the game, and take an entirely different approach – which brings us back to Open Cures, which is exactly that: an entirely different approach to the roadblocks put in the path of development by the FDA and its counterparts in other highly regulated countries.<o:p></o:p></span></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The Rise of Medical Tourism</span></strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>I’ll restate the primary challenge: that it is illegal to commercially offer medical treatments for aging in the US, and based on the lack of progress in effecting change to date, this situation will persist for the foreseeable future – regardless of how much money and effort is expended on lobbying within the system. In turn, that the clinical application of longevity science is forbidden means that there is little to no investment available to develop laboratory demonstrations into therapies. Thus the most promising and advanced biotechnologies shown to extend life or reverse specific biochemical aspects of aging in mice languish unexplored and undeveloped.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Yet if we look beyond America and Europe, we see regions in which clinical development of therapies based on cutting edge science is both possible and less restricted. To pick one example, stem cell therapies that will not be commercially available in the US for years yet have been offered for a number of years by responsible, skilled groups in China, Vietnam, Thailand, and other countries. You might look at Beike Biotech or Vescell, for example. It should make American citizens of a certain age sad that China has become an example of freedom outshining the US in any field of endeavor – not sad for the Chinese, but sad for what has become of medical development in America.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>This is a shrinking world we live in. Air fares are cheap, tourism growing, and the internet links together cultures, movements, and businesses ever more efficiently with each passing year. When the cost of travel is low compared to the cost of newly available medical technologies, we see the growth of medical tourism. Clinical development will occur wherever capable institutions exist and local law permits it, and patients will travel from restricted regions like the US to receive treatments that are not available at home.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Medical tourism is a growing business in the US precisely because forbidding and regulating medical development is also a growth concern: medicine is only expensive and unavailable because bureaucrats make it that way. Medical tourism is still a comparatively young industry, however, feeling its way and largely focused on a few major and well-known fields of medicine (such as the early therapeutic uses of stem cell transplants). It is far from the case that people are taking advantage of the full range of cost-savings and possibilities, and this is due in part to all the standard challenges inherent in establishing important business relationships across a great distance.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>When you stop to think about it, however, you’ll notice that all of these problems are well solved for traditional tourism – even where comparatively large sums of money are involved, such as in the much maligned timeshare business. People comfortably travel great distances and expect to rely on critical services at their destination: this works because intricate, long-standing industries of communication, organization, and education make that possible. It will one day be the same when people routinely travel to obtain medical services from far removed locations.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Now consider this: there is no technical barrier to, for example, clinical development of a way to replace all damaged mitochondrial DNA in humans – the basic technology has existed, demonstrated in mice, for six years. The work is published, fairly well known in the small part of the field where it matters, and were it made into a therapy there would be tens of thousands lining up to pay for it. Yet in countries where it is both possible and legal to move ahead with that commercial development, and where there is already an established, albeit nascent, medical tourism industry, that development has not yet happened. Why is this?<o:p></o:p></span></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>A Material Role for Open Biotechnology Movements</span></strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>When it comes to the passage of information, we do not live in a frictionless world. Scientists and medical development groups in widely separated regions do not in fact necessarily have good insight into the work of their far-removed peers, or even know that the work exists in the first place. They are separated by distance, culture, and language – far less so than in the past, thanks to the internet, but separated nonetheless.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The effects this has on a given field of research and development are a matter of degree: smaller fields are more affected than the larger ones, as more researchers, more funding, and more public interest means more transmission of information. Aging research and longevity science is not a very large field, as it happens, at least not in comparison to stem cell medicine or cancer research – and you can see the difference that makes in cooperation and organization across national boundaries in the resulting levels of medical tourism. The relationships for development and transmission of knowledge that exist for stem cell research, to pick one example, dwarf those developed for longevity research. Thus you don’t see clinical projects outside the US and Europe that are analogous in scope and ambition to those that presently take place in the field of stem cell medicine.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>But all is not doom and gloom: I do not expect the gaps in the transmission of knowledge to last. Institutions and cultural forces will arise to close these communication gaps, and they will arise from present-day open biotechnology movements. These movements are still young and small, but very similar in aims and ethos to the open software engineering cultures that first formed in the 1970s in the US: information and designs are freely shared, there is an emphasis on moving the ability to produce significant products out of the ivory tower and large institutions, and the result is a massive body of work that greatly lowers the barriers to entry for hobbyists and professionals alike. Software development, once an arcane art practiced only within large organizations and universities, became possible as a garage industry, and then as a hobbyist activity – which in time gave rise to a vast breadth of knowledge and practice, a staggering pace of innovation, and a community of developers that has grown in size and sophistication by leaps and bounds.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The last 40 years in the culture of developing software is a snapshot that will be repeated for the next 40 years in the development of biotechnology. Costs of equipment and processes will fall, garage developers and hobbyists will come to greatly outnumber institutional professionals, and the pace of innovation will accelerate dramatically. On the way to that end result, open biotechnology movements (such as the DIYbio groups) will play an important role in bridging the communication gaps that exist between life science professionals and clinical developers in different parts of the world.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>How will this happen? Consider that in software development today, there are no secrets and no specialty so small that it doesn’t have a hundred skilled observers in the broader open community – watching, talking, and tinkering on their own time. When an important new advance arrives, it will be echoed around the world, dissected, analyzed, and evaluated. The best new strategies rise to the top very rapidly indeed exactly because the community is very large. Unfortunately, this state of affairs is not yet realized for biotechnology and the life sciences, but that is only because the open community of demi-professionals and hobbyists is still comparatively small. It won’t remain small for many more years, however, and as the community grows, it will become increasingly unlikely that any promising biotechnologies will remain buried in scientific papers, undeveloped.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>So in short, it is my conjecture that the present scientific demonstrations that might possibly be applied to extend life or reverse aspects of aging in healthy humans go undeveloped because they haven’t been brought out into the open by a community of thousands: they haven’t been discussed, picked over, buffed up, and presented far and wide in overseas regions where provision of clinical therapies for aging is not illegal. This process would happen as a matter of course given a much larger open development community associated with the biotechnology industry, but until that community arrives, a helping hand is needed.<o:p></o:p></span></p><p style='margin:0in;margin-bottom:.0001pt;line-height:15.75pt'><strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>Information and Relationships: the Role of Open Cures</span></strong><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>And here we come to the point of the exercise: the reason for Open Cures. The high-level goal of the Open Cures initiative is to produce the communication, examination of research, and relationship building in longevity science that would naturally emerge from a larger open biotechnology community – but which is nowhere in evidence today, and will not arrive on its own for a long time yet.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The foundational items on the Open Cures to-do list are as follows:<o:p></o:p></span></p><p class=MsoNormal style='margin-left:0in;text-indent:-.25in;line-height:15.75pt;mso-list:l0 level1 lfo1'><![if !supportLists]><span style='font-size:10.0pt;font-family:Symbol;color:black'><span style='mso-list:Ignore'>·<span style='font:7.0pt "Times New Roman"'> </span></span></span><![endif]><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>- Establish a repository of how-to documentation for longevity-enhancing biotechnologies demonstrated on mice in the lab, with sufficient detail and explanation to make it comprehensible and useful for garage biotech groups, DIYbio practictioners, and overseas developers.<o:p></o:p></span></p><p class=MsoNormal style='margin-left:0in;text-indent:-.25in;line-height:15.75pt;mso-list:l0 level1 lfo1'><![if !supportLists]><span style='font-size:10.0pt;font-family:Symbol;color:black'><span style='mso-list:Ignore'>·<span style='font:7.0pt "Times New Roman"'> </span></span></span><![endif]><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'><o:p> </o:p></span></p><p class=MsoNormal style='margin-left:0in;text-indent:-.25in;line-height:15.75pt;mso-list:l0 level1 lfo1'><![if !supportLists]><span style='font-size:10.0pt;font-family:Symbol;color:black'><span style='mso-list:Ignore'>·<span style='font:7.0pt "Times New Roman"'> </span></span></span><![endif]><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>- Establish a network of relationships with the open biotechnology community, overseas developers, and the movers and shakers who are building the medical tourism industry rooted in the US.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>That might not seem like much, but we stand at a fulcrum point in the growth of three large movements: regulation of medicine, medical tourism, and open biotechnology, all driven in their changes by accelerating technological progress in computing and biotechnology. The initial Open Cures projects are a lever for that fulcrum, a foundation for the construction of lasting bridges between researchers who discover and demonstrate the biotechnologies of engineered longevity and overseas development groups who can translate that science into new medicine for clinical use.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>The bottom line is that the groundwork for a range of potentially life-extending therapies exists already, and the development groups legally able and capable of turning this science into therapies exist already: something must be done to bring these two sides together, and ensure that they build further ties for future development. If this were a better world, therapies built upon replacement of mitochondrial DNA would already be emerging, today, for example – there is no technical reason why that could not have been the case. That this has not happened is a challenge of people and organization: regulation, relationships, fundraising, the transmission of knowledge and experience.<o:p></o:p></span></p><p style='mso-margin-top-alt:12.0pt;margin-right:0in;margin-bottom:12.0pt;margin-left:0in;line-height:15.75pt'><span style='font-size:10.0pt;font-family:"Tahoma","sans-serif";color:black'>My vision for the future of Open Cures is a long-term process of growth in establishing a self-sustaining community around the process of rescuing longevity science from its current fate: discovered and published, yet unheralded and undeveloped for use. This is analogous to the long-term vision of the SENS Foundation, which is as much about the development of a culture and community of longevity research as it is about the development of true rejuvenation biotechnology capable of repairing the biochemical damage of aging. When the scientific research of SENS is complete in its first phase, perhaps twenty years from now, we want to be living in a world in which potential biotechnologies of longevity are routinely and eagerly developed into clinical applications, no matter where they were initially researched, and no matter what destructive games the regulators and bureaucrats have found to play.<o:p></o:p></span></p><p class=MsoNormal><o:p> </o:p></p></div></body></html>