今天早上，一个同事转来新闻，【1，2】说是比尔盖茨决定投资1千万美元给分子模拟软件公司薛定谔（ schrodinger.com ）。 无论如何，对于从事计算机辅助药物设计的同行们来说，这确实是个好消息，至少它对这个行业做了个很大的广告。 下面的文章【2】作者 Derek Lowe 多年来在美国制药公司从事药物化学的研究，他的博客信息量大，分析到位，非常受欢迎。 http://pipeline.corante.com/ 下面这篇就写得很好，值得阅读。 多年来比尔盖茨的基金会给医药研究投入很多钱，尤其是资助艾滋病和痢疾的研究，经常见到报道。 http://www.gatesfoundation.org/global-health/Pages/overview.aspx 希望不久看到比尔盖茨能够给美国的小型制药公司投资，因为这些公司往往建立在某个新型的技术平台上，积极地从事着新药的研发，它们也因此是很多大公司药物开发的项目来源。【通常小型制药公司把新药项目做到临床前研究，比如动物实验，然后和大公司合作，或者把知识产权转让给大公司，因为临床期间的耗费巨大，也需要很多人力资源，小公司没有能力做下去。】 参考 【1】 http://www.schrodinger.com/newsletter/14/87/ 薛定谔将如何花费那些钱？ First, additional resources will be allocated to existing projects that we view as critical, such as induced fit docking and scoring function development. Next, we will create novel tools for ADME prediction and modeling GPCRs , both of which will require major new research efforts with a long term commitment. Finally, we intend to develop a database of protein-ligand interactions , which will represent a significant advancement over currently available commercial products. 【2】 http://www.nature.com/news/2010/100507/full/news.2010.223.html Molecular modelling's $10-million comeback? Published online | Nature | doi:10.1038/news.2010.223 | Nature | doi:10.1038/news.2010.223 Is Bill Gates's decision to invest in software company Schrdinger an early sign of a new computer-aided era for drug design, asks Derek Lowe. Or is it just another small step on what's been a rather lengthy journey? Derek Lowe Computational drug design has always seemed like a good idea. Compared to traditional drug discovery, it seems to offer a way to soar over what can be a trackless swamp. Finding a lead structure from millions of possible drug molecules is no small undertaking in itself. And once found, turning such a lead into a plausible drug candidate is notoriously difficult. That level of success, though, merely buys you the chance to spend your real money in the clinic, where 90% of the compounds that go in never come out. Far better to sit at a keyboard in some quiet room, hit the 'run' button, and come back later for the answers. The greatest period of enthusiasm for this vision was probably during the late 1980s, when advances in both hardware and software put molecular-modelling technology into more hands than ever before. But the new converts soon found themselves up against a whole suite of challenging problems. The shapes of drug molecules, how they change in both the presence of water molecules and their protein targets, and the shapes of the proteins themselves all had to be dealt with. The act of 'docking' a drug candidate computationally into its target protein has to take all these factors into account, and fundamental problems remain. Even so basic (and crucial) a thing as the weak hydrogen bonds between atoms can be very difficult to model realistically. Then there's the dynamics-versus-statics problem: drug molecules and their binding targets never stop moving, folding and flexing. Modelling this realistically is hard, and increases the computational burden substantially. Billionaire investors Schrdinger, headquartered in New York and a respected company in the field, occupies an unusual niche. A number of other companies, such as their biggest competitor, Accelrys, based in San Diego, California, exist in the computational chemistry area. Unlike Schrdinger, however, very few have attempted to produce a broad range of computational products that attempt to address exactly the sort of problems listed above. Many other modelling-software vendors have left the field over the years, apparently because they could find no good way to make money at it. The Gates investment fits in well, making Schrdinger one of the few companies independently funded by two billionaires. Schrdinger, however, remains a private company, and in some ways is the most academic of the drug-discovery software vendors. It has had the benefit of a long relationship with David Shaw , a Wall Street investment manager with a scientific modelling background who has kept a hand in the area. In that sense, the Gates investment fits in well, making Schrdinger one of the few companies independently funded by two billionaires. The company does not release financial data, but has said that its revenues are somewhere above US$20 million per year. In that environment, a $10-million investment is substantial. The company is likely to use its extra dollars for long-term projects: given the complexities of molecular modelling, all meaningful improvements will probably fall into that category. One possible project would be to collaborate with industrial drug-discovery organizations to give the company's products continual real-world testing, with the results fed back to the programmers for further rounds of improvement. Patience pays For now, the dream of sitting down far away from all the flasks and the rats and coming up with a viable drug candidate let alone a viable drug remains just that. Molecular modelling has helped many drug-discovery programmes, and probably hindered others if the truth be told, but it has yet to cause drugs to appear where there were none before. And not all of the drug industry's biggest problems are amenable to computational solution . So if Gates (or those following his moves) are expecting dramatic changes, they're likely to be disappointed. But the things that can be computed are still important, and they could certainly be done much better than they are now. Is enthusiasm for computer-driven drug design on its way back to the peak of the late 1980s? Probably not but that's partly because people are in no mood to repeat that cycle of hope and disappointment. The Gates announcement more probably represents a realization that if computational drug discovery is ever going to reach the heights expected of it, then the journey is going to be a long one. And it will require money from people who are not expecting and do not need an immediate return. Derek Lowe works on drug discovery in the pharmaceutical industry. You can read more on his blog, In the Pipeline . http://pipeline.corante.com/archives/2010/05/10/bill_gates_put_some_money_on_schrodinger.php
比尔盖茨2010年4月23日在MIT Kresge Auditorium发表演讲后接受了The Tech（MIT报纸）的采访，讲述了他的慈善事业以及背后鲜为人知的故事。 In interview, Gates describes philanthropic journey Download this video (129MB; 480p H.264) （可以下载） 以下是比尔盖茨接受 The Tech（MIT报纸） 访问的 文本资料，请大家参考 As an ardent supporter of technology, Gates described his foundation as an innovation engine that takes risks and funds research, in addition to offering direct aid to the needy. Though some have criticized the Gates Foundation for investing its endowment in corporate polluters that harm the health of the people it seeks to aid, Gates said that it is the foundations positive actions that have real effect, not its investment practices. The Tech: So youve been on this three-day cross-country college tour, you spoke at Berkeley, Chicago, and youre wrapping up this afternoon at Harvard. Why are you doing this? What is the message youre trying to get out? Bill Gates: Well its an opportunity for me to learn. Im sitting down with scientist at each of the universities also Stanford and then just the questions I get, theyre very interesting. There are people: what are they worried about? You know, what are they disagreeing with? Or what do they see as an opportunity? But you know, were talking about what I call important problems and how we can get the best minds working on those problems. And Im congratulating universities like MIT. Youve done OpenCourseWare, youve got your energy initiative, you have a course on world poverty now, which is a fantastic thing. We have a lot of steps in the direction, but how do we ramp that up even more? Im starting a dialogue about that because I think it will make a huge difference to get minds like those who get to go to MIT even more involved. TT: Right, and the question that you kind of left unanswered during the talk is how does that happen? BG: Yeah, and I dont know the right answer. There are a lot of best practices that MIT and a lot of others have started, but what other ideas are there? And what are the barriers that hold people back? Is it awareness? Is it the economics? And how do we change it? TT: This morning, you met with faculty, and you saw some student projects from the PSC, and from D-Lab. What did you learn? What was really interesting to you? Gates: I saw lots of good projects, and I saw things that really relate to the developing world. What cheap reliable instruments should people have in clinics in the developing world? I saw people working on that. Theres some studies on malaria policies were trying out that students here are looking at the different varieties of how we might get the medicines out there in a better way. I saw six or seven projects, each of which I thought were quite strong. TT: Did anything surprise you? BG: Well, I had known those in advance. You know, theres some like how can we use the cell phone for health care things. You know, nothing has come out of that yet, and this idea of what really can work in these conditions verses whats the technology. That match up you know and I keep thinking about how we can make people more aware of what the needs are and whats practical because some of the ideas may not catch on. But there were really good ones. A lot of them had been out to really understand the tough delivery conditions. TT: Youve been on quite a journey, going from running Microsoft to chairing one of the worlds largest philanthropic organizations. What do you know now that you wish you had known when you were our age? BG: Well certainly I had no awareness of the depredations of poverty. I didnt really understand the health issues, I didnt understand the governance issues, the lack of infrastructure. It just wasnt a focus for me. I was doing software and fortunately that has had positive effects, but I wish I had been more aware; I wish I had been able to take a course like the world poverty course and know about vaccines and know what a magical intervention those are. TT: And having that knowledge, do you think your path would have changed? BG: Not my path in some dramatic way. I would have been giving money to these causes a little bit earlier than when I started really in 1999, the serious philanthropy. And I would have done more. Now some of these projects take a long time, like a malaria vaccine, so you want to get it going. And the research phase, the early phase, is not as expensive as the trial phases, so I feel good that I did in my forties even when I was still full time at Microsoft. I was lucky enough to bring some great scientists in. Then when I moved to full time, the foundation wasnt from scratch. We already had ten years of malaria vaccine work, and we already had a great staff of people, so I did some overlap but I would have done more of that. TT: Youve spoken a lot about the importance of innovation and of taking chances on high-risk, high-reward projects like the malaria vaccine but there are lives that can be saved right now with simple interventions like bed nets and irrigation, so where do you find that balance? BG: In terms of lives saved per dollar, there are a lot of things that we should be delivering, including some existing vaccines and new vaccines that we get here in the US Rotavirus and Pneumococcus all the kids in the US get those, but no kids in the developing world are benefiting from those, yet they have the disease pertinence, not, those things, arent as impactful in the medical environment that we live in. Those need to get out there. There are very few things that are as effective as vaccines. Bed nets are quite effective. Agricultural interventions are less about health but are more about nutrition which has this huge effect on learning ability and freeing up people from subsistence labor, just on small holdings. So the agricultural things there are some things there, but were going to have to invent to really make a dramatic difference. We cant just take the tools that we have today. Our foundation tends to fund more of the upfront discovery work, and were a partner in delivery, but governmental funding is the biggest. Take like delivering AIDS medicine: We did the pilot studies in Botswana to prove that you could deliver ARBs in Africa and then PEPFAR the US government program, which is five billion a year, which is way more than our whole foundation, just that one US government help program, just one country, came in and scaled up based on some of the lessons from that. With the vaccines, we fund, maybe fifteen percent. This government delivery system organization, whereas on the upstream, you know, malaria vaccine research would be a substantial percentage of that. So were playing to our strength, which is picking teams of scientists and sticking with them for over a decade a decade of failures and successes. TT: At Davos in 2008, you spoke of this idea of creative capitalism, which is your vision of corporations working to deliver innovations to those who need it, not necessarily just those who can pay. Could you explain how this works in practice? Some have said that this is an overly optimistic view of how business works. BG: Well certainly the large companies have responded quite well, and weve even done within industries an independent report that will take say the pharmaceutical companies and say are they doing good work in these areas. And thats been a spur for them to look a little bit. Were not saying that they should tilt all their activities. If we can get four percent to the best innovators working on these diseases that arent as remunerative, that can make a huge difference. And in many cases, that will be up from zero percent. So were not asking them to completely go against the economic incentives they live under. We want them to thrive and be successful, and its actually a little unfortunate that the drug industry discovery rate has been low these last eight years. So pharma budgets actually are going down. Now vaccines is a subset of that, and actually has gone well. Some of these new vaccines are quite profitable for these companies. We are seeing an increase in that, which is for many of our things, it is the magic piece. TT: Right, because this is sort of the same message that youre sending to students as well, isnt it? BG: Right, so this creative capitalism is the message at the institutional level for businesses. And what I was talking about today is to get individuals to think about what motivates them: what would have drawn them in, why is it that these issues have appealed to them or have not appealed to them. And we need that individual interest in doing these things and then those institutional opportunities. So creative capitalism will let the people go out and get a great job and work on these things. And you really want those things to be in balance. You know, I wouldnt want the pharma companies to say Hey, nobody wants to work on this stuff. Thats not the problem. I think the institutional side will be a limiting factor. TT: Your foundation has an endowment of over 33 billion dollars is it important to you to invest that money in socially responsible corporations? For instance, the LA Times reported in 2007 that some of the money for the foundation is invested in papermills and oil companies that pollute and harm the health of the people that youre trying to benefit. BG: Yeah, we actually have securities from a country thats at war we have US treasury securities in our foundation portfolio. Oh, its awful. You know, those guys, they polluted, theres a lot of things I think theyve done wrong. Now in terms of have we sort of decided to set up a judicial system that decides which car company, which oil company that kind of duplicates the laws of the various countries. No, we were not doing that. We dont invest in Sudan, and we dont invest in tobacco companies and things like that. But when you take your resources and say okay I want to score companies, you have to say are you saving lives? If, take for example, the fact we dont invest in tobacco companies: I would not claim to you that that has any effect at all. Now we fund anti-tobacco, anti-smoking things in a big way. We encourage the taxes to go up in China, they did that; were funding all these things in Africa. Thats where you save lives. The fact that we put our capital in those companies, you know some people might not feel good about it, but it doesnt save...thats not where it is. No, we have not created this scoring system saying should we own those treasury securities? or not. Our expertise is in vaccines, its in education, and its in working with companies to get them to put energy in. In terms of getting corporations to be positive agents of change, Id say weve done more of that than anyone. And they respond quite well, and thats a million times more powerful per dollar then setting up this scoring system of where we put our money; we wouldnt have any direct effect there. In egregious cases, yes, but in general, thats not our role. Thats more of a governmental role. 资料源： http://tech.mit.edu/V130/N21/gates/interview.html
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