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Tuesday, September 30th, 2014
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3 Questions: Jim Walsh on the elusive U.S.-Iran nuclear treaty Can the U.S. and Iran reach a permanent agreement to restrict Iran’s nuclear program? For several months, the countries have operated under an interim agreement limiting Iran’s activities, but it expires this fall. MIT will host a public event on the topic this Tuesday, Sept. 30, from 7-9 p.m. in the Stata Center’s Room 32-155, co-hosted by the Technology and Culture Forum at MIT. The forum features Jim Walsh, a research associate in MIT’s Security Studies Program and an expert in international security and nuclear nonproliferation. MIT News spoke with Walsh about the prospects for a deal.
Q. What is the status of U.S.-Iran negotiations right now, as you see them, with the expiration of the interim agreement just two months away?
A. I think we’re both very close and far away at the same time. There has been a very successful interim agreement in place, where all the parties have fulfilled their commitments. Iran stopped producing 20-percent-enriched uranium and eliminated the stockpile it had accumulated, and implemented the verification measures in the agreement. So that’s been working very, very well.
In addition, the negotiators appear to have made progress on some of the very tough issues — the Arak heavy-water reactor, the Fordow underground enrichment facility, the issue of monitoring. I’d say there are two main sticking points as we enter the final lap; one is fairly solvable, and the other is solvable in principle, but holding up a final agreement.
The issue that is resolvable … relates to Iran’s behavior in the past. It had a nuclear weapons program, according to U.S. intelligence, from 1998 to 2003, and then shut it down. But as part of the process of resolving a nuclear dispute, there has to be some accounting for those past activities. We’ve had to do this with South Africa, Iraq, South Korea, and Egypt, and my guess is we will resolve this. Those who oppose diplomacy want Iran to get down on their knees and publicly admit to everything they did, and that is just not going to happen, but it didn’t happen in the other cases, either, and I think they’ll find some resolution to that.
That leaves the major issue of the size and contours of Iran’s enrichment program — in particular, its centrifuges. The U.S. position has been that 1,500 centrifuges [can remain in Iran] … there’s no way that’s sustainable politically in Iran. Iran has about 20,000 centrifuges, of which it operates about 10,000. So their proposals of late have hovered in the 7,000 to 10,000 range.
That gap has very little to do with nonproliferation. … It’s the politics back home, in Washington and Tehran, that’s making this last issue difficult.
Q. So how can each side settle on some number of centrifuges and sell it politically?
A. The negotiators on both sides have told me that if it were left up to the negotiators, they’d have a deal already. As with all things political, it’s going to come down to the leaders and whether they have the political will to accept the deal and then win support for it.
There is a burden on President Obama. The reality is, there are people in the U.S. Congress who don’t want any negotiated agreement with Iran. And no matter what the deal is, they’re going to oppose it. My own view is, trying to get an agreement they’ll support is fool’s gold; that’s never going to happen. And so at some point you just have to say, “This is a good agreement, and I’m going to go out and sell it.”
The political advantage with an agreement in hand shifts to the president. He can say, “Look, I have this. It’s not just me, it’s Britain, France, Russia, China, this is the international community, we’ve come up with an unprecedented agreement, and if you vote against it, that’s a vote for taking us down a path toward war.” Because if there’s no agreement, Iran’s program will now be unconstrained and they can build all the centrifuges they want. … The U.S. will respond with sanctions, and the result will be Iran’s program will grow and then you’ll hear calls for military action.
So I think the president with an agreement in hand has the advantage, if he is willing to get out and lead on it. But that’s the calculation both President Rouhani and President Obama have to make. My own sense is they will get this done, and then there will be a tremendous battle in each capital.
Q. So your view is not to let the perfect be the enemy of the good, when it comes to nonproliferation?
A. As someone whose core scholarly interest is in the reasons why states who start down the nuclear path stop and reverse course — 30 countries have [done that], three times the number that became nuclear-weapons states — I can tell you this is a moment of opportunity that, if it passes, we may not ever get back.
The [U.S.] Director of National Intelligence has publicly testified that as it stands today, Iran has not yet made a decision to build nuclear weapons. And so Iran is at a crossroads. An agreement constrains their program, changes the politics within Iran, and has a chance of putting this whole issue on a different trajectory. But if you lose that opportunity, that will help the hardliners and bomb advocates in Iran, and we will end up in a very different place.
The history of nonproliferation and arms control agreements demonstrates clearly that you don’t need a perfect agreement to have success. The nuclear Non-Proliferation Treaty (NPT) of 1970, in my view the single most important factor in explaining success in nonproliferation, changed the internal politics within states. The treaty has no enforcement mechanism, and the original verification measures were very weak by today’s standards, but they got stronger over time. The NPT was not perfect, but it was effective.
So I don’t think it has to be a perfect agreement with Iran; it has to be good enough. An agreement would likely change the political relationship between Iran and the U.S. as well as the domestic policies within Iran. Rouhani’s status would improve, giving him credibility and the ability to move forward with his vision for Iran. Yes, the numbers [of centrifuges] are important, but they’re not as important as people would think, because agreements are really about political relationships. | | 12:00a |
High-speed drug screen MIT engineers have devised a way to rapidly test hundreds of different drug-delivery vehicles in living animals, making it easier to discover promising new ways to deliver a class of drugs called biologics, which includes antibodies, peptides, RNA, and DNA, to human patients.
In a study appearing in the journal Integrative Biology, the researchers used this technology to identify materials that can efficiently deliver RNA to zebrafish and also to rodents. This type of high-speed screen could help overcome one of the major bottlenecks in developing disease treatments based on biologics: It is challenging to find safe and effective ways to deliver them.
“Biologics is the fastest growing field in biotech, because it gives you the ability to do highly predictive designs with unique targeting capabilities,” says senior author Mehmet Fatih Yanik, an associate professor of electrical engineering and computer science and biological engineering. “However, delivery of biologics to diseased tissues is challenging, because they are significantly larger and more complex than conventional drugs.”
“By combining this work with our previously published high-throughput screening system, we are able to create a drug-discovery pipeline with efficiency we had never imagined before,” adds Tsung-Yao Chang, a recent MIT PhD recipient and one of the paper’s lead authors.
Peng Shi, a former MIT postdoc who is now an assistant professor at the University of Hong Kong, is the paper’s other lead author.
Fish on the fly
Zebrafish are commonly used to model human diseases, in part because their larvae are transparent, making it easy to see the effects of genetic mutations or drugs.
In 2010, Yanik’s team developed a technology for rapidly moving zebrafish larvae to an imaging platform, orienting them correctly, and imaging them. This kind of automated system makes it possible to do large-scale studies because analyzing each larva takes less than 20 seconds, compared with the several minutes it would take for a scientist to evaluate the larvae by hand.
For this study, Yanik’s team developed a new technology to inject RNA carried by nanoparticles called lipidoids, previously designed by Daniel Anderson, an associate professor of chemical engineering, member of the Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science, and an author of the new paper. These fatty molecules have shown promise as delivery vehicles for RNA interference, a process that allows disease-causing genes to be turned off with small strands of RNA.
Yanik’s group tested about 100 lipidoids that had not performed well in tests of RNA delivery in cells grown in a lab dish. They designed each lipidoid to carry RNA expressing a fluorescent protein, allowing them to easily track RNA delivery, and injected the lipidoids into the spinal fluid of the zebrafish.
To automate that process, the zebrafish were oriented either laterally or dorsally once they arrived on the viewing platform. Once the larvae were properly aligned, they were immobilized by a hydrogel. Then, the lipidoid-RNA complex was automatically injected, guided by a computer vision algorithm. The system can be adapted to target any organ, and the process takes about 14 seconds per fish.
A few hours after injection, the researchers imaged the zebrafish to see if they displayed any fluorescent protein in the brain, indicating whether the RNA successfully entered the brain tissue, was taken up by the cells, and expressed the desired protein.
The researchers found that several lipidoids that had not performed well in cultured cells did deliver RNA efficiently in the zebrafish model. They next tested six randomly selected best- and worst-performing lipidoids in rats and found that the correlation between performance in rats and in zebrafish was 97 percent, suggesting that zebrafish are a good model for predicting drug-delivery success in mammals.
“The ability to identify useful drug delivery nanoparticles using this miniaturized system holds great potential for accelerating our discovery process,” Anderson says.
“The lipidoid material screen is just an example demonstrated in this article; a similar strategy can be readily extended to other libraries or other organ systems,” Peng adds.
Jeff Karp, an associate professor of medicine at Harvard Medical School who was not part of the research team, says this work is “an excellent example of harnessing a multidisciplinary team to partner complementary technologies for the purpose of solving a unified problem. Yanik and colleagues, who have extensive expertise with high-throughput screening in zebrafish and other small animals, have teamed up with Anderson et al., who are leading experts in RNA delivery, to create a new platform for rapidly screening biologics and methods to deliver them. This approach should have utility across multiple disease areas.”
New leads
The researchers are now using what they learned about the most successful lipidoids identified in this study to try to design even better possibilities. “If we can pick up certain design features from the screens, it can guide us to design larger combinatorial libraries based on these leads,” Yanik says.
Yanik’s lab is currently using this technology to find delivery vehicles that can carry biologics across the blood-brain barrier — a very selective barrier that makes it difficult for drugs or other large molecules to enter the brain through the bloodstream.
The research was funded by the National Institutes of Health, the Packard Award in Science and Engineering, Sanofi Pharmaceuticals, Foxconn Technology Group, and the Hertz Foundation. | | 12:00a |
Studying time makes this philosopher tick We all know that time passes — or so it seems. But what do we think time is really doing? Is it moving by us? Standing still as we wade through it? Our inability to resolve this question is revealed by the indirect way in which we discuss the subject.
“When you ask people, ‘Tell me about the passage of time,’ they usually make a metaphor,” says Brad Skow, an associate professor of philosophy at MIT. “They say time flows like a river, or we move through time like a ship sailing through the sea.”
The subject gets more complex when we consider that in the theory of relativity, time is just one dimension of a universal fabric we call spacetime. Yes, things change and people age, but relativity implies that points in time are locationally different, in some sense, rather than whizzing past us and vanishing from the universe forever.
In philosophy, this view is called the “block universe” theory of time. Over the last several years, after spending a lot of time thinking about time, Skow has come to regard the block universe concept as the best way we have of describing time’s essence.
“If you could look down on the universe, you would see things spread out in time as you would see the universe spread out in space,” Skow says. “You could see that things are one way at earlier times and different at later times, but you wouldn’t say the universe as a whole is changing.”
Of course, that creates a tension with the way we experience time, with a past, an ever-changing present we inhabit, and a future. In philosophical terms, one position according to which the present is special is known as the “moving spotlight” theory, which holds that the property of being present moves over time. Yet even this theory falters, Skow believes.
“I think that the moving spotlight is metaphysically extravagant,” Skow explains. “It’s got this extra mysterious thing — ‘objective presentness’ — that moves around. I wouldn’t want to believe in that unless I saw good arguments for it.”
Many of Skow’s writings have examined the contours of the moving spotlight theory to see if it can hold up to scrutiny; unsatisfied that it can, he has become a proponent of the block universe theory. Skow has now published widely in his field, having produced many journal articles as well as a book, “Objective Becoming,” due for release in January by Oxford University Press. For his research and teaching, Skow was awarded tenure at MIT earlier this year.
Straight out of SLO
Skow grew up in San Luis Obispo, a small city in the hills of central California, close to the ocean. “It’s beautiful, it’s near the beach, the weather is perfect, it’s got this neat downtown,” Skow says. “There’s a beautiful farmers’ market with all this incredibly good produce.”
Nevertheless, Skow headed off to Oberlin College for his undergraduate studies, and soon declared an English major. As it happens, one semester Skow decided to take a philosophy course in existentialism, since it overlapped with some of his literary interests. However, the existentialism course required that students take at least one other philosophy class first.
“I took a philosophy class, and then I started taking more philosophy classes,” Skow says. Before long, he had become a double major, in English and philosophy. “I actually never ended up taking the existentialism class,” Skow recalls.
As is so often the case with successful scholars, some direct encouragement from a professor helped give Skow a needed dose of confidence. “I had a philosophy professor who told me I was good at philosophy,” Skow says, referring to Daniel Merrill, now an emeritus professor at Oberlin.
Before long, Skow landed in the graduate program in philosophy at New York University, where he started “procrastinating” about finding a dissertation topic. In his case, that didn’t mean wandering the streets of Greenwich Village — but rather, diving into relativity theory, for fun. Eventually Skow’s advisor encouraged him to take up the topic as his thesis.
“It turns out I had been pursuing this project in the philosophy of time but I didn’t know it,” says Skow, whose dissertation was on the philosophical implications of spacetime.
As a newly minted PhD, Skow taught for two years as an assistant professor at the University of Massachusetts at Amherst — “I loved it there” — but soon had the chance to move to MIT.
“Everyone on the faculty here was one of my favorite philosophers,” Skow says. “It was too good an opportunity to turn down.”
Philosophy for curious physicists
In seven years at MIT, Skow has also busied himself teaching, frequently offering introductory undergraduate courses on the philosophy of science, where he dives into other topics that are as tough as time — such as the status of scientific laws, or the relationship between philosophy and quantum mechanics. Besides philosophy students, Skow’s classes attract many physics and mathematics majors.
“They know a lot of quantum mechanics,” Skow notes, adding that his students “tend to be very curious about questions they don’t have time for” in their science classes.
As a tenured professor, Skow says, he would like to build more bridges to the sciences, to produce additional intellectual crossover running in both directions — so that scientists engage in philosophical thought, and philosophers ground arguments in science when appropriate.
“I think it’s as important for philosophers to know some physics as it is for them to know some [formal] logic,” Skow says. “Maybe more important.”
That certainly bears on Skow’s research into time: The essential equations of physics, as is well known, make no reference to the objective passage of time. And because science does not regard time as a moving part, as it were, thinkers such as Skow find it more compelling to join the block universe camp in the philosophy debates, rather than the moving spotlight side of things.
“Contemporary physics doesn’t need to use the objective passage of time to explain anything,” Skow says. Still, we all need philosophers to examine the rest of time’s intricacies. |
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