<p>Former MIT economics professor Eric S. Maskin and former graduate student Mario R. Capecchi were among the recipients of the Nobel Prizes in Economics and Medicine this year, respectively. </p>
<p>Maskin taught at MIT from 1977 to 1984 and returned as a visiting professor from 1999 to 2000. He is currently at Princeton Universitys Institute for Advanced Study. </p>
<p>Maskin shared the prize with Leonid Hurwicz and Roger B. Myerson for having laid the foundations of mechanism design theory, according to the Foundations Web site, which explains that the theory models collective decision-making in the allocation of resources. One of the applications of his research has been in the auction-style sale of government assets to the private sector, Maskin said in an interview with the Foundation. His work has influenced areas outside of economics such as regulation, corporate finance, and the theory of taxation, according to material on the Web site.</p>
<p>Capecchi came to MIT as a graduate student intending to study physics and mathematics, The Belfast Telegraph reported. While at MIT, he became interested in molecular biology and subsequently transferred to Harvard to join the lab of James D. Watson, co-discoverer of the structure of DNA with Francis Crick. In his interview with the foundation, Capecchi called Watson a fantastic mentor.</p>
<p>Capecchi shared the prize in Medicine with Sir Martin J. Evans and Oliver Smithies for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells. Gene targeting has made genetically-modified mice an indispensable part of an experimenters toolkit, according to the Foundations Web site. It allows scientists to create mice with mutations in any desired gene, enabling them to evaluate the function of any gene, according to Capecchis lab Web site.</p>
<p>More information on the prizewinners can be found at http:// nobelprize.org/nobel_prizes/.</p>
<p>All due respect and regard to the Nobel Foundation and the recipients of it's awards.</p>
<p>How does introducing gene modifications to mice pertain to humans? I have no doubt that these three brilliant men not only figured out what genes to modify but how to modify them to stimulate the predicted phenotypes. This is an act of brilliance. But how does this bring us closer to the more humanistic goals of the biological engineer?</p>
<p>I do not expect a definitive answer but it is the first question that popped into my head. So by all means, any who will, broaden my view point.</p>
<p>Gene modifications of mice allow you to test the affects of a particular gene and its associated transcribed proteins. For example, one coculd say that protein A (transcribed from gene A) is responsible for the elevation of protein B, which has been associated with Alzheimers. Scientists could knock out (essentially remove) gene A and see if protein B is still expressed and if the affects of Alzheimers are still there. In short, it allows you to determine the role of a particular protein in a physiological process. </p>
<p>Mice are a model for humans. We could have "knockout humans" as well, but obviously ethical implications prevent us from using this.</p>
<p>"But how does this bring us closer to the more humanistic goals of the biological engineer?"</p>
<p>The gene modifications are really not about advancing genetic engineering. They are just one tool to illustrate the physiological (and pathological) role of certain proteins.</p>
<p>And demonstrating this role not only encourages the study of these roles of genes but also you could say, the genes of the mouse are a test tube for further research.</p>
<p>I did not mean to doubt the accomplishment of Capecchi, Evans and Smithies.</p>
<p>
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Capecchi is credited with developing a powerful technology known as gene targeting. This technology has allowed scientists to engineer mice with conditions such as cancer, heart disease, Alzheimer's disease, cystic fibrosis, and high blood pressure—a feat that has revolutionized the study of human disease. </p>
<p>Gene targeting allows scientists to manipulate the genetic material of mice with amazing precision to create desired mutations in virtually any gene. By controlling the way a gene's DNA sequence is modified, researchers can completely disrupt—or “knock out”—the function of a gene or modify its activity. Refinements in the technique over the years now enable scientists to restrict a particular genetic modification so that it affects only certain tissues or occurs only during certain stages of life... </p>
<p>Capecchi credits the venerable James D. Watson, co-discoverer of the DNA double helix and his Ph.D. advisor at Harvard University, for inspiring his development as a scientist. “He taught me not so much about how to do science but rather provided me with the confidence to tackle any scientific question that fascinated me, regardless of its complexity,” said Capecchi. “He also taught me the importance of communicating your science clearly and to pursue important scientific questions.” (Howard Hughes Medical Institute, 2007)
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</p>
<p>Now how did they use embryonic stem cells to do this I wonder?</p>
<p>When you make a knockout mouse, you introduce the disrupted copy of your gene into mouse embryonic stem cells. You then select stem cells which have your disrupted gene copy integrated into the genome (often, you replace the coding sequence of your gene with an antibiotic resistance gene), and inject those cells into a mouse blastocyst. </p>
<p>The resulting baby mice will (ideally) be chimeras -- they will be half normal and half ES-cell-derived. Often researchers will inject ES cells from a mouse with a certain coat color (eg black) into a blastocyst of a different coat color (eg white) -- this way, you can tell which ones are the chimeras. They look like little zebras.</p>
<p>(Is that clear at all? I can definitely clarify if necessary.)</p>
<p>And I'll throw in my two cents that knockout technology is, without hyperbole, the greatest tool in biology today.</p>
<p>I think it's better than siRNA, particularly now that we have the technology to do conditional knockouts. It can be obscenely tough to convince people (and by people, I mean my PI) that the effects you're seeing from an si are specific and not just off-target.</p>
<p>I do hesitate to say that knockouts are a better tool than PCR, particularly because making targeting constructs and doing genotyping rely almost exclusively on PCR. (But at least, I suppose, Capecchi et al are sane, which is more than I can say about Kary Mullis.)</p>
<p>So perhaps it was a little bit of hyperbole. :)</p>