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53 www.hplusmagazine.com At first blush, the idea might seem farfetched. But there's a good chance this system, or something like it, will actually be in place within decades. For starters, as mentioned above, every T cell and B cell expresses a unique receptor that recognizes a very small piece of a foreign structure from viruses or bacteria, such as proteins. Advances in recent genetic technology have made it possible to reprogram B cells, directly or through stem cells, to produce antibodies against parts of viral or bacterial proteins. Similarly, a new clonal army of T cells that are genetically engineered to recognize parts of a virus or bacteria would help the B cells produce potent antibodies against soft spots of these viruses and other pathogens that would otherwise neutralize or kill them. Already scientists at Caltech, headed by Nobel laureate David Baltimore, have engineered stem cells that can be programmed into B cells, which produce potent antibodies against HIv. Meanwhile, cancer researcher Steven Rosenberg at NIH has been engineering clonal T cells capable of recognizing tumors and transferring these cells to patients with a skin cancer called melanoma. His work has shown promising results in clinical trials. Together, these results could lay the groundwork for a new future, in which relevant antibodies and T cell receptors are directly downloaded, rather than indirectly induced. Of course, many challenges remain. The first is to be able to better understand the pathogens themselves: each has an Achilles' heel, but we've yet to find a fully systematic way of finding any given pathogen's weakness, a prerequisite for any system of immunity on demand. It will also be important to develop structural models to artificially create the antibodies and T cell receptors that can recognize these regions. Eventually, as computational power continues to grow and as our structural biology knowledge increases, we may be able to design artificial vaccines completely in silico. For now, this is more dream than reality. The real obstacle, however, is not the creation or the manufacture of protective antibodies against pathogens, but the delivery of those antibodies or cells into the body. Currently the only way to deliver antibodies into the body is difficult and unreliable. One needs to isolate stem or immune cells (B and T cells) from each individual patient and then custom-tailor the receptors for their genetic backgrounds, a process that is far too expensive to implement on a mass scale. Stem cells, nonetheless, do offer real promise. Already it seems plausible that in the future, bioengineers could create new stem cells from your blood cells and freeze them until needed. If there were to be a deadly new virus, bioprogrammers could design the potential immune receptors and genetically engineer and introduce them into your stored stem cells, which can then be injected into your blood. Eventually it may even be possible to deliver the immune receptor genes directly into your body, where they would target the stem cells and reprogram them. All this is, of course, a delicate proposition. In some ways, an overactive immune system is as much of a risk as an underactive one: more than a million people worldwide a year die from collateral damage, like septic shock after bacterial infection, and inflammations that may ultimately induce chronic illness such as heart disease and perhaps even cancer. Coping with the immune system's excesses will require advances in understanding the precise mechanisms of immune regulation. This fine-tuning of the immune response could also have the bonus effect of preventing autoimmune diseases. We are not sure when this will all happen, but there's a good chance it will, and perhaps the only question is when. There was a great leap forward in medicine when sterilization techniques were first implemented. Here's to the hope that the fruits of information technology can underwrite a second, even bigger leap. Derya Unutmaz is an Associate Professor of Microbiology and Pathology at N.Y.U. School of Medicine. His current research is focused on understanding the function of human immune system. Gary Marcus is an author and a Professor of Psychology at NYU. His most recent book is Kluge: The Haphazard Construction of the Human Mind. CytotoxiC t Cell Virus infeCted Cell Killing of infeCted Cell e n g i n e e r e d t C e l l r e C e p t o r r e C o g n i z i n g V i r u s a n t i g e n Spanish Flu, 1918 http://www.mc.vanderbilt.edu/reporter/index.html?ID=6621 David Baltimore: Engineering Immunity Against HIv and other Dangerous Pathogens http://www.grandchallenges.org/cureInfection/challenges/ImmunologicalMethods/Pages/hIV.aspx Steven Rosenberg http://bethesdatrials.cancer.gov/investigator-profiles/default.aspx?investigatorid=84 Reactive Reasoning, Scientific American http://www.scientificamerican.com/article.cfm?id=reactive-reasoning Is Chronic Inflammation the Key to unlocking the Mysteries of Cancer? http://www.scientificamerican.com/article.cfm?id=chronic-inflammation-cancer resources at first blush, the idea of immunity-on-demand might seem farfetched immunity-on-demand might seem farfetched