Innovation
Using bacteria as medical robots
Does the idea of turning bacteria into cancer-fighting robots sound like science fiction? Maybe today, but not in a near future. A researcher at the University of Massachusetts Amherst has received a four-year grant of more than $1 million from the National Institutes of Health to study the feasibility of the idea. So far, he has used Salmonella as 'tiny terminator robots that use their own flagella to venture deep into tumors where conventional chemotherapy can't reach.' When they reach the tumors, the bacteria will deliver drugs trigging cancerous cells to kill themselves. Right now, the experiments have been successful with mice, but it will take years before such a treatment might become available for us. But read more...
Does the idea of turning bacteria into cancer-fighting robots sound like science fiction? Maybe today, but not in a near future. A researcher at the University of Massachusetts Amherst has received a four-year grant of more than $1 million from the National Institutes of Health to study the feasibility of the idea. So far, he has used Salmonella as 'tiny terminator robots that use their own flagella to venture deep into tumors where conventional chemotherapy can't reach.' When they reach the tumors, the bacteria will deliver drugs trigging cancerous cells to kill themselves. Right now, the experiments have been successful with mice, but it will take years before such a treatment might become available for us. But read more...
You can see above a picture of one of the bacteria used for this research project, the Salmonella typhimurium -- which causes typhoid fever -- floating in the human blood stream. (Credit: National Research Council (NRC), Canada; link to a larger version). And obviously, you can learn more about Salmonella on Wikipedia.
This research project is led by Neil Forbes, an assistant professor of Chemical Engineering and the members of his research group.
Here is how bacteria are used. "'When we get the Salmonella bacteria into the part of the tumor where we want them to be, we've programmed them to go ape,' says Forbes. 'We have the bacteria release a drug to trigger a receptor in cancer cells called the 'death receptor,' which induces cancer cells to kill themselves. We've already done this in the lab. We've done this successfully in cancerous mice, and it dramatically increases their survival rate.' Normally, mice with tumors all die within 30 days. After receiving this bacterial system and getting a dose of radiation, all the mice in Forbes' lab tests survived beyond the 30 days, which could potentially translate into many months or years in people."
Even Forbes recognizes that this sounds like science fiction. Here is another quote from him. "Salmonella are little robots that can swim wherever they want. They have propellers in the form of flagella, they have sensors to tell them where they are going and they are also little chemical factories. What we do as engineers is to control where they go, what chemical we want them to make, and when they make it."
On his Current Research Focus page, Forbes gives more details about his approach which he calls "Targeted Bacteriolytic Therapy." Here is a short quote. "To specifically target tumors we are investigating motile, facultative anaerobic bacteria that specifically target and accumulate within the therapeutically inaccessible regions of tumors. Over the past 50 years numerous strains of bacteria have been shown to localize and cause lysis in transplanted mouse tumors, but their application has had minimal success in the clinic. By specifically targeting bacteria to specific sub-regions of tumors we hope to dramatically increase their affectivity."
For more information, you might want to read a previous research work published in Biotechnology and Bioengineering under the name "Salmonella typhimurium specifically chemotax and proliferate in heterogeneous tumor tissue in vitro" (Volume 94, Issue 4, Pages 710-721, July 5, 2006).
Here is the beginning of the abstract. "Multi-drug resistance greatly limits the efficacy of conventional blood-born chemotherapeutics, which have limited ability to penetrate tumor tissue and are ineffective at killing quiescent cells far from tumor vasculature. Nonpathogenic, motile bacteria can overcome both of theses limitations. We hypothesize that the accumulation of S. typhimurium in tumors is controlled by two mechanisms: (1) chemotaxis towards compounds produced by quiescent cancer cells and (2) preferential growth within tumor tissue. We tested this hypothesis by quantifying the relative contributions of these mechanisms using the tumor cylindroid model, which mimics the microenvironments of in vivo tumors."
Finally, if you want to know more about the cylindroid used by Forbes, you can read this page at UMass Amherst describing how such a device could improve chemotherapy (March 2, 2006).
You can see above a picture of one of the bacteria used for this research project, the Salmonella typhimurium -- which causes typhoid fever -- floating in the human blood stream. (Credit: National Research Council (NRC), Canada; link to a larger version). And obviously, you can learn more about Salmonella on Wikipedia.
This research project is led by Neil Forbes, an assistant professor of Chemical Engineering and the members of his research group.
Here is how bacteria are used. "'When we get the Salmonella bacteria into the part of the tumor where we want them to be, we've programmed them to go ape,' says Forbes. 'We have the bacteria release a drug to trigger a receptor in cancer cells called the 'death receptor,' which induces cancer cells to kill themselves. We've already done this in the lab. We've done this successfully in cancerous mice, and it dramatically increases their survival rate.' Normally, mice with tumors all die within 30 days. After receiving this bacterial system and getting a dose of radiation, all the mice in Forbes' lab tests survived beyond the 30 days, which could potentially translate into many months or years in people."
Even Forbes recognizes that this sounds like science fiction. Here is another quote from him. "Salmonella are little robots that can swim wherever they want. They have propellers in the form of flagella, they have sensors to tell them where they are going and they are also little chemical factories. What we do as engineers is to control where they go, what chemical we want them to make, and when they make it."
On his Current Research Focus page, Forbes gives more details about his approach which he calls "Targeted Bacteriolytic Therapy." Here is a short quote. "To specifically target tumors we are investigating motile, facultative anaerobic bacteria that specifically target and accumulate within the therapeutically inaccessible regions of tumors. Over the past 50 years numerous strains of bacteria have been shown to localize and cause lysis in transplanted mouse tumors, but their application has had minimal success in the clinic. By specifically targeting bacteria to specific sub-regions of tumors we hope to dramatically increase their affectivity."
For more information, you might want to read a previous research work published in Biotechnology and Bioengineering under the name "Salmonella typhimurium specifically chemotax and proliferate in heterogeneous tumor tissue in vitro" (Volume 94, Issue 4, Pages 710-721, July 5, 2006).
Here is the beginning of the abstract. "Multi-drug resistance greatly limits the efficacy of conventional blood-born chemotherapeutics, which have limited ability to penetrate tumor tissue and are ineffective at killing quiescent cells far from tumor vasculature. Nonpathogenic, motile bacteria can overcome both of theses limitations. We hypothesize that the accumulation of S. typhimurium in tumors is controlled by two mechanisms: (1) chemotaxis towards compounds produced by quiescent cancer cells and (2) preferential growth within tumor tissue. We tested this hypothesis by quantifying the relative contributions of these mechanisms using the tumor cylindroid model, which mimics the microenvironments of in vivo tumors."
Finally, if you want to know more about the cylindroid used by Forbes, you can read this page at UMass Amherst describing how such a device could improve chemotherapy (March 2, 2006).
Sources: University of Massachusetts Amherst news release, February 29, 2008; and various websites
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