Relay-Version: version B 2.10 5/3/83; site utzoo.UUCP Path: utzoo!mnetor!uunet!seismo!husc6!cmcl2!philabs!aecom!werner From: werner@aecom.YU.EDU (Craig Werner) Newsgroups: sci.research,sci.med Subject: Re: Coley's toxins Message-ID: <1192@aecom.YU.EDU> Date: Wed, 8-Jul-87 00:02:41 EDT Article-I.D.: aecom.1192 Posted: Wed Jul 8 00:02:41 1987 Date-Received: Sun, 12-Jul-87 07:06:39 EDT References: <367@uop.UUCP> <858@godot.radonc.unc.edu> Organization: Albert Einstein Coll. of Med., NY Lines: 54 Keywords: Hyperthermia Summary: Tumor Necrosis Factor / Cachectin / York Ave. Xref: mnetor sci.research:191 sci.med:2625 In article <858@godot.radonc.unc.edu>, bourland@godot.radonc.unc.edu (J. Daniel Bourland) writes: > Coley was this guy who, in the late 1800s or early 1900s, noted that > individuals with tumors, when they got fevers, sometimes spontaneously > went into remission. The following is a tale of York Ave. It is true, Coley noted that some patients who came down with tuberculosis, who had known tumors, occasionally had the tumor spontaneously die, or necrose. However, this was one case where the cure 1) didn't work all the time, and when it did, worked unpredictably, and 2) sometimes killed the patient. Coley's Toxins, by the way, are derived from tubercle bacilli and occasionally from Gram Negative bacteria. Well, it became obvious that the body was making something that it was using to eliminate the bacteria, that surendipitiously killed tumors. In biochemistry and immunology, the only way to prove the existence of something is to isolate, and hope that in the pure form, it has a predictable activity. After a long time, this Tumor Necrosis Factor was isolated, and in mouse models did a reasonably good job at killing tumors. Meanwhile, on the other side of York Avenue, some other researchers were trying to solve a different problem. Why do some cancer patients lose weight no matter how much you feed them. Chemically, it can be shown that they just do not take up nutrients from the blood. They become cachectic, and die of the starvation/weight loss, long before the cancer would be terminal. They reasoned that the body must be making a factor, which they called Cachectin, which was telling teh cells to stop taking up nutrients, and the body died. They figured if they could isolate it, they could find a way to counteract it. They eventually did isolate Cachectin, and sequence it, and clone it, to finish sequencing it at the DNA level. Meanwhile, on the original side of York Avenue, the Tumor Necrosis Factor group did the same thing with their protein. And a funny thing happened upon crossing the street: Cachectin, which is lethal to the body, and Tumor Necrosis Factor, which was supposed to be beneficial, turned out to be exactly the same protein. In small doses, local to the tumor, it directed the tumor to stop eating, and it died. In larger doses, systemically, it directed all cells to stop taking up food, and the patient died. The same exact protein was good or bad, depending on whether the traffic flowed northbound or southbound outside your window. As Ralph Isberg used to say, "Biology is stranger than nature." -- Craig "Baby Doc" Werner (future MD/PhD, 3 years down, 4 to go) werner@aecom.YU.EDU -- Albert Einstein College of Medicine (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517) "... Has Determined That Cigarette Smoking Is Dangerous To Your Health"