ogical Indicators Bond ty of damage. It . prognosis, and is determined. intil the severity cations or other ynsideration. The advantages of using the biological indicator. rather than an estimated dose of the offending agent. if known, are substantial. First. one has direct information on the “proximate” cause of organ function impairmentandits severity, which permits greater confidence with respect to estimating prognosis and prescribing corrective measures. Also, to a large degree, the biological indicator is independent of the exact nature of the agent that may have caused theaffect of a may take coro- ree to Which a essel has been ‘ect is measured the fractional of the lumen. more relevant. given severity, the quality of the radiation (if that is the offending agent), and the time rate at which the offending agent was delivered. All that the organ system “cares about” so to speak, is the degree of damagethat it has sustained, and it matterslittle exactly what circumstancesled to the extant biomedical condition. The above discussion indicates why a great deal of effort has been and is going into improving methods of indicating the severity of effect, whatever the offending agent maybe, forvirtually every organ system in the body. The efforts involve biochemistry, molecular biology, physiology, immunology and a number of sophisticated instruments including SPECT, PETT, and MRI. It is only in radiotherapy, in which radiation is used as the therapeutic agent after other means have been used to make the diagnosis and estimate the prognosis, that dose tion of a large rshall Islanders external pene- ternal emitters, of iodine [2]. A lans, including nd, and R.A. mine the medto take actions res. It was real- ere might well 1 arrival in the ‘iscussion took ay out to the > what, if any, tes. The agreeugh suchesti- is used. This serves to reinforce the thesis that would play a doseat best plays only an initial and tentative role, certainly in the process of diagnosis and medical evaluation, and even in therapy. Although bone marrow damage was used above as example of the use of severity of organ effect, the principle holds for any noncancer- > action taken nts. Instead, all sught to be relAnydefinitive nd care would ¥ of the effect verity was that ous disease or injury, be it acute, subacute or chronic. The scale is always 0.0 to 1.0 (0.0% to 100%). It represents the quantification of a at the criteria €. for it to be “biological indicator.” argely if not Biological Indicators for Cancer? id prognosis. gree of organ ction for the ‘sponse of the ly S-shaped), The physician can, of course, usually diagnose a cancerthat has developed to the point of being detectable, and can take various measuresto diagnose the precise type of cancer, the degree to which it has extended or metastasized, and thus the prognosis with different types of therapy. However,at least until very recently (see below), there have been no biological markers of any kind which permits the physician (or anyoneelse), in 00% severity 1d thus, if the ent). To the gical effects S useful it is s Ul 2440 25 the absence of an overt diagnosable cancer. to say whether a given individua} will actually develop a cancer that may well be lethal. This is true even if it is known that the patient has been exposed to radiation or a chemicalcarcinogen, and has sustained detectable damage. Thus. all that a physician can do after examining the patient carefully and finding no overt cancer, is to so State (occasionally. some “precancerous”lesions, of varying prognostic value. may be detected by biopsy). Furthermore, even should that patient later develop a malignancy. there are no findings which would permit the physician to saythat the particular tumor developed from exposure to any specific carcinogenic agent. Cancers leave no “marker” indicating what particular carcino- . gen was causative. Also. the baseline or “normal” incidence of canceris quite high. i.e., some 1 out of 5 deaths tn the United States is from cancer, and some one third ofal] persons will have experienced cancer in their lifetime, even though they maydie of other causes. Thus, it is not possible to deal with cancer in the same cause-effect fashion outlined above. which is so useful for essentially all other diseases. It is for the above reasons that the occurrence of cancer mustbe treated as a public health and not a medical problem. Here epidemiological methods are used to determine whether there is -a Statistically significant increase in the numberof individuals with cancer in a carcinogen-exposed population, as compared to that in a carefully matched population that has not been so exposed. It has been determined that essentiallyal] humancancersstudied are monoclonal. and thus single cell in origin. Thus any given cancer can be regarded as simply a marker for cell! that has been damagedgenetically. so as to cause it to become carcinogenic and still capable of forming a clone of ltke cells that wil] become manifest as an overt cancer. Thus, with respect to studying mechanismsof carcinogenesis, it 1s necessary to do molecular biology and related studies at the subcellular level to see which gene changes may be involved in the cause of a particular kind of cancer. Thus it is possible that tests can be devised that would permit a physician to tell an individual pattent that he or she has an increased probability of developing a cancer of a specific type. In some cases, exact probabilities may be determinable. pene