Some interesting and consistent facts about Multiple Sclerosis[Note: Some forms of MS do not follow these patterns; And some experts think those may really be different diseases.] A) First symptoms (usually) occur suddenly (overnight! for example blindness, usually in one eye, or paralysis). B) First symptoms occur between ages 20 and 40. C) Even when very drastic (such as total blindness, or paralysis of entire arms or legs) these first symptoms somehow cure themselves (but not quite completely) in about a month or so. D) Then there is usually a delay of many years (even 8-10 years) before any more symptoms appear. E) After delays of years, recurrence of the disease usually is also sudden and extreme, such as a major paralysis of part of the body. These new symptoms also "cure themselves" almost entirely in a month or so. F) There will then be another delay, often of several years; and then a sudden onset of some new paralysis, which will be followed by spontaneous recoveries that are less complete than the earlier ones. G) More attacks then occur, closer and closer together in time, and with recoveries being less and less complete.
H) If one identical twin gets MS, then the other twin will later get MS in about a third of cases. I) If a parent or sibling gets MS, your chances are about one in fifty of getting the disease yourself. (Which implies that the genetic component depends on more than one genetic locus, and probably more than 2.) J) The frequency of MS in women is about three times larger than the rate in men. In the great majority of autoimmune diseases, there is a higher frequency in females; in thee case of Lupus the ratio is nine to one.
K) Your chances of getting MS are greater if your childhood was spent in the north, with something like a 2 or 3 to one difference between North Carolina versus New Jersey or New York. If you grew up in the extreme south, like Florida,
south Texas or Mexico, then your chances are half or less what they would be if your early years were spent in N. Carolina. L) Magnetic Resonance Imaging of brains and spinal cords show damage to the central nervous system before and after MS symptoms appear. e.g. MRI can tell you which twins are going to get MS; and can see scars of past attacks. M) Everyone's brain and spinal chord has a hollow, fluid-filled cavity inside. The fluid that fills this cavity (cerebrospinal fluid) normally does not contain cells. Inside the brains of people with Multiple Sclerosis, however, the cerebrospinal fluid contains large numbers of T-lymphocytes. N) A disease with symptoms much like MS can be deliberately induced in rabbits, mice and other animals by the simple method of dissecting out pieces of brain from one animal, then grinding it up, mixing it with a special irritant called Freund's adjuvant, and then injecting the mixture into other animals (which can be the same species, or a different species). The effect is to stimulate what amounts to an allergy against the injected animal's own brain and nerves. Do you agree with the following generalization? What examples, or counter-examples, can you suggest to the class? The less likely you would have been to guess any particular observation, the more it potentially tells you, in the sense that the more it will narrow down the possible causal explanations that can be true. (But the harder it is to figure out!) Suppose that somebody invented a theory that predicts all or many of the phenomena listed above! How can anyone invent experiments to find out what causes MS, if they can't interpret these 14 strange facts? Doesn't any surprising fact tell you as much as the results of an actual experiment? The only difference is that when you invented the experiment, and designed it to test a particular hypothesis, then you will have a better idea how to interpret the results of the experiment. Right? Either way, you still need to invent the possible explanation for the experiment, before you know what experiment to do. (Most people don't think about experiments that way, but after you have done a few thousand, you may agree with me.) The only difference is that, with natural experiments (observed facts) you have to invent the explanation after knowing what the facts are. It's like doing the experiment first, and later figuring out what the results mean. Lots of people do things in that order, anyway.
Are any of the following analogies useful to your thinking? I) Multiple Sclerosis is like California wild fires: They arise suddenly, do terrible damage for a few days or weeks; but then go away eventually, even when not treated. Then after a long delay, of as much as ten years, they suddenly happen again. II) Multiple Sclerosis is like influenza epidemics. A person suddenly gets a high fever and very bad symptoms that are often fatal. But if they don't die, they will recover almost completely, and remain well for 10 years or more, after which they may catch another strain of influenza. III) Multiple Sclerosis is like earthquakes. Suddenly, buildings fall down and dams burst. But soon the shaking stops. After many years, often as many as ten years, another earthquake will occur, usually at a somewhat different location. IV) Multiple Sclerosis is like hurricanes... etc. V) Multiple sclerosis is like flooding by big rivers.
Maybe it could help to structure your thinking around one or more of the following questions. i) What could hold back the damaging causes, until the day they strike? (like a dam breaking) ii) Or is there something autocatalytic about the harmful events? (like a forest fire) iii) What about the self-recovery from symptoms? Is it like a fire using up all the available fuel? iv) What about the long delay before the next attack? Is it like pressure building up to some breaking point? Or is it more like the accumulation of un-burned trees, and other fuel? v) If you had to guess the normal function of the genes, that when mutated result in MS, what would you expect might be the normal functions of the proteins that those genes code for? vi) Imagine that you had a powerful computer, in the memory of which you had the complete DNA sequences of ten people who suffered from MS, and also the DNA sequences of ten other people who had reached the age of 70 without getting MS, and supposing you were a really good computer programmer, how would you use the sequence information? vii) Suppose that you cloned several individual T-lymphocytes from the cerebrospinal fluid of a person suffering from MS, what differences would you look for in DNA "finger-prints" produced by electrophoresis of restriction endonuclease fragments? viii) A real cure for MS would be what sort of thing?
Putting some material into the body that the anti-self T lymphocytes would bind to, and attack, instead of attacking the myelin sheath or any other part of the brain Discovering what cause the long delay between attacks, and inventing a way to make them last forever. Discovering what had held back attacks until just before they occurred, and strengthening whatever it is. Stimulating better regeneration of myelin sheaths. |