In 1959, such a situation was found to exist in the case of persons suffering from a long-known disease called Down’s syndrome.[2] Each person so afflicted has 47 chromosomes in place of the normal 46. It turned out that the 21st pair of chromosomes (using a convention whereby the chromosome pairs are numbered in order of decreasing size) consists of three individuals rather than two. The existence of this chromosome abnormality clearly demonstrated what had previously been strongly suspected—that Down’s syndrome originates as a mutation and is inborn (see the figure on the next page). [Illustration: _Karyotype of a female patient with Down’s syndrome (Mongolism). During meiosis both chromosomes No. 21 of the mother, instead of just one, went to the ovum. Fertilization added the father’s chromosome, which made three Nos. 21 instead of the normal pair. (Compare with the normal karyotype on page 4.)_] Most mutations, however, are not associated with any noticeable change in chromosome structure. There are, instead, more subtle changes in the chemical structure of the genes that make up the chromosome. Then we have _gene mutations_. The process by which a gene produces its own replica is complicated and, while it rarely goes wrong, it does misfire on occasion. Then, too, even when a gene molecule is replicated perfectly, it may undergo change afterward through the action upon it of some chemical or other environmental influence. In either case, a new variety of a particular gene is produced and, if present in a sex cell, it may be passed on to descendants through an indefinite number of generations. Of course, chromosome or gene mutations may take place in ordinary cells rather than in sex cells. Such changes in ordinary cells are _somatic mutations_. When mutated body cells divide, new cells with changed characteristics are produced. These changes may be trivial, or they may be serious. It is often suggested, for instance, that cancer may result from a somatic mutation in which certain cells lose the capacity to regulate their growth properly. Since somatic mutations do not involve the sex cells, they are confined to the individual and are not passed on to the offspring. Spontaneous Mutations Mutations that take place in the ordinary course of nature, without man’s interference, are _spontaneous mutations_. Most of these arise out of the very nature of the complicated mechanism of gene replication. Copies of genes are formed out of a large number of small units that must be lined up in just the right pattern to form one particular gene and no other. Ideally, matters are so arranged within the cell that the necessary changes giving rise to the desired pattern are just those that have a maximum probability. Other changes are less likely to happen but are not absolutely excluded. Sometimes through the accidental jostling of molecules a wrong turn may be taken, and the result is a spontaneous mutation.