The spindle checkpoint monitors chromosome alignment on the mitotic and meiotic spindle. When the checkpoint detects errors, it arrests progress of the cell cycle while it attempts to correct the mistakes. This perspective will present a brief history summarizing what we know about the checkpoint, and a list of questions we must answer before we understand it.

Mutating a base pair may be regarded as misfortune; to lose or gain a whole chromosome looks like carelessness. Most single base pair changes are nearly neutral, even in organisms with compact genomes, but a lost or gained chromosome has major effects. Loss of chromosomes leads to the death of haploid cells and exposure of diploid cells to previously recessive mutations. Because many genes are expressed in proportion to the number of copies of the gene, gaining or losing chromosomes leads to genetic imbalance. Genetic carelessness alters human lives. Errors in chromosome segregation in meiosis can lead to spontaneous abortion and Down syndrome (an extra copy of chromosome 21). Chromosome loss in mitosis exposes mutations that inactivate tumour suppressor genes and has a major role in the initiation and progression of cancer. Eukaryotic cells stave off genetic error by detecting and eliminating its progenitors: non-traditional base pairs and other forms of DNA damage, and chromosomes that have not lined up properly on the spindle — the bipolar structure that segregates the chromosomes at mitosis and meiosis. When Boveri fertilized sea urchin eggs with multiple sperm, he produced spindles with three poles, showed that this led to dramatic errors in chromosome segregation in meiosis, and suggested that similar errors caused cancer 1 . The beginning of the 20th century saw the first clue that drugs like colchicine could affect mitosis 2 . Studies in the