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Hydrogen isotopes have the largest isotopic effect, since they have the lowest mass. It is precisely this large effect that allowed Urey to be the first person to accomplish the physical separation of isotopes, a task he was able to accomplish by the simple fractional distillation of liquid hydrogen! Although, this achievement was worthy of the Nobel Prize this was in fact the simplest possible separation. Deuterium's boiling point is 3.28K higher than the boiling point of hydrogen. The boiling point of Helium-3 is 1K lower than that of Helium-4. In heavier elements however, the boiling points of isotopes are nearly indistinguishable.
The ease of separation of gaseous isotopes is given by a dimensionless number known as the "rate ratio". The higher the rate ratio, the easier the separation. For protium (Hydrogen-1) and Deuterium the ratio is 18. For protium and tritium, (Hydrogen-3) the ratio is 60. On the other hand the ratio for the separation of I-127 (natural iodine) and I-131 (a fission product) is only 1.02, even though Iodine-131 has four more neutrons than I-127. (These values can be found in Isotope Effects in Chemical Reactions, Clair Collins, ed, ACS Monograph 167, Van Nostrand (1970) pg 16.)
Deuterium oxide (heavy water) is toxic because so much of the chemistry of our bodies is dependent on the transfer of hydrogen ions (hydrogen bonds indeed are what hold our bodies together.) Because the transfer of ions in turn is dependent on their ionic (or atomic) weight, and because the deuterium ion is twice as heavy as the hydrogen ion, metabolism is slowed appreciably. It is even worthwhile speculating that if the fraction of deuterium created in the big bang were higher, life might not have evolved at all.
The separation of the isotopes of heavy elements was historically regarded as such a difficult problem that the German nuclear scientists interned after World War II, and secretly recorded at Farm Hall in 1945, a group which included the Nobel Laureates Werner Heisenberg and Otto Hahn, on hearing of Hiroshima were less impressed by the allied achievement of a chain reaction than they were by the allies achievement of an industrial scale isotopic separation of Uranium-235 from U-238.
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