HEMOGLOBIN AND MAGNETISM

By Linus Pauling

Talk after banquet for installation of Sigma Xi, Corvallis, Oregon, Wednesday, May 12, 1937.

I am indeed happy to be here on this great occasion. When Professor Graf wrote me that Professors Milne and Simmons and their committee asked me to come, I was strongly tempted to accept, even though my better self told me that I should refuse. I don't mind lecturing to students or at scientific meeting, but a banquet is something different; talks at banquets should be left to the easy talkers - historians, lawyers, economists, philosophers. In this case, however, the tempter won - I decided that I would have the pleasure of coming here even though the audience had to suffer for it.

the general subject that I shall talk about, under the disguise of the title "Hemoglobin and Magnetism", is a new branch of chemistry, modern structural chemistry. this subject involves the determination of the structures of molecules - the exact location of the atoms in space relative to one another - and the interpretation of the chemical and physical properties of substances in terms of the structure of their molecules. the new information about the structure of the molecules is detailed and accurate and goes far beyond the classical structural formulas of the organic chemist in the same way that the final architectural drawings of a building go beyond a preliminary rough sketch. Modern structural chemistry is a new subject - twenty years ago detailed structural information was available for only a half-dozen molecules, and ten years ago for only a few dozen.

Now scores of new molecules are being studied every year, mainly by the physical methods of spectroscopy, x-ray and electron diffraction, measurement of magnetic properties, etc., and the results obtained have been found to be useful for the biochemist studying vitamins as well as for the inorganic chemist studying the complex inorganic substances.

As a single substance to use as an example of the application of the methods of modern structural chemistry I have selected hemoglobin, with particular emphasis on it magnetic properties.

Hemoglobin is the respiratory pigment, carrying oxygen from the lungs to the tissues, for all vertebrates and for many other animals. There is a lot of it around: about 7% of the body weight of a man is blood and about 1/7th of the blood is hemoglobin, so that hemoglobin comprises about 1% of body weight thus amounting to about a pound and a half per person. Hemoglobin is a good chemical substance - it can be obtained in pure crystalline form, put in a bottle, and labeled. Nevertheless, chemists tend to look at it askance, because it is such a complicated substance. It has a molecular weight of about 68,000, the molecule containing about 10,000 atoms. this means that the molecule is very big. It is about 50 Å in diameter, with an Angstrom equal to 1/100 millionth of a centimeter; that is, only five of these molecules in a row would give one millionth of an inch, and a blob containing only about one million of them would be big enough to be seen in the microscope. Hemoglobin consists of a big protein molecule called globin to which there are plastered four small groups, each of about 75 atoms, called hemes. These hemes, each of which consists of one iron atom and a porphyrin group, give hemoglobin its characteristic properties, the globin seems to be useful mainly to keep the substance in solution in the plasma. It is probably used for this purpose because the body is so full of proteins that they are called upon whenever something is needed for a special use. Each of the hemes is able to combine with one oxygen molecule; in this way each hemoglobin molecule can carry four oxygen molecules from the lungs to the tissues. hemoglobin also aids in bringing carbon dioxide from the tissues to the lungs, but it does not do this directly, as I naively supposed until I learned better. hemoglobin instead function in the main indirectly, in the following way. Oxyhemoglobin is a stronger acid than hemoglobin itself. On loosing oxygen in the tissues hemoglobin thus makes the blood plasma basic, permitting it to pick up carbon dioxide as bicarbonate ion; then in the lungs on picking up oxygen the hemoglobin makes the plasma acid, thus expelling the carbon dioxide.

I mentioned that each hemoglobin molecule contains four atoms of iron, there being thus about 3 grams of ron in the blood of the body. It is probably an accident that we eat raising and drink tonic for iron, instead of eating and drinking for copper or manganese or some other metal; for there are other respiratory pigments used by invertebrates which involve these metals in place of iron. Hemocyanin, the blood of crabs, snails, abalone, octopi, etc. Which is blue when oxygenated, colorless when deoxygenated, is a very complex substance, with a molecular weight which may go as high as five million. Hemocyanin contains copper. One of the puzzling facts about it is that it adds one molecule of oxygen for every two atoms of copper. In the old days, when for a reason that was never told to me cuprous chloride was written Cu₂Cl₂, the copper atoms being supposed to occur in pairs in cuprous compounds, this might have been understandable; but now that we know that these pairs don't occur the fact is one to be explained in the future.

It is known that iron-containing substances somewhat like hemoglobin occur in all cells, both plant nd animal. It is possible, although it has not been prove, that a copper compound related to hemocyanin is similarly widespread. If so, this would account for a number of facts. For example, there is evidence that copper is necessary for life in vertebrates, and that it is connected in some way with the formation of hemoglobin in the body. it may be that the prototypes of hemoglobin and hemocyanin are present in all living cells, and that the choice of one or the other as the starting point for developing a respiratory pigment has _____ on an accident. this would account for the widespread occurrence of these pigments nd for the apparent lock of reason in the choice between them - thus all species of snails but one use hemocyanin as respiratory pigment, this one using hemoglobin.

Besides the blue copper blood there exists a green blood (in a worm), called chlorocruorin. This also contains iron, but the pigment is somewhat different from hemoglobin. A manganese blood has been reported for a certain shellfish. Most striking of all, however, is the blood of strange animals cal ascidians, or sea-squirts. These are little animals about 3 inches long which live in sea water, henaging under floats and in similar places. When taken out of water they squirt out a little stream of water, this action having given to their name. Their blood contains corpuscles of different kinds and colors, blue, green, and red, looking in shape something like raspberries. The metal in this blood is vanadium - though how the animal picked this out of the periodic table I can't explain. The process by which the animal gets the vanadium out of the sea water is also puzzling.

Hemoglobin containing four hemes, about which a great deal is known; heme has even been synthesized. heme is a relatively simple substance, the iron salt of a reddish-brown substance called porphyrin, H₄C₃₄H₃₀N₄O₄. Heme itself, separate from globin, can be found in nature in at least one place - as crystals in the blood of the old males of the marine worm urechis. The porphyrin obtained by removing the iron atom is more widely distributed; the brown color of brown eggs is due to a prophyrin, called Ooporphyrin - it is the same as that in blood. Also, the brown stripe down the middle of the back of an angleworm is due to porphyrin. The blue pigment, called turacin, in the feathers of the South African bird Turaco is the copper salt of a porphyrin.

And with this parting word for the president of the new chapter, and with the best wishes and great hopes for the chapter itself, I come to the end.