The answer is found in the liver secretion known as bile. The bile, which is discharged into the small intestines, does not itself contain digestive enzymes but it does contain substances known as bile salts. The bile salts consist of molecules with double-jointed solubility properties. One half of the molecule is similar to fats in its structure and that half will dissolve in fats. The other half contains groups of atoms that are soluble in water.

  In order to satisfy both halves of itself, bile salt molecules group themselves along the surface where fat and water meet. In this way, the fatty portion can face the fat and dissolve in it, while the rest can face the water and dissolve there. Both halves of the molecule are happy. The more surface between fat and water that there is, the more bile salt molecules can be made happy. One way in which the amount of surface can be increased is to distribute the fat through the water in the form of small bubbles. The smaller the bubbles, the more surface there is for a given weight of fat. The addition of bile salts to a mixture of water and fat thus encourages the formation of such small bubbles.

  Bile salts are, in this manner, the body’s natural detergents. They homogenize fats in the intestines, and the tiny bubbles that result mix well with the watery digestive fluids and can be attacked by enzymes.

  There are two main varieties of bile salts, differing in the chemical structure of the water-soluble half. In order to avoid going into the chemical details, we will simply call the two varieties the G-salts and the T-salts. Both exist in the biles of various animals. Both do their detergent job adequately. In one respect, though, they behave differently. There is a fat-like substance called cholesterol which the G-salts don’t seem to handle very well. The T-salts, however, homogenize cholesterol perfectly.

  Now, in general, herbivorous animals (plant-eating) are particularly strong in G-salts and poor in T-salts. This is all right because plants are less fatty on the whole than animals are and what plant fat does occur is quite poor in cholesterol. Now since the G-substance, out of which G-salts can be made, is present in quantity in all cells, whereas the T-substance is present in much smaller amounts, why bother manufacturing T-salts that you can do without. So herbivorous animals stock up on G-salts and do well.

  The animal fat, however, that forms part of the diet of carnivorous (meat-eating) animals is rich in cholesterol. The bile of carnivorous animals is rich in T-salts. Those animals need it and even though the T-salts are more difficult to scrounge up in quantity, they do it.

  Now where does man fit in? Man is a member of the Primate order, which runs from the lemurs to himself and includes the apes and monkeys. All primates, with only one exception, are herbivorous, or, at most, will eat insects. The one exception, of course, is man himself. Homo sapiens is omnivorous in fact (that is, he will eat anything he can digest and a few things he can’t) and carnivorous by choice.

  Man has adapted himself to this kind of diet as far as morphology is concerned, but what about this biochemistry? His bile is still the bile he has inherited from his mainly herbivorous primate ancestors and is rich in G-salts and poor in T-salts, so though his diet is full of cholesterol, he lacks the equipment to handle it properly and keep it in solution, or at least well-mixed with water.

  You ask: So?

  So is there any connection between this and the fact that Homo sapiens is the one species that is plagued with gall-stones, which are conglomerations of cholesterol (usually) that has precipitated out of the bile little by little? Is there any connection between this and the fact that Homo sapiens is the one species that is plagued with atherosclerosis (our number one killer these days) which consists largely of the deposition of cholesterol little by little in the walls of the arteries?

  Is there? I honestly don’t know. The argument as I’ve presented it sounds good, but biochemistry these days is, in many ways, but the hand-maiden of medicine. Few biochemists devote themselves to the workings of various species except where some definite problem of immediate interest to Homo sapiens is concerned. Therefore not enough is known about various animal biles and their manner of working to make the above argument airtight. So far, it’s just a speculation which I’ve come across.

  Can biochemical evolution affect the morphological evolution with which we are familiar? Maybe. We can try on some more speculation for size.

  All animals produce a compound called uric acid as a waste product, some producing more than others. Birds and reptiles, for instance, produce uric acid in quantity as one of their main waste products. (I’ll have more to say about that later.) They have special ways of getting rid of it and we can forget them for now. Mammals produce only small quantities of uric acid, but its disposal raises a problem.

  The logical way for mammals to get rid of uric acid is to dump it into the urine. The trouble is that uric acid is quite insoluble so it takes a lot of urine to get rid of a little bit of uric acid. Most mammals don’t even bother, but bypass the problem completely. They have an enzyme called uricase, which breaks up uric acid to a substance named allantoin. Allantoin is considerably more soluble than uric acid and can be dumped into the urine without trouble. That ends the problem.

  Or at least it ends it for other mammals; not for man. Man and the anthropoid apes differ from all other mammals in not having uricase. (There is a variety of dog, the Dalmatian coach hound, which seems to be low in uricase, but it has some.) Any uric acid which is formed in man or ape stays uric acid. It must get into the urine as best it can since it can be eliminated only in that way. If too much gets into the urine for the latter to hold, it will precipitate out and form one variety of kidney stone. If there’s too much even to get into the urine in the first place, it may precipitate out in other parts of the body, beginning usually with the joint of the big toe, and the condition known as gout results.

  Since man and apes share this problem, the loss of uricase must go far back in time to a point where the human stock had not yet diverged from that of the anthropoid apes, unless you’re willing to believe that man and each species of ape have separately and coincidentally lost their uricase, which I’m not.

  The question is, why should the enzyme, uricase, have been lost? To be sure, in one way, there doesn’t have to be a reason. Mutations take place in haphazard fashion, and are usually for the worse. But then, mutations for the worse generally don’t survive in the long run; only mutations for the better (in the sense of better fitting the environment). If some pre-anthropoid had lost the enzyme, uricase, would not he and his descendants have been at some disadvantage because of their extra propensity for joint troubles? Would not his normal cousins have won out, survived, and passed on uricase to the anthropoids and men of today?

  The answer is, yes. That is, yes, unless the absence of uricase had survival value that made up for the disadvantages.—And here comes a piece of speculation I encountered recently in a chemical-news weekly.

  The absence of uricase means that the concentration of uric acid in the blood and tissues of apes and man is higher than in that of other species. Uric acid is a member of a group of compounds called purines, some members of which are stimulants of the nervous system. The purine stimulant you are probably best acquainted with is the caffeine in coffee. Now what if a higher concentration of uric acid in the blood of the pre-anthropoid who lost uricase kept him at a higher level of mental activity than was the case with his uricase-containing cousins? Would not that have more than made up for the off-chance possibility of gout? Could not the uric acid, in fact, have been one of the chemical factors involved in stimulating gradual development of the brain into the large specialized structures now present in apes and particularly, in man? If so, what price gout?

  Consider the manner in which life-forms moved out of the sea (in which life originated) into fresh water and onto land. That involved not only the familiar morphological evolution, but biochemical evolution as well. In the sea, cells developed in a liquid containing certain ions (chiefly sodium, potassium, calcium, magnesium, chloride and sulfate ions) in certain concentrations.

  Life made the adjustment to those concentrations once and apparently that was it for all time.

  When animals grew more complicated and became a group of cells enclosed in some form of shell, skin, protective membrane or what have you, the individual cells remained immersed in an inner liquid resembling sea water in ionic composition. The outer portions of the body, as well as many other things, changed to suit altered conditions when animals moved out onto the land, but the internal liquid, the liquid with which the cells were in actual contact, remained about the same. Our own blood, after you subtract the various blood cells and dissolved proteins and other organic material, is remarkably like a quantity of trapped sea water, and so is the interstitial fluid that exists in the spaces between our cells.

  In other words, we’ve never left the sea; we’ve taken it with us.

  (To be sure the resemblance between the ionic composition of blood and sea-water is not exact. Some people suggest that our blood resembles the primeval sea; the sea as it was when organisms first enclosed themselves; and that since then, the ocean has changed its composition somewhat, this change not being reflected in our blood.)

  This may seem to you as though biochemical evolution is something that does not happen, but remember the Red Queen’s advice that in her country it takes all the running one can do to stay in one place.

  Primitive sea creatures have no trouble maintaining the ionic composition of their internal fluids because it is mostly in even balance with sea water, and they have learned, with the millions of years, to tolerate slight changes that may develop in sea water and hence in their own fluids. But when a sea creature invades the fresh water (which, biochemically, is as difficult a feat as the invasion of land) a completely new situation develops.

  Fresh water is only a thousandth as rich in ions as is sea water. When a sea creature tries to live in fresh water, it must somehow counteract the natural tendency of the ions within itself to leak out (or, for that matter, for water to leak in) and equalize the ionic concentration inside and outside the animal.

  To do that, fresh-water animals have developed a number of intricate biochemical mechanisms to keep the ion composition of their internal liquid steady at the values to which they are accustomed. They have evolved, biochemically, like mad just to stay in the same place.

  In one way or another, the mechanisms usually involve kidney action. Water is constantly entering the fresh-water creature, and ions enter, too, by way of the food it eats. The kidneys are so designed that they pass water out again but hold back the ions. The creature is thus an ion-trapping sieve.

  It is considered that any creature that can keep a surplus of ions inside its body against a deficiency on the outside must have had some ancestor that adapted itself to fresh-water. All vertebrates apparently come into this classification and so it is deduced biochemically that the original vertebrate from which all others are descended developed in fresh-water.

  To be sure, a number of fresh-water vertebrates migrated back to the sea, to become the ancestors of the marine fish and marine sharks (the two are not the same, the fish being bony and more advanced, the sharks cartilaginous and more primitive) of today. By the time the fish and sharks returned to the sea, the sea-water was a bit richer in ions than their internal liquid was. They had the reverse problem now; to keep surplus ions from entering or (which amounts to the same thing) water from leaving. The fish solved the problem by cutting down on water loss through kidneys and by evolving special biochemical mechanisms to force ions out. (The sharks had another solution, which I’ll mention later.)

  You can find details, by the way, of this and other similar matters in an excellent little book by Ernest Baldwin called Comparative Biochemistry, published by the Cambridge University Press in 1948.

  The conquest of the dry land involved a whole new series of biochemical modifications. One of these concerned the matter of waste-disposal.

  The chief elements found in the organic materials of living creatures are carbon, hydrogen, oxygen, and nitrogen (which chemists symbolize as C, H, O, and N respectively). When foodstuffs (which include complicated molecules built up out of anywhere from dozens to millions of atoms of these elements, plus a few others) are broken down for energy, what is left behind are simple molecules which are waste-products to be eliminated. The carbon, hydrogen and oxygen end up as carbon dioxide (CO2) and water (H2O). In the case of most water-dwelling animals, the nitrogen ends up as ammonia (NH3).

  Now for any creature living in fresh water, there is no problem. Carbon dioxide and ammonia are soluble in water, and water is just water. Dump all three substances into the river. The waste water will just mix with the river-water, the carbon dioxide will come in handy to the water plants, the ammonia will eventually be utilized by plants and bacteria. The plants and bacteria will build carbon dioxide, water, and ammonia back into the complicated molecules that the animals will again swallow, digest, and use for energy and to build their own tissues. Round and round things go.

  In fact, the only suspicion of risk involves ammonia which is highly poisonous. One part in 20,000 in blood is enough to kill. Fortunately for the fresh-water fish, they’re passing so much water through their kidneys in their effort to keep up their ion content that the ammonia is flushed out as fast as it is formed and never has the chance to build up even the small concentration needed for poisoning.

  What about sea-fish which pass less water through their kidneys? They still manage to flush out the ammonia adequately, though in their case it’s much more of a near squeak.

  But then we reach the amphibia (toads, frogs, etc.), the first vertebrates to invade the land. As water-dwelling tadpoles, they excrete ammonia, but as adult, land-living creatures, ammonia is no longer possible. Water is in such short supply for any creature that doesn’t live actually immersed in it, that it can’t possibly be spent sufficiently recklessly to keep the ammonia concentration low enough.

  Before any creature could invade the land, then, it had to develop a type of nitrogen waste that was considerably less poisonous than ammonia. The adult amphibian accomplished this. It broke its nitrogen down to urea (NH2-CO-NH2). As you see, the urea molecule is made up of a fusion of the parts of two ammonia molecules and one carbon dioxide molecule. Urea is soluble in water and is much less poisonous than ammonia. It can be allowed to build up to a much higher concentration than ammonia so that a given amount of nitrogen waste can be eliminated in a much smaller quantity of urine, and precious water is conserved.

  Here we have one case where a biochemical invention was made independently more than once. The sharks (who preceded the amphibia and were not ancestral to them), after migrating from their fresh-water origin back to the sea, were faced with keeping ions from the ocean surplus from invading their body. Instead of developing ion-excreting mechanisms as the marine fish did, they worked out the trick of breaking down nitrogen compounds to urea instead of ammonia. Then they allowed urea to concentrate in the blood as they could never have done with ammonia.

  In fact, they allowed urea to accumulate to a concentration of 2 per cent, which is enough to kill other creatures. (Even though urea is less poisonous than ammonia, it isn’t entirely harmless. Nothing is.) Through the ages, shark tissue acclimated itself to urea. The urea in the blood acted as the ions did, in a way, and made the total ion content (with urea included) of shark blood higher than that of the ocean. The problem was therefore once again to keep the ions from leaking out and the sharks could use their old fresh-water adaptations for the purpose instead of having to invent new mechanisms, as the sea fish did.

  So you see, although sharks and amphibia developed the same urea dodge independently, they did so for different reasons.

  Incidentally, some sharks migrated back to fresh water after having developed the urea-waste mechanism. Once in fresh water, the presence of urea in the blood was not only unnecessary, it was downright embarrassing. It made the ion content of the blood artificially high so that it was harder than ever to keep it steady against the ion-free fresh water. The fresh-water sharks did the best they could by cutting down the urea concentration in blood from 2 per cent to 0.6 per cent, but there they reached their limit. Shark tissue had grown so accustomed to urea, it had become positively dependent upon it. Shark heart, for instance, won’t beat in blood containing no urea. (Our hearts would do fine.) So you see, biochemistry can be a tricky thing.

  Even urea requires a certain amount of water to be eliminated. It’s all right for frogs and toads. One way or another they get enough water, even those species that seem to live away from water, and their eggs are always supplied with plenty of water.

  Of the vertebrates descended from amphibia, the mammals, too, produce urea. They get ample water for the purpose and their young develop viviparously, that is, within the mother’s body, where it is always in contact with the mother’s water supply.

  The birds and reptiles are another case completely. They lay eggs and within those eggs, the young must develop. The chick egg, for instance, can contain only a certain amount of water and for the three weeks between fertilization and hatching, the young chick must make that do because it will not get one drop more.

  Water-economy becomes more important than ever. There isn’t even enough water to take care of urea, so urea becomes inadequate as a waste product. A new invention is necessary. That new invention is uric acid (which I mentioned earlier). Uric acid contains the fragments of four ammonia molecules and three carbon dioxide molecules, and its advantage over urea is this: uric acid is quite insoluble in water. (Remember, that is its disadvantage in man.) The young bird or reptile developing in the egg just piles up the uric acid wastes in a little dump heap. Little or no water is required.

  As is well-known, morphological evolution can be traced in embryos. At various times during development, a human embryo passes through a unicellular stage, an invertebrate stage, and a cartilaginous stage. It shows at various times gills, a tail and a pelt of body hair. In the same way, biochemical evolution can be traced.