The life and death mystery of your liver

THIS IS WHAT THEY’RE DOING TO FIND THE ANSWERS

ALEXANDER BARRIE September 15 1956

The life and death mystery of your liver

THIS IS WHAT THEY’RE DOING TO FIND THE ANSWERS

ALEXANDER BARRIE September 15 1956

The life and death mystery of your liver

THE DOCTORS KNOW: You can’t live without it It’s bigger than it need he It’s your hardest-working organ It can strangle itself And it can cure itself

THE DOCTORS DON’T KNOW: \\ hy it s indispensable How much of it you really need How many jobs it does How it becomes diseased How theyr can cure its ills

THIS IS WHAT THEY’RE DOING TO FIND THE ANSWERS

ALEXANDER BARRIE

One day in 1926 the head of Toronto University's physiology department put his nose through the office door of a young professor on his staff. “Young man,” he said, “I'm told you are working on the liver. Is that correct?”

“Yes, sir.”

“Then my advice is, beware. For it’s a swamp from which many never return.”

The younger professor was Dr. C. H. Best, who was to become one of Canada's most distinguished medical researchers, co-discoverer with Sir Frederick Banting of insulin, and now head of the world-famous Best Institute, named in his honor.

Thirty years have passed since the senior professor gave his warning. During this time, intensive studies of the human liver have been made in Canada and all other advanced countries. Yet there is still plenty of the swamp left in this, the most baffling of all the body’s organs.

If your liver were removed, for instance, nothing could be done to keep you alive. Why? Medical science doesn't know; it can explain what makes any other organ indispensable, but when it comes to the liver it is still wondering. It is known that the liver is very much bigger than it need be. Why? Again, the doctors don’t know; nor are they sure how much of it can be spared, but they think it may be as much as four fifths. Everyone agrees that the liver takes on many separate jobs

for the body. But how many? Some experts suggest about thirty; others guess away into the hundreds.

When it comes to liver disease, the uncertainties multiply. The doubt begins with the fact that, because liver disease is so often wrongly diagnosed, no one knows how much of it there is about. Then when disease is diagnosed, little can be done beyond diet and rest to cure it. Infectious jaundice, for example, is a common complaint. How does it spread? Through swallowing contaminated food and drink, say some doctors; but others say this is unproved. Since all attempts to give the disease to experimental animals have failed, establishing the truth is especially slow.

Cirrhosis, the worst of the purely liver diseases, attacks mankind beneath a mantle of mystery all its own. After centuries of research its causes, its cure and its effects are still debated and doubted by specialists.

It is not surprising, therefore, that after many years spent studying these puzzles, Dr. Best should have this to say about it all: “The subject is terrifying—even to the finest experts.”

Many patients are quick to blame their livers for the out-of-sorts feelings that everyone has at times. People say that they are feeling “liverish”—a very casual diagnosis that in most cases is probably wrong. One doctor in Harley Street, London’s medical temple of learning, has listed the symptoms complained of by most selfstyled “liverish” patients: headcontinued on page 64

continued on page 64

The life and death mystery of your liver

Continued from page 25

Is it to blame for that Blue Monday feeling?

ache, nausea, furred tongue, loss of appetite and spots before the eyes. Have these troubles anything to do with the liver?

Only the drug makers with ready remedies to sell seem to answer the question with real confidence. One uses the line: “It all depends on the liver.” The Canadians who spend probably more than a million dollars a year on various nostrums for the liver apparently believe it. But medical opinion, while it is tolerant, gives the investment little support. Dr. Robert Volpe, a gland specialist at Toronto General Hospital, believes that liver pills are useless to the liver. “But, on the other hand,” he adds, “they don’t do any harm.”

Doctors are not sure that the liver can go temporarily out of order. Some say it is possible; others say no. All are agreed that it would be difficult to prove the liver’s guilt for that Monday-morning feeling.

Nor have doctors solved the riddle of the liver’s size. They know that it is a mammoth, wedge-shaped organ sitting at the top and to the right of the stomach and that, at between three and three and a half pounds, it is the heaviest organ in the body. They know that they can cut away up to seven eighths of an animal’s liver before signs of impaired function begin to show. But what they don’t know is the answer to the question: could humans get along with as little?

Because surgery on the human liver is still too dangerous for anything but the removal of surface growths, no one can be sure. Back in 1936 two German researchers named Bollman and Mann, using the less-advanced tests of that time, wrote that eighty percent of the human liver could be removed without apparent harm. In absence of a newer one, this figure is still accepted. It could mean that the liver is five times bigger than it need be.

In trying to establish how much of the liver hulk might be surplus, researchers came across another phenomenon: animal liver regrows when part is taken away. No one knows why. nor does anyone know for certain that the same would be true of the human liver. All that can be determined so far is that animal liver regrows at great speed and that it keeps growing until the original size and weight have been reached.

Researchers have discovered too that, though the heart and muscles were thought to be the hardest-w'orking organs in the human body, this place of virtue actually belongs to the liver. But they still don’t know all the things that hard work is accomplishing.

Among what may he relatively few of the liver's functions that scientists are agreed on is the organ’s responsibility for making bile. It does this at the rate of about a half a gallon a day and passes the greenish-yellow bitter-tasting fluid for storage to the gall bladder. There it waits until mealtimes when it is released to the intestine.

Bile has two duties to perform: one of these is to help the liver play a role as guardian of the body. The liver w'atches for incoming poisons, intercepts them

before they reach the general circulatory system; then the bile carries them away for disposal. The bile’s second job is to convert fats into a milky fluid for easy digestion. It alone has the power to do this; without it. the absorption of fats into the body would be impaired.

But the job of making bile is a long way from being the liver’s biggest function. The liver is a very intricate chemical plant that works over the food you eat, rearranging it. storing, and distributing it in the way your body can absorb it best. Nothing can pass from the stomach into the blood stream without going through this treatment, and if one function could be isolated as the most important (which is doubtful), it is perhaps the responsibility of the liver—aided by the hormone insulin—to keep the right amount of energy-giving sugar in the blood. Without this sugar, life w'ould end in convulsions and coma after eight hours.

Carbohydrates, proteins and fats are the three food families human tissue needs. The liver can convert all of these into the critical sugar if it has to. But since carbohydrates are largely sugars already, it uses them first. If the supply is enough, it will save proteins and fats for other jobs.

Hie army was embarrassed

Even incoming sugar brings a complex chemical problem with it. The body wants its sugar in the simplest form possible— glucose. So the intestine is obliged to change all carbohydrate material into glucose before passing it along to the liver. However, the liver, which has to hold materials until it can find parts of the body to use them, cannot store glucose. So. with skill that only trained chemists would be able to measure, it processes glucose first into a material named glycogen; this it can store. When the muscles are hungry for sugar, which they "burn" as they work, it quickly completes the job by making glycogen back into glucose—a fairly simple chemical step—and releases it to the blood. And flagging energy returns.

The job of breaking down proteins tests the liver's chemical skill less but calls for immense precision in gathering, storing and releasing to the blood just the right amounts at just the right times.

Eats make fewest demands on the liver —by being a threat to its health. Fat accumulation can cause disease in the organ’s intricate and sensitive inside, so the liver stores very little of it—about four percent—checks the rest for wholesomcness and sends it quickly to "fat depots” throughout the fleshy parts of the body. This is the liver's way of providing against the risk of starvation; if it comes the liver recalls the fats, converts them to glycogen, then to glucose for ready release as energy.

A Canadian lumberjack has given medical men one of the most dramatic examples of the process in action. During the war he traded his back-straining work in the forests for the quiet life of an army quartermaster. Overnight the whole pattern of his life changed; but his appetite did not. Years of bull-mooselike eating had taken away his ability to judge input of food against output of energy. His liver faced a grave disposal problem. Far more energy-making material was coming in than his muscles burned up. Unable to reject anything but poisons it passed fats out to depots wherever it could find them and stepped up its own storage amount dangerously high. The lumberjack’s topography began to change.

Army chiefs were embarrassed at the speed and amount of the change. They

saw their quartermaster fast growing into a monster. In time he outbulked the biggest uniforms, chairs and beds. When he hit the four-hundred-and-fifty-pound mark (a fifth of a ton), he was ordered to place himself before some surprised medical experts. One was a Toronto biochemist who has never forgotten the spectacle. "Without a doubt.” he says, "he was the fattest man 1 ever saw.”

Yet no very drastic treatment was necessary. He was put on a fat-free diet, had his carbohydrate intake cut down and was made to exercise. His liver, al-

though hampered by its own gross oversize. went to work recalling and converting the fat it had spread about his body, and his weight began to come down. But it took a year to shrink him back to his normal two hundred and fifty pounds.

Three pints of blood flow through the liver every minute in two separate supply lines—one from the heart, the other from the intestines. If nothing more remarkable than this could be said of it. the liver would still be unusual on two counts, for few other organs have two

supplies and no other large organ uses secondhand unpurified blood delivered to it from a neighboring organ.

The supply from the heart is the normal flow of oxygen-loaded blood needed by all organs in the body. The other source is incoming food carried by slowmoving blood in what is called the portal vein.

As soon as food is swallowed it is attacked by digestive juices and dissolved into a rich liquid. The nutrient in this liquid seeps into the intestine walls to meet a lacework of tiny veins. These

How does the liver help make blood? The mystery opened an exciting twenty-year detective story

whisk it away, packed with nourishment, to the large portal vein leading straight to the strange and secret labyrinth of the liver’s internal cells.

I.ivcr cells all look alike under the microscope, a fact that still battles scientists, for although the cells look the same, they cannot be since they take on so many and different jobs. How? “We just don’t know,” says one research man who is trying to find out. “It’s one of the greatest mysteries we’ve run across.”

Besides cleaning out poisons and sorting carbohydrates, proteins and fats, the liver is a vitamin centre. A, Bl, B2, C, D and E—the six old, well-known ones —are all stored in its interior. But recently two more have been found—vitamins BI2 and K.

The discovery of B12 is one of those exciting achievements that rarely come to research men.

It was suspected for years that the liver helps with the making of new blood cells. But how? In prenatal life, making blood is one of the liver’s concerns. After birth it appears to leave this function to the bone marrow. Yet, although no one could explain them, there were signs that some connection between the liver and healthy blood corpuscles existed.

In the mid1920s, for instance, doctors discovered that if patients suffering from pernicious anemia ate enough animal liver, their health improved. But until 1928, when liver extract was developed. the treatment was a terrible hardship; patients had to eat as much as a pound of raw animal liver a day to stay alive. After a few months, most began to wonder if the disease was as distressing as the cure. Even when the new extract made it possible to take liver by injection, the dosage was still large because doctors, unable to say which of the liver substances caused the improvement, had to include all of them. But at least science was now quite sure that somewhere inside it, the mysterious liver secreted an active blood-making material.

Efforts to trace it began in Britain and the U. S. After twenty years only two groups were still trying—the American Merck Research Laboratories and the Glaxo Laboratories, in Britain. Both teams were reporting some progress although they were using quite different techniques. Then in 1948 the medical world heard that both had reached the answer almost simultaneously-—B12 had been found.

One of the big research difficulties has been that it comes in microscopic amounts. From four tons of animal liver just a fraction of an ounce of B12 can be found. And so far no one has found a way to make it synthetically. In 1952 an English doctor, Henry Marriott, wrote, “If a single grain of table salt were taken and divided into a hundred parts, a daily amount of B12 equal to one of those hundredth parts would be more than enough to restore a patient with pernicious anemia to good health." And from then on the same minute quantity would only have to be taken about once a month.

Vitamin K is another precious body substance that was tracked down to the liver in 1939. It is an essential part of a complex chemical cocktail that ends up by giving blood the power to clot. It works in partnership with another substance found in the liver, heparin, that acts in the other direction, as an anticlotting chemical. In delicate balance the

mixture of these and other fluids keeps the blood liquid in circulation and makes it clot when exposed to the air.

Yet, for all the knowledge that has come at last, today’s medical men still find the liver a difficult contradictory organ. One mystery in particular casts a challenging shadow: if the liver is removed but sugar is fed in proper quantities to the blood, death comes swiftly. Why? The question has not been answered, and until it is no one can tell how much there is still to learn. Some experts think there is a liver function of prime importance to the body still undiscovered.

Meanwhile, treatment of liver disease has not kept pace with the better understanding of how the healthy liver works. It is here that modern physicians and research men face their biggest challenge.

Little can be done to help the victims of liver disease. Treatment for the most part is based simply on the idea that if you give it some sort of chance, this durable organ will cure itself. And it frequently docs. It is not at all uncommon for cases of serious degeneration—cases where the liver is shrivelled—to return to health without much more than sensible diet and rest to help.

In Canada there is ignorance, too, of the extent of liver disease. Health experts are convinced it is increasing; but they can only guess how much. The Department of National Health and Welfare has few figures to show the incidence of liver complaints, and those that it does have it cannot safely trust.

A big difficulty Canadian authorities face is that each province makes its own rules about how, when and whether to report diseases to Ottawa. While this situation exists there is no hope of compiling figures of any value. Efforts are now being made to standardize reporting methods so that this statistical chaos can be tidied up. “But,” explains an unemotional Ottawa official, “it will be a few years yet before this is accomplished.”

Meanwhile, the health experts note that an ailing liver is more often listed by doctors as the cause of death today than it used to be; also that reports from the U. S. ’show sharp increases in liver disease rates throughout that country. American figures for jaundice are specially dramatic—the rate is said to have more than tripled in three years.

Infectious jaundice is the only known “catching” liver complaint. Its victim does not necessarily turn the ghostly yellow that most people expect him to. If he did, there would be fewer cases of mistaken diagnosis than there are. But the fact is that jaundice is an inflammation of the liver, which may look from the outside like flu, dysentery or typhoid. Health authorities believe that many a jaundice case is never recognized. Fortunately, it is seldom a killer. The patient usually makes a good recovery from whatever treatment is prescribed.

Another common jaundice can be caused by injections, inoculations and transfusions; it is often known as "transfusion jaundice” to distinguish it from its infectious relative. Doctors are equally nonplused by this disease which can trick them into diagnosing an ailing gall bladder, stomach, intestine or pancreas.

The U. S. army fell victim to transfusion jaundice on the biggest scale ever during W'orld War II. When some half a million men were vaccinated in 1942

against yellow fever, tens of thousands of them went down with “serum hepatitis”-—officialese for jaundice. The cost in money and man-hours was fantastic.

But it is cirrhosis that carries the rank of liver enemy number one. This disease destroys the liver; it is not an inflammation or a poisoning like other complaints although either poisoning or inflammation may sometimes result in cirrhosis. Liver attacked by cirrhosis first enlarges and then shrivels uselessly as its cells, crushed by scars, are strangled.

It has for long been believed that cirrhosis is closely connected with overindulgence. Back in 1836 an English doctor, Thomas Addison, declared that a connection existed between too much of the good life and liver decay. He was the first to do so. "The most exquisite case 1 ever saw,” he said as one piece of evidence, “occurred in a female who had for some time subsisted almost exclusively on ardent spirits.” Once the thought had been mentioned, research men went to work. Animals were fed alcohol for prolonged periods, then had their livers removed for examination. Results seemed to confirm Dr. Addison’s theory. As recently as 1947 a group of rats was fed ten percent alcohol alongside another group given the same food but no alcohol. Within two months the drinkers developed cirrhosis; the abstainers did not.

Besides this it was found that in Russia, where the common man has little to spend on luxuries, the disease is rare; only .02 percent of autopsies show it as the cause of death. But in North America where some seventy percent of the adult population drinks, the rate is close to two percent—a hundred times greater. So the case seemed closed: too much alcohol for too long adds up to cirrhosis.

But the reigning experts overlooked some signs that maybe this was less than the whole story. In Asia and Africa cirrhosis is common although alcohol is rare. In Australia, when the rains return after a lengthy drought to change the arid pastureland into a rich and juicy green, many grazing animals develop what is locally known as “walking disease.” They become excited and stupid. They kick their heels high in the air, walk blindly into anything in their way, totter unknowingly into rivers and fall over cliffs. The slaughter rate is high. And walking disease is just another name for cirrhosis of the liver.

Then too, although most cirrhotic patients have been heavy drinkers, this is by no means true of all of them. Today a young girl lies in a Toronto hospital seriously ill with cirrhosis. For three years the doctors have fought unavailingly to cure her. It is thought now that maybe she has some unnamed, especially persistent form of the disease. Yet there is nothing in the background of this girl that is not entirely healthy and wholesome.

When all the facts are assembled there is room for doubt that alcohol could cause cirrhosis. In 1949 Toronto’s Dr. C. H. Best decided to make new tests with greater accuracy than anyone had bothered with before.

He was not satisfied that past experimenters had made proper allowance for the caloric value of alcohol and its effect on diet. Again, one group of rats was fed alcohol in their drinking water while another group was not. But this time the caloric value of the alcohol was added (as sugar) to the diet of the abstaining rats. This time too Best saw to it that both groups, though eating less than normal because of the added calory intake through alcohol on the one hand and through sugar on the other, received

properly balanced diets. When the rats were killed off and their livers examined, no disease was found in either group. So the earlier experiments had been misleading; the truth was that the rats could swallow alcohol regularly and still remain fit.

Best took the test a stage farther by cutting down rats of both groups on their protein intake. Now cirrhosis developed in all the victims’ livers. The conclusion was that it is total diet that matters—not whether or not alcohol is swallowed.

A young doctor put the story in simple words: "A gin drinker’s liver depends not so much on gin before dinner as gin instead of dinner.”

So another small, hard-won step forward is ta ken.

T he alcoholic swallows up to (sometimes more than) fifteen hundred calories a day in liquid form alone. This is the equivalent of fifteen five-ounce potatoes. It is not surprising that he eats too little and the wrong kind of food. Nor is it surprising, now, that although alcohol scarcely harms the liver, alcoholism often does. For as Dr. .1. R. Bingham, of the Alcoholism Research Foundation in

Toronto, points out, alcoholics cannot be persuaded to eat. “If they controlled themselves well enough to eat,” he says, “they wouldn't be alcoholics.”

The final mystery in the whole perplexing subject is perhaps the fact that, serious as cirrhosis usually is, some people can go through life in its grip and never even know. Many an autopsy has shown advanced cirrhosis which was not the cause of death. Impossible in theory —but it happens.

So the liver adds another secret to the list. But not. perhaps, for long. For now there is a specialist trained in precision, patience and persistence who aims to tear the secrets out—the biochemist, a man much better matched for the job than anyone has been before. It is to him that medical science now turns for the answers it needs. “We can but hope." wrote a despairing Dr. A. L. Fawdry, of Aden, to the U. S. magazine Medical Press, “that he will so enlighten us that we physicians will find the patient before us, with his enlarged liver, less of an enigma than he often is at present.”

The letter might have been signed by the entire medical fraternity of the world. ★