What the Doctor Ordered
(See Cover)
Though foreign visitors might be surprised to hear it, U.S. drugstores also sell drugs. They sell quite a lot of drugs. More than twelve times every second -- almost 400 million times a year -- some worried citizen peers down the length of one of the nation's 50,000 drugstores -- past the lunch counter, the toys, the plastic raincoats, the hair lotions and tooth powders -- and finally catches sight of the little glass booth marked "Prescriptions." To the pharmacist in the booth he hands a slip of paper marked with the magical device, "R" the name of a drug and a few cabalistic symbols squiggled in abbreviated Latin. A few minutes later, the customer walks out of the drugstore again, confident that he has been given just what the doctor ordered.
That confidence, and the enormous in crease in the nation's prescription business (up 350% in the last ten years), reflect a revolution in U.S. medicine. In stead of writing a shotgun formula requiring half a dozen ingredients,* a doctor can now prescribe a single-bullet remedy, neatly packaged in advance, its purity guaranteed by the maker. Two-thirds of the drugs most commonly prescribed to day did not even exist 20 years ago. In place of the citrates and tartrates, the nux vomica and monkshood of an earlier day, the druggists' rows of glass-stoppered bottles are now filled with one or another of the long line of new "wonder drugs": the sulfas, the antibiotics, the hormones.
Back from Mephistopheles. To a large extent, this revolution was brought about by the big drug manufacturers who pour out the wonder drugs from their assembly-line factories, translating the discoveries of the laboratory into jars on the druggists' shelves. Only a generation ago, the drug industry was barely tolerated by "pure" researchers in science and medicine, who were apt to consider it as undesirable an employer as Mephistopheles. Now that attitude has completely changed. For their part, as the essential middlemen of the medical revolution, the drugmakers have accepted the fact that they are in business for other people's health. "Medicine is for the patient," says Merck & Co.'s Chairman George W. Merck. "Medicine is for the people. It is not for the profits."
Chairman Merck's own company is not quite the biggest U.S. manufacturer of "ethical" drugs.* Its 1951 sales of $120 million (plus $10 million in Canada) were topped by Parke, Davis & Co.'s $138 million. But Merck is one of the oldest (its roots go back to the Germany of 1668), its main lines are the four new classes of drugs (vitamins, sulfas, antibiotics and hormones), and its products reach every corner of the U.S. and the world.
Merck packages few drugs under its own name. But it supplies many other drug firms, which may simply package the Merck chemicals under their own labels or may use them in combination with their own products. So the chances are that any patient taking a prescription medicine today is getting something made, at least in part, by Merck. (Main exceptions: three patented antibiotics.) And more than likely, when he sits down to breakfast, he is also getting bacon from a hog that grew faster because of Merck vitamins and antibiotics in its feed, eggs from a hen protected against disease by a Merck sulfa, and bread enriched with vitamin BI made by Merck.
Pipes, Pipes, Pipes. The arsenal from which these new weapons come is as far removed from the apothecary's pestle and mortar as penicillin is from a medicine man's snake-oil elixir. In Merck's four producing plants in the U.S. (Rahway, N.J., Danville, Pa., Elkton, Va. and South San Francisco), almost 2,000 chemical operators perform their mysteries in a weird, surrealistic jungle assembled by welders, riveters and pipe fitters. Rising from the floor, which may cover an acre or more, are the great boles of the chemical forest: row on row of cylindrical stills and vats. Around and among them is a secondary growth of filters and crystallization tanks, their clusters broken by the stumps of centrifuges. Dangling like lianas from the upper branches are hundreds or thousands of pipes, from an inch to a foot in diameter, marked (usually at eye level) by a cluster of iron flowers--the handwheels of the valves. Everywhere there are pipes and more pipes. Like many another modern industry, the manufacture of the purest and most delicately constructed drugs takes place in a pipefitter's wonderland.
If the plant makes chemical synthetics, the air is charged with the warning smell of organic solvents. No one smokes, for these vapors can form highly explosive mixtures. Maintenance men must use non-sparking tools, and usually a plant guard stands by them with an explosimeter, watching the dial to see that the organic vapor is not strong enough to make an explosive mixture. At the other end of the production line, workers must use rubber gloves fitted into the front of glass-enclosed cubicles to package sterile chemicals under germ-killing rays of ultraviolet light.
In other plants, the work is done by microbes--billions of microscopic creatures, some found originally in the air (e.g., the mold which makes penicillin), some from the soil (for streptomycin and B12). Selectively bred, like racehorses or showdogs, they do their work in steel-and-concrete temples, down each side of which are rows of huge 15,000-gallon vats. The air is sickly sweet from the smell of the broth on which the microbes batten. It is vibrant with the roar of rotary agitators which keep the microbes whirling around in the vats (they work best this way). There is the whoosh of compressed air forced into the broth (though the microbes do not breathe, they would die without it).
But producing just what the doctor ordered takes more than miles of pipes and mountains of materials. It also takes the priceless catalysts of knowledge and character. Those ingredients are well compounded in the man who transformed Merck & Co. from a modest company making a conventional line of drugs and other chemicals into a flourishing medical pioneer. He is Merck's Chairman George Wilhelm Herman Emanuel Merck
("Named after all my uncles, who had to give me silver presents for ten years").
The Sign of the Angel. When Friedrich Jacob Merck took over a pharmacy called the Engelapotheke ("Angel Drugstore") in the Hessian town of Darmstadt 284 years ago, chemistry was just emerging from the shadows of alchemy. In 1827, the Merck firm started manufacturing; in the next 40 years it achieved the first commercial production of morphine, codeine and cocaine. By 1891 the company was selling so many of its products in North America that a son of the house, 24-year-old George Merck, was sent over to take a closer look at the market.
George Merck liked the country so much that he settled in Manhattan. He was quick to see the immense opportunities for technical industry in this new nation, growing up behind its protective-tariff walls. His U.S. partnership of Merck & Co. bought 150 acres at Rahway, NJ. In 1903 the plant began making much the same line of chemicals and medicinals as its parent firm was making on the other side of the tariff wall.
George Merck had already started the family which was to carry on the U.S. business. He settled with his wife (from a Darmstadt family) in Llewellyn Park, N.J., within a stone's throw of Thomas Alva Edison's home and laboratory. In 1894 his first child (of five) and only son, George, was born.
Young George Merck grew up in the pleasant country demesne of Llewellyn Park, spent his summers sailing in his father's naphtha launch on Lake Hopatcong, traveling abroad or around the U.S. In the Harvard class of 1915, Merck finished his B.A. work a year early, and planned to go to Germany for a doctorate in chemistry. World War I prevented that. His father said: "Come on into the shop. The war will be over in a few months and then you can go and get your degree." But as Merck says: "I never did, and I'm still in the shop."
In the postwar company, young George Merck moved rapidly up to the presidency (1925). His father, only 59, died a year later, and left his 32-year-old son on his own. And so, after a war-enforced severance from the Darmstadt firm, was the reorganized U.S. company.
The time had come for expansion. Merck & Co. concluded that the way for the U.S. drug industry to expand was through all-out research. It was a proud day for Merck in 1933 when the company's new and enlarged labs (part for pure research, part for applied) were dedicated. It was the right time for labs. Research chemists were already opening four new medical frontiers, and Merck has been among the first to cross all of them:
Vitamins. In 1934, Merck's head of research, Dr. Randolph Major, got a call from Biochemist Robert Runnells Williams. Said Williams: "I've isolated a minute quantity of B1." Would Merck be interested in supplying him with more of the natural substance, helping to establish its molecular structure, and maybe trying to synthesize it?
Major was interested. For more than a year, tons of rice bran poured into one end of the Merck plant in Rahway and fractions of an ounce of B1 trickled out at the other end. Williams and the Merck-men tackled the job of synthesis, and in 1936 succeeded in making B1 easily and cheaply from simple organic compounds. Merck went into big-scale production. Result: medicine at last had a weapon to vanquish beriberi.
Suddenly the chemical woods were full of vitamins: vitamin A for healthy eyes; riboflavin (B2) and nicotinic acid (niacin) to prevent pellagra; ascorbic acid (vitamin C) to prevent scurvy. Merck produced all these and many more. In no time, U.S. drugstores were selling vitamins in all doses and combinations. The Government encouraged the makers of processed foods, from which vitamins have been taken out, to enrich them by putting the vitamins back. Merck now supplies tons of vitamins a year to enrich the nation's impoverished bread, margarine and breakfast cereals.
In the whole field of vitamins, Merck's greatest triumph, by far, is its most recent. Its chemists extracted the elusive anti-anemia factor from liver in pure form: the ruby-colored crystals of vitamin B12, essential to growth and the most powerful medicinal substance known in nature. One thirty-millionth of an ounce a day is enough for a healthy man's blood-making factory; one three-millionth checks pernicious anemia.
Sulfas. By the time the vitamin frontier was thickly settled, another frontier was being opened. In 1935 the French broke the secret of a new German drug and published it: a simple substance derived from coal tar would kill the streptococcus germs that often caused fatal infections. The drug was Prontosil; from it came sulfanilamide, first of the modern "wonder drugs" and first of a long line of sulfas. Other companies were the first to find high-powered, patentable variants like sulfamerazine, sulfadiazine, sulfathiazole and sulfaguanidine. Merck chemists got what looked like a dud: sul-faquinoxaline. Never proved safe for human use, it might have been shelved. Then animal tests showed that sulfaquinoxa-line is wonderful for protecting chickens against coccidiosis, a deadly parasitic disease. By now, the sulfas have been largely superseded by newer and better drugs (mainly antibiotics) for humans, but so far nobody has found anything better than Merck's sulfa for sick chicks.
Antibiotics. After the sulfas came the antibiotics. No drug was ever launched with more drama than the first and greatest of these--penicillin. As the story is usually told in the drug trade, Merck & Co. missed out on penicillin in the early stages because it concentrated too hard on trying to find a way to synthesize it and got left behind. George Merck explains it differently: "The Government asked us to put up a plant, but insisted that Merck apply for Government money to finance it. I said 'No, that would make it look as if we were lobbying. We won't do it.' "
Other companies did, and got into penicillin faster. But Merck got a head start with the next antibiotic, streptomycin. When Rutgers' Dr. Selman Waksman found that his beloved soil bacteria had made something that killed many germs which penicillin did not affect, he took the culture to Rahway. Though half a dozen companies are making streptomycin today, the best guess is that Merck microbes, in their own temple of vats at Elkton, Va., make 40% of the U.S. output.
Hormones. Then came cortisone. In 1935, a biochemist at the Mayo Clinic, Edward Calvin Kendall, had isolated a hormone similar to those produced by the adrenal glands. But its extraction was painfully complicated; in seven years Kendall could produce only 40 or 50 grams from 120 tons of adrenal glands of cattle. Merck chemists completed the synthesis Kendall had begun. Then Merck took on the job of producing enough of the hormone for physicians to test. Merck went all out in what Kendall calls "the most complicated chemical processes ever carried out in a commercial laboratory on a production scale."
On April 20, 1949, the Mayo Clinic's Dr. Philip Hench made his first report on the Merck product, and a new era in medicine opened. Kendall and Hench shared a Nobel Prize for their part in the work: for the first time in his long rheumatic history, man could practically eliminate the symptoms of rheumatoid arthritis.
The public, tirelessly hoping for a panacea, suffers an emotional letdown as each new wonder drug in turn proves to have its limitations. Cortisone, which was hailed at first (by laymen) as the cure for arthritis, is the latest exciting disappointment. Since the first chorus of enthusiasm, doctors have learned to handle cortisone warily. It cannot be given to any patients for more than a few weeks or months without the risk of causing other disorders. It will be years before the medical profession knows just how cortisone can best be used. But Merckmen know that cortisone, like its predecessors, is not a goal but a direction marker; they know the road is long, but they believe they are on the right road.
The demand for cortisone, as a treatment if not a cure, is already tremendous. In the DanviUe plant every few days (just how often is a Merck secret), chemical operators pour 1,500 lbs. of glistening white crystalline bile acid ($37,500 worth at quoted prices) into a 1,000-gallon still. In the still are hundreds of gallons of a solvent liquid with which the bile acid goes through its first reaction in its long, tedious process toward cortisone. Within hours this reaction is complete and a precipitant is added, causing Intermediate Compound No. 1 to separate from the solution as a white powder.
From then on, through miles of pipes and batteries of stills and filters, this intermediate and its successors are dissolved and crystallized out, redissolved and re-precipitated, filtered and centrifuged, catalyzed and concentrated, evaporated and distilled, boiled and chilled below zero. These processes go on around the clock, and the bile acid gets no Sundays off.
Months after the charging of the first still, an operator opens the last centrifuge (like a housewife's spin-dryer) at the far end of the 100,000-sq. ft. production area. A label on the wall proclaims: "KE Pure" (KE is Merck's intramural abbreviation for cortisone). The bottom and sides of the centrifuge are thickly coated with a clammy white powder. From the looks of it, it might be talcum or aspirin. But it is far more precious: 35 lbs. of KE pure is enough to make 635,000 tablets of 25 milligrams each, enough to supply more than 300,000 patients for a day on average doses.
This week the first cortisone from the Danville production line, now pressed into tablets and packed 40 to a bottle, was shipped out. And after cortisone, there would soon be hydrocortisone, latest and most potent of this group of hormones. A team of Merck chemists synthesized it after others had thrown up their hands and declared the job impossible. It is as good as cortisone in many ways, better in some. Whatever its final place in medicine, there can be no question of its eventual value in probing the secrets of the human body.
What lies in the still more distant future for Merck & Co.? One of the most forward-looking experiments now under way at Merck is designed to measure fatigue. A laboratory rat is placed in a tank of water, and with each stroke of a foreleg, he sets off a series of complex electronic devices to record his acceleration. From this, Merck scientists hope to learn more about muscular fatigue in general, and how it can be influenced by hormones. Beyond that, neither George Merck nor his 425 scientific and medical researchers can tell, and probably they would not if they could.
Public Trust. At 58, George Merck looks like the priceless catalyst in this whole process that he is. A blond, blue-eyed giant (6 ft. 5 in.) with an easy smile and an exuberant capacity for work (he spends his days, he says, "half at the New York office, half at Rahway, and half at home"), he takes his company's role and reputation with dedicated seriousness. Wihen Merck researchers find a new product, the company gets it on the market as fast as it can, then lowers the price as fast as production will allow. Within a year after Merck first produced cortisone, and before any other competitors were in the field, Merck had sliced its price from $200 to $50 a gram. It is now down to $16 wholesale.
Merck sets his own public responsibilities as high as his company's. Before World War II, he served (unpaid) on the Munitions Board's Chemical Advisory Committee. At the height of the war, he also directed all the Government's sprawling research on biological warfare (for which he was later awarded the Medal for Merit). Merck still makes frequent trips to Washington as a consultant to Defense Secretary Lovett. His public-duty commitments range from his local zoning board, his local hospital and state chamber of commerce, to the executive council of the American Cancer Society and the board of visitors of the chemistry and biology departments at Harvard. He was an early Eisenhower backer and a former state treasurer for the New Jersey G.O.P.
But Merck's main interest is still in guiding Merck & Co. Because he regards his company as something in the nature of a public trust, many of Merck's directors are representatives of the public (among them, Dr. Vannevar Bush, wartime head of the nation's research and development program). Says George Merck: "I firmly believe that management should not be in control of the board in a public company, owned by the public and in public service." But George Merck himself has long provided the driving force of Merck & Co. "To get continuity in a company," he says, "you have to have direction from generation to generation." One of the strengths of the Merck name is that its reputation stretches back through almost three centuries without a break.
The Three Princes. Last week after a hurried trip to Washington, George Merck was off to his mountain-top hideaway, Wind Gap Farm, in Rupert, Vt. The 120-acre West Orange estate, Eagle-ridge Farm, where his gardener raises orchids in a $100,000 greenhouse, is too close to Rahway and New York City for leisure. In the Green Mountains with his tall, handsome, silver-haired second wife (the former Serena Stevens), he entertains such literary friends as Dorothy Canfield Fisher, John A. Kouwenhoven and John P. Marquand, a Harvard classmate. Here, too, the family tries to get together: two sons (by his first marriage), George (34) and Albert (32), who are learning the family business in Rahway; eldest daughter Serena ("Bambi"), 24; son John, 22; and Judith, 19, who hopes, when school opens, to take up one of her father's interests: conservation.
Conservation is in the Wind Gap air. Merck climbs into his jeep and sets out for a jolting ride over the 2,000 rugged Vermont acres which he is trying to bring back, after a century of neglect, into efficient use as useful farm and forest land. He has supervised the planting of 90,000 evergreens, and would rather swing a brush hook to clear the undergrowth than play golf ("I get too mad at it") or even tennis ("The only game I seem to get better at").
Sitting around his red & white "farmhouse," George Merck has one of his rare chances to philosophize at leisure. Of one thing he is confident: there is more of the unknown ahead than the scientists have left behind. And there is nothing George Merck enjoys more than the thought of unexpected adventures in the offing. "For one thing," he says, "there's always serendipity. Remember the story of the Three Princes of Serendip* who went out looking for treasure? They didn't find what they were looking for, but they kept finding other things just as valuable. That's serendipity, and our business is full of it."
* Literature's most famous prescription was not up to U.S. pharmacopoeia standards:
Fillet of a fenny snake,
In the cauldron boil and bake . . .
Gall of goat, and slips of yew
Sliver'd in the moon's eclipse,
Nose of Turk, and Tartar's lips,
Finger of birth-strangled babe
Ditch-deliver1d by a drab . . .
--Macbeth
* In drug-trade lingo, "ethical" drugs are never advertised directly to the public, but always to doctors and druggists through professional and trade journals, and are usually sold only on prescription. "Proprietary" drugs are the old patent medicines gone respectable; no holds are barred in advertising them or pushing over-the-counter sales.
* An old Arab tale which inspired Horace Walpole to add a word to the language in 1754.
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