Science and Medicine
Mosquitos and Steam Shovels
One of our most valuable engineering possessions today is the Panama Canal. This Canal saves the ships going through it as many as 9,500 miles or about a month's travelling time. The building of the Panama Canal was the first full scale test of sanitary engineering which had been started by Dr. Donald Ross in his fight against malaria and Dr. Walter Reed and Dr. Finlay in their fight against yellowjack or yellow fever.
To show you the importance of this full scale attempt to control disease, in 1880 the French organized a company under Ferdinand de Lesseps, to build a canal from the Atlantic to the Pacific Ocean. De Lesseps was the man who had built the Suez Canal and was well fitted to do this job. The French company spent hundreds of millions of dollars but they gave up in 1899, not because their machinery was inadequate for the job or their plans were wrong. The thing that stopped them was malaria and yellow fever. So effective was this stoppage that in 1900 all they had left to show for their great effort was a partly finished canal overgrown with jungle, rusted, vine-covered machinery and Monkey Hill Cemetery, which contained, as one writer says: "acres and acres of little white crosses."
Now, most people thought of this canal as being a great construction engineering project and when, in 1904, the United States bought the French concessions for about twenty million dollars, we felt that this was just another job for American ingenuity. A big job, everybody conceded, but nothing unusual for us.
When you see the finished canal with its great locks, electric mules and ships coming and going, we must wonder why we succeeded when the French failed. We knew one thing that the French did not, and that was the habits of two female mosquitoes - the distributors of yellow and malarial fever.
Major Gorgas, later General Gorgas, was on a sub-committee in charge of sanitation. When he looked over the Canal Zone, he was not particularly concerned about the engineering problems; what he saw was the tropical Jungle swarming with insects, a perfect home for yellow fever, malaria and every tropical disease and, above all, he saw the acres of little white crosses.
Doctor Gorgas had been with Doctor Walter Reed in Cuba where they first found out the facts about the two mosquitoes - the Stegomyia, carrier of yellow fever, and the Anopheles, carrier of malarial fever. Doctor Gorgas was one of the few men who recognized that if we were to ever have a Panama Canal the real problem was going to be the extermination of these two mosquitoes - it was going to be sanitation first and then steam shovels.
And it is a very fortunate thing for us today that the previous sanitation experience of Doctor Donald Ross and Doctor Walter Reed in Cuba gave Doctor Gorgas the background to win his uphill fight with many officials who didn't see this real problem but only the apparent problem of moving dirt and building locks. For three years, Gorgas conducted an intensive campaign to exterminate the carriers of fever - erecting mosquito-proof buildings, installing an efficient sewerage system and putting oil on stagnant pools.
When we finished the Canal, in 1914, the death rate in the United States was 14 people per thousand. In the Canal Zone, it was only 6 people per thousand when the French were trying to do the job, they were losing about 200 out of every thousand men. Through the effort of Gorgas and his men, the Canal Zone was made over twice as healthy to live in as the United States.
As we look back on the construction of the Panama Canal, we must admire General Gorgas' ability to see it as a great problem in medicine as well as engineering construction. (General Gorgas was gifted, through his experience, with the ability to see beyond the apparent problem of moving huge amounts of earth with steam shovels and to pick out the real obstacles - mosquitoes.
When the medical men return from the war, they will undoubtedly have many stories to tell of lives saved and battles won which can be traced back to the fundamental work in sanitation which had its first full-scale tryout in the digging of the Panama Canal.
Today, the Canal stands out as not only one of our greatest engineering assets but, as time passes, one of our greatest health assets and a monument to those pioneers in sanitation.
Twice in a Lifetime
It was knowledge gained by manufacturing our everyday necessities that gave us the background which makes the production of military materials seem so spectacular.
One can never tell when this information will be valuable until an emergency develops. The same is equally true in a research project. Many of the apparently new and amazing things produced in the war are just new uses of old peacetime products.
As an illustration, mechanical household refrigeration was in the kindergarten stage before World War I. But we had been at it long enough to appreciate the necessity for a more suitable gas. Those in use were toxic and irritating.
During this time, our Organic Chemistry Department was making laboratory experiments on new gases, along with studies on synthetic rubber and high octane fuel.
When the War was over, we finished the fuel job first by putting Ethyl gas on the market. This same material is still one of the essentials in most high octane gasoline.
When the gasoline job was finished, our division, which was making refrigerators and air conditioning units, asked Thomas Midgley, head of the Organic Chemistry Department to take up the work on refrigerants. A set of ideal specifications was written. The new gas must be non-inflammable. It must be non-toxic. It must be non-irritating, and it should not be expensive. But, studying all the available scientific tables and data, it was found that only a few things could even be considered, and there were some objections to each one.
There was a bare possibility that some could be combined so that the bad qualities would neutralize each other.
Looking at the tables, one of the most promising group of chemicals contained Fluorine, but Fluorine had a bad reputation - even to a high school chemist. Midgley said of the work, "We plotted the boiling points, worked slide rules, brushed away eraser dirt and pencil shavings and did all the other formalities that take the place of tea leaves and crystal balls in the life of a scientific fortune teller."
After this had gone on for a long time, the search focused on one compound which, for the sake of simplicity, they called F-12.
To make this unusual compound, they found in this country there were only five 1-ounce bottles of the starting material they wanted to use. One was selected at random and a few grams of the F-12 were prepared. A guinea pig was placed under a bell jar with it and, much to the surprise of a physician present, did not gasp and die - in fact, it was not even irritated. Obviously the material was non-toxic.
When the other four bottles were tried, the experiment did not work. I t was later found they were not pure. The amazing thing about this whole experiment was that only one of the five bottles of this chemical contained really good material and, by sheer accident, it was picked for the first trial. If anyone of the other four bottles had' been tried, the guinea pig would have died and probably with it the research on F-12. There is no doubt about it - luck played a great part in saving time in that experiment.
As a result of the discovery of this new refrigerant, all risk of toxic harm was removed from home or hospital refrigeration and air conditioning. No longer need people worry about the refrigerator leaking, and the gas injuring those who might be sleeping. When World War II came along, as I said in the beginning, many demands were made on our everyday products, and this tailor-made refrigerant was asked to do an entirely new job that was not even remotely considered in the original specifications.
It was found to be a most effective weapon against malaria-bearing mosquitoes on the battle front. So it may be quite possible that twice in a soldier's lifetime - once as a child at home and later on the battle field - this unusual material saved him from harm.
That is the encouraging thing about any scientific development - its ultimate usefulness can never be foretold, or even guessed, at the time of discovery. Our work in the future, as in the past, will be to concentrate our efforts on really fundamental problems - the results, many of them unpredictable, will always take care of themselves.
Purple Dye, Sun Glasses and Malaria
This is the story of a battle - a battle which began over a hundred years ago and is still being fought by doctors all over the world. It is the battle of Malaria.
Down through the years we have fought the cause of this disease with sanitation, mosquito netting, by oiling stagnant pools and with insecticides. And we have combatted the disease itself with Atabrine and - quinine. Atabrine is a substitute material but it is not synthetic quinine.
Today, we all know the importance of quinine, and so did the Belgian, Van der Heyden 300 years ago when he wrote about the healing value of an extract from the bark of the Cinchona tree.
So did the French chemists Pelletier and Caventou, the first ones to isolate pure quinine from the extract over a century ago. And so did Pasteur when he made quinotoxine from quinine in 1853.
But sometimes, quinine isn't available to do its fever fighting. Such was the case nearly 100 years ago, when the Englishman, William Henry Perkin, set out to chemically reproduce quinine to combat a Malaria epidemic. As one man has said "the chances for success then were about as good as those of a carpenter who tries to build a house at the foot of a hill by sliding shingles, rafters, doors and window casings down from the hilltop." Perkin failed in the synthesis but he did discover aniline purple, the first coal tar dye, and this started a new industry.
Some years ago quinine interested an American, Edwin Land, in connection with an entirely different project. He found that by aligning crystals of quinine and iodine in a transparent plastic sheet, he could inexpensively polarize light.
Many of you have used polarizing sun glasses based on this principle. But the new company which resulted from this development could see that trouble in the Far East might some day interfere with its supply of quinine. In March, 1942, their worst fears were verified - Japan seized Java. But in the meantime they had anticipated this event and had planned research along two lines: a substitute polarizer made without quinine and then the more difficult task that had baffled scientists for nearly a hundred years - synthesizing quinine itself.
They asked their chemical consultant, Dr. Robert Woodward, to help tackle first the job of producing the substitute optical material, and after months of work they solved the problem. Quinine was no longer necessary so there was really no need of trying to do the alternate job. But Woodward had often dreamed of synthesizing quinine and one day when the president of the company asked him if he thought there was any chance of doing it, Woodward immediately replied, "I believe it can be done!" So they tackled this very difficult job with its background of nearly a hundred years of failures - not to make a substitute for quinine but to reproduce the exact molecule.
On February 1, 1943, Woodward and his co-worker Bill Doering set out on their journey. They first built a wooden model of the quinine molecule consisting of 52 balls colored to represent the atoms of carbon, hydrogen, nitrogen and oxygen which make up the molecule. For months they labored only to discover that they were not hooking the atoms together in the right way. As Doering said, "We were ready to pack up and go home!" This happens at some time in nearly every research project. But after careful, investigation, they found a mistake had been made in the testing method. Then began the final spurt, and on April 10, 1944 - fourteen months after they started, they synthesized Pasteur's quinotoxine. Then by reversing Pasteur's process, the road was opened to the actual production of quinine itself.
This is a typical story of progress. It started a hundred years ago and dozens of men carried on the work. Out of this search has come a new method of making dyes, and a great industry. And the final answer is found as a by-product of a search for an optical material - a far cry from a medicine to combat Malaria.
But all of these men found something and added to the sum total of human knowledge. That is the secret of progress. As long as we try and patiently do our best to solve the problem, although we may not get the answer we are looking for, we always get something - even if it is only the valuable experience.
Flying Death
Just as Roger Bacon seven hundred years ago encouraged the alchemists of the Middle Ages to use a more scientific approach in their work, so our modern research men have taken the black magic of our South American jungle and separated the facts from the superstitions. By using this process they have uncovered several new principles of value to the doctor. The more we investigate the customs and medicines of so-called savage tribes, the more we appreciate their contributions to our modern world. Through their intimate contact with nature, and under the pressure of necessity, they have, through the centuries, developed or discovered drugs and cures that now have world-wide use.
We all know of the value of quinine, and our war in the tropics has greatly emphasized its importance, but it is not well known perhaps that the South American Indians used extract of quinine to treat malaria hundreds of years before a Jesuit priest brought the first knowledge of it back to civilization.
Or perhaps we do not know that the leaves of the coca bush from which Cocaine is derived was used by these Indians to reduce pain in certain skull operations hundreds of years before anaesthetics were developed here.
Only recently a material first mentioned by Sir Walter Raleigh 350 years ago has received a great deal Of attention from the medical profession. It is called Curare here and "the flying death" in the South American jungle. It gets its name "flying death" from the fact that it is used to tip the arrows shot by the Indians from their blow guns.
There is nothing particularly new about poisoned arrows as they were used in prehistoric times. The word "toxic" meaning "poisonous" is derived from the ancient Greek word "toxikos" meaning "of the bow." The Indians of the Amazon developed this unique preparation to fit their own particular needs however. To use it, the sharpened end of a small arrow about ten inches long is dipped into the Curare. Around the other end is twisted some kapok to make it air-tight when fitted into the blow gun. The gun itself is about nine feet long and by aiming at a bird or animal and then giving a sudden puff with the mouth, the hunter could bring down the game within a range of approximately one hundred feet, or about as far as one can see in the jungle.
The unusual properties of Curare become evident almost immediately after the arrow pierces the skin of the bird or animal. In a matter of seconds, the victim loses its muscular control and then can be easily picked up and carried home by the hunter. Of equal importance is the fact that the food value of game captured in this way is not in the least impaired. We usually think of poison as producing a violent reaction, but as we have seen, this material abolishes all motor impulses.
When this peculiar quality was brought to the attention of the medical profession years ago, it raised the hopes for a much-needed treatment for a very special group of patients. In the United States there were over two hundred thousand cases of a peculiar illness involving violent contractions of the muscles. Now since Curare produced just the opposite effect, it was felt that the obtaining of a test sample was of major importance to the medical scientist. Richard Gill made a successful search for the "flying death" and the process by which it is brewed in the Ecuadorian jungle. His own story of the adventure is told in the book WHITE WATER AND BLACK MAGIC.
From the comparatively large amount of material brought back from the jungle pharmacy, many tests were made. A process of purification was devised, and studies on how to make it synthetically were started. The size of the dose for medical use was very carefully determined and the practical knowledge of the jungle converted into our modern scientific terms. Clinical tests were started and a group of patients unable to talk intelligently, write or feed themselves, were so relaxed by very small doses that they could approach a more normal life soon after the treatment started.
The drug is not a cure, but it does make possible the re-education of muscles. Experiments have been made in the use of this material for many different types of ailments and undoubtedly Curare will find a definite and permanent place in the medical field.
Facts are valuable because of what they contribute to the welfare of the public, and this value is independent of the source of the information. It is fortunate that we live in a country where men are encouraged to invent and discover for here the open mind of the research chemist can examine any project and evaluate it whether it comes from the jungle or the greatest scientific laboratory.
Dr. Fleming Opens the Door
Just recently, a news item told us that the noted scientist Dr. Alexander Fleming, the discoverer of Penicillin, is in America for a visit with our doctors, scientists and manufacturers. The story of this discovery is both interesting and instructive.
One day seventeen years ago when Dr. Fleming was teaching bacteriology at St. Mary's Hospital School at the University of London, he set aside a culture of bacteria, and some hours later, when examining the plate under a microscope, he noticed it was spoiled.
The culture grew on only half the plate - the other half was spotted with a blue-green mold.
Many observers normally would have thrown the plate away - but Fleming had been looking for a special material for a long while so he wrote in his notebook these undramatic words that were to help change the science of medicine, "I was sufficiently interested in the anti-bacterial substance produced by the mold to pursue the subject."
In the first World War, as a Captain in the Medical Corps, Fleming had observed some of the antiseptics used were more harmful to white corpuscles than to the bacteria. So he gave his newly found material this test, but the white blood corpuscles came through unharmed although the new substance was two or three times as potent as carbolic acid.
In 1929, Fleming named his new drug Penicillin. It is an extract from the mold Penicillium Notatum - the name Penicillium is from the Latin for "pencil" or "brush" which describes the mold as seen under a microscope.
But during this period another sensational remedy took the lime-light. The dramatic sulfa drugs began to interest all of Science.
However, just before the present World War, their limitations were being recognized and the World of Science resumed its search for a better all-around antiseptic. And Dr. Fleming's ten year old discovery again became active.
This time a scientific team began to investigate the properties of Penicillin Dr. Howard Florey of Oxford, his wife and Dr. Ernst Chain started to grow the mold again and at last obtained enough for animal experimentation. At first they treated mice inoculated with streptococci. Those treated with Penicillin lived, the untreated ones died.
Penicillin, unlike the Sulfa drugs, combats bacteria, not by starvation, but by preventing their multiplication, thereby enabling the body defenses to overcome the primary infection. It is most effective when injected and is also an ideal antiseptic for wounds. The fact that it is non-toxic adds greatly to its value. So far as reported, few, if any patients have had to quit taking Penicillin because of unpleasant reaction.
As these remarkable characteristics became known, and with a World War on hand, the demands for Penicillin increased in England. But, unfortunately, the supply could not keep pace because the mold was still being grown in laboratory flasks. Over in this country the Boston Cocoanut Grove fire first caused American doctors to demand larger quantities of the drug that had proven so effective in healing the fire victims.
With the outbreak of the War over here our government asked over twenty drug and chemical manufacturers to study the problem and millions of dollars were put into manufacturing plants to produce Penicillin in larger quantities.
Dr. Andrew Moyer tackled the problem of growing the green mold and tried many different kinds of food material. One of the best ones he found was the water in which the starch-makers have soaked the corn. From this work the amount of Penicillin obtained from a given amount of mold has increased a hundred fold. That is 10,000 per cent. That is one of the reasons why Penicillin is available to our men at the front and to our hospitals here at home.
At a recent luncheon honoring Dr. Fleming, one of the speakers made a statement which is of unusual importance. In mentioning the great value of Penicillin, he stated that there is a good possibility that this material can save more lives in the next ten years than have been lost in England and America during the war.
This is a remarkable tribute to Dr. Fleming's discovery. Dr. Fleming says we should not look at this as a finished development. There are some 100,000 varieties of molds and fungi and he is quite sure - it would be a miraculous accident if he had - the first time - hit upon the best one. Thus is opened the door of an entirely new world for research, discovery, invention and human service.
D.D.T.
War has always been a scourge. It not only destroys lives and property in a direct manner through shot, shell, bombs and fire but it often leaves in its wake death and disease in many other forms. Among these, typhus has probably been the greatest killer, and, malaria, another destroyer, offers a constant menace because of its prevalence in the tropics. The cause of these threats to human life are the many insects that carry disease. In contrast to other great conflicts, we hear little about the loss of life due to pestilence in this war. Why is this?
As in so many cases we won't find the answer in one of today's scientific discoveries. Here we shall have to go back more than seventy years and look over the shoulder of a chemical student, Othmar Zeidler, performing an experiment in Strasbourg. Young Zeidler on this particular day in 1874 produced a new chemical which he recorded in his notes as dichlorodiphenyl trichloroethane - D.D.T. for short. But he saw no use for it, and the formula lay dormant in the records of the Chemical Society for sixty-five years.
In 1939 Swiss farmers were bothered with an unusual number of insects and since there was a great shortage of the usual insecticides the Geigy Chemical Company of Switzerland began to look around for substitutes. One of their young chemists, Paul Mueller, resurrected Zeidler's old formula and tried out some of the D.D.T.
The results were amazing. It took only the slightest contact with the chemical to kill the insects. But the Swiss scientists found the usefulness of the new insecticide was not limited to just plant destroyers - it was equally effective against flies and lice. And when the War broke out and with it came the threat of typhus the Geigy Company's American branch in New York turned over to our Army samples of the new insecticide which they had received from the parent company in Switzerland.
In Orlando, Florida, government entomologists began to test the new material and all of the amazing claims were justified. A little D.D.T. powder dusted into the clothes safeguards the wearer from typhus - for two weeks - and if the clothes were washed in a solution of the chemical the period was extended to three months!
When sprayed over a stagnant pool it completely rid the water of mosquito larvae within 24 hours - an effective answer to malaria. Next it was tried on the walls of a barn literally infested with flies. As if by magic the flies disappeared and were not seen again for over a month. D.D.T. had passed all the tests and came through as the outstanding insect-killer. But now that its potency was proven there still remained the problem of getting it in large quantities.
The pioneer company to tackle the job in this country was the Cincinnati Chemical Works. It is one thing to produce something in the laboratory test tubes and another to manufacture it by the ton. But the difficulties were overcome, and in 1943, D.D.T. began to go to the fighting fronts. As other companies went into production the new chemical joined our armed forces on the battlefronts in ever-increasing quantities. No one who has ever fought the battle of disease will underestimate the importance of this most powerful weapon.
But insects are with us not only during a war - we wage a constant battle against them at all times. They destroy the farmer's crops and spread disease among all mankind. In India alone malaria kills a million people a year and in this country the common fly transmits disease to thousands. D.D.T. is our new weapon against the great loss caused annually by some eight thousand different kinds of insects. For home protection we can spray a screen and a fly won't light on it for three months. It will kill more different kinds of insects using a smaller dose than any other chemical now known. Undoubtedly when the War is over it will be sold to the public for general use.
Little did the young Zeidler know that day in Strasbourg that he was providing man with one of his most powerful weapons against disease-carrying insects. This is nearly always the case in the most important discoveries - the inventor rarely sees the ultimate application of his idea.
For this reason we should encourage and treasure every new development - however unimportant it may seem at the time. Some day in an emergency it may turn out to be a thing of utmost importance.
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