I S D CSTRIBL A&D EitTGINEERI.VG CHEMISTRY
954
Evaluation
Closely associated with the topic of drug standardization is that of drug evaluation. Possibly in no other phase of practical synthetic chemistry is there more confusion or misunderstanding of proper procedure. Often chemists smile a t physicians for lack of certain chemical knowledge, and physicians smile a t chemists for the lack of appreciation of bedside therapeutics. What, then, in general seems proper technic for introducing a new chemical as a drug? Experience causes one to venture the following: (1) The chemistry should be well worked out, including evidence of a definite compound (together with its molecular structure). The possible impurities should be eliminated altogether or limited by proper tests. The method of assay for its control is important in order that the pharmacologic and experimental clinical work may be comparable. I n case of extracts of organs, etc., or those few potent compounds which cannot be prepared in the pure state or are relatively unstable, biologic methods of control should also be determined-for instance, “insulin units.” (2) The action on experimental animals should be studied by a competent pharmacologist. This is important, not only for information regarding the various actions of the drug, but also to determine if trials on humans are warranted. (3) The crucial test of a drug is clinical experimentation under definite conditions. But first it is scientifically imperative that the preceding steps shall have been taken. A physician is not warranted in trying a drug until careful chemical and pharmacologic evidence is provided. Clinical therapeutics is recognized as most involved; the testing of a new drug, therefore, must be under rigorously controlled conditions-not simply the uncritical procedure of “trial” on this and that patient. For example, in case of a new drug for arthritis, it would be advisable to have under observation about fifty patients suffering from “rheumatism.” They would be divided fairly into two groups. To one group the usual treatment should be given; to the other exactly the same treatment-same food, etc.-except that the new drug should be used in place of the old drug, and in a manner to rule out psychic effects as far as possible. If carefully
Vol. 18, No. 9
kept records are in favor of the second group over that of the controls, then there is evidence of superiority of the new drug. Such tests, it can be seen, can most readily be carried on a t hospitals. An added refinement, if possible, would be to label the two drugs for comparison with key numbers, known to the drug dispenser but not to the physicianthat is, the blind test, the only method that makes the results purely objective. Introduction of Drug
Often after a drug has shown promise of considerable merit, it has been introduced through the wrong channels. Many a substance has suffered because the promoters have announced the discovery and discussed the therapeutic use through the daily press rather than by presenting the claims supported by scientific data through proper scientific mediums which have a clientele capable of judging therapeutic evidence. The unfortunate premature newspaper introduction of the new synthetic fat for diabetes-a product resulting from excellent chemical reasoning-is in sharp contrast with the dignified presentation of insulin or tryparsamide which followed a period of well-matured experimentation. The selection of a proper name is important. The name should be indicative of its chemical composition. The medical profession justly looks with suspicion on a product which has a therapeutically indicative name. When the generic chemical name is too involved for practical usage, a coined contraction is quite in order-as an example, barbital for diethylbarbituric acid. Finally, purveyors of new products to the medical profession find it to their advantage to make conservative claims for a new drug; most of them present their new additions to materia medica to the official body appointed by organized medicine to inspect the competency of the evidence and to pass on the status of new or nonofficial medicaments. By these procedures the respect and confidence of progressive physicians are won. J For excellent discussion on this topic, see Sollmann, J. A m Med. A s s o c , 69, 198 (1917)
Fifty Years of Developments of Compressed Gases’ By G. 0. Carter LINDE AIR
I
PRODUCTSC O , h - E W Y O R K
K 1876
most of the gases that are now so commonly used were known to scientists and many of their properties were understood. I n some cases the development in application has been a mere refining process. Both of the very important compressed gases of today, carbon dioxide and oxygen, were then used for major purposes, for which they are still used. Carbon Dioxide and Oxygen
The well-known soda water had been developed before the centennial year, and in the inherent uses of carbon dioxide for soda water the changes do not seem to have modified the earlier principles utilized. I n the same way the use of oxygen with fuel gases to obtain a very intense and hot flame was well known, and the art of melting metals in small quantities and of lead burning was well understood. New uses have been developed for both of these gases. Carbon dioxide has been very largely utilized in refrigeration 1
Received June 26, 1926.
Y
work, and this development of mechanics has grown from practically nothing to its present importance during the fifty years. Within the past few years many interesting uses, considered by that industry to be on a small scale, have resulted in the use of carbon dioxide in the manufacture of automobile tires, in fire-extinguishing, paint-spraying, etc. The volume of gas used in almost any one of these minor applications would far exceed the total use of compressed carbon dioxide fifty years ago. Oxygen has added a new use in metal cutting, which has been developed since 1907, and now assumes very large proportions. It is interesting to note, however, that the use of oxygen for rapid burning of iron was described by Fletcher, fifty years ago, but nothing was done until oxygen was readily available in reasonably large quantities with the development of the containers, which will be mentioned later. I n 1876 the gases which are being included under the heading of compressed gases, to distinguish them from illuminating gas, were really not available in compressed
September, 1926
1 9 D U S T R I S L A,VD ELVGI.VEERI~VGCHEMISTRY
form, as we now know the compressed gases. Practically every user of gases had to generate his own gas by rather complicated chemical or expensive thermal reactions, most of which existed in this century. The earlier derelopments of soda water called for the charging of the mater a t the source of manufarture of the
955
with or have superseded the gases first used. Ammonia is very extensively used in many refrigeration plants, because it does not require such high pressures as carbon dioxide and also because it permits the use of different engineering principles, such as absorption, instead of compression, although it can be used for both types of apparatus. Several other gases are used in refrigeration sybteins, because of their physical characteristics, as they operate a t lower pressures than either of the two major gases. Among these, sulfur dioxide and ethyl chloride are in extensive use. It has recently been found that practically all of the hydrocarbon gases of the methane and olefin series are efficient refrigerants. Ethane and ethylene have very nearly the characteristics of carbon dioxide, propane and propylene those of ammonia, and butane those of the low-preqsure gase-. Hydrogen
Oficzal Pholopraph, U . S A r m y day Seraace Tank Car Devised to Transport Helium for the United States Army Air Service. Each Triple-Cylinder Car Is Capable of Holding 206,000 Cubic Feet of Helium Stored a t a Pressure of 2000 Pounds
carbonic acid gas, except where natural carbonated waters were obtained. The use of oxygen was very seriously proposed, but as an adjunct of illuminating gas, and a t about the time of the centennial there were several cities in Europe where oxygen was piped in lines parallel to illuminating gas lines. The two gases were combined as the oxygen-gas flame to make the Drummond or lime light. In S e w York City such a system was installed to furnish light for night work during the construction of the Brooklyn Bridge. Along with the development of the illuminating gas aiid the attempt to utilize oxygen with it, a business developed in the supply of each of these gases under relatively low pressure, say not to exceed 100 pounds, in tanks about onehalf the size of our present-day range boilers. This wa4 practically the beginning of the compressed gas industry and was very iiiateriallg furthered by the development of fairly economical large-scale methods of producing oxygen, such as by the Brin process, using barium oxide. This method mas discovered a year or two before thcl centennial and resulted immediately in the incorporation of the British Oxygen Company, which thirty years later adopted the liquid air method of producing oxygen, permitting the production of a much higher average grade product than with the Brin method, and also a reduction in cost of production. The present status of the compressed oxygen industry i. such that there are large production factories in practically every large city of every important nation of the world. In the United States there are a t least one liundred factories, inost of which produce oxygen by liquefaction of air, although some use the method of electrolysis of water. The production of high-purity oxygen a t a much lon-er cost than that of oxygen fifty years ago, has undoubtedly helped in the development of the present-day applications. On the other hand, the discovery of acetylene and the development of the oxy-acetylene welding and cutting process have had a big influence in developing the demand for compressed oxygen to such an extent as to warrant the production on a large scale. This is similar to the old question as to whether the high-speed elevator developed the skyscraper or whether the skyscraper developed the elevator. Refrigerating Gases
I n some directions, such as in refrigeration, other gases have been found suitable and have been developed along
The earliest known combustible gas n a s pure hydrogen. Then methane aiid ethylene were obtained and the distillation of coal gas from coal was developed. Hydrogen has been compressed in about the same type of containers as is used for oxygen, since the earliest days of compressed gases. Hydrogen is still used to some extent as a compressed gas in connection with lead burning, oxy-hydrogen cutting, inflation of toy balloons, and other rnnior uses. Hydrogen as an industrial gas in the well-known hydrogenation processes is becoming of very great importance, but a5 a conipressed fuel it seems to have served its purpose. Acetylene
Many of the hydrocarbon gases are being compressed either as pure gases or as mixtures, for use as a fuel in connection with oxygen cutting, but in the realm of fuel gases the outstanding one of today is acetylene. Calcium carbide, from which acetylene is made by decomposition of the carbide in water was discovered almost simultaneously in the United States and France in the early nineties. Its wonderful illuminating qualities were promptly noted and steps were taken to compress acetylene into cyl-
Liquid Chlorine One-Ton Containers
iiiders. From the serious accidents that occurred it was learned that acetylene should never be shipped under a pressure in excess of 15 pounds above atmospheric pressure, except when properly dissolved in a suitable solvent which is contained in a porous material. The containers for conlpressed acetylene are well known today. At the beginning of this century a Frenchman, Fouche, learned how to combine acetylene and oxygen to make the oxy-acetylene welding flame. Acetylene contains a greater percentage of carbon than any other known gas with the
exreptiuri of ht~nzene,iii addition to which acetylene has ZL very high eniiot.liermic ialue whicli gives it a flame temperature peatly.iii execs of that of any other known flame. This pennits the use nf the oxy-acetylene flarne fbr the fusion of all known metals, and gives 116the weIl-kiaiu;ll oxy-acetylene weldiiig process. Iii 1007 t,bi: iiw of a.cetylene and oxygen for the cutting of iron and &el i m s (lo~elopedand tlie two processes of miding and cutting haw: gone RkJng shonider to shoulder. Another interesting we of compressed acetylene is for lighting beacons, IJlIoyS. rl~adsignals, and even lighthouses. Compressed acetylrnr is siipplied by practically as inany jirochictiim plants as i s (isygtw, and can br readily ol)tained in almost any quaiitity frmi a fcw wbic feet, up to 300 cubic: Eeet in a cylinder. In t.lic early days of the antoniol.rileindustry, the oars were lighted at night hy nieaiis of cylinders, which were carriel1 in tlio fonn of siiiall to& on each rar. Today a large percentagc of the h e a q trucks are lighted by t,liis same system. Anesthetics
A n interesting new application of acetylene and US several of tlie gases of the olefin series is for anesthesia, in whicli field they eompi?te with the long known gas, ~litrousoxide, which in itself has had a very interesting history. Nitrous oxide WRS probably the first anesthetic used, datiug hack to tlie 1840’s. Its use was found to he difficult hecauPe an over supply could be administered without any indication in the condition of the patient until the p i n t of sutTocation had been reached. When this characteristic was noted, nitrous oxide gave way in favor of chloroform and ether for many years. The development of equipment to admiuister nitrous oxide and oxygen simultaneously
Inert Gases Certain {if the gases, such as nitrogen and argon, are useful liecause of their inertness. Each of these gases is carefully purified t,o the utmnost. h i t , then is utilized in the manufacture of incandesccnt lamps. Kitrogon in an average 1 purity of 00.5 pm cent is used in the manufacture of antoniobile tires.
Germicides and Poison Gases ‘rilgases is chlorine, which is being iisrd on an ext.eusivc si!ale for j~urificationof drinking water for many of the large
ritics in the Cnited States. Chlorine was very difficult. to triinspiirt economically and safely when its iises were first developeil and a great deal of the growth in its uses has been due to t.hc development of thc compressed gas cylinder arid t.hc further development of the one-ton chlorine container. Chlorine is also ext,ensively used in bleaching in conneetioii with the pnlp and paper industry, grinding of flonr, and in the texbile iiirlustry. Chlorine is a very active chemical reagent and is used in many important chemical processes. Cyanogen is a comparatively new gas used for germicidal purposes such as fumigation and is very effective in exterminating rnt,s on ships and rodents in ground burrows where it is difficnlt to apply a fumigant other than in gaseous form. The combination of carbon monoxide gaz, and chlorine gave the well-known war gas, phosgene. This gas was utilized along with many other gases, such as hrornine, mustard gas, tear gas, etc., industrial applications of vhich are being slowly $eveloped under the guidance of the Chemical Wariare Service, United States Army. Because of the danger involved in generating noxious gases, sncli as hydrogen sulfide, many odd gases are being compressed int,o cylinders and sold for laboratory purposes. Helium
I’rior to the World War, some little work had been done in connection with the application of hydrogen to balIoons, hut the war gave this use very great impetus. Because of t.he inflammability of hydrogen and the desirability of liaving a nonflammable balloon gas, the production of heliinn was developed, and today even helium is being shipped in quantities far in excess of shipments of all compressed gases before the beginning of this century. A recent development for the shipment of helium in large qnantities is tlie so-called “helium car,” which will contain 200,ooO cubic feet of helium in each of three large containers. Gas
Cylinders for Compressed Gm8e~
which pennits anestlietists to shut off the nibrous oxidu nnd to torn on a supply of high-purity oxygen, has resulted in a very extensive development of nitrous oxide and also of oxygen. A furt,her development of compressed oxygen in medical work is in the treatinent. of pneumonia p:,tients, where much progress has recently heen made, although oxygen has h e n inure or less inefficiently used for such treatment for a t lmpt twenty-five gears.
Containers
As was nientioned earlier in this r4suni4, the use of inany of the compressed gases has grown with the development of the container or cylinder. The earliest containers were small riveted and brazed tanks for pressures of 100 pounds only. Then similar tanks for pressures up to 300 pounds were developed, and finally, hocause of the desirability of shipping carbon dioxide in a liquid state, at a pressure of approximately 1OW pounds, the so-called high-pressure rontainer or cylinder for 2000-pound pressure was developed. Today high-pressure cylinders are used for storage of practically all the gases except acetylene, chlorine, ammonia, and sulfur dioxide, and some combust,itJle gases. The method of storing acetylene has heen noted above. Chlorine, sulfur dioxide, and ammonia are liquid a t re1at)ively low pressures and are generally shipped in large containers made of large diameter pipe. Hydrocarbon gases which liquefy at low pressures are shipped in thin-walled cylinders specially made for the purpose.
