On a November day 17 years ago, an employee of an Italian branch of Parke-Davis and Co., the American pharmaceutical firm, scooped a thimble-sized quantity of dirt, however, did not prove to be just sae, Naples Province, poured it into a plastic-bag-lined manila envelope and mailed it to company headquarters here.
Cicillo Aldo was simply doing what Parke-Davis employees have done in various places around the world 75,000 times since 1940. Aldo's package of dire, however, did not prove to be just another soil sample. It yielded a microorganism containing 9-Beta-D-ara-binofuranosyladenine, nickname vidarabin or ara-A, the first effective weapon man has found against one of the usually fatal virus-caused diseases.
Like the discovery of penicillin, medicine's first major weapon against bacterial disease - which was stumbled upon when it contaminated a bacteria sample - the discovery of ara-A in nature was in part a chance occurrence. Thus, it was typical of most scientific discoveries.
The discovery also typified many major scientific advances in that it was made almost simultaneously by two groups of researchers. in 1960, a group of scientists reported in the journal of the American Chemical Society that they had artificially produced ara-A. They were looking for anticancer agents and ara-A proved useless to them and was discarded. Parke-Davis then became the first organization to find ara-A in nature, grow it and find a use for it.
Had Aldo taken his sample of dirt a few miles, or even a few yards, away from where he gathered it, the sample might not have yielded ara-A.
"The search for antibiotics, antifungals and antivirals, grown or produced by microorganisms, requires a source of microorganisms, and the greatest source is the earth itself," explained H.E. Machamer, Parke-Davis's director of biological research and development.
"There is no rational reason to want a soil sample from any one area," he said during an interview at the firm's headquarters here. "The basis of the search is that by getting soil samples from a lot of different localities, which would change the meteorological characteristics - the soil texture, plant life, you name it - you have a better chance of getting a wide array of different organisms.
"What one is really doing is searching for a microorganism that I'd like to call a natural mutant, one which when cultivated under the proper conditions in the laboratory . . . produces a material that seemingly has no value to (the microorgansim), but when extracted and purified has the effect of destroying bacteria, or fungi, or, in this case, virus."
The search, said Machamer, is serendipitous "and empirical. It's a numbers game. The more 'isolates' you get from more and more soils, the better your chance of finding one which performs a useful, novel" function.
It all comes down then to whether a particular salesman or employee chooses to help the company by voluntarilly providing it with a soil sample, and where he decides to gather the sample.
Machamer, for example, sent the company samples gathered while he was vacationing in Brazil. They have not led to any startling discoveries.
Cicillo Aldo gathered his single sample in Italy and helped save the lives of persons suffering from herpes encephalitis, a disease which kills 70 per cent of those who contract it.
Aldo's soil sampling was the major "accident" leading to the discovering of ara-A in nature. The steps that followed over the next 17 years were anything but accidental.
Like all the other samples gathered at that time as part of a search for new antibacterial, or antibiotic, agents - the Italian soil sample was stored until the Parke-Davis scientists were ready to use it.
Using the sample meant placing bits of the dirt in a liquid solution and placing drops of the solution in a jelly-like material in a glass petridish. The drops then were incubated on various plates, at various temperatures with an without oxygen.
"The theory is that each single microorganism is so dispersed in that dish that as it grows and reproduces it produces a colony that is macroscopic, that is, it can be seen with the human eye," Machamer said.
When the colonies are developed, a small amount of the visible material from each colony is removed from the dish and examined under the microscope. if the scientists can see more than one microorganism, they repeat the process until each but of stuff removed from the dish produces a single type of microorganism.
"Now you have a pure culture," continued Machamer, but "you don't know if it produces an anti-anything. At that point, it is what we call a seed culture. It is put into (a container that is automatically shaken) for days to weeks, at the end of which time it is taken off the shakers and is . . . spun or filtered . . . and we look at the microorganism we might have made."
The scientists then place whatever they have in more petri dishes, this time "seeded" with the bacteria. If the microorganism produces a "clear zone, or halo" around itself, it has antibiotic properties. Similar tests are run with known viruses.
Unlike bacteria, viruses can not be seen with a simple light microscope. They are organisms so small they can only be viewed ander the electron microscope. Also unlike bacteria, a virus can exist only in a living cell. The virus invades the cell and forces the cell to produce more virus, and so on until the virus overruns the body.
After discovering that the microorganism has properties in which they are interested, the researchers attempt to grow large batches of it in "stir jars." "That provides you with (larger quanities) that can be worked on by a chemist in an attempt to isolate the active materials," Machamer said.
The chemist analyses small quantities - called cuts - from the jars, reporting on the content of each cut. Those that do not contain the sought after material are discarded.
The entire process is a painstaking, tedious one.
The work on the Italian dirt sample began in May, 1962. In July, 1974' researchers reported for the first time that the microorganism was active against herpes virus, one of the "bugs" against which it was tested. By August. 1965, the microorganism had been identified chemically as 9-Beta-D-arabinofuranosyladenine, almost five years after the collection of the soil sample.
One of the reasons the Parke-Davis investigators knew what they had was the 1960 report in the journal of the American Chemical Society by the cancer researchers, and a similar report by researcher at NIH.
Because ara-A had been previously discovered. Parke-Davis as unable to patent it. It is in the public domain. What the company has patented, however, is its method of growing, rather than artificially synthesizing, the chemical.
While the Parke-Davis researchers did not have an anticancer drug, what their work and subsequent work at the National Institute of Health, the Southern Research Institute, in Alabama, and more than a dozen medical centers around the county, has proven is that they do have an effective anti-viral drug.
While many vaccines have been developed to prevent infection by viruses, such as polio, mumps, measles and various forms of flu, and varios antibiotics have been developed to cure patients infected by bacterial diseases like pneumonia, ara-A is the first drug that can stop a lethal viral infection.
In addition to reducing the fatality rate in herpes encephalitis from 70 percent to less than 28 percent, the substance has also proven effective against herpes simplex - cold sores and genital soces -, an eye disease caused by the herpes virus and the scabbing condition known as shingles, a common affliction of those whose immunity is low, such as patients under going cancer chemotherapy and patients who have to take immunosuppresant drugs after after organ transplants.
All because Cicillo Aldo scooped up the right thimbleful of dirt.