Gong Gong says

This is a posthumous blog of our father's (Lim Kok Ann) life. When our father passed away on 8 March 2003, he left behind an unpublished autobiography. We'd like to celebrate his life by sharing his autobiography through this blog.

"I have dredged these anecdotes from memory just to pass the time; if they amuse my grandchildren their purpose will have been served; if they provide any instruction, it will be a happy coincidence; that they are disjointed is probably to be expected.

Aurora was the name of my grandfather’s house in Kulangsu.   Amoy, where I spent the first five or six years of my life.   I still have vivid memories of events that took place when I was barely three years old.

Lim Kok Ann
October 1996"

Sunday, August 10, 2008

2:5 Research on Penicillin.

When we enrolled for the Science course we had to choose a subject for our Honours course to follow our Ordinary Degree course. The prospect of being compared with my illustrious uncle Robert made me steer clear of Physiology while Anatomy was without any appeal as we approached the subject as an exercise in remembering the relationships between various parts of the human body. Of the third year subjects, I found Bacteriology most attractive. I had recently read an account of the life of Louis Pasteur and enjoyed very much the book “Microbe Hunters,” by an author whose name I have forgotten. Jimmy Gould and I who had signed up to take Bacteriology for Honours were invited to spend some vacation time in the department helping a member of staff in his research, to find if the work was suited to our temperaments.

The staff member to whom I was attached (apprenticed?) was Dr. Ogel who was studying Staphylococci. This is a bug responsible for suppuration of wounds and capable of massive invasion of the tissues if body resistance failed. The usual way to produce immunity was to inject the patient with killed bacteria. This would stimulate the body to produce antibodies to the bug, while the dead bug would be unable to cause any damage. In the case of Staphyloccus, however, this method did not work too well. This bacterium produced a variety of toxins, and it was not easy to produce a vaccine that would be effective against all of them. In the.1930s, the most effective way of treating staphylococcus infection was to use the recently discovered sulphonamides. Very soon it was found that staphylococci were capable of mutating to varieties which were resistant to the drug they had been exposed to,and this continued to happen when new kinds of sulphonamides or other drugs were introduced. When Dr. Ogel took me into his laboratory he was testing out a new and promising staphylococcal drug.

This was penicillin, a product of the common bread mould Penicillium notatum, just discovered by Alexander Fleming. Some people say that it was only by chance that he discovered the use of penicillin. I would say that similar chances happen to unlucky people who throw away their discoveries, “like the base Indian”(see footnote).

Ogel’s part in the work on penicillin in Edinburgh was to estimate the blood levels of penicillin in patients receiving penicillin by various methods while colleagues studied the effects of different regimes. Of patients, there was no shortage; it was war, and patients with severe war wounds, some of them with massive staphylococcal infection, were flown to Edinburgh for treatment. Ogel’s method of testing was to place 0.01 ml of patient’s serum, suitably diluted, in little cups cut in an agar plate the surface of which had been seeded with staphylococci. The penicillin in the patient’s serum diffused into the agar and inhibited the growth of staphylococci at the margins of the cups, to a width that indicated the concentration of penicillin in the patient’s blood.

A hundredth part of a millilitre (ml or cubic centimetre) is a very small quantity to measure accurately, and we would normally use a specially calibrated micro-pipette to do so. Such pipettes were expensive and could not be used for Ogel’s work as many pipettes were required in each experiment, each of which had to be sterilized between use. Someone, however, had devised a way of making 0.01 ml measuring pipettes, and I was put to making these pipettes in quantity.
To make such a pipette, I would take a short piece of glass tubing half a centimetre in diameter and soften the middle by heating in a blow-lamp (Bunsen burner). I would then pull gently at the ends to draw the middle into a narrow tube. This gave me two “Pasteur pipettes”, commonly used in bacteriological work to transfer bacterial suspensions from one flask to another. I next blew a small bulb at the end of the narrow tube that I had made and cut the narrow tube about half a centimetre from the bulb. With experience, I was able to make a bulb of just under 0.01 ml capacity. In fact, my aim would be to make a bulb of such a size that when I draw up 0.01 ml into the bulb, the liquid would fill the pipette from its tip to a little above the bulb, where I would make a little mark with white glass ink. The liquid that I used for this purpose and measured out with a 0.1 ml pipette, calibrated in l00ths of a ml, was mercury whose boundary in a glass tube was easy to mark.. Provided I was careful about maintaining everything at room temperature, I could double check the volume of mercury I used by weighing it. Physical tables were available that gave the weight of mercury per ml to very narrow limits. Mercury was used for measuring volumes because it did not evaporate during the experiment as would water, for example, and the volume it occupied was easily seen. I spent the most of one vacation making dozens and dozens of micro-pipettes.

After I completed the Ordinary Degree science course I had a talk with my Director of Studies to discuss the question whether I should take a one-year break in my medical studies to take a Science Honours course. His advice was that I should continue my medical studies and after graduation, take the Honours Science degree, if I was still interested. Some students who break off their medical studies to do the Science Honours year never resume their medical studies. “In your case,” he said, “your main objective is a medical degree so you should concentrate on that for the time being.” Very good counsel and in good time, for I was being attracted by the handicraft in research, being always clever with my hands.

In the subsequent vacations, I returned to the Bacteriology department to gain more laboratory experience and helped the Surgical team that was treating war wounds with penicillin. The antibiotic was still in short supply and our special task was to devise a continuous intramuscular drip (usually in the thigh muscle) that would deliver 100 ml of penicillin solution evenly over 24 hours. It was a good idea that failed because the muscle got irritated by the needle and after sometime refused to absorb the injected fluid and pass it on as it nonnally did. My part in the experiment was to calibrate the drip apparatuses and adjust the delivery rate appropriately.

Footnote “Whose hand, like the base Indian, threw a pearl away richer than all his tribe.’’ --Othello


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