Biologist Hans Christian Gram devised one of the most important staining techniques used in microbiology to identify bacteria under a microscope
Hans Christian Gram, the inventor of the Gram staining technique, was a pioneering biologist who devised the system of classification which led to as many as 30,000 formally named species of bacteria being investigated. He’s the subject of the latest Google doodle, created to honour his birth date of 13 September 1853. Gram, working with German pathologist and microbiologist Carl Friedlander, devised the technique in Berlin in the early 1880s. It is still known as one of the most important staining techniques used in microbiology to identify bacteria under a microscope.
Gram first dripped reagents, a substance designed to cause a chemical reaction, onto lung tissue samples. He found differences in the colouring of bacteria that is now known to be Streptococcus pneumoniae and Klebsiella pneumoniae. The differences Gram observed are a result of the composition of the bacterial cell wall. Some bacteria have a cell wall composed of peptidoglycan, a polymer of sugar and amino acids. These “gram-positive” bacterial cells retain the colour of a stain – usually a complex of crystal violet and iodine, or methylene blue – and appear purple or brown under the microscope. Others, that do not contain peptidoglycan, are not stained and are referred to as gram-negative, and appear red.
Its popularity peaked between 1940 and 1960. Pierce Gardner, an associate professor of medicine at Harvard Medical School, wrote about the Gram stain and its interpretation in 1974: “It is our feeling that the Gram-stained smear should be considered part of the physical examination of the patient with an acute bacterial infection and belongs in the repertoire of all physicians delivering primary care in acutely ill patients.”
More recently, Gram staining has been used to help identify new antibiotics, which are key in the battle against antimicrobial resistance. Teixobactin – one of two new antibiotics released to the pharmaceutical market in 2015 – was identified by employing a new twist on a tried and tested method of screening soil for bacteria that have evolved to kill their competitors.
A team at Northwestern University in Boston, Massachusetts screened 50,000 types of soil-dwelling bacteria for antibiotics that killed bugs like the hospital acquired infection MRSA and the bacteria that cause multi-drug resistant TB.
The staining technique was important as the screen identified teixobactin, which seems to act on the “gram-positive” group of bacteria by targeting a lipid on their cell walls, along with other molecules. If used correctly, the researchers behind the discovery of teixobactin could be a viable treatment option for bacterial diseases – and safe from the threat of resistance – for at least 30 years.
While differentiating bacteria into either gram-positive or -negative is fundamental to most bacterial identification systems, researchers have argued the Gram staining method is prone to error and “is poorly controlled and lacks standardisation” – something Gram himself warned of when his work was published in 1884.
“I have published the method, although I am aware that as yet it is very defective and imperfect,” he noted. “But it is hoped that in the hands of other investigators it will turn out to be useful.”
The problems with Gram’s method have led to a search for other tests, and several alternatives that claim to be improvements on it have appeared in the literature. Nonetheless, the Gram stain remains one of the most commonly performed tests in the clinical microbiology laboratory, and a foundational technique in treating bacterial infections and saving lives.
More on these topics: