The Curative “Sacred” Waters

Bookplate, Joseph Priestley, "Rushing Water", c. 1780

Another article by guest contributor Chandra Emani*

The faithful in many countries swear by them. Many a land has its share of what are known as “sacred” rivers. A drink of the water in them have mystically cured dreaded diseases.  But the story I have for you today is about one such river I grew up on. The River Ganges or Ganga Nadhi as it is known in India. Travel to India today and people revere the sacred waters known as Gangajal (“jal” in Hindi means “water”). Gangajal, I was told by my elders, gives you peace when you drink it and many a mythological story talk about drinking the waters literally bringing back the dead and cure many a disease. Being the skeptical biologist, I took this as a general eternal love people have for the waters of their land from which spring civilizations and culture. Everything changed when one fine day I was preparing to teach my recombinant DNA technology class at our university. The topic was of bacteriophages, the microbial forms I have been using in my research for the past decade. As always, I was collecting the scientific history to introduce the concepts and the story of the discovery of bacteriophage blew me away. And it involved the sacred waters of Ganga.

In 1896, when British still ruled India, a bacteriologist stationed in Delhi, Ernest Hanbury Hankin, wrote a paper for the Pasteur Institute Journal where he reported that the waters from the rivers Ganga and Yamuna (this river incidentally passes by the Taj Mahal) could cure cholera.  What he wrote in the paper was widely discussed at Oxford and Cambridge. Hankin’s remarkable observation was that even after boiling the waters, or passing them through porcelain filters, the waters from these rivers still retained a mysterious biological source that dissolved bacteria in the lab and stemmed the spread of cholera in the land. People who swore by the curative properties of the rivers unearthed recorded documents that showed that the Ganga water once reportedly cured leprosy, a fact that Hankin now recorded in his paper as completely believable. Hankin was not taken seriously simply because he was on the wrong side of science politics. He was a “vivisector” who “escaped to India”. Vivisection was the use of dissecting live animals for research, a practice scorned by the scientific elite of the times and Hankin was on the wrong side of the debate. So, his remarkable discovery languished in journals. A generation later, in 1915, another British bacteriologist Frederick Twort at the Brown institute in London rediscovered the mysterious bacterial killer. He was working on developing a smallpox vaccine from a bacteria found in the skin of calves and when he plated those bacteria in the lab, he observed that among the bacterial growth lawns in the plate, certain transparent glassy areas were seen clearly showing something killing and dissolving the bacteria. Across the ocean, French-Canadian microbiologist Felix D’Herelle independently discovered the same kind of mysterious biological source that “ate” bacteria according to him this time in a culture of dysentery bacteria. D’Herelle confirmed that the mysterious substance was in fact a virus and named it bacteriophage (“phage” in Greek means “eater”). The phenomenon was named “Twort-D’Herelle effect.” Both scientists acknowledged the record of the erstwhile Dr. Hankin and confirmed that what was found in the rivers Ganga and Yamuna was in fact the bacteriophage.  D’Herelle also recorded the remarkable case of a man affected with dysentery being cured by bacteriophages. The science behind the curative sacredness of Gangajal was complete.

In 1920s and 1930s, both the Soviet Republic of Georgia and United States widely used bacteriophages to treat bacterial infections especially in the army. This was called Phage therapy.
It did not catch on as medical trials were documented as inconclusive simply because of improper scientific methodology such as not including proper controls and also the lack of understanding the scientific concepts behind phage action. The subsequent years also saw the rise of antibiotics that were easy to make, store and prescribe and the phage therapy lost out. In the 1960s, phage biology was revived by a scientific trio of Max Delbruck, Alfred Hershey and Salvador Luria (Luria’s first research student was incidentally the legendary Jim Watson who discovered DNA). The scientists were working on phages at the legendary Cold Spring Harbor Laboratory in New York, the ground zero for DNA and molecular biological revolution. When they were working to unravel the molecular elements involved in bacteria, they chanced on bacterial cultures that suddenly showed mutations, the sudden changes seen in genes and DNA as if somebody accidentally broke a test tube while culturing the bacteria. After a long day at the lab, Luria was at a cafeteria when he saw players at a slot machine when a eureka moment chanced on him looking at the sudden wins of the slot machine players. The subsequent years saw the trio work out all the scientific basis of how phages work, the account of which Luria fondly recorded in his autobiography One Slot Machine, A Broken Test Tube. The mystery workings of phages is now complete, the feat that earned Luria, Delbruck and Hershey the Nobel Prize in 1969. In recent times, June 2009 saw clinical trials to use bacteriophage cocktails to treat infected venous leg ulcers in humans. Another clinical trial in the same year in Europe saw phage therapy on chronic ear infections. Several other trials are underway to see the efficacy of phage therapy on infected burns, antibiotic resistance and cystic fibrosis.

As for me, I will forever remember the day when I found out that the curative healing powers of Ganga and Yamuna did have a scientific basis, and the rivers were the first to witness a revolutionary discovery that led to a Nobel Prize and now throw open doors to medical revolutions. I now fully understand why they say “the best way to learn is to teach.”
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*Chandra Emani is an Assistant Professor of Biology at Western Kentucky University-Owensboro. Apart from teaching introductory and advanced courses in molecular biology and Genetics and researching on utilizing plants to make useful products such as biofuels and anti-cancerous pharmaceuticals, he enjoys explaining science in simple words to his daughter and son. He can be reached at chandrakanth.emani@wku.edu.

The Lab Mouse Story

The other day I happened to stumble onto a very interesting article that appeared in the Owensboro Messenger-Inquirer written by Chandra Emani, an Assistant Professor of Biology at Western Kentucky University-Owensboro. I thought the article was so interesting that I contacted Dr. Emani and a new friendship has developed.  As it turns out he also likes to write short articles about interesting and obscure tidbits of science.  Apart from teaching introductory and advanced courses in molecular biology and Genetics and researching on utilizing plants to make useful products such as biofuels and anti-cancerous pharmaceuticals, he enjoys explaining science in simple words to his daughter and son.   With his permission I am including here his Lab Mouse Story.  Dr. Emani has agreed to also contribute additional articles for this blog. It is our hope that he will bring our readers food for thought in the months and years ahead.  He may be reached at chandrakanth.emani@wku.edu

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The Lab Mouse Story

Chandra Emani

Ever since we were kids, whenever we visit or visualize a lab where medical or biological research is carried out, we always view a ubiquitous cute creature that the scientist experiments with, the white lab mouse. What is it with this animal that scientists always seem to test everything on and then have eureka moments in discovering new phenomena, new drugs that cure all ills? How does something tested in mice be good for humans? Let’s go back in time to see when it all started and then how these little creatures became the model research organisms for genetics, psychology and medicine.

In 1700s, the discoverer of blood circulation system William Harvey recorded the first experiments with mice to study both the processes of blood circulation and reproduction to translate the findings for use in human medicine simply because they were animals that were easy to breed and had an ideal generation time (as in going from parents to offspring) as laboratory animals. The discoverer of the microscope Robert Hooke also working in that same period used them to investigate what happens to life forms under conditions of increased air pressure in enclosed spaces. Joseph Priestley who first made oxygen in the lab tested his lab made life saving gas on lab mice.

Another remarkable scientific event that was cut short in the 1800s involved lab mice. In 1850s, the Austrian Monk Gregor Mendel wanted to study how genes transmitted from to parents to their next generation using lab mice. But in the Church where he had his small lab, his supervisor cut short his experiments to “stop the work with the smelly creatures.” Mendel then had to choose another experimental model, the pea plant and his work, though revolutionary, was published in an obscure journal that had to wait 35 years to be rediscovered (research with plants was not as recognized as animal research) and that set back the revolution known as Genetics. It was only in 1902 that the French biologist Lucien Cuenot replicated Mendel’s laws of genetics using lab mice.

But the real revolution of establishing the lab mouse as an ideal experimental model in 1900 in a farm at Granby, Massachusetts where an elementary schoolteacher named Abbie Lathrop from Illinois started a poultry business. The poultry business failed and Abbie started breeding mice for hobbyists and pet owners. The other animals she raise were ferrets, rabbits and guinea pigs (another popular lab animal of choice). She was assisted by her close friends Edith Chapman and Ada Gray. Abbie started with a pair of waltzing mice she got from her farm and soon successfully multiplied the litter to 11,000. It was at this point that some scientific researchers started looking at her unique and meticulous process of breeding and maintenance of mice in wooden boxes with straw mats fed on oats and crackers and soon the word spread. Abbie started selling mice to scientific labs. At one point, she recorded using one and a half tons of oats and over a dozen barrels of crackers in a month and paying pocket money of a pristine 7 cents an hour to local children to clean the cages of the mice. After her mice made way to the Harvard University, the United States government purchased her mice and guinea pigs to test toxic gases in the trenches of the First World War. The adage of “being used as a guinea pigs” came from.

In 1908, Abbie saw that some of her mice started developing some unusual skin lesions or scars. She wrote a letter to the famous experimental pathologist Leo Loeb at the Washington University and he identified them as cancerous tumors remarkably similar in properties to breast cancer tumors in humans. Loeb encouraged Abbie to develop inbred strains of these mice and between 1913 to 1919, the unlikely pair of a farm woman and a scientist authored 10 journal articles, some of them in Journal of Cancer Research and Journal of Experimental Medicine where they found the biological basis of cancer using a lab mouse model, and the rest as they say is history. During this time, a Harvard geneticist William Castle purchased some of Abbie’s mice and an undergraduate working in his lab by the name Clarence Cook Little (who later became famous for establishing the role of tobacco in causing cancer) was instrumental in developing the mouse strain called “Black 6” which is the frequently used lab mouse till date. Though Little patronizingly referred to Abbie as a “talented pet-shop owner”, it is a known fact now that the famous DBA (Dilute, Brown and non-Agouti) inbred mouse strain that is widely used in medical research came from a silver fawn mouse developed by Abbie. Abbie died as an unsung heroine in 1918 due to pernicious anemia, but her notebooks, observations and meticulous breeding records kept at the famous biomedical research institute, the Jackson Laboratory in California revealed that at least five strains of lab mice that are used today in labs around the world heralding many revolutionary studies came from a single female mouse that she bred in her farm.

As modern medical marvels and possibly a cure for the dreaded disease cancer would one day see the light only after clinical trials translate from countless “mouse model experiments”, let’s salute the unsung heroine behind it all, Abbie Lathrop, a home schooled elementary school teacher who worked from a modest farm in Granby, Massachusetts and heralded the greatest scientific revolutions in medical science.