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David Nalin

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David Nalin - Oral Rehydration Therapy:
Dr. Nathaniel F. Pierce estimated that between 1979 and 1990 diarrhea deaths in children declined from 4.6 million to 2.9-3.3 million annually, and from 1991 to 1999 declined further to 1.5 million annually, while ORT became available in 110 countries. These figures corroborate a British Medical Journal article in 2007 that says over 50 million lives have been saved by ORT.
--Amy R. Pearce, PhD

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David Nalin
(April 22, 1942 - )
Born in the United States
Year of Discovery: 1968
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UNICEF Proclaims His Discovery As Greatest Medical Breakthrough of 20th Century


UNICEF released a special report in 1987.  It said "No other single medical breakthrough of the 20th century has had the potential to prevent so many deaths over such a short period of time and at so little cost"  What is this miraculous breakthrough and who is the hero behind it?  The answer is Oral Rehydration Therapy, or ORT, and the scientist is Dr. David Nalin. 

Every year millions of people die from the dehydration brought on by diarrhea. Children are especially vulnerable. A patient with severe diarrhea can lose up to 20 liters of water per day (10-20% of their body weight), which can lead to severe dehydration, shock, coma and death within hours--often before medical care can be accessed. Cholera is a killer because its major symptom is just such a devastating diarrhea.

In the fall of 1968, Dr. David Nalin, at a young 26 years of age and having completed only his first year of medical residency, was working in Dacca, Bangladesh, at the Pakistan-SEATO Cholera Research Lab when a cholera epidemic broke out near Chittagong, along the eastern Burmese border. Working in a tent housing patient overflow, at a small missionary hospital carved out of the jungle, Nalin was confronted with a failed protocol that was attempting to use a drinking solution to put liquid back into cholera patients as a means of weaning them off of intravenous solutions, which was the only known treatment. Nalin realized that the treatment would work if it was changed. Further, he realized that such a treatment could completely replace IV treatment and could work for most diarrhea, not only that caused by cholera.  His breakthrough was his realization that patients needed to be rehydrated at the same rate as their fluid loss.

He and his colleague, Richard Cash, through resourcefulness and persistence in an adverse research climate, fought to perform scientific trials that would prove Oral Rehydration Therapy would work. Until the discovery of ORT, the only efficient means of rehydrating a patient suffering from serious dehydration was to provide fluids intravenously. For the vast majority of people in the developing world cholera, or any severe diarrheal illness, was too often a death sentence, since people infected usually had no recourse due to the cost and inaccessibility of IV therapy.

The effectiveness of ORT can be summed up in a single word: remarkable. The solution, which has saved millions of lives since its inception 40 years ago, can be made with household water, salt and sugar. Moreover, applying the solution can be done at home instead of in a hospital. But, it took David Nalin’s keen intellect and persistence to put all the pieces of the puzzle together and solve the problem.  Encouraging worldwide use, in 1978 the prestigious English medical journal, The Lancet, called ORT "potentially the most important medical advance of this century." Since the adoption of this inexpensive and easily applied intervention, the worldwide mortality rate for children with acute infectious diarrhea has plummeted from 5 million to about 1.3 million deaths per year. Over fifty million lives have been saved in the past 40 years by the implementation of ORT.
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by April Ingram


Table of ContentsBookcoverjacket

Introduction
Key Insight
Key Experiment or Research
Key Contributors
Quotes by David Nalin
Quotes About Nalin and ORT

Anecdotes
Excerpt from Scientists Greater Than Einstein
Similar Scientists
Fun Trivia
The Science Behind the Discovery
Personal Information
Science Discovery Timeline
Recommended Books About the Science
Books by David Nalin
Books About Nalin
Awards
Major Academic Papers

Curriculum Vitae
Links to Science and Related Information on the Subject
Sources








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Nalin with Coffee
Biographical Info on Nalin
Facts About ORT
Facts About Cholera
Facts About Gatorade
Nalin Quote About ORT
Quotes About ORT



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Key Insight


Previous oral solution research had been done with very small numbers of cholera patients, attempting to rehydrate them mostly by putting tubes into their stomachs.  Scientists knew that because
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An infant receives ORT
Photo courtesy of WHO
of osmosis the rehydration fluid had to contain salt, and they later determined sugar as well, was needed in order for water to be absorbed in the gut. Yet even given such a solution many patients became over hydrated (which can kill) or remained dehydrated and had to be saved by IV therapy.  "It was very rapidly a failure," Nalin said of the trial he observed.  This protocol failure nagged at Nalin and he had a real desire to know "Why?"  He knew that the composition of oral therapy should work. "Suddenly it hit me!" Nalin said.  He  realized it was themethodology that was the problem and hypothesized that fluid loss had to be replaced by oral solution volumes that would meet or slightly exceed volumes lost.  This was the moment when life-saving treatment for dehydration on a global scale would forever be changed.  Nalin describes that moment, "I remember a chill going up my spine when I realized this, together with the overwhelming sense of how important this would be to the countless patients who were continuing to be at risk of death in remote, resources-poor affected areas around the globe."






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Key Experiment or Research


Nalin quickly asked his colleague, Richard Cash, to help and they went to work on revising the existing methodology of previous oral rehydration research and devising a new protocol.  This new practice would measure fluid output levels from vomiting and diarrhea every hour, over a four or six hour period and then give a volume of oral solution to the patient that equaled the previous hours' output.

The experiment began in April, 1968, and included 29 of the sickest cholera patients that had been brought to the Cholera Research Laboratory in Dacca.  The condition of these patients was so dire that many were admitted having no pulse and very low or non-detectable blood pressure.  All of the patients were administered IV treatment until their blood pressure returned to normal, and then they were divided into three groups.  The first would remain on IV treatment, acting as a control group.  The second was administered the oral solution by a tube, threaded down their throat.  The third group was given the oral solution to drink.

The staff at the hospital made use of a Watten Cholera cot to measure the output of patients' fluid through vomit and diarrhea. This special bed was a wood frame cot with a hole cut in the middle, which was attached to a plastic sleeve, which would empty the patient's diarrhea output into a bucket in order to measure fluid output.  Vomit was collected in a basin and measured separately.

Originally, Drs. Nalin and Cash planned on rotating shifts with other staff. Unexpectedly, their doctor colleagues working the other eight hours of the night shift refused to adhere to the protocol, and instructed the staff to restart IV treatment for some of the patients selected to receive oral therapy only. They didn't believe the new protocol would work. Nalin and Cash had to alternate 12 hour shifts to monitor their patients around the clock and ensure the protocol was accurately followed.  Of course, they had backup tests that would indicate if their protocol was failing, so the patients were never in danger.

The results of the trial exceeded expectation.  Only three of the patients receiving oral solution through the tube required extra IV therapy and only two of the group drinking solution required IV.  All 29 patients recovered completely! Success!

These results of the original trial were published, only four months later, in The Lancet.  Oral Maintenance Therapy for Cholera in Adults. 1968 Aug 17;2(7564):370-3.

The paper concluded: "The ingredients of the oral solution are cheap and widely available in virtually all areas affected by cholera. The solution need not be sterile and it can be made up with any suitable drinking-water. Ingredients could be pre-weighed and stockpiled for use in cholera epidemics. The drastic reduction in the need for intravenous fluids which results from the use of an oral therapeutic solution should make it possible for cholera treatment centers with limited supplies of intravenous fluids to reduce the mortality from cholera to a level previously not possible in the absence of abundant intravenous fluids. Mild cases of cholera (without shock) may be treated with oral solution alone."

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Key Contributors


The Team
Explore other scientists who furthered this lifesaving advance.

Lifesavers Who Developed Oral Rehydration Therapy
Robert Phillips
His early experiments laid the groundwork for Oral Rehydration Therapy.
Richard Cash
Provided crucial collaboration, working with Nalin on the key experiments.
Norbert Hirschhorn
Proved that patients could self monitor their intake of the solution.
David Sachar
Proved that coupled glucose/sodium/water absorption were intact in cholera patients.



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Quotes by David Nalin


"Previously, I had a great love for clinical medicine, but I found myself drawn toward research.  That surprised me, because I never thought of myself as a researcher."

"Both my scientific career in cross-cultural medicine and my artistic avocation took root in those years"
-Speaking of the years during his sojourn in college in Guyana.

"I remember a chill going up my spine when I realized this, together with the overwhelming sense of how important this would be to the countless patients who were continuing to be at risk of death in remote, resources-poor affected areas around the globe."
-When Nalin realized why the protocol had failed.

"My initial impressions of Dacca were wondrous, sometimes bewildering and spellbinding. On being picked up at the airport by Dr. James Taylor, a beggar boy of perhaps eight years of age grabbed the open window of Jim's Volkswagen as we were about to leave, and with a grimace and tears gestured with cupped hand at his mouth that he wanted money for food.  My heart melted, but imagine my amazement when Dr. Taylor spoke a few words to him in Bengali asking his name and age.  The demonstration of interest in him in his native language fractured his act and transformed him into a smiling, bashful boy who totally forgot about begging. I gave him a coin anyway, and was driven away, mind boggled."

Nalin recalls that when he arrived at the Memorial Christian Hospital at Malumghat, where he would make his breakthrough, "patients were dying in their villages because the only hospital was run by Christian Missionaries, and the local mullahs had preached that any Muslim who went there would be branded with the sign of the pig. So we had to go out to these remote villages with our intravenous solutions and try to coax some parents to let us use them in the huts. A few finally let us do this, and the results were so dramatic that rumors circulated that this could not be cholera after all, because they had never seen a cholera outbreak where anyone survived!"


Quotes about Nalin and Oral Rehydration Therapy

"No other single medical breakthrough of the 20th century has had the potential to prevent so many deaths over such a short period of time and at so little cost"
-UNICEF 1987

"Potentially the most important medical advance of this century."
-The Lancet

"Which medicine has saved more lives than any other and can be made by anyone in their kitchen, back bedroom, shantytown hut or dwelling built of sticks - as long as they have access to clean water?  The answer is:  eight teaspoons of sugar, half a teaspoon of salt and one litre of water.  Mix.  Drink......It requires no specialized equipment; uses ingredients that are ubiquitous and have a long shelf life; has few side effects; and can be made up in any quantity - the prefect medicine."
-Jeremy Laurance, British Journalist
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Anecdotes


The program that allowed David Nalin to first study internationally no longer exists at Albany Medical College.  Therefore, in 2006 he generously established the David R. Nalin '65 Endowed Fund for International Research.  Endowment income from the fund will be used annually to support international, non-sectarian research for medical students. 

In 1979, Dr. Nalin took charge of the malaria research centre in Lahore, Pakistan. Three years later he was expelled by Pakistani authorities due to unfounded Soviet allegations that the research being conducted there was for the benefit of the CIA.  He also received a death threat before he was told to leave the country or  be arrested.

Dr. Nalin attended and photographed a chakra puja, a Hindu religious ceremony in Sylhet, Bangladesh in 1978.  These photos would be published in Clinical Infectious Diseases in 2004.

Dr. Nalin has collected art wherever he went in the world and donated many pieces to the Vermont Fleming Museum.

In college Dr. Nalin went to Guyana. Until Dr. Nalin became proficient in some of the Guyanese languages, there was some confusion when attempting to question and examine patients.  "Operations" means diarrhea, "cut" means surgery and "chop" means wounds.  It is easy to see how problems could arise!  To assist, Dr. Nalin collected and tape recorded a brief medical questionnaire in seven Guyanese Amerindian languages during the summer. Somewhat of a polyglot, Nalin then prepared questionnaires in several languages.

Dr. Nalin has published many works in medical journals, some with eye catching titles, such as: 

O come, let us wallow in glorious mud.  (Trans R Soc Trop Med Hyg. 1996 Nov-Dec;90(6):717) and A spoonful of sugar... (Lancet. 1978 Jul 29;2(8083):264).
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Excerpt from Scientists Greater Than Einstein: The Biggest Life Savers of the Twentieth Century

Buy a copy in the online store


A Mantra of Failure

As the cholera epidemic rolled on into November, then December, Nalin and his associates worked out of the Memorial Christian Hospital at Malumghat, a portentous name meaning "port of perception." The hospital site had been carved out of the jungle just the year before, and cobras and jackals were still occasionally seen on the grounds. Located up a tidal river from the Bay of Bengal, laborers from the numerous nearby indigenous ethnic groups rafted bamboo down from the jungle, past the hospital, to bayside ports where it was loaded onto old wooden boats and taken to the offshore islands.

The hospital was now crowded from the cholera outbreak and many patients had family members staying with them. Having only a few dozen beds, the staff erected a large tent next to the hospital to handle the overflow, moving patients there to convalesce. Day after day Nalin administered IV's. Something of a polyglot, he was learning Bengali so that he could communicate with the local staff and the patients. Particularly poignant were the emaciated children. Sometimes they had to be strapped down to keep them from pulling out their IV tubes. 
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Similar Scientists

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Heroes Featured in Scientists Greater than Einstein


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Alfred Sommer

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Fun Facts/Trivia about the Science


Some members of the research team responsible for the discovery of ORT had not yet completed their medical residencies. At the time, there was a military draft in the U.S. and many medical students joined the Epidemiological Intelligence Service, where they were shipped overseas to do research or offer medical care.

Every letter that went through the Bangladesh post office from 1993-1994 was stamped with a printed rhyme about ORT.  Translated into English, it read (gur is a molasses):

Mix with much care,
Good water, a liter,
A pinch of salt with a fistful of gur,
Remove the menace for good.


Stomach acid provides a natural defense against cholera infestation.  Researchers gave billions of cholera bacteria to healthy individuals and none of them became ill, except when subjects were given an antacid.  This decrease in stomach acid immediately made them susceptible to cholera!

If ORT were applied to all patients who needed it, some estimate more than an additional million lives could be saved annually, and global savings in healthcare from home use of ORT would reach U.S. $10-15 billion each year.

500 million packs of the oral rehydration solution are used each year in more than 60 developing countries.

A person with cholera can lose up to 20 liters of water a day, 10-20% of their body weight, leading to death by dehydration.

Gatorade is a type of  ORT.  But, although it works based on the same physiological mechanisms, it is formulated to replace sweat loss in healthy individuals, not fluid loss due to diarrhea in the sick, so should not be used to treat diarrhea.

In October 2006, The Independent, A British newspaper, reported on the greatest achievements in medical science in 150 years.  The second on their list was Oral Rehydration Therapy (first was oral contraception).
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The Science Behind the Discovery


Diarrhea is not a disease itself, although it can be deadly.  It is a symptom usually caused by bacteria or viral infection. The accompanying dehydration can quickly destroy the body's ability to function.  It is particularly dangerous for children who, on average, exchange more than half of their extracellular fluid in their intestines each day, compared to one seventh in adults.  Before sanitary sewer systems and chlorination of water, diarrhea was the fourth-leading killer in the United States.  Currently, the Centers for Disease Control and Prevention (CDC) estimates there are 1.5 billion episodes of diarrhea every year around the world.

While cholera raises our awareness of diarrheal dehydration because it comes in attention-grabbing epidemics, it accounts for only a small portion of diarrhea sickness in the world. Other common causes of diarrhea include dysentery caused by bacteria or amoebas, traveler's diarrhea, usually caused by E. coli strains, and norovirus that contaminates food and water. In 2002, there were norovirus outbreaks on 25 cruise ships, sickening 2,648 passengers.

The most prevalent cause of diarrhea is the rotavirus. It affects all income groups, because poor sanitation is not its vector. Spread by direct human-to-human contact, the CDC estimates that rotavirus causes 39 percent of all childhood hospitalizations for diarrhea worldwide and up to 50 percent of all deaths.

ORT has proven to be the main line of defense against dehydration for diarrhea, no matter the cause. In fact, in 1972 Dr. Norbert Hirschhorn, a key player in the discovery of ORT, concluded that IV use in the treatment of diarrhea was "old fashioned" and said that ORT was clearly the superior treatment.

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Vibrio cholerae - the bacterium that causes cholera
Cholera: The breakthrough in treating diarrhea came from cholera research. Cholera is caused by bacteria attacking the small intestine.  It has the unfortunate distinction of being one of the fastest killers, potentially killing a patient within hours of the first symptom, usually diarrhea.  Cholera outbreaks usually begin with zooplankton blooms, which contain the bacteria, found in costal estuary areas.  Animals will eat the zooplankton andbecome contaminated and humans will eat the animals or drink contaminated water.  Human feces carry the bacteria into the sewer system and, if the sewer becomes intermingled with the water system, cholera can spread very quickly.


Essentially, cholera was and is an Asian disease, but in modern times it has escaped to cause seven pandemics. In 1817, cholera broke out onto the trade routes into China and southern Russia. A second pandemic erupted in 1829, which spread to Western Europe, across the Atlantic to America and Canada, striking in New York, Philadelphia and the southern states, and eventually made its way to Central America. A third pandemic caused more than a million fatalities in Russia and, in 1853, more than 10,000 died in London alone. Later pandemics

Later pandemics erupted from Indonesia in the 1960s, spreading through theMiddle East and across Africa by the 1970s, reaching Peru in 1991. From there, it expanded to every country in the Western Hemisphere. Another outbreak was reported in India in 1991. On Feb. 14, 1992, an Aerolineas Argentinas 747 landed in Los Angeles with 336 passengers and crew. Seventy-five of them had cholera, acquired from a seafood salad loaded onto the plane in Peru. Ten were hospitalized and one person died, but the disease did not spread. Another pandemic erupted from Indonesia in 2000.

Famous victims include former U.S. President James Polk, the composer Tchaikovsky, and both the son and brother of Mary Shelley, the author of Frankenstein. Robert Frost's son, Elliot, died of cholera at the age of three in 1900.

Cholera's affect on the human body begins with understanding how our bodies absorb water. An ion is an atom or molecule that has lost or gained one or more electrons, making it electrically charged. Electrolytes are simply ions dissolved in water. In our bodies, electrolytes come mainly from dissolved salts such as sodium chloride (table salt), which contains equal amounts of positive sodium ions and negative chloride ions. These electrolytes play vital roles in many cellular processes, and our bodies regulate very carefully the concentrations of different ions inside and outside of our cells, using highly specialized ion channels located in our cell membranes. For instance, virtually all our cells have hundreds of thousands, or even millions, of sodium-potassium pumps that are constantly at work exchanging three sodium ions inside the cell for two potassium ions outside the cell. As cells in the intestinal wall pump out sodium ions into the bloodstream, more sodium ions enter the cells from the intestine. Nature has a tendency to create equilibrium-in other words, to balance the concentration of electrolytes/ions/salt on either side of a semi-permeable barrier such as a cell membrane.

Cells also have chloride ion channels, and these are what the cholera toxin attacks. When negative chloride ions flood the intestine, sodium can no longer easily move into the intestinal wall cells, because of another simple natural tendency-to avoid concentrations of electrical charge. This phenomenon is no different from what happens when you build up charge by scuffing your feet across the floor in winter and then touch a doorknob or other metal object. Nature wants to get rid of the concentration of negatively charged electrons on your body, so they jump from your finger to the metal object and get absorbed by the ground-and you get a shock. Likewise, positive sodium ions are needed in the intestine to balance all the negative chloride ions, and this in turn causes a massive volume of water to travel across the intestinal lining due to a principle called osmosis, by which water moves to balance the concentrations of both types of ions. The chemical imbalance literally sucks water out of the body, the excess liquid cascading into the colon, which can only reabsorb a maximum of about 4.5 liters per day. The only place the rest of the water can go is out.

Diarrhea - watery, profuse, and often painless-begins abruptly, twelve to twenty-four hours after infection. Vomiting may also occur early on.  As this vomiting and defecation draws water out of the body, the patient's skin becomes cold and withered, the face becomes drawn, blood pressure falls, and the pulse becomes faint. Death comes from dehydration, after the patient has plunged into shock and coma.

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Historical background


Through the ages, spiritual leaders and medical practitioners in many cultures have used fluids to treat diarrhea. In the Indian subcontinent, for example, a thick gruel consisting of soft-cooked rice seasoned with rock salt was used as a remedy for diarrhea 3,000 years ago. Few worked well.

19th Century

In 1831, while Europe was reeling from a cholera pandemic, the Irish doctor W.B. O'Shaughnessy told participants at a medical meeting that the potpourri of treatments being used at the time didn't work. Some doctors used tartar emetics to induce vomiting; others used complex mixtures of herbs, chalk, vegetables, and opium, all to no avail. Some even recommended putting a plug in the anus to prevent the flow, which boggles the imagination-the patient may well have exploded. None were effective and the death rate for cholera ran as high as 70 percent.

The most popular treatment, used for a host of diseases doctors didn't know how to treat, was bloodletting. If a dehydrated patient's blood was too thick to bleed when lanced, doctors attached leeches to remove the blood. O'Shaughnessy said that removing blood did considerable harm, depriving the patient of even more fluid than was already being lost through diarrhea. By analyzing the blood of a cholera patient, O'Shaughnessy found that the patient had lost not only much water but much of the salt required for life-blood being a saline solution. His recommendation, published in The Lancet, was to insert a goose quill needle into a vein and inject a tepid saline solution. IV treatment of cholera was born.

The medical profession largely ignored O'Shaughnessy's suggestion for 50 years, because of complications, including chills and sepsis, resulting from inadequate knowledge of sterilization techniques.

Meanwhile, in 1854, after repeated epidemics in Europe, John Snow made the link between cholera and contaminated water in a famous epidemiology study in London. Three decades later the German physician Robert Koch tracked the disease with his microscope to the villain-the bacterium V. cholerae. Koch also set up the sanitation rules that are still used today for controlling epidemics. Thanks to Koch's protocol, the sixth pandemic that began in 1899 had little effect in Europe, but cholera remained endemic in Asia.

By the late 1800s, medicine began to use antiseptics, so IV saline solutions began to successfully be used, cutting the death rate of cholera to 40 percent. In the early 1900s, further refinements to the IV solution dropped the death rate to 20 percent. IV therapy worked because fending off dehydration for a long enough period of time allowed the body's immune system to rev up and eliminate the infectious agent.

20th Century

In the 1940s, Daniel Darrow of Yale became the leading expert on IV solutions for dehydration. He believed that to treat a patient successfully, one had to know exactly what chemicals were being excreted, how much and how that changed the body chemistry. He came up with a good approximation of what the body was losing and hence what needed to be replaced. In a series of experiments, he showed that IV replacement solution should include the sugar, glucose, and the salts, potassium and sodium chloride. Thanks to Darrow, the intravenous treatment of extreme diarrhea, including cholera, now had the beginnings of a scientific basis.  While IV therapy worked well, it required doctors, nurses, equipment, and sterile procedures to prevent infection, and in most of the places where cholera was endemic, that was not practicable or even possible.

1960s

In the 1960s, Dr. Stanley Schultz demonstrated that glucose and sodium absorption in the small intestine were intimately coupled, and glucose could facilitate the absorption of sodium and water. This pioneering work provided the scientific foundation for the later use of the oral rehydration solution consisting of salt, sugar and water in the treatment of dehydration in diarrhea patients.

In 1962, Robert A. Phillips, a successful Navy researcher who had reduced cholera deaths below five percent using the latest intravenous techniques, tested three oral solutions: water, water with salt, and water with salt and glucose, on two patients in exploratory tests in the Philippines. The solution with both salt and sugar was so successful that he quickly tried it on a larger group of 30 patients. The results were disastrous, with five dying. Phillips did not publish this mistake, but concluded that cholera shut down the body's ability to use sodium to transport water in the gut. Depressed over his tragic trial, and believing an oral solution would never work for cholera, he became an obstacle to future research. Nevertheless, he moved into the head position of running the Pakistan-SEATO Cholera Lab in Bangladesh.

Several years after Phillip's disaster, David Sachar proved that Phillip's conclusion was incorrect and that a cholera patient's body could absorb water with sodium and sugar.

Nalin's Discoveries
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Nurses administering Oral Rehydration Therapy

After Nalin's key insight, and the proof of concept trial run by Nalin and Cash outlined in detail above, they planned their next phase of work.  They wanted to do a large scale study, with hundreds of patients, to convince the scientific community of ORT's value, and they wanted to do it in a remote area where patients with severe diarrhea would rarely have access to hospital facilities.  There was a field hospital at Matlab Bazaar, remotely located 40 miles east of Dacca, Bangladesh, that was ideal.  The new trial would include only a drinkable solution without the need for feeding tubes.

Nalin's and Cash's enthusiasm for this next trial was crushed when a letter came from the National Institutes of Health, removing approval until further review.  Doing so would delay the study at least for a year, since cholera comes in seasonal epidemics, and by then both Nalin and Cash would be back in the U.S. It was suspected that the head of the Dacca lab, Robert Phillips, had instigated the letter.  Phillips had kept secret from the lab the work he had done on a "cholera cocktail" in the Philippines that had five fatalities. His belief that an oral solution was not possible seemed to make him want to block all further trials.  Very disheartened by the unexpected barriers to their work, and realizing they could be court marshaled (since technically they worked for the military), Nalin and Cash approached Henry Mosely, head of epidemiology at the lab.  Mosely, who worked for the Center for Disease Control (CDC), offered a solution.  He could run the project through four CDC officers that would be given direction from Nalin and Cash.  Mosley was particularly interested because he was working in a hospital outside Dacca where IV fluid was hard to come by. This offered the opportunity to complete the research and not leave Nalin and Cash in a position of violating NIH orders. 

Five hundred and eight patients were treated with oral therapy during this second trial.  These patients' records were compared to those patients treated the previous year, using IV therapy.  The astonishing results were that:  "Medical and paramedical personnel were easily trained in the preparation and use of oral solutions. Oral therapy practically eliminated the need for intravenous fluids in patients with mild cholera. It seems possible that if patients with severe cholera were treated from the time of onset, they might be maintained on oral therapy alone. The public health implications of oral therapy are obvious; it is inexpensive, simple, and effective. Its widespread use should reduce mortality due to cholera even in remote districts where little or no intravenous fluid is available."

Cash, R.A. Nalin, D.R.., Rochat, R.L., Reller, B., Haque, Z.A., Rahman, A.S.M.M. 1970. A Clinical Trail of Oral Therapy in a Rural Cholera-treatment Center. American Journal of Tropical Medicine, 19:4 653-656.

Other Discoveries

In a follow-up to their landmark study, Nalin and Cash showed that ORT can treat even the most severe cases of cholera. Then they proved that it works on children. In fact, later studies demonstrated that infants as young as one month old can be given ORT. They also demonstrated that the addition of glycine substantially reduced both the duration and volume of diarrhea in cholera patients, which set the stage for numerous other studies refining and improving the solution. Nalin and Cash also demonstrated that cholera patients could be fed food along with the oral solution, not long after shock was corrected, overturning the wrongly held tradition of starving patients for several days. In fact, nourishment can help a patient fight off the cause of the diarrhea.

A big surprise was discovered by Norbert Hirschhorn when, in a study of Apache children in Arizona, he revealed that people instinctively know how much solution to drink to properly rehydrate their bodies.  It is in a doctor's nature to want to prescribe specific doses of treatments.  But it turns out that without a doctor's prescription, even children usually drink as much as they need, then stop (although there are certain conditions that may inhibit this ability). In hindsight, this makes a lot of sense - people live their whole healthy lives regulating the amount of water in their bodies, and being sick doesn't impair their ability to do so.

Other Diarrheas

Most significantly, and surprisingly to many doctors, Nalin and Cash demonstrated that ORT is "as effective in the non-cholera diarrhea patients as in cholera patients." The importance of this finding was monumental. While cholera raises our awareness of diarrheal dehydration, because it comes in attention-grabbing epidemics, it accounts for at most 10 percent of the cases of diarrhea sickness in the world.

Why drinking water doesn't work to combat dehydration

For centuries, every scientist knew that cholera victims could not rehydrate their bodies by drinking water. When O'Shaughnessy suggested using a saline solution for IV treatment, scientists tried to add salt to water for an oral solution. This didn't work either, even though scientists learned that salt played a crucial role in the body's ability to move water around by way of osmosis. The key to the mystery of how the body absorbs water in the gut proved to be sugar. Sugar was slow to be recognized as crucial because it plays no role in osmosis. Although scientists don't completely understand all the details even today, they began in the 1960s to unravel the intricacies of how water is absorbed in the gut. Specialized proteins in cell membranes bind to and transport sodium and glucose (sugar) across cell membranes simultaneously-one glucose molecule for every two sodium ions-and neither can be transported without the other. Hundreds of water molecules are bound to each of these glucose molecules, and this is how water is absorbed. A number of other sugars and amino acids can act in the same way. A driving force behind this transport mechanism is the concentration gradient-or difference-of sodium ions between the intestine and the insides of the intestinal wall cells. Scientists first learned that water absorption requires salt; scientists then learned that water absorption requires sugar; therefore for water to be absorbed in the gut, all three-water, salt, and sugar-are absolutely required.

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ORT Goes Global

To get ORT to the masses, researchers faced huge obstacles: A medical culture that clung to IV therapy as superior to what they perceived as a primitive oral form; a very high prevalence of illiteracy, especially among women; and no way to distribute ORS packets to remote, roadless areas. 

Dilip Mahalanabis, a pediatrician working with the Calcutta Cholera team, organized and applied exclusive Oral Rehydration Therapy to adults and children in refugee camps during the Bangladesh War of Independence. This was one of the first uses of ORT in emergency situations that required the administration of resuscitation fluids by family members, rather than medically trained personnel. This demonstration encouraged widespread use of the technique.

Nalin himself worked in the worldwide public health campaign promoting ORT in Costa Rica, Jamaica, Jordan, and Pakistan. "We realized for this to have optimal effects, we really had to get it out of the hands of doctors and nurses and into the hands of experienced mothers," Nalin said. "One tool that proved very successful was to teach doctors and nurses that they had to communicate three or four rules to a mother when the mother is concerned her child is sick. Are the child's eyes sunken? A mother knows better than a doctor when a child is ill. ...At the first signs of diarrhea, take out a packet, mix with a liter of water and start giving it to the child, every half hour or so until the child looks normal and starts to pee. We told her to watch the child's eyes; give fluids until the eyes return to normal. We taught her to keep pinching the skin on the back of the hand - it will ‘tent' if the child is still dehydrated and needs more oral solution. Mothers were sent back to villages with the packets. That sometimes met resistance from the local medical community, which had been making money giving IVs or charging several dollars for packets that cost pennies. But one mother back in the village would spread the word."

BRAC

Bangladesh had a war of Independence in 1971 and broke away from West Pakistan. Abed Fazle Hasan, who had been an accountant working for Shell Oil in Chittagong, fled the war. When he returned, he chose to help rebuild his country by forming a private foundation, the Bangladesh Rural Advancement Committee (BRAC).

BRAC went on a 10-year campaign to turn a scientific discovery into a home remedy. Beginning in 1980, BRAC sent an army of 10,000 female health workers into the Bengali countryside, where they taught ORT to 13 million illiterate mothers. Children, too, learned the ORT recipe through one-room schools set up by BRAC, that today number 37,000. In time, this simple solution became part of the national lore. A poem about ORT became so common that the government eventually put it on a stamp (gur is a molasses made from sorghum).

Mix with much care,
Good water, a liter,
A pinch of salt with a fistful of gur,
Remove the menace for good

At least 75 percent of Bangladesh families use ORT to treat diarrhea, according to government surveys. The acceptance and use of ORT for treating diarrhea, regardless of patient age or cause of diarrhea, have been important to the development of the WHO Global Diarrheal Diseases Control Program. As a result of these successful ORT programs, diarrhea case-fatality rates have declined dramatically. 

ORT in the West

Surprisingly, despite these results, many clinicians in industrialized countries have been reluctant to use ORT. Many physicians continue to recommend a variety of "clear liquids" to treat patients with diarrhea, instead of an appropriately composed ORT.  These "clear fluids" can cause osmotic diarrhea and electrolyte imbalance. 

Without the encouragement of doctors, most American parents don't even know that drugstores sell ORT in packets or solution over the counter.

ORT is an example of a less technological solution being superior to a more complex solution, making some parents who believe that the best treatment for their child is what costs the most money reluctant to use it. More cynical critics suggest that the medical industry is simply greedy. The cost of ORT is a few dollars a treatment. The cost of putting a child or elderly person on an IV, and often keeping him or her overnight in a hospital for observation, can run into the thousands of dollars. Estimates suggest that ORT use could save billions of dollars annually in the U.S.

Gatorade - An Oral Rehydration Solution

It's especially odd that ORT hasn't caught on as a treatment for diarrhea in the U.S., considering that most Americans have used an oral rehydration solution. In the South, in the 1960s, football players were falling from heat exhaustion like flies on DDT. University of Florida assistant coach Dewayne Douglas, himself a past player who had experienced heavy sweating and no urine output during games, asked physicians at the college to develop a drink for the football team. They found the water-salt-sugar coupling research and formulated a solution for the players to drink. The rest is history. That year the moribund Florida Gators began using Gatorade and finished 7-4, winning many games in the second half. It was their first winning season in more than a decade. The next season they went 9-2. Soon every team was using Gatorade, an out-and-out, scientifically formulated oral rehydration therapy.

While Gatorade works based on the same physiological mechanisms as ORT, it is not a substitute for ORT in diarrhea cases because it is formulated for healthy athletes, chiefly to replace sweat loss, not for sick children or adults who have diarrhea, which is significantly different in composition, so requires a different solution. In order to make it easier for busy Americans to take, Abbot Laboratories created a ready mixed ORT drink for diarrhea, available in a bottle, called Pedialyte. And, only in America, does taking medicine have to be fun. To encourage its use, Abbot began producing Pedialyte Freezer Pops in numerous flavors. So maybe ORT will yet catch on in the United States.
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Personal Information

David Nalin was born in New York on April 22, 1941.  His father had wanted to become a physician himself but, when his own father, David's grandfather, died of pneumonia and his mother had to support the family, it was not possible.  He later became a pharmacist and pharmaceutical manufacturer. As David and his brother grew up it was suggested that, now that the family economy had improved, it might be a good thing to become a doctor.  

As a child, David began collecting many different things.  Some collections were as simple as baseball cards, some as exotic as turtles and salamanders.  Not a common sight in most Manhattan bathtubs!  He credits his parents' high level of tolerance for nurturing his curiosities and collections.  A young Nalin also liked to visit local museums and auctions in search of interesting beads or antiquities.

David Nalin soared academically.  He skipped several grades and, after graduating from Bronx School of Science, was accepted to Cornell, studying zoology by age 16.  He was then accepted to Albany Medical College at age 20, making him one of the youngest medical students in their history.  Nalin applied for a cross cultural clerkship in his third year and went to Guyana in South America, where he would visit three times, saying that this is where his life changed. He was confronted with the developing world, fascinating art, and became interested in research.  After completing only his first year of residency he signed on to the Pakistan-SEATO Cholera Research Lab in Dacca, Bangladesh. 

Dr. Nalin worked for the National Institutes of Health (NIH) from 1967 to 1970.  He later accepted a series of academic appointments at Harvard, Johns Hopkins, and the University of Maryland which took him and his research skills all over the world.  As a WHO consultant, he helped establish a number of highly successful national programs on the Oral Rehydration Therapy for diarrhea diseases in Costa Rica, Jamaica, Jordan, and Pakistan.  Dr. Nalin became the Director of Clinical Research for Infectious Diseases at the pharmaceutical company, Merck, in 1983 and remained at that position until his retirement in 2002.

Likely beginning in his early years, rooted in his affinity for collections, Nalin developed a passion for ancient Indian art, which he collected as he traveled the world.  His collection grew to be so extensive that Harvard University produced three catalogues of it.  He donated much of his substantial collection to a University of Vermont Fleming Museum exhibit in 2006.

The scientist's other research

Dr. Nalin has over 120 peer reviewed publications, spanning 40 years of work.  In addition to ORT related discoveries, these publications chronicle his remarkable contributions to:

-The development of hepatitis A vaccine.

-Anthrax identification and treatment.

-Study of mumps, measles and rubella vaccines.

-Malaria.

-Use of vitamin A.

-Antimicrobial effects of statins.

David Nalin's Life: A Timeline

1941 - David Nalin was born in New York City.

1965 - Graduated from Albany Medical College.

1967 - Arrived in Dhaka (the capital of East Pakistan, as Bangladesh was known before gaining independence)  to do cholera research at the Pakistan-SEATO Cholera Research Laboratory (CRL), as a research associate at the U.S. National Institutes of Health (NIH).

1973 - Established and served at the Johns Hopkins Center for Medical Research in Dacca, Bangladesh.

1975 - The World Health Organization (WHO) and the United Nations Children's Fund (UNICEF) agreed to promote a single, orally administered solution of oral rehydration salts to prevent dehydration caused by diarrhea.

1979 - Nalin arrived in Lahore, Pakistan to take charge of the malaria research centre where he was later expelled by Pakistani authorities, early in 1982, due to unfounded Soviet allegations that the research being conducted there was for the CIA.

1983 to 2002 - Director of Vaccine Scientific Affairs at Merck's Vaccine Division.

2002 - Received the first ever Pollin Prize in Pediatric Research.

2007 - Received the Mahidol Medal from His Royal Highness the King of Thailand, presented at a ceremony at the Chakri Throne Hall in Bangkok.



Scientific Discovery Timeline





Recommended Books about the Science of Oral Rehydration Therapy





Books by David Nalin


Displaying Many Faces: Art and Gandharan Identity Selections form the David R. Nalin Collection by Chandreyi Basu, David Robert Nalin January 2004.  http://www.allbookstores.com/book/9780961441616/Chandreyi_Basu/Displaying_Many_Faces.html



Books about Nalin


Casey, J.A. Medieval Sculpture from Eastern India: Selections from the Nalin Collection. Nalini Intl. Pub., 1986.

Woodward, Billy, Shurkin, Joel and Gordon, Debra. Scientists Greater than Einstein: The Biggest Lifesavers of the Twentith Century. Linden Publishing, 2009.




Awards


2002 - Among many distinctions of his career, Nalin received the first ever Pollin Prize in Pediatric Research.  This honor was shared with Dr. Norbert Hirschhorn, Dr. Dilip Mahalanabis, and Dr. Nathaniel Pierce.

2007 - The Mahidol Medal from His Royal Highness the King of Thailand was presented at a ceremony at the Chakri Throne Hall in Bangkok, in recognition of the discovery and implementation of Oral Rehydration Therapy.



Major Academic Papers


Dr. David Nalin has published over 120 Peer reviewed academic papers, spanning his work over 40 years.  Some highlights include:

Nalin DR, Cash RA, Islam R, Molla M, Phillips RA. 1968. Oral maintenance therapy for cholera in adults. Lancet, Aug 17;2(7564):370-3.

This paper in Lancet is the original report of Dr. Nalin and colleagues' work with ORT.

Cash, R.A. Nalin, D.R.., Rochat, R.L., Reller, B., Haque, Z.A., Rahman, A.S.M.M. 1970. A Clinical Trail of Oral Therapy in a Rural Cholera-treatment Center. American Journal of Tropical Medicine, 19:4 653-656.

Oral or nasogastric maintenance therapy in pediatric cholera patients.  Nalin DR, Cash RA.

J Pediatr. 1971 Feb;78(2):355-8.

This paper describes the use of ORT in pediatric patients.

Worldwide experience with the CR326F-derived inactivated hepatitis A virus vaccine in pediatric and adult populations: an overview. Nalin DR, Kuter BJ, Brown L, Patterson C, Calandra GB, Werzberger A, Shouval D, Ellerbeck E, Block SL, Bishop R, et al. 

J Hepatol. 1993;18 Suppl 2:S51-5.

This paper describes Dr. Nalin's work with Hepatitis A vaccine.

Mumps, measles, and rubella vaccination and encephalitis. Nalin DR.  BMJ. 1989 Nov 11;299(6709):1219.

Oral therapy for diarrheal diseases. Nalin DR.  J Diarrhoeal Dis Res. 1987 Dec;5(4):283-92.

This paper provides an overview of how ORT can be used for dehydration resulting from diarrheal diseases, not only cholera.

Recognition and treatment of anthrax. Nalin DR.  JAMA. 1999 Nov 3;282(17):1624-5.



Curriculum Vitae





Links to Science and Related Information on the Subject


World Health Organization fact sheet for Cholera
http://www.who.int/mediacentre/factsheets/fs107/en/index.html

Against the Odds - Making a difference in global health - A Simple Solution
http://apps.nlm.nih.gov/againsttheodds/exhibit/community_health/simple_solution.cfm

UNICEF statement
http://www.unicef.org/sowc96/joral.htm

Link to Dr. Nalin's biography as the recipient of the Prince Mahidol award.
http://www.princemahidolaward.org/laureate-bio.en.php?type=ind&id=2006-11-22%2005:48:15
http://thaiembdc.org/pressctr/pr/pr0349.pdf

Link to A Life Changing Experience. Albany Medical College Alumni Bulletin
http://amc.edu/Academic/Alumni/documents/Bulletin_Spring_2007.pdf

Link to New York-Presbyterian Hospital Announcement of First Pollin Prize In Pediatric Research
http://www.icddrb.org/images/glimpse2502_profiles.pdf

Link to Albany Medical Centre press release for Establishment an Endowment fund to Encourage International Student Research
http://www.amc.edu/foundation/investment_at_work/investment_med_edu.html

Link to Press release for Merck Hepatitis A vaccine, August 1992
http://findarticles.com/p/articles/mi_m1200/is_n7_v142/ai_12549189



Sources/References


Cash, R.A. Nalin, D.R.., Rochat, R.L., Reller, B., Haque, Z.A., Rahman, A.S.M.M. 1970. A Clinical Trail of Oral Therapy in a Rural Cholera-treatment Center. American Journal of Tropical Medicine, 19:4 653-656.

Elliot, J. 2007. A Life Changing Experience. Albany Medical College Alumni Bulletin.

Farthing, M.J.G. (1988) History of ORT. Drugs. 36 supplement 4:80-90.

Foex, B.A. 2003. How the cholera epidemic of 1832 resulted in a new technique for fluid resuscitation. Emergency Medical Journal, 20, 316-318.

Fontaine, O., Garner, P., Bhan, M.K. 2007. Oral rehydration therapy: the simple solution for saving lives. British Journal of Medicine 334(suppl 1):s14.

Guerrant, R.L., Carneiro-Fiho, B.A. & Dillingham, R. 2003. Cholera, Diarrhea, and Oral Rehydration Therapy: Triumph and Indictment. Clinical Infectious Disease, 37, 398-405/

Harrison, H., Darrow, D., Yannet, H., 1935. The total electrolyte content of animals and its probable relation to the distribution of body water. The Journal of Biological Chemistry. http://www.jbc.org/cgi/reprint/113/2/515 (accessed November 20, 2008). 

Hirschhorn, N. 1990. Speech at the Charles A. Dana Awards For Pioneering Achievements in Health and Education.

Horn R., Perry, A., Robinson, S. 2006. Diarrhoea: why is a simple and inexpensive treatment not more widely used?  IRC International Water and Sanitation Center. http://www.irc.nl/page/31514. accessed October 2, 2007).

Mendler, J. 2007. Take the Science to the Problem! Oral Rehydration Salt Solution solves one of humanity's most dire problems. The Concord Consortium. Concord.org. (accessed October 1, 2007).

Nalin D.R., Cash, R.A., Islam, R., Molla, J., Phillips, R.A. 1968. Oral Maintenance Therapy for Cholera in Adults. The Lancet, 292, 370-375.

Nalin, D.R., Cash, R.A. 1970. Oral or nasogastric maintenance therapy for diarrhoea of unknown etiology resembling cholera. Trans. R. Soc. Trop. Med. HI-g., 64 (5): 769.

Parashar UD, Gibson CJ, Bresee JS, Glass R.I. 2006. Rotavirus and severe childhood diarrhea. Emerg Infect Dis [serial on the Internet]. http://www.cdc.gov/ncidod/EID/vol12no02/05-0006.htm (accessed October 28, 2007).

Phillips, R.A. 1964. Water and Electrolyte Losses In Cholera, Federation Proceedings, 23: 705-712

Quotah, E. 2006. A Not-So-Simple Solution. Harvard Public Health Review.

Ruxin, J.N. 1994. Magic Bullet: The History of Oral Rehydration Therapy. Medical History, 38, 363-397.

Victora, C.G., Bryce, J., Fontaine, O., Monasch, R. 2000. Reducing deaths from diarrhoea through oral rehydration therapy. Bulletin of the World Health Organization. 78(10).

Woodward, B. 2008.   Scientists Greater Than Einstein:  The Biggest Live Savers of the Twentieth Century.

1992. The Management of Acute Diarrhea in Children: Oral Rehydration, Maintenance and Nutritional Therapy. MMWR

1998. Cooking for the Gods: The Art of Home Ritual in Bengal. Mount Holyoke College Art Museum http://www.mtholyoke.edu/offices/artmuseum/news/s98/exhibitions.html. (accessed October 1, 2007)

2001. The Oral Rehydration Therapy. Rainbow Pediatrics Knowledgebase. http://www.rainbowpediatrics.net/faq/12.3.html. (accessed September 27, 2007)

2003. The History of Gatorade. Gatorade. http://www.gatorade.com/history/ accessed September 38, 2007.
 
Comments (3)
3 Tuesday, 24 January 2012 12:56
DarkAngel
lol (Alex) but thats true. . . if you dont want to get dehydrated DRINK DRINK DRINK
2 Wednesday, 19 May 2010 11:11
Homeschool girls rock
Exactly! I completely agree!
1 Thursday, 06 May 2010 10:23
Alex
So... To prevent dehydration, drink? I could have told you that, no way does that deserve a Nobel prize!

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