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Alfred Sommer

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Al Sommer - Vitamin A deficiency:
The vitamin A supplement campaign was launched globally in the 1990s and UNICEF tracks this statistic. I was able to make a pretty solid inference because the numbers are fairly stable, averaging between 300,000-500,000 lives saved yearly since the campaign was initiated. Over 100 million young children suffer from vitamin A deficiency and supplements are given biannually, mostly to children 0-5 years of age.  Vitamin A deficiency is a contributing factor in the 2.2 million deaths each year from diarrhea among children under five and the nearly 1 million deaths from measles.
--Amy R. Pearce, PhD

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Alfred (Al) Sommer
(October 2, 1942 - )
Born in the United States
Year of Discovery: 1982
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Discovered that Providing Vitamin A Tablets to Children Saves Lives

 

Alfred Sommer discovered that children with vitamin A deficiencies are at a greatly increased risk of death. Children in developing countries are especially at risk. But, for less than five cents per year, Sommer found, these children can be saved.

Sommer made his remarkable finding after studying the impact of vitamin A deficiency in Indonesia. It was well known that vitamin A deficiency caused blindness, so Sommer and his colleagues spent three years performing studies Sommer designed on groups of children, both those who were healthy and those with signs of nutritional blindness. He made some landmark discoveries about the epidemiology of the disease, and an effective treatment.

Sommer had a restless mind, so even after finishing his analysis, he periodically re-examined his studies. During one such re-analysis, during Christmas break in Baltimore, he suddenly realized that vitamin A deficiency did not just cause blindness in children - it also caused death! It was a major medical breakthrough, with significant consequences for the entire world's population.

 

Not only did Sommer discover the deadly effects of vitamin A deficiency, he also developed the most effective and economical treatment. At the time, vitamin A injections were used to treat any deficiency. The vitamin A he was provided for the study did not work well as an injection and it would take months for the manufacturer to develop a properly constituted injection. So Sommer innovated. He began squirting vitamin A into children's mouths. It worked wonderfully well and he backed up his success with a study.

Initially, neither Sommer's findings about oral doses or the increased mortality of children with vitamin A deficiency were well received by the medical community. Some thought the fix was too simple to prevent such a devastating pattern of deaths. Others thought the reduction in mortality was too large to be true. So Sommer set about performing new studies in the Philippines, Nepal, India, Ghana - essentially, all over the world. In the end, Sommer's evidence was overwhelming. The world's health professionals became convinced, and his treatment methods became the standard.

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by Tim Anderson



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Table of Contents

Introduction
Key Insight
Key Experiment or Research
Quotes by Alfred Sommer
Quotes About Sommer
Anecdotes
Excerpt from Scientists Greater than Einstein
Similar Scientists
Fun Trivia
The Science Behind the Discovery of Oral Vitamin A Treatment
Personal Information
Key Contributing ScientistsScience Discovery Timeline
Recommended Books About the Science
Books by Alfred Sommer
Books About Sommer
Awards
Major Academic Papers
Curriculum VitaeLinks to Science and Related Information on the Subject
Sources

 

 








Photos of Sommer with Patients
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Sommer Quote About Forrest Gump
Alfred (Al) Sommer
Quote About the Wonder of Vitamin A
Sommer Quote on His Passion for Data
Sommer Quote on Epidemiology
Sommer Quote on Disaster Work
Sommer's Shocking Discovery
Vitamin A Facts






Pics in Indonesia
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Click the image to view Alfred Sommer's Lasker Foundation interview

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Key Insight

When Sommer approached vitamin A deficiency the health field believed its only serious manifestation was in causing blindness.

At Christmas time in 1982, a year after completing the normal analysis of three studies he had created and executed in Indonesia in the late 1970s, Sommer re-examined the datasets. As he immersed himself in the information "it became apparent that something very funny was going on with the data." Sommer said to himself, "Gosh, what in the world is going on here?" Children who had night blindness seemed to disappear from the study. They wound up in the "don't know" category far more than did kids who had normal eyes. What happened to those children with their big eyes? Why did they leave the study?

"Holy cow!" Sommer exclaimed, suddenly realizing the children weren't showing up for examinations because they were dead! "I got really excited," Sommer said, "and using my little hand calculator, I redid the data by hand, going from cell to cell....What was the risk of kids with night blindness dying? What was the risk of kids with Bitot's spots dying? How about kids with spots and night blindness? Kids with normal eyes? I checked them through six intervals."

Sommer's original dataset did not measure childhood deaths because death was not thought to be related to vitamin A deficiency. By using epidemiological studies, Sommer found that children with vitamin A deficiency have a drastically higher rate of death than children with normal levels of vitamin A. Nutritional blindness, as it turned out, was not the endpoint of vitamin A deficiency, death was.

Sommer's key insight seems to have come from his asking of the dataset more than the normal epidemiologist would ask. One of his famous quotes is: "I say ‘data talk to me, tell me what you have to say.... You have to know your data, you have to smell it, you have to be in it. If you're not living inside the data you are going to miss the most interesting things, because the most interesting things are not going to be the questions you originally proposed; the interesting things are going to be questions you hadn't thought about." Rather than asking rote questions of the dataset he had prepared before the studies were executed, he used inductive logic to listen to any and everything the dataset told him. Doing so a year after the initial questions had been answered, he made his additional, and revolutionary, discovery that vitamin A deficiency was more than an eye problem.

Another of his key insights was that taking vitamin A orally was as good for a child as receiving an injected shot, which was the accepted method throughout the world. This insight had begun when he ran out of injectable vitamin A. Confronted with the shortage, he didn't simply make do until a new supply was found. He designed a study that would measure if oral doses were as beneficial. That they were was revolutionary, because it meant that anyone in the world could give a child a dose of vitamin A, at a cost of less than a nickel. It is speculated that this insight came from previous work Sommer had done in Bangladesh, with Oral Rehydration Therapy, that treated diarrhea from cholera with drinking specially designed fluids-a much simpler and more useful method than intravenous treatment that had long been recognized as the best method.

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Key Experiments or Research

Vitamin A Supplementation Can Save Lives

Sommer's most noted discovery occurred in 1982 when he found that vitamin A deficiency was life threatening to children. His studies led to twice a year vitamin A supplementation worldwide for children, an inexpensive and extremely effective method for enhancing children's immune systems and helping their tissues to mature enough to fight off disease.

Sommer A, Tarwotjo I, Hussaini G, Susanto D. Increased mortality in children with mild vitamin A deficiency. Lancet 1983;2:585-588.

Oral Doses of Vitamin A Work as Well as Injections

Worldwide, it was thought that an injection of vitamin A was necessary to cure vitamin A deficiency. Sommer proved that oral doses were just as effective. Oral doses are much less expensive and don't require a doctor, or any medical training, so this finding revolutionized delivery of lifesaving vitamin A.

Sommer A, Muhilal, Tarwotjo I, Djunaedi E, Glover J. Oral versus intramuscular vitamin A in the treatment of xerophthalmia. Lancet 1980;1:557-559.


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Quotes by Al Sommer

"I began to think of hundreds of thousands, if not millions, of people," he said. "From then on, my orientation was different. I was always looking at bigger issues as far as research was concerned. It gave me a population perspective. That's also where I became very interested in epidemiology and public health."
-After assessing health care needs following a massive cyclone in Bangladesh

"In the broader context, if we improve health in the world, we're improving our own health at the same time."
-During an interview for the Lasker Foundation

"I think it's real goofy but governments have multiple objectives - one of them is warfare, and one of them is peace, and one of them is health, and sometimes they get them confused."
-During an interview for the Lasker Foundation

"A profound amnesia appears to have settled over the broader context of vitamin A deficiency once it ceased to be a major concern of wealthier nations."
-On the failure of researchers to remember the proven seriousness of vitamin A deficiency

"To be fascinated with what you're doing - I went overseas and had this marvelous experience working in the field and literally having millions of people's welfare and lives hinging upon decisions that I made and investigations that I carried out and I found that extraordinarily exhilarating - that the amount of leverage, the amount of impact I could have was so much greater than I could on a one-to-one patient-physician basis. As fulfilling as that is in its own right, I made then the commitment to public health. And public health research is an area where I knew that I was going to enjoy myself."
-On the role of public health

"There's a curious paradox at the heart of public health: When it works, nothing happens. Nobody wakes up in the morning and says, 'Boy, it's great that I don't have cholera, or Isn't it wonderful that my children aren't crippled by polio?' ... We dream one day of ridding the world of blinding trachoma, death during childbirth, autism and AIDS. We know that when we realize those dreams, we shall perpetuate the paradox that lies at the heart of public health. ... [It is] a remarkable achievement ... when nothing happens."
-On the role of public health

Sommer remembers the Bangladesh smallpox epidemic as: "a horrific time. Ten million Bengali refugees were streaming back home. I was dealing with smallpox epidemics in both urban neighborhoods and dense refugee camps. The only thing you could do was pray for early detection and then mass immunization, to prevent the disease. Once someone had the disease, one-third would die. The key to success was immunizing everyone in the camps. Many refused immunization; I had to resort to holding back ration cards until they agreed to vaccination."
-On a Smallpox Epidemic

"My guiding philosophy has always been, 'Chance favors a prepared mind,' which is a quote from Louis Pasteur. My own complement to that: 'If a research project turns out as expected, you haven't learned anything.'"
-On the need to be fully prepared

"I say ‘data talk to me, tell me what you have to say.... You have to know your data, you have to smell it, you have to be in it. If you're not living inside the data you are going to miss the most interesting things, because the most interesting things are not going to be the questions you originally proposed; the interesting things are going to be questions you hadn't thought about."
-On the nature of epidemiology

"As you peel back the layers of the onion one at a time, there's always another mystery behind it, another medical detective story. Often the answers come at odd times. You don't get the insights you need-either the answer or how you are going to approach a question-while you are actively thinking about it. I'll wake up at two in the morning, and I'll say, ‘Aha, I know how I'll approach that now.' Unfortunately, a lot of times in the morning what I wrote makes no sense."
-On the nature of epidemiology

"Whatever contributions I have made have largely been something other than what I started out looking for, as is the case with many contributions in science. Basically, there are lots of important issues and lots of hints that come your way. I have had that opportunity many times, that when you are concentrating on an issue in a broad perspective, some clue comes along, a hook that gives you a unique insight that you wouldn't otherwise have had."
-On the nature of epidemiology

"An area of medical research and investigation and endeavor that I didn't know very much about and literally fell in love with - epidemiology - which, in its best sense, is medical detective work. It's Sherlock Holmes played out in the medical arena and clearly has had and still has the opportunity to impact positively on the lives of literally millions of people at any one time."
-On the nature of epidemiology

"Nobody was willing to accept that two cents worth of vitamin A was going to reduce childhood mortality by a third or half, let alone when that information was coming from an ophthalmologist. A lot of people had spent their lives studying the complex amalgam of elements leading to childhood deaths, and here we are suggesting that we can cut right through this complex, causal web and give two cents worth of vitamin A and prevent those deaths. It didn't sit well."
-On the lack of acceptance of his discovering the effectiveness of oral vitamin A treatments

"All the trials came out the same, which was really quite to my amazement, given all the different cultures and environments in which the trials were done. Yet, all the studies had a 35% to 55% reduction in childhood mortality, whether you gave the capsule once every 6 months, every 4 months, or every week, or if you put a little vitamin A into something they ate once a day. It all came out essentially the same, which was quite heartening."
-On his satisfaction in successfully replicating his vitamin A studies in several other countries

"My first and most important rule is attributable to that great twentieth century philosopher, Woody Allen-‘90 percent of success is showing up.' Nothing will happen, or come to mind, if you are not around to observe or experience it. Of course not everything you observe or experience is worth a second thought, but I'd be surprised if you haven't already exchanged some nuggets of potentially brilliant opportunity-even if rare and far between-over beer and pretzels at Friday Happy Hour."
-At his last convocation speech as Dean of the Johns Hopkins Bloomberg School of Public Health, 2005

"Yogi Berra famously exclaimed, ‘When there is a fork in the road, take it.' He actually said this-I heard him on an old TV documentary. I'm still not entirely certain what Yogi meant-but I've interpreted it as a recommendation to ‘follow your nose.' At every point in my career I've chosen to do what seemed most important and most interesting at the time, never what might best position me for the next step in my career. In fact, I've never thought in terms of a career, only of a string of interesting challenges and opportunities. Might a different "fork" have been more rewarding? Perhaps. But one can never know. ‘Forks in the road' are not susceptible to randomized trials. But not taking a fork, whichever it is, leaves you stuck on the same old path."
-At his last convocation speech as Dean of the Johns Hopkins Bloomberg School of Public Health, 2005

"My becoming a doctor in the first place was very easy. I truly believe that my grandmother, on the day of my birth, imprinted it somehow on my soul and, in fact, I can never remember a time when I did not want to be a doctor. She was somebody who had been an immigrant to the United States from Eastern Europe and just thought that physicians were somebody who did good and did well while doing good and thought that her grandson couldn't choose a better career for his life and it was never a tussle."
-On his grandmother's influence on his becoming a doctor

"I ought to provide a disclaimer. Some people are far more directed and deliberate than I am and I have lived most of my career by doing whatever seemed most interesting at that particular moment."
-On his own nature

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Quotes About Sommer and vitamin A

"Dhaka changed him forever."
-W. Henry Mosley, who hired Alfred Sommer in 1970 to work in the epidemiology division of the Cholera Research Laboratory in Dhaka, Bangladesh. Mosley sent Sommer and his team to Dhaka to assess the health care needs after a massive cyclone killed more than 240,000 people.

"There are relatively few absolute, new ideas in the world. If you have one in your life, you're really something. Al Sommer has had several of them."
-Bruce Spivey, Secretary General and President-Elect, International Council of Ophthalmology.

"Over and above being a friend and mentor, I'd call him the greatest advocate of public health in our modern day."
-Keith West, The George G. Graham Professor in Infant and Child Nutrition, Johns Hopkins Bloomberg School of Public Health.


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Anecdotes

No Girls Allowed

Sommer chose to attend Union College, a small, then all-male college in upstate New York, because, "it would keep my raging hormones in control and I could get some work done."

Take a Vacation - Please!

Sommer's first position after Harvard Medical School was in the Epidemic Intelligence Service, a division of the CDC. He threw himself into his work and soon began generating numerous proposals for new initiatives he believed the center should pursue. All this activity made his colleagues and superiors nervous, so one day his boss cornered him. "Al," he said, "we have all voted for you to go home for two weeks and relax." Shortly after he returned, he was on his way to East Pakistan to study cholera.

Going My Way?

When the Bangladesh Liberation War broke out in 1971, the government especially targeted intellectuals and Hindus. Sommer's research group was forced to evacuate. In a final act of service, before being evacuated with all the other westerners, Sommer made multiple trips toward the border, carrying Bengali intellectuals in the trunk of his car. He often encountered road blocks manned by tough, AK47-toting militants from Pakistan's Northwest frontier province along the way, forcing him to use his smile and ease of talking to spirit them through. He finally let them out where it was safe to cross the Indian border.

Action Over Academics Anytime...

Sommer was invited to join the faculty at Johns Hopkins when he graduated, but he was not the conservative, academic-tenure track type of doctor. He told them of the opportunity to do research in Indonesia. Colleagues warned him that he would lose his place on the faculty and would be forgotten, but Sommer told them, "No, I have this wonderful opportunity to go overseas, work with people in another culture. I have something to contribute and it is intrinsically a very interesting series of questions that need to be answered."

Are You Talking To Me?

The research Sommer completed became quite personal. Indonesia is a country with over 300 languages. Both he and his wife learned to speak Malay, the Austronesian language spoken throughout Indonesia, Malaysia, Singapore, Brunei and Thailand.

Mother Knows Best

Sommer found that sometimes science is simply no match for mothers. In Indonesia, the mother's recollection of their child's inability to see at dusk or dawn was every bit as accurate as any objective measure. In fact, the mother's memory had a higher correlation to low serum vitamin A levels than the objective measures.

A Taste of Their Own Medicine?

A folk remedy was described to Dr. Sommer about which he was quite doubtful. The Java locals said they were lightly roasting lamb's liver and then dropping its juices into the children's eyes. They claimed this successfully treated the night blindness. Sommer and his colleagues went out into the field to observe the ceremony. They soon saw the reason the remedy persisted. After the ritual, the villagers cooked and fed the liver to the children. Since the liver is the best source of vitamin A, the mystery of the treatment's persistence was solved.

A Little Squirt for the Little Squirts

When Sommer and his team discovered the injectable vitamin A was not working, they improvised. Sommer drew on his experience in treating cholera victims with a treatment known as Oral Rehydration Therapy, in which patients are given fluids by mouth. So, he decided to squirt a vitamin A preparation into the mouths of the sick children instead of injecting them. It worked wonderfully well and, eventually, oral supplementation by pills became the worldwide standard of treatment for vitamin A deficiencies

Too Much of a Good Thing?

Sommer's initial studies with vitamin A were too good to be believed. After he reported the results in the medical journal Lancet, critics quickly said such a simple intervention could not be so powerful. Some said that if Sommer had claimed vitamin A could reduce death rates by 10 percent, they would have accepted it. But Sommer's claim of reducing deaths by 34 percent was too much. A critic of Sommer's work, who publicly stated his findings were "too good to be true," eventually wrote an editorial in the New England Journal of Medicine tilted, "Vitamin A - Too good not to be true."

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Excerpts from Scientists Greater Than Einstein: The Biggest Life Savers of the Twentieth Century

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A New Adventure

Alfred Sommer was hanging onto his seat as he rode the harrowing roads into the highlands of Indonesia. His family was wide-eyed at the new sights. The barely two-lane road was crooked and cramped, much too narrow for the comfort of a doctor who knows the carnage that can litter rural roads. They rose in altitude, with a 2,000-foot drop off one side and a blind switchback up ahead. A car raced past them with nowhere to go if another vehicle appeared ahead, and Sommer grimaced and shut his eyes - but there was no crash of metal, just the laboring of the engine as it chugged on up the mountain. The vegetation had been incredibly profuse in the rainforest of the lowlands - bamboo and orchids and palm trees - and it was green and lush here, too. The road leveled out for a while, then climbed some more, then flattened as they rode past rice paddies, past tea plantations, past tall cinnamon trees. It grew cooler as they rose, slowly heading southeast, toward Bandung, The Flower City.

Folk Remedies

There were folk remedies worthy of study as well. One widely used in Java on children with either night blindness or Bitot's spots consisted of dropping the juices of lightly roasted lamb's liver into their eyes. Sommer relates that "We were bemused at the appropriateness of this technique and wondered how it could possibly be effective. We, therefore, attended several treatment sessions, which were conducted exactly as the villagers had described, except for one small addition - rather than discarding the remaining organ, they fed it to the affected child. For some unknown reason this was never considered part of the therapy itself." Sommer and his associates were amused, but now understood why the folk remedy had persisted through the centuries. Liver, being the organ where vitamin A is stored in a lamb or any other animal, is the best food to eat to obtain vitamin A.

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Fun Trivia About Vitamin A and Alfred Sommer

UNICEF estimates over 400 million capsules of vitamin A were administered to children in 2002, saving the lives of more than a quarter million children worldwide that year alone.

The World Bank has ranked vitamin A supplementation as perhaps the most cost-effective health intervention in all of medicine.

The UN's Declaration on the Rights of Children, framed in 1990, included the right to an adequate vitamin A status.

On April 2, 1998, eight former Surgeons General and Dr. David Satcher, the then current Surgeon General and Assistant Secretary for Health, joined Dr. Sommer at the Johns Hopkins University School of Hygiene and Public Health to celebrate the 200th Anniversary of the United States Public Health Service, and the 50th Anniversary of the Declaration of Human Rights.

Xerophthalmia often begins with nightblindness, which in some cultures in called "chicken blindness," because afflicted children mimic chickens' inability to see at dusk.

The ancient Egyptians treated nightblindness with animal liver (where vitamin A is stored) 3,500 years ago.

By the early 1900s, the connection between xerophthalmia (severe dry eyes, caused by malfunctioning tear glands, due to vitamin A deficiency), overall resistance to infection, and vitamin A was well documented by American and Danish nutritionists, who treated their patients with cod liver oil, butter, and whole milk. For all practical purposes, xerophthalmia was erased from the medical map in Europe and North America.

During his tenure as dean of Johns Hopkins Bloomberg School of Public Health, the school's endowment under his leadership grew from $32 million to $160 million, and full-time faculty nearly doubled, to 500.

Three ounces of beef liver provide 545 percent of the recommended vitamin A daily value, and one-half cup carrot juice, 450 percent. One cup of whole milk provides just 5 percent, and one peach only 6 percent.

The Recommended Daily Allowance (RDA) of vitamin A is: adult males, 3,000 IU (International Units); adult females, 2,310 IU; during pregnancy, 2,564 IU; when lactating, 4,300 IU.

Zinc deficiency often accompanies vitamin A deficiency. Adequate zinc levels are required to produce a specific protein that helps transport vitamin A from the liver to the body's tissues.

Excess alcohol depletes vitamin A in the body. But, because their livers may be more susceptible to damage through toxicity, alcohol abusers are not good candidates for vitamin A supplementation.

Vitamin A deficiency reduces the body's ability to fight infection, which may lead to respiratory distress, such as pneumonia, and diarrheal infections.

A very high intake of provitamin A carotenoids, the type of vitamin A found in colorful fruits and vegetables (carrots, spinach, kale, cantaloupe...) can turn the skin yellow - but it is not harmful to your health.

Casimir Funk, a Polish biochemist, is credited with the discovery of vitamins. He isolated what would come to be known as vitamin B1 (Thiamine) in brown rice, which had been shown to have a protective effect against beri-beri. He originally called the substance vitamine, because it contained an amine group, and then theorized these newfound substances could also cure other diseases.

Carl E. Bloch, a pediatrician at the University of Copenhagen, is credited with the discovery of vitamin A. He noticed a difference in the health of two groups of children, housed in separate buildings, and began to investigate. He concluded the sickly group of children were not receiving sufficient fat intake, a factor he called "fat-soluble accessory factor A," later to become known as vitamin A.

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Statistics About Vitamin A Deficiency

Vitamin A deficient children have a 23% greater risk of dying from the measles, diarrhea or malaria.

Over 80 percent of the vitamin A intake in developing countries is from non-animal sources.

The established goals call for providing children 6-59 months with 2 rounds of vitamin A annually.

UNICEF classifies 61 countries as "high mortality" countries due to vitamin A deficiencies.

UNICEF lists 35 additional countries as being "priority countries."

As of 2005, all major regions of the world exceeded 70 percent compliance in administering 2 annual doses.

The number of priority countries delivering 2 rounds increased from 9, in 1999, to 35 in 2005.

Globally, the number of children fully protected rose from 16 percent, in 1999, to 72 percent in 2005.

Nutritional blindness responds to treatment with vitamin A within 24 hours.

In 1980, Sommer estimated 63,000 cases of nutritional blindness occurred each year in Indonesia.

In 1996, Sommer estimated 125 million pre-school age children worldwide were vitamin A deficient.

In 1996, Sommer estimated that 1 to 2.5 million vitamin A deficient children would die each year.

Thanks to Sommer's discovery of the oral vitamin A treatment, over 6 million lives have been saved.


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The Science Behind the Discovery of Oral Vitamin A Treatment

Basic Science Primer on Epidemiology

Epidemiology focuses on the disease process in groups of people, rather than in a single patient. It digs out the causes of diseases and establishes the best treatments by using measurement, one of the basic tools of science. An epidemiologist uses accurate measurement to discover hidden causes of disease, by conducting large studies of both sick and healthy individuals. By analyzing the data they gather, epidemiologists are able to pinpoint the key factors causing an illness. Then, based on their study, they devise a treatment protocol to stop the onset or spread of the disease. Epidemiologists are the world's frontline defense in the face of disease outbreaks. They often complete their work in harsh environments, including impoverished third-world nations. Their efforts have led to major medical breakthroughs, including the eradication of smallpox, and the discovery that vitamin A supplementation can save millions of lives.

Science - Vitamin A

Vitamin A is not one substance, but a generic term for a variety of related compounds. There are two basic categories of vitamin A, depending on its source. They are the active forms of retinol and retinal, which are interconvertible, and retinoic acid, which can be produced from retinal.

When animals are the source of vitamin A it is known as preformed vitamin A. This form of vitamin A is absorbed as retinol, one of the most active and useable forms of the vitamin. Animal sources with high levels of vitamin A include liver, meats, fish oil, and dairy products. Normally, more than 90 percent of a person's vitamin A is stored in the liver, which is why fish and animal livers, and foods prepared from them, such as cod liver oil, are such good sources of the vitamin.

When vegetables are the source of vitamin A it is known as provitamin A carotenoid. Carotenoids are named after their most famous source, the carrot, and include the well-known molecule beta-carotene. There are over 500 identified carotenoids, but the body can utilize less than 10 percent of these to produce vitamin A. The ability of the body to absorb carotenoids from food varies widely, depending upon the way the food is prepared and consumed - because carotenoids are fat-soluble, and often strongly bound in raw vegetables, uptake increases significantly when vegetables are cooked in fat. Some provitamin A carotenoids have also been shown to function as antioxidants, which help protect the body from damaging free radicals.

Science - Vitamin A's Function

The importance of Vitamin A, though certainly taken for granted in modern society, cannot be overstated. Vitamin A has many functions in the body. Retinal is the form in which the vitamin plays its well-known role in promoting night vision. Retonoic acid has been shown to play a crucial role during embryological development. In all its active forms, vitamin A acts as a hormone that regulates the expression of over 300 genes, including many that play a role in cellular growth and differentiation. This regulatory role is most evident in its effect on the mucous membranes of a number of organs, including those of the genitourinary tract and respiratory system, and the membrane over the cornea of the eye - hence the correlation between vitamin A deficiency and dry eyes.

When a person suffers from vitamin A deficiency the protective linings of the body begin to breakdown. These include the linings of the eyes, and of the respiratory system (there is some indication of mal-absorption of vitamin A in cystic fibrosis patients), urinary system, and intestinal tracts. When this occurs it becomes easier for bacteria and viruses to invade the body and cause serious illness. A lack of vitamin A also reduces the ability of the skin and mucous membranes to act as barriers against disease.

Science - Nutritional Blindness

As Sommer would later describe it, "a child who is night-blind in a village in India or Bangladesh or Nepal literally can't fend for him or herself. While other kids are walking around the village or playing with toys, these children huddle in a corner." Infants rarely show signs of night blindness, but in older children it is obvious to all-their behavior changes drastically at dusk. And the consequences of leaving the condition untreated could be tragic.

Nutritional blindness is one of the first symptoms of a condition formally known as xerophthalmia, which is Greek for "dry eyes." First, the eyes dry out. Then, waxy spots, known as Bitot's spots, appear on the conjunctiva, the membranes that cover the whites of the eyes. The dryness spreads over the cornea, causing the cornea to ulcerate and shrivel. As Sommer says, "The children will go truly blind, because what happens is the cornea, that clear front of the eye, just melts away. And it can melt away in the course of one day." The victims are consequently blind for life.

At the time Sommer began studying the problem, as many as one-half million kids a year were losing their sight. It was well known that vitamin A deficiency caused nutritional blindness, so some scientists had recommended biannual vitamin A supplementation as a preventative measure, but this had never been proven in controlled trials. When a child with symptoms was presented to the medical community, a shot in the arm of vitamin A was the accepted treatment, and it worked very well, if administered before the cornea was permanently damaged. In fact, nutritional blindness responds to a dose of vitamin A within 24 hours. Unfortunately, this treatment was rare.

Many countries, including the Untied States, have vitamin A fortified food. In other countries supplementation is often required.

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Sommer's Discoveries Revolutionized Treatment for Vitamin A Deficiency

Sommer's studies demonstrated that vitamin A deficiency is a large contributor to childhood death. He also demonstrated that taking vitamin A orally was effective. Today, the World Health Organization encourages children in countries that have vitamin A deficiency to take vitamin A supplements twice a year.

Nutritional Blindness Project in Indonesia

At the behest of Dr. Susan Pettis, of what is now Helen Keller International, in 1974, Sommer attended the first international conference on nutritional blindness. The conference was in Indonesia, and Indonesian officials were so impressed by Sommer they asked for his help in developing a comprehensive study of nutritional blindness in Indonesia. After planning three studies, he returned in 1976.

Indonesian Study Number One

The first study was a countrywide survey of 36,060 pre-school aged children from the urban slum and rural population areas of Indonesia. This study provided the researchers with baseline statistics, and informed the government about the nature of the crisis. Parents of any child with symptoms of nutritional blindness were asked dietary questions, as were the parents of 20 percent of all children examined. Free medical care was provided to any child in need.

Indonesian Study Number Two

The second study was set up in the biggest eye hospital in Bandung-the Cicendo Eye Hospital. The team tracked every case of nutritional blindness so they could accurately outline the progression of the affliction. Over the course of the three years, about 350 children came in who were going blind, and another thousand came in with precursor symptoms. A pediatrician, an ophthalmologist, and a nutritionist saw each child-and also gathered data. Each patient's eyes were photographed and blood specimens were collected. Because they conducted their study in a tightly controlled environment, Sommer and his colleagues could do specific randomized studies on different aspects of the disease. For controls, they went to the children's homes, and they examined 25 children residing in nearby houses, finding healthy children who were the same age and sex as each sick child. Some of these children were also found to have nutritional blindness, so were switched from the control group to the nutritional blindness group. They were then also treated.

Indonesian Study Number Three

The third study focused on a single geographic area. This allowed Sommer and his team to assess several factors that might contribute to nutritional blindness. They located this study in Purwakarta Regency, West Java, a two-hour drive north from Bandung.

First, they performed a census of six villages, involving a total of 6,598 preschool-aged children. They next categorized the children by neighborhoods. Each team consisted of eight enumerators, two nurses, an ophthalmologist, a pediatrician, and a nutritionist. They measured and examined the children and recorded the data. Because of local taboos, many parents refused to allow examination of babies under three months old, so that data set was substandard. Otherwise, parents were very cooperative-only one percent refused.

The children with nutritional blindness symptoms were identified. Other children, matched to the sick children for age and sex, were found nearby and used as study controls. Blood samples were taken from the sick children, the controls, and from five percent of the entire population of children.

Children with advanced symptoms of nutritional blindness (corneal symptoms) were treated and removed from the study. That left two groups-those with mild symptoms and those with no symptoms. The researchers found a striking correlation between the children's age and their symptoms. Mild symptoms were totally absent in children below the age of one; at the age of four, seven percent of the children exhibited symptoms. The goal of the study was to find out why some children got nutritional blindness and vitamin A deficiency, and others didn't. To accomplish this the team used a longitudinal study, in which all the children were reexamined every three months, for 18 months.

Breakthrough in Bandung

Sommer and his team had barely initiated the three Indonesian studies when they ran into trouble. The accepted treatment, endorsed at the time by the World Health Organization, was to inject children with shots of vitamin A. Unfortunately, they did not have a good quality vitamin A to inject, and it would be months before they obtained any additional supplies. Sommer took to squirting liquid vitamin A into children's mouths and found that it worked remarkably well. When the injectable solution arrived, Sommer decided to run a study to see if it worked better than an oral solution. He proved they worked the same.

This was a monumental change in protocol. A child who comes down with night blindness, or other symptoms of nutritional blindness, is in a state of emergency. Time matters. But to receive an injection of the vitamin, an Indonesian child had to be transported-sometimes for days-to a health care center. But anyone could squirt the vitamin into a child's mouth, and it only cost a few cents a dose. Thanks to an unforeseen problem, and a ready mind, Dr. Sommer discovered a simple treatment that would eventually save millions of lives. It took him another five years, though, to convince the medical establishment of this.

Data Analysis in London

When the three-year study was completed, there was still much work to do. The secrets of epidemiology hide in the data, so Sommer set off for London, England, for a year to see what the data would reveal.

His analysis revealed:

-The incidence of nutritional blindness was 2.7 per every 1,000 children in Indonesia per year.

-That meant that 63,000 cases per year of nutritional blindness occurred in Indonesia.

-If the data were extrapolated to the Philippines, India, and Bangladesh, which had similar dietary and other conditions, there could be 500,000 cases of nutritional blindness per year in these four countries.

-Half of untreated cases of nutritional blindness lead to blindness, so potentially 250,000 children a year could go blind in these four countries, if the problem was not addressed aggressively.

-Half the population of seemingly normal rural Indonesian children had low levels of vitamin A in their blood-that explained why night blindness was a big problem in Indonesia.

-Breast feeding provides an important source of vitamin A-children age two who were not being breast-fed were at eight times the risk of developing Bitot's spots, compared to those who were being breast-fed.

-Children with nutritional blindness ate fewer eggs, carrots, mangos, papaya, dark leafy vegetables, and fish than the control children.

-Vitamin A deficiency was a neighborhood phenomenon, and rarely occurred in isolated cases. Thus, treating whole neighborhoods of children at once might be beneficial.

-Children with corneal disease were shorter than children who had Bitot's spots, who were themselves shorter than the healthy controls.

-The discovery with the greatest potential impact was that children could take vitamin A by mouth. This meant that treatment was cheap and could be made available even in remote, undeveloped parts of the world.

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Sommer Revisits the Data and Makes a Revolutionary Discovery

Sommer moved back to the U.S. and finally became a full-time professor at Johns Hopkins. He continued his vitamin A deficiency research, but also did research on glaucoma. He also saw patients and performed surgery one day a week. In 1982, when things were slow at the eye clinic due to Christmas, Sommer decided to revisit the data from Indonesia. Sommer doesn't believe in leaving the important work of analysis to a statistician or computer program. "I say ‘data talk to me, tell me what you have to say....' You have to know your data, you have to smell it, you have to be in it. If you're not living inside the data you are going to miss the most interesting things, because the most interesting things are not going to be the questions you originally proposed; the interesting things are going to be questions you hadn't thought about."

Sommer immersed himself in the data. Long before the age of desktop computers, Sommer dealt with hard copy printouts, the kind with alternating green and white horizontal columns. There were lots and lots of ways of looking at the data. He could group it by age; he could group it by sex. As he dug through the data, he kept asking more questions. What proportion developed night blindness, or the white Bitot's spots in the next round? How many had night blindness in one examination and still had it in subsequent examinations?

"It became apparent that something very funny was going on with the data," Sommer said to himself. "Gosh, what in the world is going on here?" Children who had night blindness seemed to disappear from the study. They wound up in the "don't know" category far more than did kids who had normal eyes. What happened to those children with their big eyes? Then, he asked the most important question of all. Why did they leave the study? The answer would revolutionize health care in poor countries worldwide.

About 90 percent of the children usually showed up for their next examination, but the children with night blindness simply disappeared. "Holy cow!" Sommer exclaimed. He suddenly realized the children were not missing the exams because they were out working in the fields, or traveling with relatives. The children weren't showing up because they were dead!

Sommer was ecstatic. He quickly recalculated the results to make sure he hadn't made an error. He hadn't. He called in a statistician to also recalculate the data. They looked at other possible causes of death, including respiratory infection, diarrhea related illness, and malnourishment. None of these factors explained the deaths.

"When you summed it all up," said Sommer, "the kids who had night blindness were dying at three times the rate of kids who had normal eyes. The kids with spots died at seven times the rate, and the kids who had blindness and spots were dying at nine times the rate."

It became clear that vitamin A deficiency was the cause of the deaths. Sommer concluded nutritional blindness was a sign of advanced deficiency that was causing the children's immune system and organ tissues to deteriorate. This left them vulnerable, allowing them to die of other causes. It seemed likely vitamin A deficiency became manifest in the eyes only at the end of the process.

The Fight to Establish a New Treatment Protocol

Sommer was soon to learn his peers would not immediately welcome his remarkable discovery. After the results of his study were reported in the prestigious British medical journal Lancet, nothing happened: "Nobody paid any attention to it. Lead article," Sommer says, "no attention. Not one letter to the editor. Nothing."

Sommer established another study in Aceh province, Indonesia, which later would become famous for the 2005 tsunami. Over 25,000 children, in about 450 villages, were enrolled in the one-year study. One group was given 200,000 IU of vitamin A at the onset, and then again six months later. The control group received no vitamin A supplements. The results were even better than in the previous studies. Those receiving the vitamin A pill had a decrease in mortality of 34 percent.

Indonesian health officials were convinced vitamin A deficiency was a life or death problem, and drew up plans for a nationwide vitamin A intervention program. The rest of the medical community was skeptical. Critics said Sommer's data was "too good to be true." The results were so impressive that many felt the study must have been flawed. Others objected to the fact that Sommer didn't use placebos with the control group. He had refrained form doing so at the request of the government, and he also believed they were unnecessary in this study. He reasoned that since the end point in this study, for those untreated, was death, that there was no need to use a placebo, since no one would fake death.

On the advice of a good friend, Sommer decided to "bury them in data." He established new studies all over the world to prove his theory. He started a study in the Philippines, but had to abandon it when a local guerilla organization forced his team out. He moved to Nepal to continue his work. Here, his study showed vitamin A supplementation reduced the death rate by 40 percent. India showed a 50 percent reduction, and Ghana 23 percent.

Sommer remembers that, "All the trials came out the same, which was really quite to my amazement, given all the different cultures and environments in which the trials were done. Yet, all the studies had a 35% to 55% reduction in childhood mortality, whether you gave the capsule once every 6 months, every 4 months, or every week, or if you put a little vitamin A into something they ate once a day. It all came out essentially the same, which was quite heartening."

A new paper was published in the British Medical Journal, and a colleague wrote an editorial in Sommer's support in The New England Journal of Medicine. The final victory came in Italy, at a Rockefeller retreat center. Sommer gathered his colleagues to settle the issue once and for all. He felt the proof was by now so overwhelming that to disregard it was simply unethical. In the end, his colleagues agreed. The oral vitamin A treatment protocol was now mainstream medicine.

Vitamin A pills are now standard treatment for children in 70 countries. UNICEF supplies the pills, the Canadian government pays for most of it, and 600 million doses-half of what is needed-are distributed annually. Still, more than 100 million young children don't get the pills and suffer from vitamin A deficiency. But, the inexpensive pills make a huge difference for those children receiving them. According to UNICEF, one-half million children are saved from death every year, which means more than 6 million lives have been saved since the pills became policy in the 1990s.

In Indonesia, Sommer's creative solution to an ineffective vitamin A vaccine lays the foundation for what will eventually become the standard worldwide treatment for vitamin A deficiency.

A Dynamic Study

The studies were dynamic. If the researchers couldn't proceed due to unplanned events, they had to adapt. Sometimes this led to new discoveries.

They ran into one roadblock as soon as they began. The accepted treatment, endorsed at the time by the World Health Organization, was to inject children with shots of vitamin A. Vitamin A is naturally fat-soluble, but animal testing showed that using it in a fat-soluble form wasn't effective. As Sommer says, the vitamin A "sat there as a lump and didn't get out," into the blood. Processing the vitamin to make it water-soluble seemed the answer. The process resembled homogenizing milk-the fat containing the vitamin A is distributed in the liquid instead of sitting like cream on the top. The problem, he immediately discovered, was that there was no water-soluble vitamin A available-no one had bothered to make any. It would take months before Roche, the pharmaceutical company, could produce some and ship it to Bandung. "What am I going to do in the meantime?" Sommer asked. Sommer had worked in Bangladesh, where it was shown that dehydration from cholera was fought more successfully by patients drinking fluids (Oral Rehydration Therapy) than by having fluids injected with IV's. So, he wondered what would happen if he took the fat-soluble vitamin A and, instead of injecting it, squirted it into the children's mouths? He found that it worked remarkably well.

When the shipment from Roche finally arrived, Sommer was presented with a dilemma-keep using the method that worked, or revert to the book treatment. Sommer is one of the more prominent members of a movement to bring evidence-based science into modern medicine. This movement seeks to base medical conclusions on real, statistically significant, verifiable evidence-not guesses, not anecdotes, not traditional methods. Hard as it is to believe, there is no statistical support for many of the cookbook treatments doctors use or believe in, even to this day.

So Sommer set up a controlled study. He established a trial in which 69 children with corneal symptoms of nutritional blindness were given 200,000 IU of oil-based vitamin A by mouth, and a matched group of 45 children were given the book dose of 100,000 IU of water-based vitamin A, injected by a shot into a muscle. All were given another oral dose the next day. There was no detectable difference in the children's clinical response to the two methods of delivery. This was a monumental change in protocol. A child who comes down with night blindness, or other symptoms of nutritional blindness, is in a state of emergency. Time matters. But to receive an injection of the vitamin, an Indonesian child had to be transported-sometimes for days-to a health care center and, once the child got there, a health care worker had to provide the injection using needles and syringes, which introduced an associated risk of hepatitis infection. But, anyone could squirt the vitamin into a child's mouth, and it only cost two cents a dose. Thanks to what at first had seemed to be a serious hindrance, Sommer had found a way to bring healing directly to the patient.

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Personal Information

Early Life

Sommer was born in New York City, on October 2, 1942. His family moved to Queens when he was a teenager, where he pursued his great interest in history. He loved to draw maps and could imagine himself living as a professor in a small New England college town. A future in medicine seemed to have always been with him. Sommer said, "My becoming a doctor in the first place was very easy. I truly believe that my grandmother, on the day of my birth, imprinted it somehow on my soul and, in fact, I can never remember a time when I did not want to be a doctor." His grandmother was an Eastern European immigrant who respected physicians and thought her grandson couldn't choose a better career.

Education

1963 - Bachelor of Science (BS), Union College.
1967 - Medical Diploma (MD), Harvard Medical School.
1973 - Masters of Health Science (MHS), Johns Hopkins School of Hygiene & Public Health.

Professional Training

1967-1969 - Medical Intern and Resident, Beth Israel Hospital, Harvard University.
1972-1973 - Fellow in Epidemiology, Johns Hopkins School of Hygiene & Public Health.
1973-1976 - Resident and fellow in Ophthalmology, Wilmer Eye Institute, Johns Hopkins Hospital.

Certification

1968 - Diplomate, National Board of Medical Examiners.
1977 - Diplomate, American Board of Ophthalmology.

Family

Wife - Jill
Son - Charles
Daughter - Marni

Resides In

Baltimore, MD

Present Positions

Johns Hopkins Bloomberg School of Public Health - Professor, Dean Emeritus
T. Rowe Price - Board of Directors
Becton Dickinson - Board of Directors
Albert and Mary Lasker Foundation - Board of Directors
Foundation of the National Institutes of Health - Board of Directors
International Trachoma Initiative (ITI) - Board of Directors
International Council of Ophthalmology Foundation - Board of Directors
Academy for Educational Development (AED) - Executive Committee

Sommer's Early Career

Fresh out of Harvard Medical School, Sommer and his wife, Jill, decided to pursue service-oriented careers. Said Sommer, "I received my MD training at the time that Kennedy had been President. We were all, of course, traumatized and we can all remember where we were the day that he was killed, but we had been inspired. I remember his inaugural address, as does my wife: ‘Ask not what your country can do for you, but what you can do for your country.' That was inspiring to young people in those days."

Epidemic Intelligence Service

They wanted to work for the Peace Corps, but a new draft law would have drafted Sommer out of the Peace Corps. So, he instead went to work for the Centers for Disease Control and Prevention (CDC), as an alternate form of service. He was accepted into the Epidemic Intelligence Service and began work at the CDC's headquarters in Atlanta. After completing the one-month introductory course, he was assigned to an office for vaccine trials. His first assignment was to work with the new rubella (measles) vaccine. Sommer said later that he was unimpressed with many of his colleagues who, it seemed, were far too interested "in the price of eggs in the commissary." He started firing off proposals for initiatives he thought the office should launch. The torrent of requests made everyone nervous. "Al," his boss said, "we have all voted for you to go home for two weeks and relax." He went home to his pregnant wife and made baby furniture. After he returned, a group of CDC employees who were working in East Pakistan on cholera research, came through looking for an additional person to join the group. Though he disliked the idea of East Pakistan's heat and humidity, he was drawn to the doctors. They "were excited about what they were doing," so he signed on.

Dacca, Bangladesh

Dacca is where Sommer first learned the value of studying the impact of disease on groups of people. The Cholera Research Laboratory had made remarkable progress in the fight against cholera, by developing Oral Rehydration Therapy. Their findings were still not conclusive, nor widely accepted, so they were doing additional studies. Sommer worked on finding out if vaccinating family members of cholera victims would prevent them from getting cholera-no. Then he worked on questions of safe water supplies-they protected some, but not all. Cholera vaccination in an epidemic was also found to be ineffective.

In November of 1970, disaster struck the city of Bhola, about seventy miles south of Sommer's home. A massive cyclone killed more than 240,000 people. It was the biggest epidemiological natural disaster in history.
Sommer coordinated ten two-man teams that went door-to-door to 2,973 families two months after the storm, recording mortality, injury, shelter, and food conditions. It was a tremendous introduction to epidemiology.

In 1971, the Bangladesh Liberation War broke out. Previously called East Pakistan, the war liberated the country, and it became known as Bangladesh. Bangladesh quickly faced its first crisis. An outbreak of smallpox swept through the country. The World Health Organization requested assistance from the CDC and Sommer joined the hastily assembled team.

Sommer's job was to organize containment activities, which meant isolating the virus by vaccinating people around local outbreak areas. Sommer remembers it as: "a horrific time. Ten million Bengali refugees were streaming back home. I was dealing with smallpox epidemics in both urban neighborhoods and dense refugee camps. The only thing you could do was pray for early detection and then mass immunization, to prevent the disease. Once someone had the disease, one-third would die. The key to success was immunizing everyone in the camps. Many refused immunization; I had to resort to holding back ration cards until they agreed to vaccination."

Sommer not only treated patients, he also collected data. In what was both an obsession and a calling, he routinely recorded data about all his patients. And, he instructed his team to do so as well. In the end it paid off. "Since I'm compulsively driven to collect data without thinking about it," said Sommer, "I had these teams not only vaccinate but collect data. I was able to demonstrate that if you got vaccinated within five days of exposure you were completely protected from smallpox, and if you are inoculated within eight days, you wouldn't die of smallpox."

The information Sommer gathered here had a profound impact. The United Sates decided against mass vaccinations following 9/11, based on these findings. Sommer joined with thousands of other health care workers to help eliminate smallpox across the globe. The last case of naturally occurring smallpox in the world was recorded in Somalia, in 1977.

Sommer heard of an incomplete study of childhood nutrition in Bangladesh. Nutritionists were on a search to develop a means of accurately measuring childhood malnutrition. Standard measures, like measuring body fat or protein content of blood, were too technically difficult for application in the developing world. Weight-to-age ratios were also ineffective, because it was often difficult to discover a child's exact age. In the 1960s, Quaker medical missionaries in Nigeria had developed a physical test, in which they measured the circumference of a child's upper arm (a good indirect measure of muscle mass) against a height table to determine who might be undernourished, that could easily be put on a stick that could be taken anywhere by health care workers. It was called a QUAK stick. In the 1970s, health workers in East Pakistan had accumulated arm and height measurements for 8,292 Bengali children, but had done no follow up. Sommer tracked as many of the children down as he could. Combing through death records, he made a startling discovery: During the first month after the children had their arms measured, 1 to 4-year olds in the lowest nutritional category were at almost 20 times greater risk of death than those whose ratio was normal. Predicting the mortality of children could be as simple as measuring their arms.

Dedication to Public Health

Sommer's experiences in Bangladesh changed the direction of his life. Here he came face to face with the medical problems of millions of people-problems he could fix. The experience exhilarated him and convinced him to dedicate himself to continuing his work in public health. "To be fascinated with what you're doing - I went overseas and had this marvelous experience working in the field and literally having millions of people's welfare and lives hinging upon decisions that I made and investigations that I carried out and I found that extraordinarily exhilarating - that the amount of leverage, the amount of impact I could have was so much greater than I could on a one-to-one patient-physician basis. As fulfilling as that is in its own right, I made then the commitment to public health. And public health research is an area where I knew that I was going to enjoy myself."

Formal Epidemiology Training

Though Sommer was a seasoned veteran in epidemiology-having spent the last 3 years immersed in its practice-he still had no formal training in the field. So, he decided against starting his course of study in ophthalmology, and enrolled in the John Hopkins School of Hygiene and Public Health. He would earn a masters degree in epidemiology.

The study of epidemiology would shape his perspective for years to come. "I came to ophthalmology with a whole different perspective,' said Sommer, "in which I would think about populations of people and populations of eyes much more so than the variation you see with one individual."

While he was completing his ophthalmology residency, he was introduced to Susan Pettis, the director of the American Foundation for Overseas Blind (now Helen Keller International). The group was expanding its research and Dr. Sommer seemed to be a perfect fit. He agreed, and soon was setting up small studies in Haiti and El Salvador to study what would eventually lead to major health advances worldwide: nutritional blindness.

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Sommer's Other Major Discoveries

Measles

Sommer also proved that vitamin A could fight measles, since, as he says, "measles is a viral disease that infects and damages epithelial tissues throughout the body." He found a missionary physician in Tanzania who reported that many children with measles were going blind. He set up a randomized trial with vitamin A and demonstrated that children receiving vitamin A supplementation were 50 percent less likely to die.

Barclay AJG, Foster A, Sommer A. Vitamin A supplements and mortality related to measles: a randomised clinical trial. Br Med J 1987;294:294-296.

Smallpox Vaccination is Effective even after Exposure

While conducting research in Bangladesh in 1972, Sommer discovered that vaccination against smallpox was effective even after the initial exposure. Those vaccinated within five days were completely protected, and those vaccinated within eight days were able to avoid death. Following 9/11, the United States government relied on these findings when they decided against mass vaccinations.

Along with thousands of others, Sommer participated in the smallpox vaccination campaign that helped eradicate smallpox worldwide.
Sommer A, Foster SO. The 1972 smallpox outbreak in Khulna municipality, Bangladesh. I. Methodology and epidemiologic findings. Am J Epidemiol 1974;99:291-302.
Sommer A. The 1972 smallpox outbreak in Khulna municipality, Bangladesh. II. Effectiveness of surveillance and containment in urban epidemic control. Am J Epidemiol 1974;99:303-313.

An Effective Childhood Malnutrition Measurement

Sommer says that he's "compulsively driven to collect data without thinking about it." When Sommer was in Bangladesh, he found an incomplete nutritional study that involved measuring children's upper arms. At the time, nutritionists were trying to develop a means of accurately measuring childhood malnutrition. Standard measures, like measuring body fat or protein content of blood, were too technically difficult for application in the developing world. Weight-to-age ratios were also ineffective, because it was often difficult to discover a child's exact age. In the 1960s, Quaker medical missionaries in Nigeria had developed a physical test in which they measured the circumference of a child's upper arm (a good indirect measure of muscle mass) against a height table to determine who might be undernourished using a QUAK stick. A decade later, health workers in East Pakistan had accumulated arm and height measurements for 8,292 Bengali children. But, there had been no follow up. Sommer decided to track as many of the children down as he could.

Combing through death records, he made a startling discovery: During the first month after the children had their arms measured, 1 to 4-year olds in the lowest nutritional category were at almost 20 times greater risk of death than those whose ratio was normal. He found that predicting the mortality of children could be as simple as measuring their arms! His findings were so startling he had trouble getting the study published.

Sommer A, Loewenstein M. Nutritional status and mortality. A prospective validation of the QUAC stick. Am J Clin Nutr 1975;28:287-292.

Glaucoma's Magic Number Debunked

Sommer is one of the more prominent members of a movement to bring modern medicine into evidence-based science. That means you have to have real evidence-not guesses, not anecdotes, not assumptions-before you come to conclusions. Believe it or not, there is no statistical support for some of the things doctors do or believe. For instance, there is the problem of magic numbers.

The magic number in determining if a patient has glaucoma is 21 millimeters of mercury pressure in the eye, the intraocular pressure. If the pressure is higher than 21, you have glaucoma. If it is less, you don't. Ophthalmologists could always find patients with more pressure than 21 who show no signs of glaucoma, and people with pressures below 21 who have optic nerve damage.

Sommer was not satisfied with such an inexact variable, so he executed a study in Baltimore that demonstrated the magic number was of little use. Success or failure in treating glaucoma did not depend on the pressure relative to any number, but on what was happening to the optic nerve. The magic number of 21 still isn't dead, but there now is less emphasis on it. Sommer's study gradually found its way into the common wisdom.

Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch J, Javitt J, Singh K. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol 1991;109:1090-1095.

The Increased Risk of Developing Glaucoma in Blacks

Because his glaucoma study was done in a racially mixed neighborhood of east Baltimore, he also ferreted out another unknown variable. He found that blacks were four times more likely to get glaucoma than whites, for reasons unknown.

Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J. Racial variations in the prevalence of primary open-angle glaucoma: the Baltimore Eye Survey. JAMA 1991;266:369-374.

Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt JC, Martone JF, Royall RM, Witt KA, Ezrine S. Racial differences in the cause-specific prevalence of blindness in East Baltimore. N Engl J Med 1991;325:1412-1417.

Vitamin A Supplementation ability to Reduce Mother's Childbirth Mortality

Sommer has continued to study vitamin A, after his revolutionary discovery, for the past twenty-five years. His latest findings demonstrate that vitamin A supplementation to mothers lowers childbirth death rates.

West KP Jr, Katz J, Khatry SK, LeClerq SC, Pradhan EK, Shrestha SR, Connor PB, Dali SM,
Christian P, Pokhrel RP, Sommer A. Double blind, cluster randomised trial of low dose
supplementation with vitamin A or carotene on mortality related to pregnancy in Nepal. Br Med J
1999;318:570-575.

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Some of Sommer's Mentors

Louis Pasteur

Sommer was a fan of Pasteur's. He was especially taken by Pasteur's philosophy, "Chance favors the prepared mind," and followed the principal as a guide throughout his career. He often encouraged others to do so as well, as he did when delivering the convocation address at the Johns Hopkins Bloomberg School of Public Health in 2005: "The requisite corollary to ‘Woody Allen's Law' (90 percent of success is showing up) is Pasteur's admonition: ‘Chance favors the prepared mind.' ‘Showing up' provides the chance encounter; the ‘prepared mind' turns ‘encounters' into valuable insights."

W.H. Mosley

Mosley served as the director of the Cholera Research Laboratory in East Pakistan, where Sommer worked in 1970. Two significant influences from this work helped guide Sommer in the years ahead. The first was his collaboration with Mosley, and their successful use of Oral Rehydration Therapy to treat stricken cholera patients. Sommer would subsequently draw on this knowledge in deciding to experiment with oral administration of vitamin A in Indonesia.

The second major influence involving Mosley revolves around direct relief work. Following a massive cyclone in Dacca, East Pakistan (Bangladesh), Mosley assigned Sommer to assess the needs of the victims. It was this experience that first opened Sommer's eyes to the power of epidemiology. He quickly came to appreciate the ability for this work to impact millions of lives at one time, and he knew he would be deeply involved with epidemiology the remainder of his life.

Susan Pettis

Sommer met Susan Pettis, whom he considered a "remarkable woman," while studying for his masters in epidemiology at Johns Hopkins. Pettis was the director of prevention for the American Foundation for Overseas Blind (now Helen Keller International). She recruited Sommer to help her group widen its research and Sommer established his first studies involving night blindness, in Haiti and El Salvador.

Pettis was also instrumental in Sommer's eventually landing in Indonesia to conduct his breakthrough studies. It was Pettis who managed to get Sommer an invitation to the first international conference on nutritional blindness, held in Indonesia. While attending the conference, Sommer became acquainted with several workers form the Indonesian Ministry of Health. The officials thought Sommer's background, in epidemiology and ophthalmology, was the perfect fit to study their higher than normal incidence of nutritional blindness. They asked him to come help, and he accepted.

Alfred Sommer's Life: A Timeline

1942 - Born in Brooklyn, New York - moved to Queens as a teenager.
1963 - Bachelor of Science (BS), Union College.
1963 - Married to Jill.
1967 - Medical Diploma (MD), Harvard Medical School.
1967-1969 - Medical Intern and Resident, Beth Israel Hospital, Harvard University.
1967 - Began work with the CDC-Epidemic Intelligence Service-in Dacca, Bangladesh.
1968 - Diploma, National Board of Medical Examiners.
1969 - Birth of his son, Charles.
1970 - Assessed survivors' needs in East Pakistan (Bangladesh) following massive cyclone.
1971 - Birth of his daughter, Marni.
1971 - Helped Bengali intellectuals escape during the early stages of the Bangladesh Liberation War.
1972 - Headed team to stop the outbreak of smallpox in the newly formed nation of Bangladesh.
1972 - Discovered the smallpox vaccine works even for those already exposed.
1972 - Confirmed the measurement of arm circumference is an accurate predictor of death among children.
1972-1973 - Fellow in Epidemiology, Johns Hopkins School of Hygiene & Public Health.
1973 - Masters of Health Science (MHS), Johns Hopkins School of Hygiene & Public Health.
1973-1976 - Began to learn about nutritional blindness and set up studies in Haiti and El Salvador.
1973-1976 - Resident and fellow in Ophthalmology, Wilmer Eye Institute, Johns Hopkins Hospital.
1974 - Attended the first international conference on nutritional blindness in Indonesia.
1976-1979 - Nutritional Blindness Prevention Project-three years studying nutritional blindness in Indonesia.
1976 - Discovered that vitamin A taken by mouth is as effective as an injection, a major breakthrough.
1977 - Diploma, American Board of Ophthalmology.
1979-1980 - Spent one year in London analyzing the data from his Indonesian study.
1980 - Returned to the United States to become a professor at Johns Hopkins.
1982 - Revisited his Indonesia data and discovered that vitamin A deficiency is a major childhood killer.
1982 - Discovered vitamin A deficiencies were a leading cause of childhood deaths in developing nations.
1983 - Published results of Indonesian study, linking vitamin A deficiency and higher death rates, in Lancet.
1983 - Onward-developed additional studies to confirm the importance of vitamin A to health.
1980-1990 - Director, Dana Center for Preventive Ophthalmology, Johns Hopkins University.
1985 - Launched the Baltimore Eye Survey, the first community-based eye survey of adults.
1987 - Published study demonstrating that vitamin A doses lower mortality for childhood measles.
1990-2005 - Dean, Johns Hopkins Bloomberg School of Public Health.
1991 - Published results dispelling the magic number of ocular pressure as a definitive sign of glaucoma.
1991 - Published results indicating blacks have a much higher rate of glaucoma than whites in the U.S.
1999 - Published a study showing that vitamin A supplementation aids in pregnant women's survival.
2002 - Chaired the Expert Group on Health for the World Economic Forum's Global Governance Initiative.



Key Contributing Scientists to the Science of Vitamin A

Casimir Funk

A Polish biochemist, Funk is credited with the discovery of vitamins in 1912. He isolated what would come to be known as vitamin B1 (Thiamine) in brown rice, which had been shown to have a protective effect against beri-beri. He originally called the substance vitamine, because it contained an amine group, and then theorized these newfound substances could also cure other diseases.

Elmer McCollum and Marguerite Davis

Working at the University of Wisconsin, in 1913, Elmer McCollum and Marguerite Davis discovered both Vitamin A and B. They at first called it "fat-soluble factor A," since it was found in milk and fats. Earlier, Casimir Funk had named unknown nutrients in foods vitamines, because they were vital and amines. McCollum and Davis wanted to use letters, but opposed Funk's name because these nutrients were not true amines. The name was changed to its current spelling in 1920.

Carl E. Bloch

A pediatrician at the University of Copenhagen, Bloch discovered the importance of vitamin A to health. In 1917, he noticed a difference in the health of two groups of children, housed in separate buildings, and began to investigate. He concluded the sickly group of children were not receiving sufficient fat intake, which contained vitamin A. In the western world, this led to children being encouraged to drink buttermilk, or to take cod liver oil. Since this was so successful, the importance of vitamin A to children came to be ignored, and then forgotten by nutritionists. As Sommer says, "a profound amnesia appears to have settled over the broader context of vitamin A deficiency once it ceased to be a major concern of wealthier nations."



Scientific Discovery Timeline




Recommended Books About Vitamin A and Vitamin A Deficiency

Blomhoff, R. Vitamin A in Health and Disease. New York: Marcel Dekker, Inc., 1994.

Loessing, I. Vitamin A: New Research. New York, Nova Science Publishers, Incorporated, 2007.

Vitamin A Supplementation: A Decade of Progress. New York: United Nations Children's Fund, The, 2007.

Vitamin A Intake, Status & Improvement Using the Dietary Approach: Studies of Vulnerable Groups in Three Asian Countries. Stockholm: Almqvist & Wiksell International, 2001.



Books by Alfred Sommer

Sommer A. Field Guide to the Detection and Control of Xerophthalmia. Geneva, World Health
Organization, 1978. (Published in English, French, Spanish, Russian, Portuguese and Arabic.)

Sommer A. Field Guide to the Detection and Control of Xerophthalmia. Second Edition. Geneva:
World Health Organization, 1982. (Published in English, French, Spanish, Russian, Portuguese and
Arabic.)

Sommer A. Vitamin A Deficiency and Its Consequences: A Field Guide to Detection and Control.
Third Edition. Geneva: World Health Organization, 1995. (Published in English, French, Spanish,
Bengali, Chinese)

Sommer A. Epidemiology and Statistics for the Ophthalmologist. New York: Oxford University Press,
1980.

Sommer A. Nutritional Blindness: Xerophthalmia and Keratomalacia. New York: Oxford University
Press, 1982.

West KP, Sommer A. Periodic, Large Oral Doses of Vitamin A for the Prevention of Vitamin A
Deficiency and Xerophthalmia. International Vitamin A Consultative Group. Washington: Nutrition
Foundation, 1984.

Sommer A, West KP Jr. Vitamin A Deficiency: Health, Survival, and Vision. New York and Oxford:
Oxford University Press, 1996.



Books about Sommer

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



Awards

Sommer has been honored with many awards during his career, including:

Helen Keller Foundation Prize for Vision Research, 2005
The Pollin Prize in Pediatric Research, 2004 (Dr. Sommer was the first individual researcher to receive the Pollin Prize. Previously, the award had gone to teams of researchers.)
Thomas E. Hobbins Health Care Justice Award, Maryland Health Initiative, 2003
Warren Alpert Foundation Research Prize, Harvard Medical School, 2003
Lucien Howe Medal, American Ophthalmological Society, 2003
Special Recognition Award for Leadership, Association for Research in Vision and Ophthalmology (ARVO), 2002
Danone International Prize for Nutrition, 2001
Bristol-Myers Squibb/Mead Johnson Award for Distinguished Achievement in Nutrition Research, 2001
Gold Jose Rizal Medal, Asia Pacific Academy of Ophthalmology, 2001
F. Parke Lewis Lifetime Achievement Professional Service Award, Prevent Blindness America, 2001
E.H. Christopherson Award, American Academy of Pediatrics, 2000
Albert Lasker Clinical Medical Research Award, 1997
Helmut Horten Medical Research Award, Helmut Horten Stiftung, Switzerland, 1997
Prince Mahidol Award for International Contributions to Medicine and Public Health, Thailand, 1997
Charles A. Dana Award for Pioneering Achievements in Health, 1988
National Academy of Sciences, elected 2001
Institute of Medicine, elected 1992



Major Academic Papers Written by Alfred Sommer

Sommer A, Tarwotjo I, Hussaini G, Susanto D. Increased mortality in children with mild vitamin A deficiency. Lancet 1983;2:585-588.

Sommer A, Muhilal, Tarwotjo I, Djunaedi E, Glover J. Oral versus intramuscular vitamin A in the treatment of xerophthalmia. Lancet 1980;1:557-559.

Barclay AJG, Foster A, Sommer A. Vitamin A supplements and mortality related to measles: a randomised clinical trial. Br Med J 1987;294:294-296.
Sommer A, Foster SO. The 1972 smallpox outbreak in Khulna municipality, Bangladesh. I. Methodology and epidemiologic findings. Am J Epidemiol 1974;99:291-302.
Sommer A. The 1972 smallpox outbreak in Khulna municipality, Bangladesh. II. Effectiveness of surveillance and containment in urban epidemic control. Am J Epidemiol 1974;99:303-313.
Sommer A, Loewenstein M. Nutritional status and mortality. A prospective validation of the QUAC stick. Am J Clin Nutr 1975;28:287-292.

Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch J, Javitt J, Singh K. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. The Baltimore Eye Survey. Arch Ophthalmol 1991;109:1090-1095.

Tielsch JM, Sommer A, Katz J, Royall RM, Quigley HA, Javitt J. Racial variations in the prevalence of primary open-angle glaucoma: the Baltimore Eye Survey. JAMA 1991;266:369-374.

Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt JC, Martone JF, Royall RM, Witt KA, Ezrine S. Racial differences in the cause-specific prevalence of blindness in East Baltimore. N Engl J Med 1991;325:1412-1417.

Sommer A. Vitamin A deficiency disorders: Origins of the problem and approaches to its control.
Rockefeller Foundation. New York, NY 2001.

Sommer A. How public health policy is created: Scientific process and political reality. Am J
Epidemiol 2001; 154:12 (Suppl): S4-S6.

Sommer A. Visionary leadership: The fourth John Wilson Lecture, delivered at the XXIX International
Congress of Ophthalmology, Sydney Australia. Asia-Pacific Journal of Ophthalmology, July
2002;14(3): 35-38.

Sommer A, Davidson FR. Assessment and control of Vitamin A Deficiency: The Annecy Accords. J
Nutr 2002; (132): 2845S-2850S.

Sommer, A. The Genomic Revolution and Public Health. Science Asia 2002; 28(S1), 5-7.

Sommer A. Epidemiology and the health care revolution. Ann Epidemiol 1997;7:526-529.

Sommer A. Clinical research and the human condition: moving from observation to practice.
Nature Medicine 1997;3:1061-1063.

Sommer A. Xerophthalmia and vitamin A status. Progress in Retinal and Eye Research 1998;17:9-31.

West KP Jr, Katz J, Khatry SK, LeClerq SC, Pradhan EK, Shrestha SR, Connor PB, Dali SM,
Christian P, Pokhrel RP, Sommer A. Double blind, cluster randomised trial of low dose
supplementation with vitamin A or carotene on mortality related to pregnancy in Nepal. Br Med J
1999;318:570-575.

Sommer A. Health, medicine and ophthalmology: facing the facts and paying the piper. LVI Edward
Jackson Memorial Lecture. Am J Ophthalmol 1999;128:673-679.

Alfred Sommer has written over 300 academic papers.



Curriculum Vitae

http://www.laskerfoundation.org/learn/sommer_cv.htm.


Links to Information on Vitamin A

Office of Dietary Supplements: http://ods.od.nih.gov/factsheets/vitamina.asp

Linus Pauling Institute: http://lpi.oregonstate.edu/infocenter/vitamins/vitaminA/

The World's Healthiest Foods http://www.whfoods.com/genpage.php?tname=nutrient&dbid=106

eMedicine from WebMD: http://www.emedicine.com/med/topic2381.htm

World Health Organization: http://www.who.int/vaccines/en/vitamina.shtml

Video Links

Interview of Sommer by the Lasker Foundation.
http://www.laskerfoundation.org/learn/sommer_text.htm




Sources/References


Rx for Survival - description of a PBS program heralding pioneering physicians, including Sommer.
http://www.pbs.org/wgbh/rxforsurvival/series/champions/index.html

One World Sight Project - Article on Sommer being awarded the 1997 Albert Lasker Clinical Research Award.
http://www.owsp.org/Home/InternationalParticipants/AlfredSommerMD/tabid/483/Default.aspx

Johns Hopkins University PR on Sommer being awarded the 1997 Albert Lasker Clinical Research Award.
http://www.jhu.edu/news_info/news/univ97/sep97/lasker1.html

Sommer's faculty page at the Johns Hopkins Bloomberg Public School of Health.
http://faculty.jhsph.edu/?F=Alfred&L=Sommer

Sommer's faculty page at the Wilmer Eye Institute at Johns Hopkins.
http://www.hopkinsmedicine.org/wilmer/employees/cvs/Sommer.html

Sommer's faculty page at the Johns Hopkins Center for Global Health.
http://research.hopkinsglobalhealth.org/GlobalFacultyPage.cfm?global_faculty_id=1105

Article detailing New York-Presbyterian's award of the Pollin Prize to Sommer in 2004.
http://www.nyp.org/news/hospital/2004-pollin-prize.html

Sommer's convocation address to graduates at Johns Hopkins Bloomberg Public School of Health, 2005.
http://www.jhsph.edu/publichealthnews/articles/2005/sommer_convocation.html

A synopsis of Sommer's professional career.
http://www.nndb.com/people/523/000171010/

A photograph of Sommer with 9 Surgeons General - 8 former and the then current Surgeon General.
http://profiles.nlm.nih.gov/QQ/B/C/J/Y/

An article detailing Sommer's being awarded the Warren Alpert Foundation Scientific Prize, 2003.
http://www.scienceblog.com/community/older/2003/E/20033063.html

Synopsis of an interview of Sommer by the Lasker Foundation.
http://www.laskerfoundation.org/learn/sommer_text.htm

Article, The Other Al Sommer, by B. Simpson, in Johns Hopkins Public Health, the school's official magazine.
http://magazine.jhsph.edu/2005/fall/prologues/

Avery, Mary Ellen. 1997. An Interview with Alfred Sommer. Lasker Foundation. http://www.laskerfoundation.org/awards/1997_c_interview_sommer.htm (accessed June 23, 2007).

Hussaini, G., Tarwotjo, I.T., Sommer, A. 1978. Cure for night blindness. Letter to editor. American Journal of Clinical Nutrition. Sep 31(9): 1489.

Keusch, G.T. 1990. Vitamin A supplements - too good not to be true. New England Journal of Medicine Oct 4; 323(14) 985-986.

Mosley W.H., Bart, K., Sommer A. 1972. An epidemiological assessment of cholera control programs in rural East Pakistan. International Journal of Epidemiology 1:5-11.

Simpson, Brian W. 2005. The Other Al Sommer. Johns Hopkins Public Health. http://magazine.jhsph.edu/2005/fall/prologues/ (accessed June 23, 2007).

Sommer, A., interview, July 31, 2007, Baltimore, MD.

Sommer, A. 1974. The 1972 smallpox outbreak in Khulna municipality, Bangladesh. II. Effectiveness of surveillance and containment in urban epidemic control. American Journal of Epidemiology 99:303-313.

Sommer, A. 1982. Nutritional Blindness: xerophthalmia and keratomalcia. Oxford University Press.

Sommer A. 1983. Mortality associated with mild, untreated xerophthalmia (Thesis). Trans Am Ophthalmol Soc 81:825-853.

Sommer, A. 1995. Vitamin A deficiency and its consequences; A field guide to detection and control. World Health Organization.

Sommer, A. 1995. A bridge too near. The Progress of Nations - Nutrition. http://www.whale.to/v/sommer.html (accessed June 28, 2007).

Sommer, A. 2006. Rx for Survival, A Global Challenge, Public Broadcasting System. http://www.pbs.org/wgbh/rxforsurvival/series/champions/alfred_sommer.html

Sommer, A., Hussaini, G., Muhilal, Tarwotjo, I., Susanto, J., Saroso, J.S. 1980. History of nightblindness: a simple tool for xerophthalmia screening. American Journal of Clinical Nutrition 33:887-891.

Sommer, A., Khan, M., Mosley, W.H. 1973. Efficacy of vaccination of family contacts of cholera cases. Lancet 1:1230-1232.

Sommer A, Mosley WH. 1972. East Bengal cyclone of November 1970: Epidemiological approach to disaster assessment. Lancet;1:1029-1036.

Sommer, A., Mosley, W.H..1973. Ineffectiveness of cholera vaccination as an epidemic control measure. Lancet 1:1232-1235.

Sommer, A., Loewenstein, M. 1975. Nutritional status and mortality. A prospective validation of the QUAC stick. American Journal of Clinical Nutrition 28:287-292.

Sommer, A., Tarwotjo, I., Hussaini, G., Susanto, D. 1983. Increased mortality in children with mild vitamin A deficiency. Lancet 2:585-588.

Sommer, A., Tarwotio, I., Muhilal, Djunaedi, E., Glover, J. 1980. Oral versus intramuscular vitamin A in the treatment of xerophthalmia. Lancet 315(8168) Mar:557-559.

Sommer, A., Tarwotjo, I., Djunaedi, E., West, K.P., Loedin, A.A., Tilden, R., Mele, L., and the Aceh Study Group. 1986. Impact of vitamin A supplementation on childhood mortality: a randomised controlled community trial. Lancet 1:1169-1173.

Sommer, A., West, Jr., K.P. 1996. Vitamin A Deficiency - Health, Survival and Vision. New York: Oxford University Press.

Sommer, A.; West, Keith P. 1987. Delivery of oral doses of vitamin A to prevent vitamin A deficiency and nutritional blindness. Center for Epidemiologic and Preventive Ophthalmology.

Sommer A, Woodward W.E. 1972. The influence of protected water supplies on the spread of classical/Inaba and El Tor/Ogawa cholera in rural East Bengal. Lancet 2:985-987.

Tarwotjo, I. Sommer, A., Soegiharto, T., Susanto, D. Muhilal. 1982. Dietary practices and xerophthalmia among Indonesian children. American Journal of Clinical Nutrition. Mar 35(3):574-81.

Tielsch, J.M., Sommer, A. 1984. The epidemiology of vitamin A deficiency and xerophthalmia. Annual Revue of Nutrition 4:183-205.

Villamor, E., Fawzi, W.W. 2005. Effects of Vitamin A supplementation on immune responses and correlation with clinical outcomes. Clinical Microbiology Revue July 18(3): 446-464.