March 24, 2016

Florida Atlantic University

Like humans, fruit flies sleep at night, caffeine affects their sleep, and if they get a lousy night’s sleep it can affect their memory performance. But what can they tell us about the connection between sleep deprivation and metabolic disorders like diabetes and obesity? A lot, according to a new study that is the first to identify that a conserved gene — translin — works as a modulator of sleep in response to metabolic changes.



Man unable to sleep (stock image). Acute sleep loss in humans is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease.
Credit: © Focus Pocus LTD / Fotolia



The sleep habits of fruit flies are remarkably similar to humans. They get most of their sleep at night, certain drugs and stimulants like caffeine can negatively affect their sleep, and if they get a lousy night’s sleep it can even affect their memory performance. But what can they tell us about the connection between sleep deprivation and metabolic disorders like diabetes, obesity, and blood glucose levels? A lot, according to a new study that is the first to identify that a conserved gene — translin — works as a modulator of sleep in response to metabolic changes.

Spearheaded by researchers at Florida Atlantic University, findings from this study are published in the April 4 issue of Current Biology, which establishes that translin is an essential integrator of sleep and metabolic state, with important implications for understanding the neural mechanism underlying sleep deprivation in response to environmental challenges.

Acute sleep loss in humans is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease. Conversely, metabolic state has a potent impact on modulating sleep and our body clocks.

“In humans, sleep and feeding are tightly interconnected, and pathological disturbances of either process are associated with metabolism-related disorders,” said Alex C. Keene, Ph.D., corresponding author and associate professor in the Department of Biological Sciences on FAU’s John D. MacArthur Campus in Jupiter. “Despite the widespread evidence for interactions between sleep loss and metabolic dysfunction, little is known about the molecular basis of this interaction and how these processes integrate within the brain.”

When fruit flies are hungry, they sleep less because they will sacrifice sleep for their quest to search for food. Keene and his collaborators used fruit flies in their study and created various scenarios between sleeping and foraging to test each gene one at a time to determine which gene didn’t affect their sleep. They carried out a nervous system-specific RNAi screen to identify the genes required to keep hungry flies awake. What they discovered is that translin, when knocked down in neurons, causes starving flies to sleep as soundly as they would on a full stomach. They also observed the same inability to suppress sleep while in starvation mode in the flies that carried a null mutation in translin.

Fruit flies were placed on specific diets as the researchers measured their sleep, and glycogen, triglycerides and free glucose levels. They broke down the starvation response in the fruit flies into separate mechanisms for hunger and sleep-suppression.

“While many genes have been identified as genetic regulators of sleep or metabolic state, mounting evidence from our study indicates that translin functions as a unique integrator of these processes,” said Kazuma Murakami, co-first author and a Ph.D. student in the FAU/Max Planck Florida Institute Integrative Biology and Neuroscience (IBAN) program. “We also have been able to show that this gene is not required for general modulation of sleep. Furthermore, we now know that the energy stores in mutant flies are normal and that the starvation-induced sleep suppression phenotype is not due to increased nutrient storage.”

Results of this study provide important evidence that translin is not required for the perception of starvation or to stimulate hunger-related behaviors, but is required to stimulate wakefulness in the absence of food.

“The identification of genes regulating sleep-feeding interactions will provide important insight into how the brain integrates and controls the expression of complex behaviors,” said Keene.

Story Source:

The above post is reprinted from materials provided by Florida Atlantic University. The original item was written by Gisele Galoustian. Note: Materials may be edited for content and length.

Journal Reference:

  1. Kazuma Murakami, Maria E. Yurgel, Bethany A. Stahl, Pavel Masek, Aradhana Mehta, Rebecca Heidker, Wesley Bollinger, Robert M. Gingras, Young-Joon Kim, William W. Ja, Beat Suter, Justin R. DiAngelo, Alex C. Keene. translin Is Required for Metabolic Regulation of Sleep.Current Biology, 2016; DOI: 10.1016/j.cub.2016.02.013


Source: Florida Atlantic University. “Sleep tight, fruit fly: Scientists find gene responsible for sleep deprivation and metabolic disorders.” ScienceDaily. ScienceDaily, 24 March 2016. <>.

March 22, 2016

Griffith University

Groundbreaking research is leading the way in clean energy, with the use of carbon as a way to deliver energy using hydrogen.



Drop of water. “Hydrogen production through an electrochemical process is at the heart of key renewable energy technologies including water splitting and hydrogen fuel cells,” says Professor Yao.
Credit: © Deyan Georgiev / Fotolia



Groundbreaking research at Griffith University is leading the way in clean energy, with the use of carbon as a way to deliver energy using hydrogen.

Professor Xiangdong Yao and his team from Griffith’s Queensland Micro- and Nanotechnology Centre have successfully managed to use the element to produce hydrogen from water as a replacement for the much more costly platinum.

“Hydrogen production through an electrochemical process is at the heart of key renewable energy technologies including water splitting and hydrogen fuel cells,” says Professor Yao.

“Despite tremendous efforts, exploring cheap, efficient and durable electrocatalysts for hydrogen evolution still remains a great challenge.

“Platinum is the most active and stable electrocatalyst for this purpose, however its low abundance and consequent high cost severely limits its large-scale commercial applications.

“We have now developed this carbon-based catalyst, which only contains a very small amount of nickel and can completely replace the platinum for efficient and cost-effective hydrogen production from water.

“In our research, we synthesize a nickel-carbon-based catalyst, from carbonization of metal-organic frameworks, to replace currently best-known platinum-based materials for electrocatalytic hydrogen evolution.

“This nickel-carbon-based catalyst can be activated to obtain isolated nickel atoms on the graphitic carbon support when applying electrochemical potential, exhibiting highly efficient hydrogen evolution performance and impressive durability.”

Proponents of a hydrogen economy advocate hydrogen as a potential fuel for motive power including cars and boats and on-board auxiliary power, stationary power generation (e.g., for the energy needs of buildings), and as an energy storage medium (e.g., for interconversion from excess electric power generated off-peak).

Professor Yao says that this work may enable new opportunities for designing and tuning properties of electrocatalysts at atomic scale for large-scale water electrolysis.

Story Source:

The above post is reprinted from materials provided by Griffith University.Note: Materials may be edited for content and length.

Journal Reference:

  1. Lili Fan, Peng Fei Liu, Xuecheng Yan, Lin Gu, Zhen Zhong Yang, Hua Gui Yang, Shilun Qiu, Xiangdong Yao. Atomically isolated nickel species anchored on graphitized carbon for efficient hydrogen evolution electrocatalysis. Nature Communications, 2016; 7: 10667 DOI: 10.1038/ncomms10667


Source: Griffith University. “Carbon leads the way in clean energy: New method uses cheap carbon-based catalyst to deliver energy using hydrogen.” ScienceDaily. ScienceDaily, 22 March 2016. <>.

March 22, 2016

University of Texas at Austin

More cities than previously assumed could soon grapple with the Zika virus if two species of mosquitos are found to be equally effective carriers of the disease, a disease ecologist and his colleagues argue.



The circles depict the top 100 cities to which Zika virus might be imported from current infected regions of Latin America and which have suitable habitat for Aedes aegypti or Aedes albopictus in the surrounding region. The size of the circle is the estimated relative risk. Solid red indicates the risk from A aegypti alone. Open circles indicate total risk from both species. The inset shows the status of south Florida, the Caribbean, and nearby areas in more detail.
Credit: Lauren Gardner



More cities than previously assumed could soon grapple with the Zika virus if two species of mosquitoes are found to be equally effective carriers of the disease, a University of Texas at Austin disease ecologist and his colleagues argue in the current edition of The Lancet Infectious Diseases.

Even if only one mosquito species proves capable of spreading Zika, the scientists say cities such as Miami and Houston are at high risk of seeing more of the disease this summer.

Sahotra Sarkar, a faculty member in the Department of Integrative Biology and Department of Philosophy at The University of Texas at Austin, and his colleagues Lauren Gardner and Nan Chen at the University of New South Wales in Australia, mapped how Zika is likely to spread in 100 cities worldwide under two different scenarios, taking into account air travel to and from affected areas in Latin America and the prevalence of two common mosquito species associated with the disease.

Although both mosquito species have been detected with Zika, the researchers point out that only one type of mosquito is known to be effective at spreading the virus. If the second species also is capable of spreading Zika among people, more places in the United States, Europe and Asia than previously thought will probably experience outbreaks.

“The spread depends critically on if a second mosquito species is a very good transmitter of Zika,” Sarkar says. “If it is, then the risk is even worse than what has been forecast so far.”

Public health officials with the World Health Organization (WHO) and other agencies have forecast the spread of Zika with too little information about the effectiveness of different types of mosquitoes in spreading the disease, Sarkar says. Under the first scenario, in which only one mosquito species spreads Zika, existing models significantly overestimate the danger of the Zika virus in most of the world. In the United States, for example, only Florida, Texas and Louisiana — home to the Aedes aegypti mosquito — would probably experience widespread cases of Zika.

“Among urban areas in the U.S., Miami and Houston are at the greatest risk,” Sarkar says. “In general there is greater risk to Florida than Texas because more travel to Latin America and the Caribbean occurs there.”

Under the second scenario, however, in which another species — Aedes albopictus, known to harbor the disease but not yet known to be good at transmitting it — is also capable of spreading Zika, the WHO model underestimates the likelihood of transmission, Sarkar and his colleagues find. Parts of the world previously believed to be at low risk — such as Canada, Chile and many countries in Europe and Asia — would probably experience a spread in Zika. Under this scenario within the United States, New York would face an even greater risk than Houston.

Sarkar and Gardner’s findings came out the same day as a study from the National Center for Atmospheric Research that looked at how Zika would be likely to spread in U.S. cities this summer. In taking into account the ecology of the two mosquito species worldwide and explicitly showing the difference in risk levels if Aedes albopictus proves capable of spreading the virus, the map from Sarkar and Gardner points to the importance of learning immediately whether both mosquito species can effectively spread the Zika virus to ensure an appropriate public health response in different regions, the scientists say.

Regardless, Sarkar says, cities such as Miami, Orlando, Houston, Tampa and New Orleans should step up efforts to sample and monitor local mosquito populations and be prepared to implement drastic mosquito control measures. And travelers to Latin America should continue to take precautions to protect themselves, notes Gardner at the University of New South Wales.

“The risk of additional Zika spread is further heightened,” she says, “by the upcoming 2016 Summer Olympics, which will be hosted in Rio de Janeiro, Brazil, the epicenter of the Zika virus outbreak.”

Story Source:

The above post is reprinted from materials provided by University of Texas at Austin. Note: Materials may be edited for content and length.

Journal Reference:

  1. Lauren M Gardner, Nan Chen, Sahotra Sarkar. Global risk of Zika virus depends critically on vector status of Aedes albopictus. The Lancet Infectious Diseases, 2016; DOI: 10.1016/S1473-3099(16)00176-6


Source: University of Texas at Austin. “Global spread of Zika linked to types of mosquitoes that transmit it.” ScienceDaily. ScienceDaily, 22 March 2016. <>.


March 21, 2016

University of Southampton

The season a person is born in influences a wide range of things: from risk of allergic disease, to height and lifespan. Yet little is known about how a one-time exposure like the season of birth has such lasting effects. Researchers have now discovered specific markers on DNA that link the season of birth to risk of allergy in later life.



DNA markers link season of birth and allergy risk, say investigators.
Credit: © hunna / Fotolia



Researchers at the University of Southampton have discovered specific markers on DNA that link the season of birth to risk of allergy in later life.

The season a person is born in influences a wide range of things: from risk of allergic disease, to height and lifespan. Yet little is known about how a one-time exposure like the season of birth has such lasting effects.

The Southampton study, published in the journal Allergy, conducted epigenetic scanning on DNA samples from a group of people born on the Isle of Wight. They found that particular epigenetic marks (specifically, DNA methylation) were associated with season of birth and still present 18 years later. The research team was also able to link these birth season epigenetic marks to allergic disease, for example people born in autumn had an increased risk of eczema compared to those born in spring. The results were validated in a cohort of Dutch children.

John Holloway, Professor of Allergy and Respiratory Genetics at the University and one of the study’s authors, comments: “These are really interesting results. We know that season of birth has an effect on people throughout their lives. For example generally, people born in autumn and winter are at increased risk for allergic diseases such as asthma. However, until now, we did not know how the effects can be so long lasting.

“Epigenetic marks are attached onto DNA, and can influence gene expression (the process by which specific genes are activated to produce a required protein) for years, maybe even into the next generation. Our study has linked specific epigenetic marks with season of birth and risk of allergy. However, while these results have clinical implications in mediating against allergy risk, we are not advising altering pregnancy timing.”

Dr Gabrielle Lockett, of the University of Southampton and first author of the study, adds: “It might sound like a horoscope by the seasons, but now we have scientific evidence for how that horoscope could work. Because season of birth influences so many things, the epigenetic marks discovered in this study could also potentially be the mechanism for other seasonally influenced diseases and traits too, not just allergy.”

The team say that further research is needed to understand what it is about the different seasons of the year that leads to altered disease risk, and whether specific differences in the seasons including temperature, sunlight levels and diets play a part. More study is also needed on the relationship between DNA methylation and allergic disease, and whether other environmental exposures also alter the epigenome, with potential disease implications.

Story Source:

The above post is reprinted from materials provided by University of Southampton. Note: Materials may be edited for content and length.

Journal Reference:

  1. Gabrielle A. Lockett, Nelís Soto-Ramírez, Meredith A. Ray, Todd M. Everson, Cheng-Jian Xu, Veeresh K. Patil, William Terry, Akhilesh Kaushal, Faisal I. Rezwan, Susan L. Ewart, Ulrike Gehring, Dirkje S. Postma, Gerard H. Koppelman, S. Hasan Arshad, Hongmei Zhang, Wilfried Karmaus, John W. Holloway. Association of Season of Birth with DNA Methylation and Allergic Disease. Allergy, 2016; DOI:10.1111/all.12882


Source: University of Southampton. “DNA markers link season of birth, allergy risk.” ScienceDaily. ScienceDaily, 21 March 2016. <>.

Clinical Trials of the Future – Tking the Study to the Patient


Now that clinical trial data can be entered at the time of the patient encounter using web-based systems, and remote mobile diagnostic devices are being validated for use in clinical trials, the time has arrived for new drugs, biologics and devices to reach the market in a more efficient and cost-effective manner. As part of the process, when developing new products, the pharmaceutical industry will take the clinical trial to the patient using novel study designs and modern technology. Imagine the concept that any patient could be a study subject and any clinician could be a clinical investigator. This is not a new concept. In the 1950’s there was a major polio outbreak and there was a crisis in healthcare. Here is what happened with more on the NIH website:


The polio vaccine field trials of 1954, sponsored by the National Foundation for Infantile Paralysis (March of Dimes), are among the largest and most publicized clinical trials ever undertaken. Across the United States, 623,972 schoolchildren were injected with vaccine or placebo, and more than a million others participated as “observed“ controls. The results, announced in 1955, showed good statistical evidence that Jonas Salk’s killed virus preparation was 80-90% effective in preventing paralytic poliomyelitis


The first effective polio vaccine was developed in 1952 by Jonas Salk and a team at the University of Pittsburgh that included Julius Youngner, Byron Bennett, L. James Lewis, and Lorraine Friedman, but it required years of subsequent testing. To encourage patience, Salk went on CBS radio to report a successful test on a small group of adults and children on 26 March 1953; two days later the results were published in JAMA. Beginning 23 February 1954, the vaccine was tested at Arsenal Elementary School and the Watson Home for Children in Pittsburgh, Pennsylvania. The Salk vaccine was used in a test called the Francis Field Trial, led by Thomas Francis; the largest medical experiment in history. The test began with some 4,000 children at Franklin Sherman Elementary School in McLean, Virginia, and would eventually involve 1.8 million children, in 44 states from Maine to California.


However, no matter how the virtual trial evolves, to get it to work, clinical trial subjects will need to interact with their treating physicians, pharmacists and other healthcare workers. Once we have standardized trials on the Web, it is all doable.


Magnolia x Soulangeana (saucer magnolia)


Magnolia x soulangeana (saucer magnolia) is a hybrid plant in the genus Magnolia and family Magnoliaceae. It is a deciduous tree with large, early-blooming flowers in various shades of white, pink, and purple. It is one of the most commonly used magnolias in horticulture, being widely planted in the British Isles, especially in the south of England; and in the United States, especially the east and west coasts


The following photo is contributed by our friend and colleague and photographer extraordinaire James Farley (Vtv Therapeutics). James told us that this was shot on his Canon 5D Mark III with 100mm Macro f2.8 lens at f8.




Magnolia x Soulangeana (saucer magnolia) ©J Farley photography 2016


ON TARGET is the newsletter of Target Health Inc., a NYC – based, full – service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.


Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor



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Helicobacter and Stomach Ulcers


Credit: Zina Deretsky, National Science Foundation – NSF – Public Domain:


Editor’s note: This bacteria, H. pylori, evolved into a boring bacteria, one that could survive away from the acidic environment and into the mucus layer of the stomach, instead; no doubt, aided by its multiple flagella. Also, interesting is that it requires oxygen, but at lower concentration than is found in the atmosphere. It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) produced by intestinal bacteria. We had dinner, last night with a brilliant young scientist. The conversation got onto the topic of climate change. A truly dismal topic, with apparently no possible way out, for our species. Then David suggested that perhaps humans could evolve a system that was able to deal with the huge mega tons of methane, pouring into the earth’s atmosphere, daily. The next day, when I was reading about H. pylori’s adaptation to acidic climate with lowered oxygen, I thought, if this little bacteria could adapt, why couldn’t humans do as well – adapt to higher levels of methane thus lower levels of oxygen.


Helicobacter pylori, previously Campylobacter pylori, is a gram-negative, microaerophilic bacterium found usually in the 1) ____. It was identified in 1982 by Australian scientists Barry Marshall and Robin Warren, who found that it was present in a person with chronic gastritis and gastric ulcers, conditions not previously believed to have a microbial cause. It is also linked to the development of duodenal ulcers and stomach cancer. However, over 80% of individuals infected with the bacterium are asymptomatic, and it may play an important role in the natural stomach ecology. More than 50% of the world’s population harbor H. pylori in their upper gastrointestinal 2) ____. Infection is more prevalent in developing countries, and incidence is decreasing in Western countries. H. pylori’s helical shape (from which the genus name is derived) is thought to have evolved to penetrate the mucoid lining of the stomach. Up to 85% of people infected with H. pylori never experience 3) ___ or complications. Acute infection may appear as an acute gastritis with abdominal pain (stomach ache) or nausea. Where this develops into chronic gastritis, the symptoms, if present, are often those of non-ulcer dyspepsia: stomach pains, nausea, bloating, belching, and sometimes vomiting or black stool.


Individuals infected with H. pylori have a 10 to 20% lifetime risk of developing peptic ulcers and a 1 to 2% risk of acquiring stomach cancer. Inflammation of the pyloric antrum is more likely to lead to duodenal ulcers, while inflammation of the corpus (body of the stomach) is more likely to lead to gastric ulcers and gastric carcinoma. However, H. pylori possibly plays a role only in the first stage that leads to common chronic 4) ___, but not in further stages leading to carcinogenesis. A meta-analysis conducted in 2009 concluded the eradication of H. pylori reduces gastric cancer risk in previously infected individuals, suggesting the continued presence of H. pylori constitutes a relative risk factor of 65% for gastric cancers; in terms of absolute risk, the increase was from 1.1% to 1.7%. H. pylori has been associated with colorectal polyps and colorectal cancer. It may also be associated with eye disease.




Helicobacter pylori. Source: Yutaka Tsutsumi, M.D., Professor Department of Pathology, Fujita Health, University School of Medicine, Copyrighted free use,


H. pylori is a helix-shaped (classified as a curved rod, not spirochaete) Gram-negative bacterium about 3 um long with a diameter of about 0.5 um. It is microaerophilic; that is, it requires 5) ___ , but at lower concentration than is found in the atmosphere. It contains a hydrogenase which can be used to obtain energy by oxidizing molecular hydrogen (H2) produced by intestinal bacteria. It produces oxidase, catalase, and urease. It is capable of forming biofilms and can convert from spiral to a possibly viable but nonculturable coccoid form, both likely to favor its survival and be factors in the epidemiology of the bacterium. H. pylori possesses five major outer membrane protein families. The outer membrane contains cholesterol glucosides, which are found in few other bacteria. H. pylori has four to six lophotrichous flagella; all gastric and enterohepatic Helicobacter species are highly motile owing to 6) ___.


If you burp a lot or have burning in your stomach or chest, particularly when your stomach is empty, you probably have either an infection, a tumor, or a condition called GERD (reflux or regurgitation). Infection with bacteria such as helicobacter pylori is by far the most common cause. Your doctor will probably order an upper GI series X ray to rule out a tumor. That almost always comes back negative to tell you that you do not have tumor. Then you get a blood test for bacteria called Helicobacter pylori and you should be treated with antibiotics even if the blood test is negative, because there are at least 23 other species of bacteria that this test does not detect. Your gastroenterologist will want to put a tube down your mouth and into your stomach, but the biopsy that he will do to find the Helicobacter can often miss the germ even when it is there. If your doctor does not offer the antibiotic treatment, you will be stuck with a diagnosis of regurgitation, called GERD, which means you have pain and no one can tell you why. You will need to take medication for the rest of your life.


An article in the medical journal GUT reported that at least 24 different 7) ___ have been shown to cause stomach ulcers. Since doctors do not have any way to check for all 24 different bacteria, all people with belching and burning in the stomach should be given a one-week course of antibiotics that are used to treat the most common cause of stomach ulcers, called Helicobacter Pylori.


Twenty years ago, stomach ulcers were treated by giving a patient a dairy diet. Today, almost everyone with belching and burning in the stomach should be treated with antibiotics. In 1983 they laughed at Dr. Barry Marshall when he reported that stomach ulcers were caused by infection with helicobacter pylori and could be cured with 8) ___. Fellow physicians were so negative to his ideas, that lacking animals to do studies with, he responded by swallowing a vial of helicobacter and almost died. He received the Nobel Prize in 2005, for his pioneering work. Now almost every physician agrees that all people who have belching and burning in the stomach and a positive blood test for helicobacter pylori can be cured with antibiotics, but some gastroenterologists refuse to treat patients with ulcer symptoms and a negative blood test or biopsy for that germ; although, the literature shows that at least 24 germs cause an irritation in the stomach, including H. helmannii, H. felis, H. rappini, H. cinaedi, H sp. Strain Mainz H. fennelliae and H. pullorum, H. hepaticus, H. Billis, H. canis, H. Hills, cytomegalovirus and mycoplasma, and Helicobacter mesocricetorum sp nov.


Helicobacter species have been isolated from the stomachs of dogs, cats, ferrets, pigs, monkeys and cheetahs, birds, mice, chickens. The standard treatment of one week of clarithromycin 500 mg twice a day, metronidazole 500 mg twice a day and omeperazole 20 mg once a day is safe and effective. These germs also grow in 9) ___, so they can be transmitted between family members and pets. So some doctors prescribe antibiotics to all people with belching and stomach burning, and check the other members of the household for symptoms.

After twelve weeks of the antibiotic regimen, comes a follow up blood test for helicobacter. If symptoms are gone and the titre drops, chances are the patient is cured. If the helicobacter titre is still high, the patient’s helicobacter is probably resistant to metronidazole and will need to be treated for at least ten days with amoxacillin 500 mg four times a day, tetracycline 500 mg three times a day and omeperazole 20 mg once a day. If symptoms persist, the patient may need a tube down the throat by a gastroenterologist. If there is regurgitation of stomach acid into the esophagus (reflux, hiatal hernia), patients may need to be treated with 20 mg omeperazole once a day. Some people who are not infected with helicobacter may benefit from taking clarithromycin or other antibiotic for a longer period of time. Helicobacter may also cause liver disease, blood vessel diseases such as clotting and 10) ___ attacks, and certain skin conditions such as rosacea.


ANSWERS: 1) stomach; 2) tract; 3) symptoms; 4) inflammation; 5) oxygen; 6) flagella; 7) bacteria; 8) antibiotics; 9) saliva; 10) heart



Barry Marshall MD 1951 to Present



Barry Marshall MD in 2008



Barry James Marshall, AC, FRACP, FRS, FAA, DSc (born 30 September 1951) is an Australian physician, Nobel Prize laureate in Physiology or Medicine (the only laureate born in Western Australia), and Professor of Clinical Microbiology at the University of Western Australia. Marshall and Robin Warren showed that the bacterium Helicobacter pylori (H. pylori) is the cause of most peptic ulcers, reversing decades of medical doctrine holding that ulcers were caused by stress, spicy foods, and too much acid. This discovery has allowed for a breakthrough in understanding a causative link between Helicobacter pylori infection and stomach cancer.


Marshall was born in Kalgoorlie, Western Australia and lived in Kalgoorlie and Carnarvon until moving to Perth at the age of eight. He is the eldest of four siblings and attended Newman College and the University of Western Australia, where he received a Bachelor of Medicine, Bachelor of Surgery (MBBS). In 1979, Marshall was appointed as a Registrar in Medicine at the Royal Perth Hospital where he met Robin Warren, a pathologist interested in gastritis, during internal medicine fellowship training. Together, they studied the presence of spiral bacteria in association with gastritis. In 1982, they performed the initial culture of H. pylori and developed their hypothesis related to the bacterial cause of peptic ulcer and gastric cancer. It has been claimed that the H. pylori theory was ridiculed by the establishment scientists and doctors, who did not believe that any bacteria could live in the acidic environment of the stomach. Marshall has been quoted as saying in 1998 that “everyone was against me, but I knew I was right.“


However, after failed attempts to infect piglets in 1984, Marshall, after having a baseline endoscopy done, drank a Petri dish containing cultured H. pylori, expecting to develop, perhaps years later, an ulcer. He was surprised when, only three days later, he developed vague nausea and halitosis (due to the achlorhydria, there was no acid to kill bacteria in the stomach, and their waste products manifested as bad breath). On days 5-8, he developed achlorydric (no acid) vomiting. On day eight, he had a repeat endoscopy and biopsy, which showed massive inflammation (gastritis), and H. pylori was cultured. On the fourteenth day after ingestion, a third endoscopy was done, and Marshall began to take antibiotics. Interestingly, Marshall did not develop antibodies to H. pylori, suggesting that innate immunity can sometimes eradicate acute H. pylori infection. Marshall’s illness and recovery, based on a culture of organisms extracted from a patient, fulfilled Koch’s postulates for H. pylori and gastritis, but not for peptic ulcer. This experiment was published in 1985 in the Medical Journal of Australia and is among the most cited articles from the journal.


After his work at Fremantle Hospital, Marshall did research at Royal Perth Hospital (1985-86) and at the University of Virginia, USA (1986-Present), before returning to Australia while remaining on the faculty of the University of Virginia. He held a Burnet Fellowship at the University of Western Australia (UWA) from 1998-2003. Marshall continues research related to H. pylori and runs the H. pylori Research Laboratory at UWA.


In 2005, the Karolinska Institute in Stockholm awarded the Nobel Prize in Physiology or Medicine to Marshall and Robin Warren, his long-time collaborator, “for their discovery of the bacterium Helicobacter pylori and its role in gastritis and peptic ulcer disease“. Marshall also received the Warren Alpert Prize in 1994; the Australian Medical Association Award and the Albert Lasker Award for Clinical Medical Research in 1995; the Gairdner Foundation International Award in 1996; the Paul Ehrlich and Ludwig Darmstaedter Prize in 1997; the Dr. A.H. Heineken Prize for Medicine, the Florey Medal, and the Buchanan Medal of the Royal Society in 1998 and was elected a Fellow of the Royal Society (FRS) in 1999. His certificate of election to the Royal Society reads:


Barry Marshall, together with Robin Warren, discovered spiral bacteria in the stomachs of almost all patients with active chronic gastritis, or duodenal or gastric ulcers, and proposed that the bacteria were an important factor in the aetiology of these diseases. In 1985, Marshall showed by self-administration that this bacterium, now called Helicobacter pylori, causes acute gastritis and suggested that chronic colonization directly leads to peptic ulceration. These results were a major challenge to the prevailing view that gastric disorders had a physiological basis, rather than being infectious diseases. Marshall showed that antibiotic and bismuth salt regimens that killed H. pylori resulted in the cure of duodenal ulcers. The view that gastric disorders are infectious diseases is now firmly established and there is increasing evidence for a role of H. pylori infection in gastric cancers. The work of Marshall has produced one of the most radical and important changes in medical perception in the last 50 years.


Read below, Dr. Marshall’s 2005, Nobel Prize acceptance speech


I was born in 1951 in Kalgoorlie, a prosperous mining town 370 miles east of Perth, Western Australia. Kalgoorlie was a gold rush town which sprang up in the desert after the Irishman Paddy Hannan struck gold there in 1892.

At the time I was born my father was 19 years old and in the final year of his apprenticeship as a fitter and turner. My mother quit her nursing training to have me at the age of eighteen years.

We moved quite a bit through my early childhood. After my father finished his apprenticeship, my parents decided to go and work in the new Uranium mine in Rum Jungle in the Northern Territory. They drove their Model A Ford up Australia’s west coast about 1000 miles but stopped at Carnarvon when the car broke down. The whaling station at Carnarvon was also offering excellent wages for good tradesmen and my father was one of the best. We lived near the whaling station while I grew from two to four years and my brother William was born there.

My first memories are of life in Carnarvon. I recall a boat trip back to Perth on one occasion and a DC3 aeroplane flight to Perth on another. Our house was on Babbage Island about 100 yards from the beach. We had electricity, an outhouse toilet, dirt floors in parts of the house, a telephone, refrigerator, a car, a cat and a dog. Nearby was a derelict steam engine on a railway siding. We had neighbors close by and other kids to play with.

By then, my grandparents had the license on the Tower Hotel in Kalgoorlie and periodically we would return there to live. In Kalgoorlie I remember doing all kinds of things as a six and seven year old including making bows and arrows, slingshots and lighting crackers after school.

After a period back in Kalgoorlie, my mother decided to move the family to Perth where my second brother, Andrew, was born in 1958. I was seven years old at the time. I suppose my mother could see the young boys in Kalgoorlie leaving school at 16 and going down the mines to work. It was an attractive proposition for them. They earned high salaries and had a wild social life drinking and partying on their off days. She wanted more for her children and hoped we would study and enter a profession. Moving to the city was the first step. We are lucky she made that decision. My two brothers and sister all went through University and have highly successful careers and happy lives.

In school I sporadically hit the top of the class but mostly did not work hard enough to stay up there. At home I had plenty of interesting reading material. Dad always explained the car engine when he repaired it and he had many technical books so I was making electromagnets by age eight as well as reading my mother’s medical and nursing books. I suspect I was born with a boundless curiosity and this was encouraged through my childhood.

Being the eldest of four children, I was expected to be the responsible one and often found myself controlling two younger brothers who shared my exuberant and inquisitive nature. I still feel guilty about the time I advised my younger brother to jump out of a tree and he broke his arm.

My first exposure to fame came at age twelve when I was left in charge of the younger siblings while my mother attended to the grocery shopping. I had a history of responsible baby-sitting by this time so nothing should have gone wrong. During the morning my 18 month-old sister found a milk bottle half full of kerosene and drank some, perhaps also aspirating a little so that my brothers and I found her choking but did not know why. I called the emergency services and an ambulance arrived about fifteen minutes later. During the wait, as I had learned some basic CPR at the Royal Lifesaving Society Swimming training, I tried to perform mouth to mouth resuscitation on my little sister. I know now that it was pointless because she was actually still breathing. However, my close mouth contact enabled me to smell the kerosene and make the diagnosis of poisoning. I featured in the newspaper a few days later, with my fully recovered little sister on my lap. It was a good story about how to call the emergency number, and why you should not put poison into drink containers. Very kindly my mother did not leak to the press the fact that it was I who had left the kerosene within reach of young Marie!

In our dad’s shed, my brothers and I had access to all the tools needed to build or dismantle anything. I frequently got into trouble doing both. My favorite book as a child was an old Newne’s Children’s Encyclopedia which my grandfather had bought just before World War II and donated to our family after seeing how interested we were in it. Each volume had special chapters called “Things Boys can Do“. My brothers and I would pick out interesting projects. As the years went by, and I grew up, I recall building a slingshot, a crystal set, a Morse-code set, various guns, a hydrogen generator for balloons, electric devices and minor explosives. In those days fireworks had been banned, but chemicals were easily available from pharmacies and chemical suppliers so, in the tradition of Alfred Nobel, we would create various explosive mixtures and make firecrackers and bombs. This started rather benignly with simple gunpowder but graduated to more dangerous oxidizing agents after a few years. Many times we were in trouble after disturbing the neighbors, but were fortunate never to cause serious injury. I often found myself in trouble with my parents when someone was hurt, but despite the minor punishments, I know my parents were quite proud of my ingenuity.

Occasionally my father, Bob, was on the receiving end of my “brilliant“ work. Observing a fraying cord on his electric drill, I repaired it but accidentally swapped the neutral and earth wire. He jumped rather high when he tried to use it a few days later while standing on wet grass. On another occasion my brothers decided to fly lighter-than-air balloons for our team at the school sports carnival. Since helium was not available, we built a device which pressurized domestic house gas and filled the balloons. Our technology was rather primitive however and these balloons contained quite a bit of air as well, but they did float satisfactorily. My father recognized this and warned us that they might be a little dangerous if they came in contact with an open flame. As an example, he demonstrated the risk by touching a lighted cigarette to one of the balloons as it floated under the back patio. He was enveloped in a ball of flame and his eyebrows were singed off. This did not worry us very much because we had seen him in this state before as he often seemed to be washing engine parts in gasoline and then testing the spark plugs of engines nearby.

After high school, at Newman College, although interested in science and mathematics, I felt that my mathematical ability was not strong enough to do electrical engineering, so I chose medical school as an alternative which was at least as interesting, and which did not require daily exposure to calculus! In addition the opportunity to study biological sciences was an attraction, particularly biochemistry which was not available in high school.

I met my wife Adrienne, a psychology student, at the University of Western Australia and we married in 1972 while I was doing my fifth year in medicine. I graduated from the University MBBS (Bachelor of Medicine, Bachelor of Surgery) in 1975 and thereafter performed internship and residencies in internal medicine at the Queen Elizabeth II Medical Centre (Sir Charles Gairdner Hospital). In those days I had no definite goals in medicine, but was interested in all aspects of clinical medicine including geriatrics, oncology and rheumatology. I was more interested in an academic career combining research with clinical medicine in a university hospital environment. I began my training as a specialist physician in 1978. In 1979 I moved to Royal Perth Hospital in order to become more experienced with cardiology and open heart surgery, which was only performed at that hospital in Perth.

Although we didn’t appreciate it at the time, my wife Adrienne and I must have been very busy during those years. We had four children, Luke, born in 1973, Bronwyn in 1975, Caroline in 1978 and Jessica in 1981. Adrienne was finishing the honors year of her psychology degree as Luke was being born. She was working in-between babies as a counsellor with the Education Department. My non-medical time was spent delivering children to various child-minding facilities, renovating our house, and indulging in my hobby of computers and electronics.

In the second half of 1981, my rotation took me to the gastroenterology division. It was there that I met Robin Warren. As part of my training I was encouraged to perform a clinical research project each year. I was already totally engrossed in a study of heat stroke in “fun runners“ and might have progressed to sports or environmental medicine from there. However, I asked my boss, Dr Tom Waters, if there was a gastroenterology project I could start. He told me that Robin Warren had given him a list of patients with curved bacteria present on their stomach biopsies and needed someone to follow-up the patients to see what clinical diseases they had. I was especially interested because one of the people on Robin’s list was a woman I had seen in my ward, who had severe stomach pain but no diagnosis. In desperation we had referred her to a psychiatrist and commenced antidepressant medication for want of a better treatment. The only abnormal finding had some redness in the stomach and Robin’s bacteria on the stomach biopsy.

So I called Robin in the basement area of Royal Perth Hospital where the Pathology Department resided. It was to be the first of many afternoon visits in the next year. In those days, Robin used to drink strong black coffee and smoke small cigars, “cigarillos“ I believe they were called. I too used to indulge occasionally, and would try out one of Robin’s cigars from time to time during our meetings. In our first meeting, Robin showed me slides of the curved bacteria he had seen, and explained the histopathology of the gastric mucosa to me.

I am often asked what made me listen to Robin and take up the research with him. Clearly this was an interesting thing to study, previously undescribed bacteria living in the acid-filled stomach. But I may have had other advantages compared with colleagues Robin had approached over the previous two years.

I was undifferentiated in that I wasn’t coming from a background in gastroenterology so that my knowledge and ideas were founded in general medical basic science rather than the dogma one was required to learn in specialist medicine. As a trainee general physician with broader training, I was comfortable with the notion of infectious disease and antibiotic therapies. I am told by others that I have a lateral thinking broad approach to problems, sometimes to my detriment. In school my grades always suffered because I was continually mucking about with irrelevant side issues which I often found to be more interesting.

At around that time also, I was aware of publications in the literature describing Campylobacter jejuni as a newly discovered common cause of food-borne gastroenteritis and colitis. Thus, I had seen pictures of campylobacters and could identify that Robin’s organisms appeared to be quite similar. In retrospect, one advantage of doing this research in Perth was that, as a modern Western society, H. Pylori was already in decline by 1981, so that rather than 80% of persons having the CLO, bacteria were only present in 30-50%. Thus, in any biopsy collection taken that year, Robin could see both infected specimens with inflammation (gastritis) and uninfected specimens which hardly ever had gastritis i.e. a “control group“. A further advantage I did have in 1981 was the new connection we had from the medical library to the National Library of Medicine at the NIH (Medline). Perhaps because of my interest in computer programming, this resource appealed to me and enabled me to enlist the librarians at Royal Perth Hospital to extensively search the past and current literature on gastric bacteria.

By the end of that first afternoon with Robin I was very interested. Over the next six months I followed the literature from book chapters, to their references, to deeper references, to material in library archives. I found that spiral gastric bacteria had been reported again and again but passed over. I could see an interesting paper being produced, perhaps in an obscure microbiological journal, but had no idea at the time of what we were really about to discover.

At the end of 1981, my gastroenterology term had almost finished and my term allocations for 1982 had been chosen. In the midst of all this time consuming and interesting research work I was still a physician in training. I was fitting in the research around education and patient commitments. In the first 6 months of 1982, I was to be a hematology registrar looking after the bone marrow transplant patients. In the second 6 months I was to be the physician at Port Hedland Hospital, a rotation to a point 2,000 kilometers north of Perth which attracted “hardship bonus“, i.e. $5,000 extra over 6 months. By then, I was very excited about the spiral bacteria. I had developed a degree of confidence in our methodology, and believed that we could safely carry out a study on 100 or so patients. I was able to keep the work going, continuing the research by fitting it around my other duties.

In November 1981, Adrienne had delivered our fourth child, Jessica. I was beginning a project which would occupy every minute of my spare time for the next 6 months. Adrienne was on maternity leave and was full time at home. It meant I could leave much of the parenting to her. We never did find the time to complete our home renovations and at the last minute in 1986 took out an extra home loan to pay someone to finish it for us. We had to have it in a rentable condition while we were in the USA.

I was fortunate to have a partner who was as enthusiastic about the work as I was. She also enjoys a challenge and shares my sense of adventure. Adrienne’s background in Psychology and experimental research was invaluable and she was always around to discuss the design of studies and the results of various other research works I had found. Over the years we took lots of chances. I took jobs on inadequate pay for many years. As my contemporaries were making their careers and achieving success I seemed to be falling further behind. I always had Adrienne’s full support. When she urged caution or vetoed some of my excesses, I knew it was time to really listen and re-evaluate. As time went on she became my unofficial editor. All my early papers were edited by her and she helped with much of the discussion. Her liberal arts background means she is a more fluent writer than I. Over the past 25 years she has also helped to write and edit most of my books and speeches. All of the talks and speeches given in Stockholm were written with her substantial help.

My hobby of electronics was also an important aid in my research. In the evenings during 1981, I continued with my hobby of computing and electronics, so that by the end of that year I had completed the construction of a home computer capable of word processing. I was able to type grant proposals, consent forms and protocols. I was always on the leading edge of technology and my communication with overseas researchers was efficient because of that. It also meant I was able to access information not readily available. By 1981 I could function better as a single unfunded scientist than many units with multiple support staff.

The family moved to Port Hedland in July 1982 and I took all my references and textbooks with me. It was an important period. I had time to do an extensive literature search by correspondence and also had time to digest the results of our study and write it up for presentation. It was a great time for the family too. Winter in Port Hedland was beautiful, every day sunny with a temperature in the 80’s. We had a bit of extra money and we spent many weekends travelling in remote communities and camping with the kids under the stars.

In October 1982, I presented the preliminary findings from our study to the local College of Physicians meeting, where it received a mixed response. I found that my contract at Royal Perth would not be renewed the following year. I had successfully completed my training as a physician and now wanted to work in gastroenterology or microbiology to continue the work. These jobs at Royal Perth were not available.

Fortune stepped in when I was approached by Drs. Norm Marinovich and Ian Hislop at Fremantle Hospital who suggested they would find me a senior registrar position and fund me to continue. Fremantle is the third and smallest of the teaching hospitals in Perth and has a tradition of openness and experimentation. In the next two years at Fremantle I had an enthusiastic group of people working with me. Dr Ian Hislop, Norm Marinovich, Harvey Turner, David McGechie, Ross Glancy, Neil Noakes, Graeme Francis, Peter Rogers, Neil Stingemore, as well as great support from the Medical Superintendent, Peter Smith. The only downside of the appointment was that I was forced to halt my collaboration with Robin Warren. Robin did not have an appointment at Fremantle so the pathologist there, Ross Glancy, joined the team.

They were happy and very productive years. I was able to confirm very quickly that our observations of the bacteria at Royal Perth Hospital also applied in other parts of the city, the majority of peptic ulcer patients having the organism. I was still officially unfunded. The hospital was picking up all the costs of my work. It was at Fremantle in those two years that the first effective treatments were devised. I solved the conundrum of why bismuth has been such an effective stomach treatment for the past 200 years. I did my famous self experimentation and the early urease tests were developed.

A great piece of luck in early 1983 was finding Dr Martin Skirrow in the UK. I got his phone number from David McGechie. Skirrow arranged for the first presentation at the European Campylobacter Meeting in September 1983. Harvey Turner arranged a travel grant to take me to Brussels and the Gist Brocades Company, helped so that I could extend the trip, visit Martin in the UK and Guido Tytgat’s group in Amsterdam.

In September 1983, I visited Martin Skirrow in Worcester England, and attended an endoscopy session at the Worcester Infirmary. Martin’s registrar, Cliodna McNulty, was able to successfully isolate the organism 3 days later, showing that the spiral bug was not merely an Australian phenomenon but was present in ulcer patients in the UK as well. Martin Skirrow in Britain and Adrian Lee in Sydney were enormously encouraging, helping me with the microbiology in those early years.

In 1984 therefore, there were several groups around the world obtaining results which paralleled those of our group in Perth. In Australia, Adrian Lee in Sydney with Stuart Hazel and Hazel Mitchell also Nick Talley, John Lambert and Tom Borody were early researchers who made significant advances in the H. Pylori work. After the Brussels meeting, a core of researchers in Europe immediately picked up the research and much of the most important work on HP has been done by that group: my old friends, Mario Quina in Portugal, Tony Axon and Ashley Price in the UK, Francis Megraud in France, Peter Malfertheiner in Germany, Manuel Lopez Brea and Jose Pajares Garcia in Spain, Penti Sipponen in Finland, Dino Vaira and Giovanni Gasparini in Italy, Colm O’Morain in Ireland, Leif Andersen in Denmark, Alexander Hirschl in Austria, Guido Tytgat, Ernst Kuipers and Erik Rauws in The Netherlands, Michel Deltenre in Belgium, Pierre Michetti in Switzerland, Torkel Wadstrom and Lars Engstrand in Sweden. We became a closely knit group. The European group grew out of the campylobacter group I had met in Brussels in 1983 and today I count the members of that group amongst my closest friends. We have shared a remarkable story together.

In the USA David Graham, Pete Peterson and Martin Blazer began as critics. They set out to disprove the hypothesis but quickly became leaders in the field of HP research in the USA. With Tadetaka (Tachi) Yamada, although he was not directly involved in the HP research, they played an important role in moving various bodies such as the NIH towards action and acceptance of HP as an ulcer cause. In Asia, Takashi Shimoyama, Ken Kimura, Susumu Okabe, Yoshihiro Fukuda, Toshio Fujioka, Bow Ho, and K.L. Goh, were doctors who I was in contact with through the 1980s. They were developing their own HP research and supporting mine. In Asia, the H. Pylori research was taken up very quickly and I made my first visit to Japan in 1985 to present my work. There are too many others to list here. Needless to say, reports that I was alone in the promotion of HP as a pathogen are somewhat exaggerated.

But 1984 was a difficult year. I was unsuccessfully attempting to infect an animal model. There was interest and support from a few but most of my work was rejected for publication and even accepted papers were significantly delayed. I was met with constant criticism that my conclusions were premature and not well supported. When the work was presented, my results were disputed and disbelieved, not on the basis of science but because they simply could not be true. It was often said that no one was able to replicate my results. This was untrue but became part of the folklore of the period. I was told that the bacteria were either contaminants or harmless commensals.

At the same time I was successfully experimentally treating patients who had suffered with life threatening ulcer disease for years. Some of my patients had postponed surgery which became unnecessary after a simple 2 week course of antibiotics and bismuth. I had developed my hypothesis that these bacteria were the cause of peptic ulcers and a significant risk for stomach cancer. If I was right, then treatment for ulcer disease would be revolutionized. It would be simple, cheap and it would be a cure. It seemed to me that for the sake of patients this research had to be fast tracked. The sense of urgency and frustration with the medical community was partly due to my disposition and age. However, the primary reason was a practical one. I was driven to get this theory proven quickly to provide curative treatment for the millions of people suffering with ulcers around the world.

Becoming increasingly frustrated with the negative response to my work I realized I had to have an animal model and decided to use myself. Much has been written about the episode and I certainly had no idea it would become as important as it has. I didn’t actually expect to become as ill as I did. I didn’t discuss it with the ethics committee at the hospital. More significantly, I didn’t discuss it in detail with Adrienne. She was already convinced about the risk of these bacteria and I knew I would never get her approval. This was one of those occasions when it would be easier to get forgiveness than permission. I was taken by surprise by the severity of the infection. When I came home with my biopsy results showing colonization and classic histological damage to my stomach, Adrienne suggested it was time to treat myself. I had a successful infection, I had proved my point.

At the end of 1984 I was funded by the Australian Medical Research Council to conduct a prospective double blind trial to see if antibiotics could cure duodenal ulcers. It was conditional on getting a large number of patients into the study so I decided to move back to Royal Perth Hospital where the patient load is far higher. It meant I would be leaving my Fremantle colleagues and it was with some reluctance that I moved. When I returned to Australia in 1996, I was asked to be Patron of the Fremantle Hospital Research Foundation and I take great pride in having that position. At Royal Perth I was again working with Robin, John Armstrong, Len Matz, John Pearman, Stewart Goodwin, Doug Annear and Helen Royce.

Even though I was not officially collaborating with Robin when I was working at Fremantle Hospital in 1983-84, we still met to discuss the papers we were writing for the Lancet and would meet for dinner with our wives. We had one of these dinners only a few weeks after my self experimentation experiment. I was enthusiastic about the results and the severity of my illness. It was also the first confirmation of infection with documented results. I was eager to share the news with Rob and he was equally excited about it. Early the next morning he had a call from a journalist in the USA at 5 am who had his timing totally off. No one is ever able to figure out what time it is in Perth. When asked the usual question about “How do you know it’s a pathogen and not a harmless commensal?“ Rob blabbed the results of my still unreleased work with “I know because Barry Marshall has just infected himself and damn near died“; a slight exaggeration, but it made for good copy. What he didn’t know was that the journalist he was speaking to was from the “Star“ newspaper, a tabloid that often features with stories about alien babies being adopted by Nancy Reagan. This was right up their alley. The next day the story appeared, “Guinea-pig doctor discovers new cure for ulcers … and the cause.“

This became one of the serendipitous, life changing events in my life and I have Rob’s temper to thank for it. Firstly, I was contacted by a continuous line of patients in the USA who read the story and were desperate for treatment. I was able to help. I was treating patients by proxy in the USA as early as 1984.

Ten years later this became important in a dispute with another doctor who claimed to be the first. I still had the records from some of these patients and was able to get in touch with them to prove my claim to be first.

The second result was that it was read by Mike Manhart, a microbiologist working for Proctor and Gamble in the USA. He tracked down my published letters and realized the economic potential for P & G who made a bismuth drug and set up a business relationship. P & G later patented much of my work and also helped me with patents on my diagnostics. There was little money in any of this for the first 10 years but after 1995 it became a significant income for us. P & G funded a fellowship for me in the USA to replicate and push the research there. We departed Australia, believing that it shouldn’t take more than 2-3 years to convince the world that antibiotics would cure most gastric diseases.

It also brought Bruce and Claudette McCarty into my life. Bruce was head of Health and Personal Care products at P & G and became an important mentor. He arranged support funding to set up a lab at University of Virginia. Bruce became a good friend and a keen advocate for H. Pylori research in the USA. He taught me a lot about how business works best in a trusting and responsible way to benefit everyone. It also seemed to me that he and Claudette spent lots of time in their life just having fun with family and friends. Tragically, Bruce died in 2004. It was a great sadness for me and Adrienne that he and Claudette were not there in Sweden to see me receive the Prize. He always believed in me and his faith in the work and great enthusiasm never failed.

The ten years spent at University of Virginia, were a chance to extend my research, particularly in the area of treatment and diagnostics. I became an advocate for treatment though many called me a zealot. They were often hard years for the family particularly the first few years when we were on a financial shoestring. They were rewarding as well. I had continuous stream of letters from patients who had been treated and freed from a lifetime of pain and disruption. I worked with a great team at UVA. Richard McCallum was head of Gastroenterology and Dick Guerrant in Infectious Diseases. McCallum gave me free rein and sponsored my academic rise in the USA. I also did great collaborative work with Dick over the years. David Peura, a long-time H. Pylori enthusiast from the US Army, moved to UVA in 1992. My team included nurse Susie Hoffman, nuclear technician Michael Plankey, post-doc Matthew Coombs, data manager Linda Mosen, programmer Sherry Boyd, assistant Nancy Noblette and many others. We were regarded as being outside the mainstream but were a great enthusiastic group and became life­long friends.

I also met Bill and Sandy Fry in 1987. Bill owned a company Tri-Med along with Phil Patterson and Kevin Dye. Bill Fry bankrolled a USA study for my CLO-test diagnostic and launched it in the USA. Later he was to also pick up the C14-Urea Breath Test and shepherded it through the FDA at a cost of several million dollars. I count Bill amongst my closest friends, a brilliant salesman and an example of a team leader. No matter how black things looked, Bill could always find a silver lining for us even though I am certain he was secretly concerned about our chances of success. Bill’s credo which he lives by is that “Good things happen to good people“. We have done a lot of good stuff together and had many great times.

Patients often wanted to make a donation to the work so I set up a foundation to use the money for patient and doctor education about the research. On one occasion there had been a story about the cure in the Sunday papers across the USA. In the following weeks we received 30,000 letters all with donations of a dollar or two to pay for postage and photocopying of information. We had to hire in students to handle it all.

Over the years the journalists who covered the story helped significantly in educating the public to ask for and later demand the new treatments from unwilling doctors. Suzanne Chazin in the Readers Digest, Terry Monmany in the New Yorker, Mark Ragg in the Bulletin and Larry Altman in the New York Times all wrote detailed reviews of the work that became important sources of information. The BBC show Ulcer Wars produced by Michael Mosley is still shown around the world.

The tide of acceptance began to turn in the early 1990s and by 1992 I could go to meetings and receive as much praise as criticism. 1994 was a watershed year for us. In February 1994 the NIH held a consensus meeting in Washington DC which ended after 2 days with the statement to the effect that the key to treatment of duodenal and gastric ulcer was detection and eradication of Helicobacter pylori.

I had been waiting for ten years for this day and I felt a combination of relief and satisfaction that I had achieved what I set out to do. Years before, I had developed the hypothesis, tested it, proved it and now it had reached official acceptance.

The next year proved to be harder. I began to receive awards and recognition. At the hospital, I was still carrying a full load of patient care and research. However, I was increasingly dissatisfied. Much of my time was being spent attending meetings and travelling. I think the pressure of the previous 10 years was beginning to show. Because I had been so involved in the exponential rise of Helicobacter, I had been unable to update my training in new areas of molecular biology which by then were coming to represent a large proportion of the Helicobacter publications.

In typical fashion Adrienne took over the decision-making and at the end of 1994, I took a year of leave from the university. We cashed in my superannuation and decided to live on that for a year to figure out what would be next in our lives. In that year I still travelled and lectured but my primary work was with Tri-Med, getting the breath test through the FDA regulatory process. I am proud of my diagnostics tests, the CLOtest and PYtest. They are often my forgotten children, eclipsed by my work on treatment. Although less glamorous than high impact papers, reliable cheap and available diagnostics are just as important in medicine as treatments. They don’t always get the same recognition. After 1994 my business interests became more important. The diagnostics were starting to earn an income. In Australia, close friend Rod Blechynden took on the role of managing it for me. Rod and Adrienne take care of the business aspects of my work. Their work frees me to focus on my research.

Once I had completed that project, Adrienne decided it was time for us all to go home. I was still unsure but it has turned out to be the best decision for me and the family. We moved back to Perth in 1996. I was awarded the McFarlane Burnet Fellowship which funded my lab at the University of WA for a 5 year period. In 1998, Tri-Med USA bought the manufacturing rights to CLOtest. I was keen to keep the manufacturing in Western Australia. It has been a long term ambition of mine to develop industry here in Perth. I set up a new manufacturing facility here but, sadly, it didn’t last. Tri-Med in the US was later sold and the new owners moved all the manufacturing back to the USA. Tri-Med in Perth continues in a small way doing R&D and selling medical products.

Before finishing I want to acknowledge all those scientists who failed to recognize HP. Without them I would have had a very different career. Some of their stories are described in my book “Helicobacter Pioneers“. I also want to thank Irvin Modlin for the foreword he wrote for it. He is a great guy and was able to say things about the joy of scientific research that I never could.

One of the truly great things about winning the Nobel Prize in 2005 was that I was living and working back home. I got to share it and celebrate with those who had been involved in the initial work at Royal Perth and Fremantle Hospital.

I continue to live in Perth Western Australia. I have an appointment at The University of Western Australia and still see patients at the gastroenterology department at Sir Charles Gairdner Hospital. My other interests continue. I take an active role in Tri-Med and in 2005 began a new project with vaccine company Ondek.

There were many occasions when luck played a role in my life; meeting with Robin, the first culture of the bacteria and chance meetings with many people who helped me and collaborated with me. I look back and am grateful to the many friends and family who helped me along the way, most importantly, my wife Adrienne, and my children, their partners and my grandchildren.


Fish and Insects Guide Design for Future Contact Lenses


Imagine a contact lens that autofocuses within milliseconds. That could be life-changing for people with presbyopia, a stiffening of the eye’s lens that makes it difficult to focus on close objects.


Presbyopia affects more than 1 billion people worldwide, half of whom do not have adequate correction. While glasses, conventional contact lenses and surgery provide some improvement, these options all involve the loss of contrast and sensitivity, as well as difficulty with night vision. Making the most of the low light in the muddy rivers where it swims, the elephant nose fish survives by being able to spot predators amongst the muck with a uniquely shaped retina, the part of the eye that captures light. In a new study, researchers looked to the fish’s retinal structure to inform the design of a contact lens that can adjust its focus. The project included designing the lens, algorithm-driven sensors, and miniature electronic circuits that adjust the shape of the lens, plus creating a power source — all embedded within a soft, flexible material that fits over the eye.


The study, published in Proceedings of the National Academy of Sciences (14 March 2016), the authors focused on a design for the image sensors that were extremely small and capable of acquiring images under low-light conditions, so they need to be exquisitely sensitive to light. The team took their inspiration from the elephant nose fish’s retina, which has a series of deep cup-like structures with reflective sidewalls. That design helps gather light and intensify the particular wavelengths needed for the fish to see. Borrowing from nature, the authors created a device that contains thousands of very small light collectors. These light collectors are finger-like glass protrusions, the inside of which are deep cups coated with reflective aluminum. The incoming light hits the fingers and then is focused by the reflective sidewalls. The authors tested this device’s ability to enhance images captured by a mechanical eye model designed in a lab.


In separate studies, the authors designed and tested a couple of different approaches for the contact lens material. For one approach, they formed a liquid lens from a droplet of silicone oil and water, which won’t mix. The droplet sits in a chamber atop a flexible platform, while a pair of electrodes produces an electric field that modifies the surface tension of each liquid differently, resulting in forces that squeeze the droplet into different focal lengths. The lens is able to focus on objects as small as 20 micrometers, roughly the width of the thinnest human hair. The authors developed another type of lens having a flexible array of artificial microlenses, inspired by the compound eyes of insects and other arthropods. Insect eyes comprise thousands of individual microlenses that each point in different directions to capture a specific part of a scene. Each microlense is made out of a forest of silicon nanowires and together with the microlenses, an even greater resolution than the liquid lens was provided. The array’s flexibility makes it suitable not only for contact lenses, but for other potential uses. Wrap it around a laparoscopic surgical scope and you’ve got a high-resolution, 360-degree view inside a patient’s body. Mount it on a lamppost and you can see the surrounding intersection from all sides.


In order to change focus, the contact lens will also need to be equipped with an extremely small, thin power source. The solution is a solar cell that simultaneously harvests electrons from sunlight, converting them into electricity, and that also stores energy within a network of nanostructures. It works much the way a conventional solar panel does, but the addition of storage capability within a single device is novel. The device still needs tweaking, but the team is optimistic that it will be powerful enough to drive the lens yet small enough to fit the space available.


According to the authors, a prototype for clinical testing may still be five to 10 years off but once it’s available, however, it may not cost much more than conventional contact lenses.


Experimental Dengue Vaccine Protects All Recipients


Dengue fever, prevalent throughout the tropics and subtropics, is caused by any of four related dengue viruses — called serotypes — that are spread by Aedes mosquitoes, the same mosquitoes that spread Zika virus. Most of the estimated 390 million people who are infected with dengue virus each year develop either no symptoms or a mild illness. However, some people develop serious or life-threatening illness and large outbreaks lead millions to seek care, severely straining health care infrastructure in endemic countries.  The high prevalence of natural dengue infections in endemic areas means that many people have experienced infection at some point in the past and therefore may have immunity to the infecting serotype. A high degree of partial immunity in a population can make it difficult to assess the efficacy of any candidate dengue vaccine. A model of dengue infection in humans is one way to overcome the absence of animal models and the challenge of high background immunity in endemic areas. It is important to note that human challenge studies are conducted according to strict criteria designed to provide meticulous attention to volunteer safety and challenge studies would never be used for certain deadly pathogens, such as Ebola.


A clinical trial in which volunteers were infected with dengue virus six months after receiving either an experimental dengue vaccine developed by scientists from the National Institutes of Health (NIH) or a placebo injection yielded starkly contrasting results. All 21 volunteers who received the vaccine, TV003, were protected from infection, while all 20 placebo recipients developed infection. The study, published in Science Translational Medicine (March 2016), underscores the importance of human challenge studies, in which volunteers are exposed to disease-causing pathogens under carefully controlled conditions.


The experimental vaccine was developed primarily at NIAID’s Laboratory of Infectious Diseases. Scientists from the U.S. Food and Drug Administration Center for Biologics Evaluation and Research also contributed to the vaccine’s development. The candidate vaccine is made from a mixture of four live, weakened (attenuated) viruses targeted to each of the four serotypes. A total of 48 healthy adult volunteers enrolled at two trial sites, the University of Vermont College of Medicine, Burlington, and Johns Hopkins Bloomberg School of Public Health, Baltimore, and were randomly assigned to receive either vaccine or placebo injection.


Six months later, 41 people returned for the challenge with dengue virus. The authors also developed the challenge virus used in the trial, which is a genetically modified version of a dengue-2 serotype virus isolated in the Kingdom of Tonga in 1974. The original virus was notable for causing only mild illness. In previous human challenge trials with this modified virus, the authors established the virus dose that would cause all recipients to develop viremia — the presence of virus in the blood — and most to develop a mild rash. This modified dengue virus is very attractive for use as a challenge virus because we can use it to reliably induce dengue infection in a very high percentage of inoculated volunteers without causing serious illness. In addition, by inducing only rash (without fever) in the majority of recipients, the challenge virus mimics natural dengue virus infection, which often features such a rash.


Because there are no specific therapies for dengue fever, it is desirable to have a challenge virus that causes infection, but does not result in significant symptoms of disease. The reliably high percentage of those who develop viremia following exposure to this challenge virus is another advantage — when most or all volunteers develop viremia or other signs of infection, clinical trials can enroll relatively small numbers of people but still achieve answers to such questions as whether a candidate vaccine protects against infection.


In this study, all 20 placebo recipients developed viremia, 16 (80%) developed mild rash and 4 (20%) had a temporary drop in white blood cell count following challenge with the virus. None of the 21 TV003 vaccine recipients developed viremia or any other sign of infection after challenge.


The authors are currently developing a human challenge model using a modified dengue serotype-3 virus. This challenge virus could be used in future clinical trials to test the efficacy of candidate dengue vaccines or therapies.


FDA and NIH Release a Draft Clinical Trial Protocol Template for Public Comment


The following was extracted from FDA Voice (16 March 2016), authored by Peter Marks, M.D., Ph.D., Director of FDA’s Center for Biologics Evaluation and Research.


Enhancing important efforts around clinical trials continues to be a key scientific priority. One way FDA can encourage clinical trials is to look for ways to help clinical investigators make clinical trials more efficient. On March 16, FDA announced the release of a draft clinical trial protocol template developed by the FDA and NIH that could help the clinical trial enterprise.


The clinical trial protocol is a critical component of any medical product development program. It’s defined in the International Conference on Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E6 Good Clinical Practice: Consolidated Guidance, as describing the objective(s), design, methodology, statistical considerations, and organization of a trial and usually also gives the background and rationale for the trial. Similarly, for medical devices, some direction has been provided in the International Organization for Standardization (ISO) Clinical Investigation of Medical Devices for Human Subjects – Good Clinical Practice (ISO 14155:2011). Although guidance provides information on the important content that should be included in a protocol to help ensure human subject protection and data quality, it does not describe a standardized format for presenting this information. Time spent identifying the specific elements that should be included in a protocol and how best to organize them can delay the start of a clinical trial, and lead to delays in getting important new treatments to patients. What’s more, because up to 85% of investigators have only participated in one clinical trial in their careers, many investigators lack significant experience in protocol development. It’s likely that investigators could benefit from additional help in this area.


NIH, which supports and conducts biomedical research, and FDA, which evaluates the safety and effectiveness of medical products and depends on high quality research to inform its decisions, realized this represents an opportunity to help improve the design of clinical trials. Now, the NIH-FDA Joint Leadership Council (JLC) has launched a project to develop a template that could be used by investigators developing a clinical trial protocol. Representatives from the NIH institutes and FDA’s medical product centers collaborated to develop a template containing instructional and sample text for investigators writing phase 2 or phase 3 clinical trial protocols that require investigational new drug (IND) or investigational device exemption (IDE) applications. FDA hopes that the availability of the template and instructional information will enable investigators to prepare protocols that are consistent and well organized, contain all the information necessary for the clinical trials to be properly reviewed, and follow the ICH E6 Good Clinical Practice guidance. Better organized, high-quality protocols will also expedite the review process at both agencies.


FDA aware of other efforts in this area, including one undertaken by TransCelerate Biopharma Inc. (TransCelerate), which has issued a common protocol template intended to be the basis for a forthcoming electronic protocol. Although our initial target audiences differ, FDA plans to collaborate with groups like TransCelerate to help ensure consistency for the medical product development community. FDA sees the template as a way to facilitate creativity and innovation, not inhibit it. Just as ICH E6 allows considerable flexibility in the actual operations of trials using quality by design principles, the template includes the appropriate elements to be considered, but does not dictate exactly how the trial should be done – that is the work of the investigators.


NIH and FDA are seeking public comment on the draft template. Comments are accepted through April 17, 2016. FDA welcomes feedback from investigators, investigator-sponsors, institutional review board members, and other stakeholders who are involved in protocol development and review. FDA is particularly interested in hearing your views on the utility of the template and whether the instructional and sample text is useful and clear.


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