Cancer, while always dangerous, truly becomes life-threatening when cancer cells begin to spread to different areas throughout the body. Now, researchers at the University of Missouri have discovered that a molecule used as a communication system by bacteria can be manipulated to prevent cancer cells from spreading. Senthil Kumar, an assistant research professor and assistant director of the Comparative Oncology and Epigenetics Laboratory at the MU College of Veterinary Medicine, says this communication system can be used to “tell” cancer cells how to act, or even to die on command.
“During an infection, bacteria release molecules which allow them to ‘talk’ to each other,” said Kumar, the lead author of the study. “Depending on the type of molecule released, the signal will tell other bacteria to multiply, escape the immune system or even stop spreading. We found that if we introduce the ‘stop spreading’ bacteria molecule to cancer cells, those cells will not only stop spreading; they will begin to die as well.”
In the study published in PLOS ONE, Kumar, and co-author Jeffrey Bryan, an associate professor in the MU College of Veterinary Medicine, treated human pancreatic cancer cells grown in culture with bacterial communication molecules, known as ODDHSL. After the treatment, the pancreatic cancer cells stopped multiplying, failed to migrate and began to die.
“We used pancreatic cancer cells, because those are the most robust, aggressive and hard-to-kill cancer cells that can occur in the human body,” Kumar said. “To show that this molecule can not only stop the cancer cells from spreading, but actually cause them to die, is very exciting. Because this treatment shows promise in such an aggressive cancer like pancreatic cancer, we believe it could be used on other types of cancer cells and our lab is in the process of testing this treatment in other types of cancer.”
Kumar says the next step in his research is to find a more efficient way to introduce the molecules to the cancer cells before animal and human testing can take place.
“Our biggest challenge right now is to find a way to introduce these molecules in an effective way,” Kumar said. “At this time, we only are able to treat cancer cells with this molecule in a laboratory setting. We are now working on a better method which will allow us to treat animals with cancer to see if this therapy is truly effective. The early-stage results of this research are promising. If additional studies, including animal studies, are successful then the next step would be translating this application into clinics.”
- Ashwath S. Kumar, Jeffrey N. Bryan, Senthil R. Kumar. Bacterial Quorum Sensing Molecule N-3-Oxo-Dodecanoyl-L-Homoserine Lactone Causes Direct Cytotoxicity and Reduced Cell Motility in Human Pancreatic Carcinoma Cells.PLoS ONE, 2014; 9 (9): e106480 DOI: 10.1371/journal.pone.0106480
University of Missouri-Columbia. “Bacterial ‘communication system’ could be used to stop, kill cancer cells, study finds.” ScienceDaily. ScienceDaily, 24 September 2014. <www.sciencedaily.com/releases/2014/09/140924145016.htm>.
Firelight talk of the Kalahari Bushmen: Did tales told over fires aid our social and cultural evolution?
After human ancestors controlled fire 400,000 to 1 million years ago, flames not only let them cook food and fend off predators, but also extended their day.
A University of Utah study of Africa’s Kalahari Bushmen suggests that stories told over firelight helped human culture and thought evolve by reinforcing social traditions, promoting harmony and equality, and sparking the imagination to envision a broad sense of community, both with distant people and the spirit world.
Researchers previously studied how cooking affected diets and anatomy, but “little is known about how important the extended day was for igniting the embers of culture and society,” anthropology professor Polly Wiessner writes in a study published online today in the journal Proceedings of the National Academy of Sciences.
“There is something about fire in the middle of the darkness that bonds, mellows and also excites people. It’s intimate,” says Wiessner, who has studied the Bushmen for 40 years. “Nighttime around a fire is universally time for bonding, for telling social information, for entertaining, for a lot of shared emotions.”
Wiessner’s study, which she calls “exploratory,” analyzed scores of daytime and firelight conversations among !Kung Bushmen — also known as Ju/’hoansi Bushmen — some 4,000 of which now live in the Kalahari Desert of northeast Namibia and northwest Botswana. (The exclamation, slash and apostrophe symbols represent click sounds in their language.) They are among several groups of Kalahari Bushmen.
Why study the campfire tales of Bushmen?
“We can’t tell about the past from the Bushmen,” Wiessner says. “But these people live from hunting and gathering. For 99 percent of our evolution, this is how our ancestors lived. What transpires during the firelit night hours by hunter-gatherers? It helps answer the question of what firelit space contributes to human life.”
She writes: “Stories are told in virtually all hunter-gatherer societies; together with gifts, they were the original social media.”
From the Workaday World to Nights of Bonding and Wonder
In her study, “Embers of Society: Firelight Talk among the Ju/’hoansi Bushmen,” Wiessner says archaeological evidence indicates human ancestors had sporadic control of fire 1 million or more years ago, and regularly used it after 400,000 years ago.
“Fire altered our circadian rhythms, the light allowed us to stay awake, and the question is what happened in the fire-lit space? What did it do for human development?” asks Wiessner, who earlier this year was among three University of Utah researchers elected to the National Academy of Sciences.
Wiessner says !Kung Bushmen hold firelight gatherings most nights in groups of up to 15 people. A camp has hearths for each family, but at night people often converge at a single hearth. She analyzed only conversations involving five or more people.
Firelight stories deal with topics such as past hunts, fights over meat, marriage, premarital customs, murder, bush fires, birth, getting lost, interactions with other groups, truck breakdowns, being chased by animals, disputes and extramarital affairs. And there also are traditional myths.
For her study, Wiessner analyzed two sets of data:
– Notes she took in 1974 (initially for another purpose) of 174 daytime and nighttime conversations at two !Kung camps in northwest Botswana. Each conversation lasted more than 20 to 30 minutes and involved five to 15 people.
– Digital recordings, transcribed by educated Bushmen, of 68 firelight stories Wiessner originally heard in the 1970s but came back to have retold and recorded during three visits in 2011-2013 to !Kung villages in Botswana and Namibia.
Wiessner found daytime conversations differed much from firelight discussions. Of daytime conversations, 34 percent were complaints, criticism and gossip to regulate social relationships; 31 percent were economic matters, such as hunting for dinner; 16 percent were jokes; only 6 percent were stories and the rest were other topics
But at night, 81 percent of the conversations involved stories, and only 7 percent were complaints, criticism and gossip and 4 percent were economic.
Bonding with People Near and Far — and with the Supernatural
Wiessner found how conversations reinforced major !Kung social institutions and values: arranged marriages, the kinship system, a social structure based on equality, the sharing of food during times of hardship, land rights, trance healing and xaro, a system of exchange that involved pledges of mutual assistance, including housing and food, in troubled times.
“What I found was a big difference between day and night conversation, the kinds of information transmitted and the use of imaginary thought,” Wiessner says.
“Day conversation has a lot to do with economic activities — working, getting food, what resources are where,” she says. “It has a lot to do with social issues and controls: criticism, complaints and gripes.”
“At night, people really let go, mellow out and seek entertainment. If there have been conflicts in the day, they overcome those and bond. Night conversation has more to do with stories, talking about the characteristics of people who are not present and who are in your broader networks, and thoughts about the spirit world and how it influences the human world. You have singing and dancing, too, which bonds groups.”
Healers dance and go into trances, “travel to god’s village and communicate with the spirits of deceased loved ones who are trying to take sick people away,” Wiessner says.
She says nonhuman primates don’t maintain mutually supportive ties outside their group: “We are really unique. We create far-flung ties outside our groups.”
Such extended communities allowed humans “to colonize our planet because they had networks of mutual support, which you see expressed today in our capacity for social networking” she adds. “Humans form communities that are not together in space, but are in our heads — virtual communities. They are communities in our heads. For the Bushmen, they may be up to 120 miles away.”
Wiessner suggests that firelight stories, conversations, ceremonies and celebrations sparked human imagination and “cognitive capacities to form these imagined communities, whether it’s our social networks, all of our relatives on Earth or communities that link us to the spirit world.” She says they also bolstered the human ability to “read” what others are thinking — not just their thoughts or intentions, but their views toward other people.
What Has Electricity Done to Us?
Examining how firelight extended the day prompted Wiessner to wonder about modern society, asking, “What happens when economically unproductive firelit time is turned to productive time by artificial lighting?”
Parents read stories or show videos to their children, but now, “work spills into the night. We now sit on laptops in our homes. When you are able to work at night, you suddenly have a conflict: ‘I have only 15 minutes to tell my kids a bedtime story. I don’t have time to sit around and talk.’ Artificial light turned potential social time into potential work time. What happens to social relations?”
Her research raises that question, but doesn’t answer it.
- Polly W. Wiessner. Embers of society: Firelight talk among the Ju/’hoansi Bushmen. PNAS, September 2014 DOI: 10.1073/pnas.1404212111
University of Utah. “Firelight talk of the Kalahari Bushmen: Did tales told over fires aid our social and cultural evolution?.” ScienceDaily. ScienceDaily, 22 September 2014. <www.sciencedaily.com/releases/2014/09/140922152809.htm>.
sleep-promoting circuit located deep in the primitive brainstem has revealed how we fall into deep sleep. Discovered by researchers at Harvard School of Medicine and the University at Buffalo School of Medicine and Biomedical Sciences, this is only the second “sleep node” identified in the mammalian brain whose activity appears to be both necessary and sufficient to produce deep sleep.
Published online in August in Nature Neuroscience, the study demonstrates that fully half of all of the brain’s sleep-promoting activity originates from the parafacial zone (PZ) in the brainstem. The brainstem is a primordial part of the brain that regulates basic functions necessary for survival, such as breathing, blood pressure, heart rate and body temperature.
“The close association of a sleep center with other regions that are critical for life highlights the evolutionary importance of sleep in the brain,” says Caroline E. Bass, assistant professor of Pharmacology and Toxicology in the UB School of Medicine and Biomedical Sciences and a co-author on the paper.
The researchers found that a specific type of neuron in the PZ that makes the neurotransmitter gamma-aminobutyric acid (GABA) is responsible for deep sleep. They used a set of innovative tools to precisely control these neurons remotely, in essence giving them the ability to turn the neurons on and off at will.
“These new molecular approaches allow unprecedented control over brain function at the cellular level,” says Christelle Ancelet, postdoctoral fellow at Harvard School of Medicine. “Before these tools were developed, we often used ‘electrical stimulation’ to activate a region, but the problem is that doing so stimulates everything the electrode touches and even surrounding areas it didn’t. It was a sledgehammer approach, when what we needed was a scalpel.”
“To get the precision required for these experiments, we introduced a virus into the PZ that expressed a ‘designer’ receptor on GABA neurons only but didn’t otherwise alter brain function,” explains Patrick Fuller, assistant professor at Harvard and senior author on the paper. “When we turned on the GABA neurons in the PZ, the animals quickly fell into a deep sleep without the use of sedatives or sleep aids.”
How these neurons interact in the brain with other sleep and wake-promoting brain regions still need to be studied, the researchers say, but eventually these findings may translate into new medications for treating sleep disorders, including insomnia, and the development of better and safer anesthetics.
“We are at a truly transformative point in neuroscience,” says Bass, “where the use of designer genes gives us unprecedented ability to control the brain. We can now answer fundamental questions of brain function, which have traditionally been beyond our reach, including the ‘why’ of sleep, one of the more enduring mysteries in the neurosciences.”
The work was funded by the National Institutes of Health.
- Christelle Anaclet, Loris Ferrari, Elda Arrigoni, Caroline E Bass, Clifford B Saper, Jun Lu, Patrick M Fuller. The GABAergic parafacial zone is a medullary slow wave sleep–promoting center. Nature Neuroscience, 2014; 17 (9): 1217 DOI:10.1038/nn.3789
The eClinical Forum, started in 2000, was the idea of a group of people who were keen to create something unique – a group run by its members for its members. Independence, openness and public dissemination have been hallmarks of its success. Pharmaceutical, healthcare, regulatory, academic and support industry members participate in open discussions, network and freely exchange information. This process provides the practical information, approach and learning experiences required to maximize the success of eClinical initiatives. Many eClinical Forum deliverables are made freely available within the public domain.
As a member of the eClinical Forum, Target Health Inc. is pleased to announce that it will be participating at the eClinical Forum Meeting being held in Cambridge, MA (22-24 October 2014). The meeting is being hosted by Biogen Idec
Dean Gittleman, Sr. Director at Target Health will be chairing the session on EDC Hosting- Review of issues and proposed solutions- Outcome of engagement with industry and regulatory stakeholders in US and Europe
Jules Mitchel, President of Target Health will make a presentation on Challenges and recommendations when implementing new eSystems – Barriers to entry (for new technology such as eTMF, eSource and ePortals) and how to avoid resistance and inefficiencies.
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. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchelor 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
Is an Unusual Virus Spreading in the Midwest?
The CDC is closely monitoring the outbreak of a rare respiratory 1) ___ afflicting people in Illinois and Missouri. No one is sure just how bad is it, and what can be done to stop the spread. This severe respiratory illness is knocking the wind out of Midwesterners, sending hundreds of children coughing and wheezing to the 2) ___. The primary suspect in the outbreak is the seldom seen Enterovirus D68 (EV-D68), kin to the common cold’s viral culprit. The U.S. Centers for Disease Control and Prevention has identified EV-D68 in 19 of 22 intensive care patients from Missouri and 11 of 14 in Illinois. EV-D68 targets the upper 3) ___ tract and causes breathing difficulties. First discovered in the 1960s, EV-D68 has rarely been reported in the U.S. population. From 2009 to 2013 the CDC recorded only 79 cases of the virus but this year there have already been more confirmed cases than in any previous year.
At the University of Chicago’s Comer Children’s Hospital where the 11 Illinois cases were identified, there has been an unusually high number of children with 4) ___ symptoms and breathing problems this summer, according to Rachel Wolfson, an intensive care unit physician who treats patients there. Some children in her care only needed nebulizer treatment yet others were substantially more ill. One patient’s lungs were in such bad shape that the doctors needed to connect the child to a blood oxygenator. Despite the debilitating effects of EV-D68, so far no one has died during its current immergence.
At the CDC, Mark Pallansch is one of many 5) ___ investigating the viral suspect in order to confirm if it is driving the current rise in respiratory illness. The following explains what researchers and doctors are finding and whether EV-D68 may be on the rise. Enteroviruses are a family of more than 100 6) ___ that cause a diversity of illnesses. The CDC reports more than 10 million enterovirus-related illnesses every year. Generally, their afflictions are common and mild. People with Enterovirus D70, for example, develop conjunctivitis. But some types – including poliovirus, which causes paralysis – are dangerous. Others can cause SARS, and viral meningitis. Researches are worried about EV-D68 because it can severely disturb the respiratory system. EV-D68 spreads the same way that many other enteroviruses do, through contact with infected people, such as being in the line of fire of a cough or 7) ___. Adults are much less likely than children to contract EV-D68 because of their stronger immune systems. Children can also catch the virus by touching a surface like a doorknob that may have the virus on it and then rubbing their eyes.
Like other similar enteroviruses, EV-D68 spreads through contact with infected feces as well. This may be most likely to occur in small children, but infections that spread this way occur most often in underdeveloped countries where sanitation is poor. Washing your 8) ___ is key to preventing the spread. Every day different states contact the CDC reporting new cases of respiratory illness that may potentially be EV-D68. So far about a dozen states have reported cases. It’s too early to know if we’re watching a spread or if it has already happened and we’re just figuring out that it’s happened. If the 9) ___ can identify EV-D86 as the definite cause behind the severe respiratory illness seen in the Midwest, then its next step is to figure out whether EV-D68 infections have been increasing in recent years or whether EV-D68 cases have stayed the same but now scientists have better tools for detecting them. School-aged children are most likely to contract the virus, although not everyone with EV-D68 becomes severely ill. Individuals with a history of asthma are more likely to develop serious respiratory complications, but many previously healthy children are also catching the virus.
The number of respiratory cases is unusually high for August and September. The rate is much closer to what the hospital expects to see mid-November when flu season is in full force. About one third of the patients tested positive for EV-D68, although more cases with similar symptoms are arriving each day. Keep children safe by 10) ___ your hands and having them wash theirs. None of the staff or other patients at Comer Children’s Hospital has contracted the virus, which we attribute to meticulous washing.
ANSWERS: 1) infection; 2) hospital; 3) respiratory; 4) cold; 5) virologists; 6) viruses; 7) sneeze; 8) hands; 9) CDC; 10) washing
Felix d’Herelle (1873 – 1949)
Felix d’Herelle (April 25, 1873 – February 22, 1949) was a French-Canadian microbiologist and the co-discoverer of bacteriophages (viruses that infect bacteria). d’Herelle experimented with the possibility of phage therapy and has also been credited for his contributions to the larger concept of applied microbiology. D’Herelle was born in Montreal, Quebec, the son of French emigrants. Following his father’s death, Felix, his mother and his younger brother Daniel, moved back to Paris. From 7 to 17 years of age, d’Herelle attended school in Paris, including the Lycee Condorcet and Lycee Louis-le-Grand high schools. d’Herelle only obtained a high school education and was self-taught in the sciences. When 16 years old, he started to travel through Western Europe by bike. When 17, after finishing school, he traveled through South America. Afterwards, he continued his travels through Europe, including Turkey, where he, at 20 years of age, met his wife, Marie Caire. At age 24, now father of a daughter, d’Herelle and his family moved back to Canada. He built a home laboratory and studied microbiology from books and his own experiments. Through the influence of a friend of his late father, he earned a commission from the Canadian government to study the fermentation and distillation of maple syrup to schnapps. His father’s friend shrewdly pointed out that Pasteur made a good beginning by studying fermentations, so it might be interesting to you, too. He also worked as a medic for a geological expedition, even though he had no medical degree or real experience. Together with his brother, he invested almost all his money in a chocolate factory, which soon went bankrupt. During this period, d’Herelle published his first scientific paper, De la formation du carbone par les vegetaux in the May 1901 issue of Le Naturaliste Canadien. The paper is noteworthy for two reasons: it shows an exceptional level of scientific development for a self-taught scientist and reveals a broad level of interest, namely the global balance of carbon in nature. However, the claims of the paper were in error, as d’Herelle contended that the results of his experiments indicated that carbon was a compound, not an element.
With his money almost gone and his second daughter born, he took a contract with the government of Guatemala as a bacteriologist at the General Hospital in Guatemala City. Some of his work included organizing defenses against the dread diseases of the time: malaria and yellow fever. He also studied a local fungal infection of coffee plants, and discovered that acidifying the soil could serve as an effective treatment. As a side job, he was asked to find a way to make whiskey from bananas. Life in the rough and dangerous environment of the country was hard on his family, but d’Herelle, always adventurer at heart, rather enjoyed working close to real life, compared to the sterile environments of a civilized clinic. He later stated that his scientific path began on this occasion. In 1907, he took an offer from the Mexican government to continue his studies on fermentation. He and his family moved to a sisal plantation near Merida, Yucatan. Disease struck at him and his family, but in 1909, he had successfully established a method to produce sisal schnapps. Machines for mass production of sisal schnapps were ordered in Paris, where he oversaw the machines’ construction. Meanwhile, in his spare time, he worked for free in a laboratory at the Pasteur Institute. He was soon offered the job of running the new Mexican plant, but declined, considering it too boring. He did, however, take the time to attempt stopping a locust plague at the plantation using their own diseases. He extracted bacteria pathogenic to locusts from their guts. This innovative approach to locust plagues anticipated modern biological pest control using Bacillus thuringiensis also known as Bt.
D’Herelle and his family finally moved to Paris in early 1911, where he worked again as an unpaid assistant in a lab at the Pasteur Institute. He got attention in the scientific community the same year, when the results of his successful attempt to counter the Mexican locust plague withCoccobacillus were published. At the end of the year, restless d’Herelle was again on the road, this time in Argentina, where he was offered a chance to test these results on a much larger scale. Thus, in 1912 and 1913, he fought the Argentinian locust plagues with coccobacillus experiments. Even though Argentina claimed his success was inconsistent, he himself declared it a full success, and was subsequently invited to other countries to demonstrate the method. During World War I, d’Herelle and assistants (his wife and daughters among them) produced over 12 million doses of medication for the allied military. At this point in history, medical treatments were primitive, compared to today’s standards. The smallpox vaccine, developed by Edward Jenner, was one of the few vaccines available. The primary antibiotic was the arsenic-based salvarsan against syphilis, with severe side effects. Common treatments were based mercury, strychnine, and cocaine. As a result, in 1900, the average life span was 45 years, and WWI did not change that to the better. In 1915, British bacteriologist Frederick W. Twort discovered a small agent that infects and kills bacteria, but did not pursue the issue further. Independently, the discovery of an invisible, antagonistic microbe of the dysentery bacillus by d’Herelle was announced on September 3, 1917. The isolation of phages by d’Herelle works like this:
1. Nutritional medium is infected with bacteria; the medium turns opaque.
2. The bacteria are infected with phages and die, producing new phages; the medium clears up.
3. The medium is filtered through porcelain filter, holding back bacteria and larger objects; only the smaller phages pass through.
In early 1919, d’Herelle isolated phages from chicken feces, successfully treating a plague of chicken typhus with them. After this successful experiment on chicken, he felt ready for the first trial on humans. The first patient was healed of dysentery using phage therapy in August 1919. Many more followed. At the time, none, not even d’Herelle, knew exactly what a phage was. D’Herelle claimed that it was a biological organism that reproduces, somehow feeding off bacteria. Others, the Nobelist Jules Bordet chief among them, theorized that phages were inanimate chemicals, enzymes specifically, that were already present in bacteria, and only trigger the release of similar proteins, killing the bacteria in the process. Due to this uncertainty, and d’Herelle using phages without much hesitation on humans, his work was under constant attack from many other scientists. It was not until the first phage was observed under an electron microscope by Helmut Ruska in 1939 that its true nature was established. In 1920, d’Herelle travelled to Indochina, pursuing studies of cholera and the plague, from where he returned at the end of the year. D’Herelle, officially still an unpaid assistant, found himself without a lab. d’Herelle later claimed this was a result of a quarrel with the assistant director of the Pasteur Institute, Albert Calmette.
The biologist Edouard Pozerski had mercy on d’Herelle and lent him a stool (literally) in his laboratory. In 1921, he managed to publish a monograph, The Bacteriophage: Its Role in Immunity about his works as an official Institute publication, by tricking Calmette. During the following year, doctors and scientists across western Europe took a heightened interest in phage therapy, successfully testing it against a variety of diseases. Since bacteria become resistant against a single phage, d’Herelle suggested using phage cocktails containing different phage strains. Phage therapy soon became a boom, and a great hope in medicine. In 1924, January 25, d’Herelle received the honorary doctorate of the University of Leiden, as well as the Leeuwenhoek medal, which is only awarded once every ten years. The latter was especially important to him, as his idol Louis Pasteur received the same medal in 1895). The next year, he was nominated eight times for the Nobel prize, though he was never awarded one. After holding a temporary position at the University of Leiden, d’Herelle got a position with the Conseil Sanitaire, Maritime et Quarantenaire d’Egypte in Alexandria. The Conseil was put in place to prevent plague and cholera spreading to Europe, with special emphasis on the sanitary concerns about muslim pilgrim groups returning from Mecca and Medina. D’Herelle used phages he collected from plague-infected rats during his 1920 visit to Indochina on human plague patients, with claimed success. The British Empire initiated a vast campaign against plague based on his results. In 1927, d’Herelle himself changed his focus to new targets: India and cholera. D’Herelle isolated phages from cholera victims in India. As usual, he did not choose a hospital run by European standards, but rather sought out a medical tent in a slum. According to his theory, one had to leave the sterile hospitals and study and defeat illness in its natural environment. His team then dropped phage solution in the wells of villages with cholera patients; the death toll went down from 60% to 8%. The whole India enterprise took less than seven months. D’Herelle refused a request the following year by the British government to work in India, as he had been offered a professorship at Yale University, which he accepted. Meanwhile, European and US pharmaceutical companies had taken up the production of their own phage medicine, and were promising impossible effects. To counteract this, d’Herelle agreed to co-found a French phage-producing company, piping the money back into phage research. All of the companies suffered from production problems, as results from commercial phage medicine were erratic. This was most likely due to the attempt to mass-produce something that was barely understood, leading to damaged phages in the product, or to insufficient amounts. Another possibility is that wrong diagnoses lead to the use of the wrong type of phages, which are specific in the choice of their hosts. Furthermore, many studies on the healing effects of phages were badly conducted. All this led to important parts of the scientific community turning against d’Herelle, who, known for his temper, had made enemies.
On the move again, around 1934, D’Herelle went to Tbilisi, Georgia, where he was welcomed to the Soviet Union as a hero, bringing the knowledge of salvation from diseases ravaging the eastern states all the way to Russia. He accepted Stalin’s invitation for two reasons: it was said he was enamored of communism, and he was happy to be working with his friend, Prof. George Eliava, founder of the Tbilisi Institute, in 1923. Eliava had become friendly with d’Herelle during a visit to the Pasteur Institute in Paris, where he had learned about phages in 1926. D’Herelle worked at the Tbilisi Institute off and on for about a year – and even dedicated one of his books, The Bacteriophage and the Phenomenon of Recovery, written and published in Tbilisi in 1935, to Comrade Stalin. He had planned to take up permanent residence in Tbililsi and had already started to build a cottage on the grounds of the Institute (it would later house the KGB’s Georgian headquarters). Tragedy fell, at this time, his friend Eliava fell in love with the woman with whom the head of the secret police, Lavrenty Beria, also happened to be in love, and Eliava’s fate was sealed. He was executed and denounced as an enemy of the people during one of Stalin’s purges. D’Herelle ran for his life and never returned to Tbilisi. His book was banned from distribution. Then, World War II began. The Georgian period in d’Herelle’s career has been investigated on site by the author and medical scientist David Shrayer-Petrov.
Phage therapy boomed, despite all problems, driven by the military on both sides in an effort to keep the troops safe, at least from infections. D’Herelle could not really enjoy this development; he was kept under house arrest by the German Wehrmacht in Vichy, France. He used the time to write his book The Value of Experiment, as well as his memoirs, the latter being 800 pages in length. After D-Day, the new antibiotic drug penicillin became public knowledge and found its way into the hospitals in the west. As it was more reliable and easier to use than phage therapy, it soon became the method of choice, despite side effects and problems with resistant bacteria. Phage therapy remained a common treatment in the states of the USSR, though, until its deconstruction.
Felix d’Herelle was stricken with pancreatic cancer and died a forgotten man in Paris in 1949. He was buried in Saint-Mards-en-Othe in the department of the Aube in France. In the 1960s Felix d’Herelle’s name appeared on a list published by the Nobel Foundation of scientists who had been worthy of receiving the Nobel Prize but did not, for one reason or another. It is believed that d’Herelle was nominated for the prize eight times. France did not completely forget Felix d’Herelle. There is an avenue that bears his name in the 16th arrondissement in Paris. D’Herelle became widely known for his imaginative approaches to important problems in theoretical, as well as applied, microbiology. At the same time, he was widely reviled for his self-advertisement, his exaggerated claims of success and his sharp financial practices. He also had a talent for making enemies among powerful senior scientists. D’Herelle’s main legacy lies in the use of phage in the molecular revolution in biology. Max Delbruck and the phage group used bacteriophages to make the discoveries that led to the origins of molecular biology. Much of the initial work on the nature of genetic expression and its regulation was performed with bacteriophages by Francois Jacob, Andre Lwoff and Jacques Monod. In fact, immediately before his studies of the structure of DNA, James Watson had earned his Ph.D. by working on a bacteriophage-related project in Salvador Luria’s laboratory. As one of the earliest applied microbiologists, d’Herelle’s microbe-centered worldview has been noted for its prescience, since microbes are playing increasingly important roles in bioremediation, microbial fuel cells, gene therapy, and other areas with relevance to human well-being. The novel Arrowsmith written by Sinclair Lewis with scientific help from Paul de Kruif was based to a certain extent on the life of d’Herelle. The novel The French Cottage (Russ. Frantsuzskii kottedzh) by David Shrayer-Petrov deals at length with d’Herelle’s experience in Soviet Georgia.
Jules Bordet (1870 – 1961)
Jules Jean Baptiste Vincent Bordet was a Belgian immunologist and microbiologist. The bacterial genus Bordetella is named after him. Bordet was born at Soignies, Belgium. He graduated in the year 1892 as Doctor of Medicine at the Universite Libre de Bruxelles (Brussels, Belgium) and began his work at the Pasteur Institute in Paris in 1894, in the laboratory of Elie Metchnikoff, who had just discovered phagocytosis of bacteria by white blood cells, expression of the cellular immunity. In 1898 Bordet described hemolysis evoked by exposure of blood serum to foreign blood cells. In 1900, he left Paris to found the Pasteur Institute in Brussels, and made his discovery that the bacteriolytic effect of acquired specific antibody is significantly enhanced in vivo by the presence of innate serum components which he termed alexine (but which are now known as complement). This mechanism became the basis for complement-fixation testing methods that enabled the development of serological tests for syphilis (specifically, the development of the Wassermann test by August von Wassermann). The same technique is used today in serologic testing for countless other diseases. With Octave Gengou he isolated Bordetella pertussis in pure culture in 1906 and posited it as the cause of whooping cough. He became Professor of Bacteriology at the Universite Libre de Bruxelles in 1907. In March 1916 he was elected a Fellow of the Royal Society and in 1930 delivered their Croonian Lecture. In this lecture Bordet also concluded that bacteriophages the invisible virus of Felix d’Herelle, a self-taught microbiologist, did not exist and that it was bacteria themselves which produce the lytic principle. He was to be proven incorrect later with Bacteriophage therapy then recognized as an alternative/complementary therapy in the fight against bacterial infections, starting with the treatment of patients in Paris by Felix d’Herelle. The Nobel Prize in Physiology or Medicine was awarded to him in 1919 for his discoveries relating to immunity. Bordet died in 1961 and was interred in the Ixelles Cemetery in Brussels.
Will Homo Sapiens Become Robo Sapiens in 50 Years
The landmark Diabetes Control and Complications study has long shown that maintaining as normal a blood glucose level as possible early on can stave off complications, including heart, kidney and eye diseases, decades later.
According to the NIH, just as a thermostat helps control a home’s temperature, the normal pancreas senses blood glucose levels and adjusts the hormones that control it. People with type 1 diabetes, whose pancreas produces little or no insulin, have been using the equivalent of a manual thermostat, needing constant checking and adjustment. A bionic pancreas — like the one used in the studies described below, would function more like an automated thermostat, automatically monitoring blood glucose and delivering insulin or glucagon when needed to keep glucose within the normal range. As well, these bionic pancreas devices could be monitored remotely by the patient’s medical provider or parent.
Currently, people with type 1 diabetes walk an endless tightrope. Because their pancreas doesn’t make the hormone insulin, their blood glucose levels can veer dangerously high and low. Several times a day they must use fingerstick tests to monitor their blood glucose levels and manually take insulin by injection or from a pump. An article funded by the National Institutes of Health, and published online in the New England Journal of Medicine (15 June 2014), showed that people with type 1 diabetes who used a bionic pancreas instead of manually monitoring glucose using fingerstick tests and delivering insulin using a pump, were more likely to have blood glucose levels consistently within the normal range, with fewer dangerous lows or highs. According to the authors, the process of blood glucose control could improve dramatically with the bionic pancreas. In two scenarios, a bi-hormonal bionic pancreas was tested which uses a removable tiny sensor located in a thin needle inserted under the skin that automatically monitors real time glucose levels in tissue fluid and provides insulin and its counteracting hormone, glucagon, via two automatic pumps. In one scenario, 20 adults wore this device combination and carried a cell phone-sized wireless monitor around Boston for five days, unrestricted in their activities. In the other, 32 youth wore the device combination for five days at a camp for children with type 1 diabetes. Both groups were also monitored for five days wearing their own conventional pumps that deliver insulin.
Results showed that there was about 37% fewer interventions for low blood glucose (hypoglycemia) and a more than twofold reduction in the time in hypoglycemia in adults using the bionic pancreas than with the manual pump. For adolescents using the bionic pancreas, results showed more than a twofold reduction in the need for interventions for hypoglycemia. As well, both groups had significant improvements in glucose levels with the bionic pancreas, particularly during the night. According to the authors, system performance in both adults and adolescents exceeded their expectations under very challenging real-world conditions. The authors added that while a cure is always the end goal, since that goal remains elusive, a truly automated technology, which can consistently and relentlessly keep people healthy and safe from harm of hypoglycemia, would lift an enormous emotional and practical burden from the shoulders of people with type 1 diabetes.
Age-specific Population Frequencies of Cerebral beta-Amyloidosis and Neurodegeneration Among People with Normal Cognitive Function
Expert international workgroups convened by the Alzheimer’s Association and the National Institute on Aging (NIA), an agency of the U.S. National Institutes of Health (NIH), have jointly issued four new criteria and guidelines to diagnose Alzheimer’s disease (AD). These new criteria update, refine and broaden previous widely used guidelines jointly issued by the Alzheimer’s Association and the NIH over the past 30 years. Three of the new guidelines focus on three stages of AD: (1) dementia due to Alzheimer’s, (2) mild cognitive impairment (MCI) due to Alzheimer’s, and (3) preclinical (presymptomatic) Alzheimer’s. Now, as preclinical AD becomes a target for therapeutic intervention, the overlap between imaging abnormalities associated with typical ageing and those associated with AD needs to be recognized. As a result, a study published in The Lancet Neurology (2014;13:997-1005), was performed to characterize how typical ageing and preclinical AD overlap in terms of beta-amyloidosis and neurodegeneration.
For the study, age-specific frequencies of amyloidosis and neurodegeneration were measured in individuals with normal cognitive function aged 50-89 years. Potential participants were randomly selected from the Olmsted County (MN, USA) population-based study of cognitive ageing and invited to participate in cognitive and imaging assessments. To be eligible for inclusion, individuals had to have been judged clinically to have no cognitive impairment and have undergone amyloid PET, 18F-fluorodeoxyglucose (18F-FDG) PET, and MRI. Imaging results were obtained from 2006 – 2013. Amyloid status (positive [A+] or negative [A-]) was determined by amyloid PET with 11C Pittsburgh compound B. Neurodegeneration status (positive [N+] or negative [N-]) was determined by an AD signature 18F-FDG PET or hippocampal volume on MRI. Age-specific frequencies of the four groups (amyloid negative and neurodegeneration negative [A-N-], amyloid positive and neurodegeneration negative [A+N-], amyloid negative and neurodegeneration positive [A-N+], or amyloid positive and neurodegeneration positive [A+N+]) cross-sectionally was measured using multinomial regression models. The study also investigated associations of group frequencies with APOE e4 status (assessed with DNA extracted from blood) and gender by including these covariates in the multinomial models.
The study population consisted of 985 eligible participants. The population frequency of A-N- was 100% (n=985) at age 50 years and fell to 17% by age 89 years. The frequency of A+N- increased to 28% at age 74 years, then decreased to 17% by age 89 years. The frequency of A-N+ increased from age 60 years, reaching 24% by age 89 years. The frequency of A+N+ increased from age 65 years, reaching 42% by age 89 years. The results from the multinomial models suggest that A+N- and A+N+ were more frequent in APOE e4 carriers than in non-carriers and that A+N+ was more, and A+N- less frequent in men than in women.
According to the authors, accumulation of amyloid and neurodegeneration are nearly inevitable by old age, but many people are able to maintain normal cognitive function despite these imaging abnormalities. The authors added that changes in the frequency of amyloidosis and neurodegeneration with age, which seem to be modified by APOE e4 and gender, suggest that pathophysiological sequences might differ between individuals.
National Strategy to Combat Antibiotic-Resistant Bacteria
Extracted from FDA Voice by: Margaret A. Hamburg, M.D. (September 18, 2014)
The Centers for Disease Control and Prevention (CDC) estimates that each year at least 2 million illnesses and 23,000 deaths in the United States are caused by antibiotic-resistant bacteria. Few issues in public health today are as critical and time urgent as combating the growing threat of antibiotic resistance. Fighting antibiotic resistance is both a public health and national security priority. FDA has played a key role in the development of this important effort, and has made strides on many fronts to make sure that effective antibiotics are available for the future. Antibiotics are precious medicines that have saved millions of lives by treating infections caused by bacteria. But their misuse, and overuse, has serious health consequences and has contributed to antibiotic resistance – in which these drugs become less effective, or ineffective, against harmful bacteria. The consequences of antibiotic resistance must not be underestimated, and concern mounts every day that more patients will have few or no therapeutic options because of resistance to available therapies. It is a high priority for FDA to work with partners to find solutions for this serious public health problem. To address the need for effective antibiotics, FDA is working hard to ensure development of new strategies. These include vaccines to help prevent infection with bacteria in the first place; devices to aid in the accurate diagnosis of the cause of infection and of resistant infections; and new drugs to treat patients with serious infections for whom we have few, or no, treatment options because of resistance to currently available antibiotics. FDA has been engaging with outside groups to advance the science of clinical trials. For instance, FDA worked with the Clinical Trials Transformation Initiative (CTTI), where Target Heath is an active member of the Steering Committee and Dr, Mitchel, President of Target Health, is a member of the Executive Committee, on increasing the efficiency of clinical trials; with the Engelberg Center for Health Care Reform at the Brookings Institution to address overarching issues in antibiotic development, such as the major technical and financial barriers; and with the Biomarkers Consortium of the Foundation for the National Institutes of Health (NIH) on endpoints for studying antibiotics in clinical trials. FDA recently joined NIH to hold a workshop to examine the technical challenges related to antibacterial product development and to discuss innovative regulatory and clinical trial approaches for bringing new products to market. FDA also has been actively implementing the Generating Antibiotics Incentives Now (GAIN) Act, a provision within the Food and Drug Administration Safety and Innovation Act (FDASIA) to promote the development of antibacterial and antifungal drugs. To date, FDA has granted 57 Qualified Infectious Disease Product (QIDP) designations under GAIN to 39 different unique molecules. Antibiotics that have a QIDP designation receive, upon request, priority review, typically shaving four months off review times, and fast track designation, which results in early consultation, including on clinical trial design, between FDA and antibiotic sponsors. QIDPs also can receive an additional five years of marketing exclusivity in addition to existing exclusivity periods at the time of approval. There are already three QIDP designated antibacterial drugs have been approved in the past few months: Dalbavancin in May 2014, Tedizolid Phosphate in June 2014 and Oritavancin in August 2014. Furthermore, FDA promotes the appropriate and responsible use of antibiotics in clinical medicine.
Antibiotic labels contain information for health care professionals and patients on appropriate use, and FDA continues to work to improve the integrity of the global supply chain for pharmaceutical products to minimize the chance of a patient receiving a substandard drug, which in some instances could promote antimicrobial resistance. In addition, FDA has developed – and is working to implement – two strategies to ensure the judicious use of medically important antimicrobial drugs in food-producing animals. This is a vital step to better protect antibiotic effectiveness for both human and animal populations. Accordingly, FDA has asked the manufacturers of these antibiotics used in food-producing animals to remove all growth promotion indications. Once their labels have been changed, the products can no longer be used legally for growth promotion purposes, or without veterinary oversight. FDA has secured the commitment of all 26 affected animal health companies, and 31 products have been withdrawn from the market. Two other companies have implemented label changes and we will be working with the other companies to make sure that they do so as well. The second track will ensure that all remaining therapeutic uses of the affected medically important antibiotics in food-producing animals will take place under the supervision of a veterinarian. The agency continues to work under a three-year transition period, and remains encouraged by the process. However, a successful strategy to combat antibiotic-resistant bacteria will require effort and input from all involved groups, including from health care professionals and patients themselves.
Roasted Beet Salad with Arugula, Figs, Goat Cheese and Walnuts
A delicious and beautiful salad! ©Joyce Hays, Target Health Inc.
Start by getting all the ingredients together, so you don’t go scurrying around, while you’re in the middle of doing something. ©Joyce Hays, Target Health Inc.
8 ounces fresh feta cheese (or goat)
2 large Beets
1/2 red onion, very thinly sliced or chopped
1/2 Tablespoon extra virgin olive oil
Pinch Salt and Pepper
5 Fresh figs, sliced
20 red seedless grapes, cut in half
1/2 cup toasted walnuts, coarsely chopped
1/2 cup artificial bacon bits
1 bunch fresh Arugula, washed, dried
2 cloves garlic, juiced
2 Tablespoons Champagne Vinegar
1/2 cup Walnut Oil
Pinch Sea Salt
Pinch Black Pepper or grind to your taste
Preheat oven to 375 degrees.
Rinse beets, and pat dry. Oil-spray a cookie sheet, also rub each beet with oil, put the beets on sheet and into the oven for abut 45 minutes, or when fork tender. Then, remove from oven and cut each beet into bite-sized cubes.
Meanwhile, toast the walnuts and place figs, grapes, walnuts and red onion in a bowl and set aside.
Add arugula and artificial bacon bits to the fig and walnut mixture and toss
In a salad bowl, mix the vinegar, oil, garlic cloves juiced, salt and pepper until combined. Try to get walnut oil and champagne vinegar. These flavors really make a difference. I got both on Amazon.
Add the fig/walnut mixture to the dressing in the salad bowl.
When beets are done roasting, add them to the mixture and toss to combine well, but toss lightly.
Serve immediately, while beets are still a little warm.
This luscious salad is a meal in itself. ©Joyce Hays, Target Health Inc.
We’re stuck on this Cloudy Bay Sauvignon Blanc, from New Zealand. And we don’t get anything in return for saying that. We just really like it. Its one of those gems, that gets great reviews but doesn’t break the bank. Plus, a nice label.
Tired, coming back from another DC meeting, Jules again had a veggie burger on the Acela, to tide himself over. This recipe was timed perfectly for his arrival mid-evening. I mentioned, above, that this is a meal in itself, and it was a nice assortment of veggies, fruit, nuts and protein. Figs are still ripe plump and in season. If you’ve noticed, I’ve been using figs a lot lately in recipes, because they’re so fresh, soft and worth sinking your teeth into, right now.
We had the beet salad with warm flat bread and chilled glasses of (above) Sauvignon Blanc. This was the perfect repast and we were as happy as can be expected after a long day. The only downside was that we listened to the news (a no-no during dinner) and heard more about ISIS/ISIL morphing over decades into various threatening jihad groups that the world will have to deal with as a never ending planetary issue. They’ve spread to Australia and all over northern africa now. Ugh – Indigestion, pass the tums, please. Later, it felt good to get into bed, all cozy and safe. For how long, I wondered.
From Our Table to Yours! And this week, especially to all of our friends and colleagues in the British Isles! Thanks for staying united!
Bon Appetit !