BioSpectrum Top 20: How Countries Fared? | |||||||||||||||||||||||||||||||||||||||||
How countries fared? The total life sciences business of the publicly listed companies stood at $26.2 billion in 2007 compared to $19.4 billion in 2006
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Wednesday, October 28, 2009
Biotechnology industry in India!!!
Wednesday, September 9, 2009
India patent rejections welcomed by HIV/AIDS groups
NEW DELHI, Sept 9 (Reuters) - India's rejection of patent applications on two life-saving HIV/AIDS drugs last week has been welcomed by health officials, who say it will ensure wider access to the medicines.
India has the world's third highest caseload, with 2.5 million infections, behind Nigeria and South Africa.India's Patent Office rejected applications for leading antiretroviral drug tenofovir, manufactured by U.S. biotechnology group Gilead (GILD.O), and darunavir, which is made by Ireland's Tibotec Pharmaceuticals, officials said."This is a welcome decision and we have always been supporting AIDS drugs should not be patented, because if they are patented it will reduce their access to common people," said B.B. Rewari, a senior official at India's National AIDS Control Organisation (NACO), the main government agency battling the deadly disease.
A patented tenofovir drug would have cost 3,000 rupees ($62) each, but a generic would be cost around 570 rupees, he said."It is a welcome decision for Indian patients and for other developing countries who are battling the disease," said Rewari, who heads the country's anti-HIV/AIDS national programme.A spokeswoman for Tibotec Pharmaceuticals said the company was reviewing the decision and was not making any comment immediately.
AIDS workers say both companies could challenge the decision by filing a second patent application. The decision could also affect some Indian companies who have a fixed price for HIV/AIDS drugs, targeted towards rich clients."At the end of the day, the decision is good for the people who need these generic drugs for a lower price," Christy Abraham, the ASIA coordinator for Action Aid said.
Monday, August 17, 2009
SWINE FLU: Revised swine flu guidelines categorises patients
According to the new guidelines, at first all individuals seeking consultation for flu-like symptoms should be screened at healthcare facilities - both government and private - or examined by a doctor. The patients have been categorised as follows:
Category A: Patients with mild fever plus cough/sore throat with or without bodyache, headache, diarrhoea and vomiting. They do not require Oseltamivir and should be treated for the symptoms mentioned above. The patients should be monitored for their progress and re-assessed every 24 to 48 hours by the doctor. No testing of the patient for H1N1 is required. Patients should confine themselves at home and avoid mixing with the public and high risk members in the family.
Category B: (i) In addition to all the signs and symptoms of Category A, if the patient has high grade fever and severe sore throat, he/she may require home isolation and Oseltamivir;
(ii) In addition to all the signs and symptoms of Category A, individuals having one or more of the following high risk conditions shall be treated with Oseltamivir: children under five, pregnant women, those above 65 years, those with lung diseases, heart disease, liver disease, kidney disease, blood disorders, diabetes, neurological disorders, cancer and HIV/AIDS; Patients on long term cortisone therapy. No H1N1 tests are required for Category-B (i) and (ii). Such patients should confine themselves at home and avoid mixing with public and high-risk members in the family.
Category C: In addition to the symptoms of Categories A and B, if the patient has one or more of the following: - Breathlessness, chest pain, drowsiness, fall in blood pressure, sputum mixed with blood, bluish discolouration of nails; - Irritability among small children, refusal to accept feed; - Worsening of underlying chronic conditions. Such patients require H1N1 testing, immediate hospitalisation and treatment.
HOW TO AVOID SWINE FLU
1. Stay Home: If you are sick or have any flu-like symptoms, its better to stay home. Do not school or work. Swine flu sysmptoms may mimic those of regular flu and cold sysmptoms.
2. Contain Your Cough: Cough or sneeze into the crook (inside elbow) of your arm. This way you do not transfer the germs to your hands and then to every object you touch. You can spread Swine flu easily by touching an infected object and then touching your face. A flu mask will help you avoid infection in enclosed spaces.
3. Wash Hands Frequently: Wash your hands frequently to avoid swine flu. Anything you touch may be affected, so keeping hands clean will help you avoid infection.
4. Hand Sanitizer: Carry hand sanitizer with you. If you have things others have touched, use your hand sanitizer to avoid swine flu infection.
5. Avoid Crowds: Stay out of crowds as much as possible. Wear a surgical mask in areas of high traffic concentration.
6. Eating and Drinking: Do not eat or drink after others without complete sensitization of containers or utensils. Swine flu can be transmitted by contact with infected eating utensils.
7. Visit Your Doctor: Get to a doctor immediately if you develop sysmptoms of swine flu including high fever and body aches.
2. Contain Your Cough: Cough or sneeze into the crook (inside elbow) of your arm. This way you do not transfer the germs to your hands and then to every object you touch. You can spread Swine flu easily by touching an infected object and then touching your face. A flu mask will help you avoid infection in enclosed spaces.
3. Wash Hands Frequently: Wash your hands frequently to avoid swine flu. Anything you touch may be affected, so keeping hands clean will help you avoid infection.
4. Hand Sanitizer: Carry hand sanitizer with you. If you have things others have touched, use your hand sanitizer to avoid swine flu infection.
5. Avoid Crowds: Stay out of crowds as much as possible. Wear a surgical mask in areas of high traffic concentration.
6. Eating and Drinking: Do not eat or drink after others without complete sensitization of containers or utensils. Swine flu can be transmitted by contact with infected eating utensils.
7. Visit Your Doctor: Get to a doctor immediately if you develop sysmptoms of swine flu including high fever and body aches.
Friday, May 29, 2009
Biotechnology in India
Bio-Technology is a research oriented science, a combination of Biology and Technology. It covers a wide variety of subjects like Genetics, Biochemistry, Microbiology, Immunology, Virology, Chemistry and Engineering and is also concerned with many other subjects like Health and Medicine, Agriculture and Animal Husbandry, Cropping system and Crop Management, Ecology, Cell Biology, Soil science and Soil Conservation, Bio-statistics, Plant Physiology, Seed Technology etc. Bio-Technology is the use of living things, especially cells and bacteria in industrial process. There is a great scope in this field as the demand for biotechnologist are growing in India as well as abroad.
There are many applications of biotechnology such as developing various medicines, vaccines and diagnostics, increasing productivity, improving energy production and conservation. Biotechnology's intervention in the area of animal husbandry has improved animal breeding. It also helps to improve the quality of seeds, insecticides and fertilizers. Environmental biotechnology helps for pollution control and waste management.
Most of the information that has led to the emergence of biotechnology in the present form has been generated during the last five decades. The setting up of a separate Department of Biotechnology (DBT) (http://www.dbtindia.nic.in/ ) under the Ministry of Science and Technology in 1986 gave a new impetus to the development of the field of modern biology and biotechnology in India. More than 6000 biotechnologists of higher skill are required in India as per the report from the Human Resource Development Ministry. To overcome this vast requirement the department of Biotechnology (DBT) has highlighted the need to set up a regulatory body for the maintenance of standard education under the name of 'All- India Board of Biotechnology Education and Training' under the AICTE .
For Eligibility, Job Prospectus, Remuneration and Institutes offering Biotechnology course go to -
Thursday, May 28, 2009
More research needed to develop successful swine flu vaccine: WHO
The World Health Organization isn't yet ready to advise vaccine makers on whether they should divert production to make swine flu shots instead of vaccines for seasonal flu, it said Tuesday.
"We are in the process of the most basic development of the vaccine," acting WHO assistant director general Keiji Fukuda told reporters.
Research on candidate swine flu vaccines will continue until the end of June or July, at which time drug companies could start to test a possible vaccine for H1N1 influenza, he said. But without knowing how effective the vaccine might be, it's too early to recommend that drug makers commit manufacturing resources to it, Fukuda said.
The WHO also said it would consult influenza experts before formally changing its criteria on when to declare a pandemic. The UN health agency has faced pressure from several countries to consider the mild severity of swine-flu infections so far as a deterrent to raising its pandemic alert to Phase 6, the highest. Normally, the alert scale doesn't consider the severity of an illness itself, but the WHO said it was amenable to changing that, if experts agreed.
Earlier this week, it was confirmed that the U.S. government has awarded $660 million US in contracts to three pharmaceutical giants to make swine-flu vaccines.
The companies — GlaxoSmithKline, Sanofi Pasteur, and Novartis — are to receive seed virus from the U.S. Centers for Disease Control and Prevention, with the aim of starting commercial production in June.
The virus has been linked to 92 deaths and infected 12,954 people in 46 countries since it was first uncovered last month, the WHO said in its update Tuesday.
The Persian Gulf kingdom of Bahrain reported its first confirmed case of H1N1 swine flu on Monday.
In the U.S., New York City's health commissioner announced Tuesday that two more deaths have been linked to swine flu, bringing the number of deaths in the city to four.
In its most recent update on Monday, the Centers for Disease Control said there were 6,764 confirmed cases of swine flu in the U.S., most of them mild.
The Public Health Agency of Canada's most recent update on Monday reported 921 confirmed cases in nine provinces and one territory.
"We are in the process of the most basic development of the vaccine," acting WHO assistant director general Keiji Fukuda told reporters.
Research on candidate swine flu vaccines will continue until the end of June or July, at which time drug companies could start to test a possible vaccine for H1N1 influenza, he said. But without knowing how effective the vaccine might be, it's too early to recommend that drug makers commit manufacturing resources to it, Fukuda said.
The WHO also said it would consult influenza experts before formally changing its criteria on when to declare a pandemic. The UN health agency has faced pressure from several countries to consider the mild severity of swine-flu infections so far as a deterrent to raising its pandemic alert to Phase 6, the highest. Normally, the alert scale doesn't consider the severity of an illness itself, but the WHO said it was amenable to changing that, if experts agreed.
Earlier this week, it was confirmed that the U.S. government has awarded $660 million US in contracts to three pharmaceutical giants to make swine-flu vaccines.
The companies — GlaxoSmithKline, Sanofi Pasteur, and Novartis — are to receive seed virus from the U.S. Centers for Disease Control and Prevention, with the aim of starting commercial production in June.
The virus has been linked to 92 deaths and infected 12,954 people in 46 countries since it was first uncovered last month, the WHO said in its update Tuesday.
The Persian Gulf kingdom of Bahrain reported its first confirmed case of H1N1 swine flu on Monday.
In the U.S., New York City's health commissioner announced Tuesday that two more deaths have been linked to swine flu, bringing the number of deaths in the city to four.
In its most recent update on Monday, the Centers for Disease Control said there were 6,764 confirmed cases of swine flu in the U.S., most of them mild.
The Public Health Agency of Canada's most recent update on Monday reported 921 confirmed cases in nine provinces and one territory.
Monday, May 25, 2009
De-Bugging Your Food
Before your food makes it to your refrigerator or even the supermarket, it often starts on a farm. And with the lay of the land comes a farmer's worst nightmare! They're creepy. They're crawly. And you want 'em gone. We're talking about bugs, and if they get under your skin, just imagine how farmers feel.
It's a never-ending battle to save their crops, but pesticides are proven to hurt the environment and our health. Five-million pounds of pesticides a year are used to zap bugs and insects that burrow down on fruits and veggies. But these colorless, odorless gasses pose a threat to the environment and to you.
So before biting into another apple, check out a new, safer alternative. Physical Chemist Manuel Lagunas-Solar is creating a new pest control system called Metabolic Stress Disinfection and Disinfestation, or MSDD.
"This method that doesn't use chemicals but uses forces and controls the air to achieve the same objective," Lagunas-Solar tells DBIS.
After the food is harvested, it's put into a chamber where a vacuum is applied, reducing air pressure by about 90 percent. Repeating this cycle kills bugs, their eggs, and controls microbes that spoil food.
Lagunas-Solar says, "We eliminate the oxygen, and at the same time we replace it with carbon dioxide, which is a toxic chemical."
Unlike most pesticides used today, MSDD is non-toxic to humans and is entirely safe for the environment, making it a simple fix to a pesky problem. The next challenge is to apply MSDD on a commercial level. Lagunas-Solar believes the chambers will be easy to develop on a large enough scale for farmers to use.
It's a never-ending battle to save their crops, but pesticides are proven to hurt the environment and our health. Five-million pounds of pesticides a year are used to zap bugs and insects that burrow down on fruits and veggies. But these colorless, odorless gasses pose a threat to the environment and to you.
So before biting into another apple, check out a new, safer alternative. Physical Chemist Manuel Lagunas-Solar is creating a new pest control system called Metabolic Stress Disinfection and Disinfestation, or MSDD.
"This method that doesn't use chemicals but uses forces and controls the air to achieve the same objective," Lagunas-Solar tells DBIS.
After the food is harvested, it's put into a chamber where a vacuum is applied, reducing air pressure by about 90 percent. Repeating this cycle kills bugs, their eggs, and controls microbes that spoil food.
Lagunas-Solar says, "We eliminate the oxygen, and at the same time we replace it with carbon dioxide, which is a toxic chemical."
Unlike most pesticides used today, MSDD is non-toxic to humans and is entirely safe for the environment, making it a simple fix to a pesky problem. The next challenge is to apply MSDD on a commercial level. Lagunas-Solar believes the chambers will be easy to develop on a large enough scale for farmers to use.
BACKGROUND: A team of researchers in California has designed an effective alternative to pesticide treatments commonly used to rid popular fruits and vegetables of harmful insect infestation after the produce has been harvested. Known as metabolic stress disinfection and disinfestation (MSDD), the new pest control system is more reliable and cost-effective, and is also non-toxic to humans and safe for the environment. The method has been successfully tested on table grapes, oranges, grapefruit, stone fruit, kiwi, and bananas.
HOW IT WORKS: Post-harvest fruits and vegetables are typically loaded into a large chamber filled with methyl bromide gas for about eight hours. Methyl bromide kills most of the pests (insects and their larvae), but is costly and time-consuming. It is also scheduled for a worldwide ban, because it is classified as an ozone-depleting substance. In contrast, MSDD kills pests using carbon dioxide, a vacuum pump, and a little alcohol. Insects need oxygen, like all living creatures. MSDD eliminates their oxygen supply. The produce is put into a chamber, and a vacuum is then applied, reducing the interior air pressure by about 90 percent. After a few minutes, the chamber is filled with pure carbon dioxide for several more minutes. The process repeats several times, periodically augmented with ethanol vapor to make sure the bugs are dead.
WHAT IS A VACUUM: Vacuum technology has become a valuable industrial tool since the introduction of the light bulb and vacuum tube in the early 20th century. A vacuum is a volume of space that is essentially empty of matter, so there is almost no air pressure. A vacuum chamber, like the one used in the MSDD method, is a rigid enclosure from which air and other gases are removed by a vacuum pump. The resulting low pressure is known as a vacuum. Much of outer space has the density and pressure of a vacuum, with almost no friction, allowing stars and planets and moons to move freely in their paths or orbits. However, there is no such thing as a perfect vacuum, even in outer space.
HOW IT WORKS: Post-harvest fruits and vegetables are typically loaded into a large chamber filled with methyl bromide gas for about eight hours. Methyl bromide kills most of the pests (insects and their larvae), but is costly and time-consuming. It is also scheduled for a worldwide ban, because it is classified as an ozone-depleting substance. In contrast, MSDD kills pests using carbon dioxide, a vacuum pump, and a little alcohol. Insects need oxygen, like all living creatures. MSDD eliminates their oxygen supply. The produce is put into a chamber, and a vacuum is then applied, reducing the interior air pressure by about 90 percent. After a few minutes, the chamber is filled with pure carbon dioxide for several more minutes. The process repeats several times, periodically augmented with ethanol vapor to make sure the bugs are dead.
WHAT IS A VACUUM: Vacuum technology has become a valuable industrial tool since the introduction of the light bulb and vacuum tube in the early 20th century. A vacuum is a volume of space that is essentially empty of matter, so there is almost no air pressure. A vacuum chamber, like the one used in the MSDD method, is a rigid enclosure from which air and other gases are removed by a vacuum pump. The resulting low pressure is known as a vacuum. Much of outer space has the density and pressure of a vacuum, with almost no friction, allowing stars and planets and moons to move freely in their paths or orbits. However, there is no such thing as a perfect vacuum, even in outer space.
Wasps: Man's New Best Friend!
Entomologists Train Insects to Act Like Sniffing Dogs
July 1, 2006 — If rewarded with sugary water, wasps can be trained in minutes to follow specific smells. The olfactory sensors in their antennae can sense chemicals in the air in concentrations as tiny as a few parts per billion. Wasps could be cost-effective helpers in searching for explosives, toxic chemicals, and even fungi on crops.
ATHENS, Ga. -- Wasps are not man's best friend -- probably their worst. But when it comes to sniffing out trouble, scientists believe they may be better than dogs.
They ward off intruders, track down criminals, find bombs and detect toxic chemicals, but dogs could soon be replaced by wasps. They have the same sensitive odor detection as dogs and are now being trained to sniff out trouble.
"The advantages of a wasp over a dog is you can produce them by the thousands. They are real inexpensive, and you can train them in a matter of minutes," Joe Lewis, a research entomologist at University of Georgia in Athens, tells DBIS.
He and Biological and agricultural engineer Glen Rains are doing just that. Olfactory sensors on the wasps' antennae can smell chemicals in concentrations as tiny as a few parts per billion in the air.
"So far, they've been able to detect, to some level, any chemical that we've trained them to," Rains tells DBIS.
Training is simple and quick. The wasps are fed sugar water. At the same time they're introduced to a smell for 10 seconds. The process is repeated two more times.
Lewis says, "We can train a wasp within a matter of 10 to 15 minutes."
For example, a set of wasps is trained to detect the smell of coffee. When they are put into a simple container, a tiny web camera watches their actions. When the smell of orange is pumped into the pipe, nothing. But when it's coffee, the wasps crowd around the smell.
So far, Rains and Lewis have not found anything the wasps cannot be trained to detect. They can be trained to detect everything from drugs to human remains to fungi on crops. They could one day even be able to detect deadly diseases like cancer.
They ward off intruders, track down criminals, find bombs and detect toxic chemicals, but dogs could soon be replaced by wasps. They have the same sensitive odor detection as dogs and are now being trained to sniff out trouble.
"The advantages of a wasp over a dog is you can produce them by the thousands. They are real inexpensive, and you can train them in a matter of minutes," Joe Lewis, a research entomologist at University of Georgia in Athens, tells DBIS.
He and Biological and agricultural engineer Glen Rains are doing just that. Olfactory sensors on the wasps' antennae can smell chemicals in concentrations as tiny as a few parts per billion in the air.
"So far, they've been able to detect, to some level, any chemical that we've trained them to," Rains tells DBIS.
Training is simple and quick. The wasps are fed sugar water. At the same time they're introduced to a smell for 10 seconds. The process is repeated two more times.
Lewis says, "We can train a wasp within a matter of 10 to 15 minutes."
For example, a set of wasps is trained to detect the smell of coffee. When they are put into a simple container, a tiny web camera watches their actions. When the smell of orange is pumped into the pipe, nothing. But when it's coffee, the wasps crowd around the smell.
So far, Rains and Lewis have not found anything the wasps cannot be trained to detect. They can be trained to detect everything from drugs to human remains to fungi on crops. They could one day even be able to detect deadly diseases like cancer.
BACKGROUND: Scientists from the University of Georgia and the USDA Agricultural Research Service are training wasps to detect the telltale odors of concealed explosives, drugs and human remains, and possibly one day certain diseases like cancer. They are now investigating whether it is possible to train mosquitoes as living odor detectors as well, and plan to eventually study other insects with excellent sniffing ability, like honeybees and moths.
HOW IT WORKS: The Georgia scientists have built a device they call the Wasp Hound: an odor-detection device that costs around $60. It is made of a small PVC tube containing five wasps that can be trained to detect any target odor within minutes. The device has a fan at the top, which draws odors into the tube through a filter. If the wasps catch a whiff of whatever they've been trained to smell, they crowd around a hole in the filter. A web cam inside the tube is attached to a computer, which alerts the operator to the wasps' reaction with a beep or a flashing light. The Wasp Hound could be used by farmers to monitor crops for diseases and pests; to check for explosives in airport security applications; to help doctors monitor diseases, or even by defense forces searching for buried land mines.
ADVANTAGES: Unlike dogs and the electronic sensors more commonly used today, wasps are cheap and disposable. It costs pennies and takes minutes to train them: Feed them sugar water while introducing them to a target smell for 10 seconds; give them a 30-second break, repeat the process twice more, and they are completely trained to track that single scent.
ABOUT WASPS: Wasps have olfactory sensors on their antennae that they use to stay alive. For instance, one strain of wasp lays its eggs inside a specific variety of caterpillar. The insects are attracted to the caterpillars by chemicals released by plans as the caterpillars much on them -- a type of SOS signal from the plants. This is also how wasps attract mates. Wasps can sense chemicals in concentrations as tiny as a few parts per billion in the air ý the same range to which dogs and chemical sensors are sensitive. Some species can pick up scents at concentrations as low as one part in a thousand billion, which is a hundred thousand times weaker that the concentrations detectable by commercial "electronic noses."
Why BCG lost its effectiveness against pulmonary TB?
ScienceDaily (May 24, 2009) — A team of Vanderbilt University Medical Center investigators has cracked one of clinical medicine's enduring mysteries – what happened to the tuberculosis vaccine. The once-effective vaccine no longer prevents the bacterial lung infection that kills more than 1.7 million people worldwide each year.
Their solution, reported in the journal PLoS One, could lead to an improved TB vaccine and also may offer a novel platform for vaccines against other pathogens.
"Our findings represent nearly a 180-degree reversal from the dogma of the last 60 years – that the TB vaccine stopped working because it became over-attenuated and was too 'wimpy' to be effective," said Douglas Kernodle, M.D., associate professor of Medicine.
Instead, Kernodle and colleagues found that the TB vaccine has acquired some traits that make it less effective in evoking a sustained immune response. When they take away these traits, the TB vaccine induces stronger immune responses in mice.
The current TB vaccine, known as BCG (bacille Calmette-Guérin), has been around since the 1920s. It was made by weakening (attenuating) a strain of bacteria that causes tuberculosis in cows and that genetically is 98 percent identical to the human TB germ.
During the early years of its use, BCG was 80 percent effective against pulmonary TB. But because there were no long-term storage options for bacterial strains until the 1960s, BCG was grown continuously in culture, with "sub-cultures" of the original BCG maintained in laboratories around the world. Over time, BCG changed – the original vaccine ceased to exist and the daughter sub-cultures lost effectiveness against pulmonary TB.
Today, although BCG no longer protects against lung disease, it is still 80 percent effective against "disseminated TB" (TB infection in many parts of the body) in early childhood. Because of this protection, BCG is given annually to 100 million newborns worldwide – not in the United States and a few other countries – and is estimated to prevent about 40,000 cases each year of TB meningitis and other disseminated TB, Kernodle said.
But the question of why BCG lost its effectiveness against pulmonary TB has not been fully investigated. Researchers accepted the notion that as BCG was grown in culture, it changed genetically and became too weak to evoke the kind of immune response needed for protection.
Kernodle and colleagues came to the problem of BCG's poor activity against pulmonary TB from a different angle. They had reported in 2001 that one way TB itself evades the immune system is by producing antioxidants. Since BCG also produces antioxidants, they suggested that removing BCG's antioxidant-producing capacity might improve the vaccine.
"Our idea to take something away from BCG – and therefore theoretically attenuate it even further – was met with a lot of skepticism," Kernodle said. "But we believed our data that we could make BCG more immunogenic and safer."
Two years ago, after the Kernodle group had modified BCG and was beginning to test it for immune responses, researchers at the Institut Pasteur in Paris published a paper describing the genomic evolution of BCG. They found that in addition to containing gene deletions consistent with attenuation of the vaccine, the BCG genome also had regions of gene duplication and increased gene expression. Some of the duplicated and over-expressed genes were for antioxidants already being targeted by the Kernodle group.
It was suddenly obvious what had happened to BCG, Kernodle said.
"It had not become too weak – instead, by making more antioxidants it had become better at suppressing immune responses."
In the current studies, first author Lakshmi Sadagopal, Ph.D., research instructor of Medicine, vaccinated mice with a modified BCG (genetically changed in three ways to reduce or eliminate the production of several antioxidants) and examined the immune response in the days following vaccination and later with a "challenge" dose of BCG.
She found that, compared to BCG, the modified BCG induced greater cytokine (immune regulatory factor) production during the early phase of the immune response, more CD8 cell-killing T cells at the peak of the primary response, and more CD4 helper T cells during the memory phase. Modified BCG also produced greater recall immune responses and was eliminated better by the vaccinated host animal than the parent BCG vaccine, which might correlate with improved safety in humans.
"At each time point of the immune response, the modified BCG vaccine worked better than the parent BCG vaccine," Kernodle said. "By targeting antioxidants that had increased in expression during decades of cultivation, we ended up making BCG more like it was back in the 1920s when it was 80 percent effective against pulmonary TB. We fixed it."
Using modern molecular techniques to reduce the activity of antioxidants below levels in naturally occurring strains, "it should be possible to make it even better than the original BCG," he added.
The Aeras Global TB Vaccine Foundation, supported by the Bill & Melinda Gates Foundation, has already licensed the modification technology developed by Kernodle and colleagues. Aeras is working to make the best possible modified BCG vaccine, and it has built the infrastructure to conduct clinical trials in South Africa, Kenya and India – countries with a high incidence of TB.
Kernodle and colleagues say the results are also encouraging for other vaccine development. Because the modified BCG produces a better immune response profile than existing vaccine technologies, it could be a useful vector for vaccines directed against other pathogens, including HIV and the parasites that cause malaria.
The National Institutes of Health, a VUMC Discovery Award and the Aeras Global TB Vaccine Foundation supported the research. Kernodle is the David E. Rogers Associate Professor of Medicine.
"Our findings represent nearly a 180-degree reversal from the dogma of the last 60 years – that the TB vaccine stopped working because it became over-attenuated and was too 'wimpy' to be effective," said Douglas Kernodle, M.D., associate professor of Medicine.
Instead, Kernodle and colleagues found that the TB vaccine has acquired some traits that make it less effective in evoking a sustained immune response. When they take away these traits, the TB vaccine induces stronger immune responses in mice.
The current TB vaccine, known as BCG (bacille Calmette-Guérin), has been around since the 1920s. It was made by weakening (attenuating) a strain of bacteria that causes tuberculosis in cows and that genetically is 98 percent identical to the human TB germ.
During the early years of its use, BCG was 80 percent effective against pulmonary TB. But because there were no long-term storage options for bacterial strains until the 1960s, BCG was grown continuously in culture, with "sub-cultures" of the original BCG maintained in laboratories around the world. Over time, BCG changed – the original vaccine ceased to exist and the daughter sub-cultures lost effectiveness against pulmonary TB.
Today, although BCG no longer protects against lung disease, it is still 80 percent effective against "disseminated TB" (TB infection in many parts of the body) in early childhood. Because of this protection, BCG is given annually to 100 million newborns worldwide – not in the United States and a few other countries – and is estimated to prevent about 40,000 cases each year of TB meningitis and other disseminated TB, Kernodle said.
But the question of why BCG lost its effectiveness against pulmonary TB has not been fully investigated. Researchers accepted the notion that as BCG was grown in culture, it changed genetically and became too weak to evoke the kind of immune response needed for protection.
Kernodle and colleagues came to the problem of BCG's poor activity against pulmonary TB from a different angle. They had reported in 2001 that one way TB itself evades the immune system is by producing antioxidants. Since BCG also produces antioxidants, they suggested that removing BCG's antioxidant-producing capacity might improve the vaccine.
"Our idea to take something away from BCG – and therefore theoretically attenuate it even further – was met with a lot of skepticism," Kernodle said. "But we believed our data that we could make BCG more immunogenic and safer."
Two years ago, after the Kernodle group had modified BCG and was beginning to test it for immune responses, researchers at the Institut Pasteur in Paris published a paper describing the genomic evolution of BCG. They found that in addition to containing gene deletions consistent with attenuation of the vaccine, the BCG genome also had regions of gene duplication and increased gene expression. Some of the duplicated and over-expressed genes were for antioxidants already being targeted by the Kernodle group.
It was suddenly obvious what had happened to BCG, Kernodle said.
"It had not become too weak – instead, by making more antioxidants it had become better at suppressing immune responses."
In the current studies, first author Lakshmi Sadagopal, Ph.D., research instructor of Medicine, vaccinated mice with a modified BCG (genetically changed in three ways to reduce or eliminate the production of several antioxidants) and examined the immune response in the days following vaccination and later with a "challenge" dose of BCG.
She found that, compared to BCG, the modified BCG induced greater cytokine (immune regulatory factor) production during the early phase of the immune response, more CD8 cell-killing T cells at the peak of the primary response, and more CD4 helper T cells during the memory phase. Modified BCG also produced greater recall immune responses and was eliminated better by the vaccinated host animal than the parent BCG vaccine, which might correlate with improved safety in humans.
"At each time point of the immune response, the modified BCG vaccine worked better than the parent BCG vaccine," Kernodle said. "By targeting antioxidants that had increased in expression during decades of cultivation, we ended up making BCG more like it was back in the 1920s when it was 80 percent effective against pulmonary TB. We fixed it."
Using modern molecular techniques to reduce the activity of antioxidants below levels in naturally occurring strains, "it should be possible to make it even better than the original BCG," he added.
The Aeras Global TB Vaccine Foundation, supported by the Bill & Melinda Gates Foundation, has already licensed the modification technology developed by Kernodle and colleagues. Aeras is working to make the best possible modified BCG vaccine, and it has built the infrastructure to conduct clinical trials in South Africa, Kenya and India – countries with a high incidence of TB.
Kernodle and colleagues say the results are also encouraging for other vaccine development. Because the modified BCG produces a better immune response profile than existing vaccine technologies, it could be a useful vector for vaccines directed against other pathogens, including HIV and the parasites that cause malaria.
The National Institutes of Health, a VUMC Discovery Award and the Aeras Global TB Vaccine Foundation supported the research. Kernodle is the David E. Rogers Associate Professor of Medicine.
Genes of new flu virus show it's not so new
Fri May 22,
WASHINGTON (Reuters) – The most complete analysis yet of the new H1N1 swine flu virus shows it must have been circulating undetected for years, most likely in pigs, researchers said on Friday.
They said pigs are clearly a potential source of human pandemics.
"The results of the study show the global need for more systematic surveillance of influenza viruses in pigs," Dr. Nancy Cox, chief of the influenza division at the U.S. Centers for Disease Control and Prevention, told reporters in a telephone briefing.
The report by Cox and international team of researchers in the journal Science said the virus "might have been circulating undetected among swine herds somewhere in the world."
The researchers confirmed the odd mixture of human, pig and bird genes in the new virus, which has infected more than 11,000 people in 42 countries, and killed 86. The World Health Organization is poised to declare a full pandemic of the virus, which so far causes mostly mild disease in people.
The researchers said it is likely other odd mixtures are infecting pigs but simply have not yet been seen. They sequenced the genetic codes of 70 different samples of the new virus from the United States and Mexico.
"We can actually determine where each of the genes ... originated," Cox said.
The new virus is a mixture of mixtures -- it includes part of a so-called triple reassortant virus first seen in 1998 that contains elements of human, bird and swine strains.
It also includes bits from so-called Eurasian strains of flu, including a segment most closely related to a sample from a patient in Hong Kong infected with a swine flu in 1999.
GENESIS SCENARIO
How this particular new mixture arose is still a mystery, the researcher said.
"Several scenarios exist, including reassortment in Asia or the Americas, for the events that have lead to the genesis of the novel A(H1N1) virus," they wrote.
It is possible another animal acted as the so-called reservoir, which means an animal that can be infected by a pathogen but does not get sick from it. Cox noted that researchers only recently learned, for instance, that cats, from lions to house cats, can be infected with H5N1 avian flu.
"We do know that our veterinary colleagues at USDA (the U.S. Department of Agriculture) and elsewhere in the world are now looking to see if samples in freezers from pigs or other animals that might provide the missing link," Cox said.
"If we can determine the origin we can also take measures to ensure that the virus doesn't reemerge in a slightly different form," she said.
The researchers said they do not know how this particular virus acquired the ability to infect people. It does not have the usual mutations that allow animal viruses to jump into people and then to pass easily from one person to another.
Flu experts get worried when viruses go straight from animals to people. Usually they do not pass any further than one person -- for example the feared H5N1 avian influenza virus that has infected 429 people and killed 262 of them rarely passes from person to person.
But all three recent pandemics -- in 1918, 1957 and 1968 -- occurred when a new avian flu virus started infecting people.
So far sampling of the new H1N1 virus shows very little genetic mutation -- a sample from a patient in Mexico is virtually identical to samples from various U.S. states and other countries.
This "indicates that this virus may have been introduced into humans in sort of a single event," Cox said. Or if more than one person was infected directly from an animal or other source, they were infected with genetically identical viruses.
They said pigs are clearly a potential source of human pandemics.
"The results of the study show the global need for more systematic surveillance of influenza viruses in pigs," Dr. Nancy Cox, chief of the influenza division at the U.S. Centers for Disease Control and Prevention, told reporters in a telephone briefing.
The report by Cox and international team of researchers in the journal Science said the virus "might have been circulating undetected among swine herds somewhere in the world."
The researchers confirmed the odd mixture of human, pig and bird genes in the new virus, which has infected more than 11,000 people in 42 countries, and killed 86. The World Health Organization is poised to declare a full pandemic of the virus, which so far causes mostly mild disease in people.
The researchers said it is likely other odd mixtures are infecting pigs but simply have not yet been seen. They sequenced the genetic codes of 70 different samples of the new virus from the United States and Mexico.
"We can actually determine where each of the genes ... originated," Cox said.
The new virus is a mixture of mixtures -- it includes part of a so-called triple reassortant virus first seen in 1998 that contains elements of human, bird and swine strains.
It also includes bits from so-called Eurasian strains of flu, including a segment most closely related to a sample from a patient in Hong Kong infected with a swine flu in 1999.
GENESIS SCENARIO
How this particular new mixture arose is still a mystery, the researcher said.
"Several scenarios exist, including reassortment in Asia or the Americas, for the events that have lead to the genesis of the novel A(H1N1) virus," they wrote.
It is possible another animal acted as the so-called reservoir, which means an animal that can be infected by a pathogen but does not get sick from it. Cox noted that researchers only recently learned, for instance, that cats, from lions to house cats, can be infected with H5N1 avian flu.
"We do know that our veterinary colleagues at USDA (the U.S. Department of Agriculture) and elsewhere in the world are now looking to see if samples in freezers from pigs or other animals that might provide the missing link," Cox said.
"If we can determine the origin we can also take measures to ensure that the virus doesn't reemerge in a slightly different form," she said.
The researchers said they do not know how this particular virus acquired the ability to infect people. It does not have the usual mutations that allow animal viruses to jump into people and then to pass easily from one person to another.
Flu experts get worried when viruses go straight from animals to people. Usually they do not pass any further than one person -- for example the feared H5N1 avian influenza virus that has infected 429 people and killed 262 of them rarely passes from person to person.
But all three recent pandemics -- in 1918, 1957 and 1968 -- occurred when a new avian flu virus started infecting people.
So far sampling of the new H1N1 virus shows very little genetic mutation -- a sample from a patient in Mexico is virtually identical to samples from various U.S. states and other countries.
This "indicates that this virus may have been introduced into humans in sort of a single event," Cox said. Or if more than one person was infected directly from an animal or other source, they were infected with genetically identical viruses.
Monday, March 16, 2009
Key details matter for better communication
We skip mentioning important details in our conversation simply because we know them ourselves, without considering whether the audience knows them too
One common problem with communication is the way we skip mentioning important details in our conversation simply because we know them ourselves, without considering if the audience knows them too. For instance, sometimes we just start saying “there was this nice big clock and it had this man coming out, and striking the chimes…”
And it doesn’t make too much sense to anyone. But instead, start by saying that you visited the Salar Jung Museum the other day, and everything will be clearer.
This seems to be simple common sense, but in fact it’s a lot harder to get this right than most people imagine.It is common to get carried away and imagine that the audience knows what one is talking about. But why should this be difficult at all? Because, really, you cannot tell people what they need to know, unless you clearly understand what they know and also what they do not know. Know your audience
In short, you must know your audience well. Let’s take a very simple example: “The Seven Samurai, Kurosawa’s finest work has influenced people across the world.” With a sentence like that, there’s a good chance that many people would not understand what I’m saying. So I need to take a step back. Does my audience know about Kurosawa? Have they heard of The Seven Samurai? Depending on the answer to these questions, I might revise my sentence:
“Kurosawa, one of the finest filmmakers in the world, influenced world cinema greatly with his film The Seven Samurai, which shows a poor village standing up to a gang of ferocious robbers with courage and intelligence.”
In simple day-to-day situations, like the one about the museum visit, this doesn’t seem to be important—after all, if your friend doesn’t understand something, you can always explain it again.One chance
But there are many instances in life, when you’ll get just that one chance. I had one such experience while interviewing one young graduate for a company. When asked a basic question like “What would you like to do as an alternate career?” he answered that he wanted to start a college in his village. Running a college can be a lucrative and ambitious business, and he didn’t seem like someone who had such ambitions. It was only after some probing that I found out there was no college in his village at present, and he saw it as a service to the people, rather than as a business.Solution
How do you avoid such gaps in communication? The solution is to consciously ask yourself: “What does this person know about me / this topic?” Make a list in your mind, if you wish. Once you have this, you will be able to clearly identify what it is that you need to communicate.
---
Online edition of India's National Newspaper The Hindu Monday, Mar 16, 2009
One common problem with communication is the way we skip mentioning important details in our conversation simply because we know them ourselves, without considering if the audience knows them too. For instance, sometimes we just start saying “there was this nice big clock and it had this man coming out, and striking the chimes…”
And it doesn’t make too much sense to anyone. But instead, start by saying that you visited the Salar Jung Museum the other day, and everything will be clearer.
This seems to be simple common sense, but in fact it’s a lot harder to get this right than most people imagine.It is common to get carried away and imagine that the audience knows what one is talking about. But why should this be difficult at all? Because, really, you cannot tell people what they need to know, unless you clearly understand what they know and also what they do not know. Know your audience
In short, you must know your audience well. Let’s take a very simple example: “The Seven Samurai, Kurosawa’s finest work has influenced people across the world.” With a sentence like that, there’s a good chance that many people would not understand what I’m saying. So I need to take a step back. Does my audience know about Kurosawa? Have they heard of The Seven Samurai? Depending on the answer to these questions, I might revise my sentence:
“Kurosawa, one of the finest filmmakers in the world, influenced world cinema greatly with his film The Seven Samurai, which shows a poor village standing up to a gang of ferocious robbers with courage and intelligence.”
In simple day-to-day situations, like the one about the museum visit, this doesn’t seem to be important—after all, if your friend doesn’t understand something, you can always explain it again.One chance
But there are many instances in life, when you’ll get just that one chance. I had one such experience while interviewing one young graduate for a company. When asked a basic question like “What would you like to do as an alternate career?” he answered that he wanted to start a college in his village. Running a college can be a lucrative and ambitious business, and he didn’t seem like someone who had such ambitions. It was only after some probing that I found out there was no college in his village at present, and he saw it as a service to the people, rather than as a business.Solution
How do you avoid such gaps in communication? The solution is to consciously ask yourself: “What does this person know about me / this topic?” Make a list in your mind, if you wish. Once you have this, you will be able to clearly identify what it is that you need to communicate.
---
Online edition of India's National Newspaper The Hindu Monday, Mar 16, 2009
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