World Health Day 2014

World TB Day: Reach the 3 million_ LIVESTREAM from LSTMH, London

Watch live streaming video from lshtm at livestream.com

Key Facts: Tuberculosis

• Tuberculosis (TB) is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent.
• In 2012, 8.6 million people fell ill with TB and 1.3 million died from TB.
• Over 95% of TB deaths occur in low- and middle-income countries, and it is among the top three causes of death for women aged 15 to 44.
• In 2012, an estimated 530 000 children became ill with TB and 74 000 HIV-negative children died of TB.
• TB is a leading killer of people living with HIV causing one fifth of all deaths.
• Multi-drug resistant TB (MDR-TB) is present in virtually all countries surveyed.
• The estimated number of people falling ill with tuberculosis each year is declining, although very slowly, which means that the world is on track to achieve the Millennium Development Goal to reverse the spread of TB by 2015.
• The TB death rate dropped 45% between 1990 and 2012.
• An estimated 22 million lives saved through use of DOTS and the Stop TB Strategy recommended by WHO

Source for further details: http://www.who.int/mediacentre/factsheets/fs104/en/

TB profile of Nepal: http://www.who.int/tb/country/data/profiles/en/

CDC Grand Rounds: Multi-Drug Resistant Tuberculosis

Measles

Key facts

• Measles is one of the leading causes of death among young children even though a safe and cost-effective vaccine is available.
• In 2012, there were 122 000 measles deaths globally – about 330 deaths every day or 14 deaths every hour.
• Measles vaccination resulted in a 78% drop in measles deaths between 2000 and 2012 worldwide.
• In 2012, about 84% of the world's children received one dose of measles vaccine by their first birthday through routine health services – up from 72% in 2000.
• Since 2000, more than 1 billion children in high risk countries were vaccinated against the disease through mass vaccination campaigns ― about 145 million of them in 2012.

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Measles is a highly contagious, serious disease caused by a virus. In 1980, before widespread vaccination, measles caused an estimated 2.6 million deaths each year.

It remains one of the leading causes of death among young children globally, despite the availability of a safe and effective vaccine. Approximately 122 000 people died from measles in 2012 – mostly children under the age of five.

Measles is caused by a virus in the paramyxovirus family. The measles virus normally grows in the cells that line the back of the throat and lungs. Measles is a human disease and is not known to occur in animals.

Accelerated immunization activities have had a major impact on reducing measles deaths. Since 2000, more than one billion children in high risk countries were vaccinated against the disease through mass vaccination campaigns ― about 145 million of them in 2012. Global measles deaths have decreased by 78% from an estimated 562 400 to 122 000.

Signs and symptoms

The first sign of measles is usually a high fever, which begins about 10 to 12 days after exposure to the virus, and lasts four to seven days. A runny nose, a cough, red and watery eyes, and small white spots inside the cheeks can develop in the initial stage. After several days, a rash erupts, usually on the face and upper neck. Over about three days, the rash spreads, eventually reaching the hands and feet. The rash lasts for 5 to 6 days, and then fades. On average, the rash occurs 14 days after exposure to the virus (within a range of seven to 18 days).

Severe measles is more likely among poorly nourished young children, especially those with insufficient vitamin A, or whose immune systems have been weakened by HIV/AIDS or other diseases.

Most measles-related deaths are caused by complications associated with the disease. Complications are more common in children under the age of five, or adults over the age of 20. The most serious complications include blindness, encephalitis (an infection that causes brain swelling), severe diarrhoea and related dehydration, ear infections, or severe respiratory infections such as pneumonia. As high as 10% of measles cases result in death among populations with high levels of malnutrition and a lack of adequate health care. Women infected while pregnant are also at risk of severe complications and the pregnancy may end in miscarriage or preterm delivery. People who recover from measles are immune for the rest of their lives.

Who is at risk?

Unvaccinated young children are at highest risk of measles and its complications, including death. Unvaccinated pregnant women are also at risk. Any non-immune person (who has not been vaccinated or was vaccinated but did not develop immunity) can become infected.

Measles is still common in many developing countries – particularly in parts of Africa and Asia. More than 20 million people are affected by measles each year. The overwhelming majority (more than 95%) of measles deaths occur in countries with low per capita incomes and weak health infrastructures.

Measles outbreaks can be particularly deadly in countries experiencing or recovering from a natural disaster or conflict. Damage to health infrastructure and health services interrupts routine immunization, and overcrowding in residential camps greatly increases the risk of infection.

Transmission

The highly contagious virus is spread by coughing and sneezing, close personal contact or direct contact with infected nasal or throat secretions.

The virus remains active and contagious in the air or on infected surfaces for up to two hours. It can be transmitted by an infected person from four days prior to the onset of the rash to four days after the rash erupts.

Measles outbreaks can result in epidemics that cause many deaths, especially among young, malnourished children. In countries where measles has been largely eliminated, cases imported from other countries remain an important source of infection.

Treatment

No specific antiviral treatment exists for measles virus.

Severe complications from measles can be avoided though supportive care that ensures good nutrition, adequate fluid intake and treatment of dehydration with WHO-recommended oral rehydration solution. This solution replaces fluids and other essential elements that are lost through diarrhoea or vomiting. Antibiotics should be prescribed to treat eye and ear infections, and pneumonia.

All children in developing countries diagnosed with measles should receive two doses of vitamin A supplements, given 24 hours apart. This treatment restores low vitamin A levels during measles that occur even in well-nourished children and can help prevent eye damage and blindness. Vitamin A supplements have been shown to reduce the number of deaths from measles by 50%.

Prevention

Routine measles vaccination for children, combined with mass immunization campaigns in countries with high case and death rates, are key public health strategies to reduce global measles deaths. The measles vaccine has been in use for 50 years. It is safe, effective and inexpensive. It costs less than one US dollar to immunize a child against measles.

The measles vaccine is often incorporated with rubella and/or mumps vaccines in countries where these illnesses are problems. It is equally effective in the single or combined form.

In 2012, about 84% of the world's children received one dose of measles vaccine by their first birthday through routine health services – up from 72% in 2000. Two doses of the vaccine are recommended to ensure immunity and prevent outbreaks, as about 15% of vaccinated children fail to develop immunity from the first dose.

WHO response

The fourth Millennium Development Goal (MDG 4) aims to reduce the under-five mortality rate by two-thirds between 1990 and 2015. Recognizing the potential of measles vaccination to reduce child mortality, and given that measles vaccination coverage can be considered a marker of access to child health services, routine measles vaccination coverage has been selected as an indicator of progress towards achieving MDG 4.

Overwhelming evidence demonstrates the benefit of providing universal access to measles and rubella-containing vaccines. Globally, an estimated 562 400 children died of measles in 2000. By 2012, the global push to improve vaccine coverage resulted in a 78% reduction in deaths. Since 2000, with support from the Measles & Rubella Initiative (M&R Initiative) over 1 billion children have been reached through mass vaccination campaigns ― about 145 million of them in 2012.

The M&R Initiative is a collaborative effort of WHO, UNICEF, the American Red Cross, the United States Centers for Disease Control and Prevention, and the United Nations Foundation to support countries to achieve measles and rubella control goals.

In 2012, the MR Initiative launched a new Global Measles and Rubella Strategic Plan which covers the period 2012-2020. The Plan includes new global goals for 2015 and 2020:

By the end of 2015

• To reduce global measles deaths by at least 95% compared with 2000 levels.
• To achieve regional measles and rubella/congenital rubella syndrome (CRS) elimination goals.

By the end of 2020

• To achieve measles and rubella elimination in at least five WHO regions.

The strategy focuses on the implementation of five core components:

• achieve and maintain high vaccination coverage with two doses of measles- and rubella-containing vaccines;
• monitor the disease using effective surveillance, and evaluate programmatic efforts to ensure progress and the positive impact of vaccination activities;
• develop and maintain outbreak preparedness, rapid response to outbreaks and the effective treatment of cases;
• communicate and engage to build public confidence and demand for immunization;
• perform the research and development needed to support cost-effective action and improve vaccination and diagnostic tools.

Implementation of the Strategic Plan can protect and improve the lives of children and their mothers throughout the world, rapidly and sustainably. The Plan provides clear strategies for country immunization managers, working with domestic and international partners, to achieve the 2015 and 2020 measles and rubella control and elimination goals. It builds on years of experience in implementing immunization programmes and incorporates lessons from accelerated measles control and polio eradication initiatives.

Source: http://www.who.int/mediacentre/factsheets/fs286/en/

Microscope at less than NRS 100 !!

 Source: http://www.ted.com/talks/manu_prakash_a_50_cent_microscope_that_folds_like_origami

ADV 2014 Seoul

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Improving the reach of vaccines to the developing world with Nanopatches

Oral vaccines: making them work in children who need them

WHO DG Speech for Polio Event in India

WHO Director-General celebrates polio-free India

Dr Margaret Chan
Director-General of the World Health Organization

Address at the “India celebrates triumph over polio” event
New Delhi, India 
11 February 2014

His Excellency, the President of India, the honourable Prime Minister of India, honourable Minister of Health and Family Welfare, the President of Rotary International, distinguished guests, ladies and gentlemen,

I am most pleased to join others in celebrating India’s triumph over polio. Everyone loves a success story, especially one of this magnitude. India has now gone three consecutive years without a single case of polio.

Confidence in this achievement is supported by a world-class surveillance system and a level of vigilance and preparedness ready to manage any imported case as a public health emergency.

In fact, the surveillance system in India not only meets all international standards for high-quality performance. It surpasses them.

After three years, we can say with certainty that the soil of this vast and densely populated country is now free of a virus that killed and crippled children for centuries.

Many critics believed that this day would never come, that the polio virus was too firmly entrenched in India, that India would never be polio free. In their view, India had limited means and unlimited challenges.

They could point to the country’s huge population, high birth rate, dense pockets of poverty, poor sanitation, widespread diarrhoea, difficult terrain, and resistance to vaccination among some groups.

These were real and daunting challenges, but the doubters missed one decisive factor: the power of India’s determination to achieve the impossible, to go from the world’s heaviest burden of polio cases to zero.

Viewed against the challenges, India’s achievement is an epic success story, a proof that any country that really wants to can defeat polio.

Government ownership of the eradication initiative, at union, state, and district levels, was decisive, as were the billions of dollars poured into the effort by the government.

India worked together seamlessly with its international partners, including Rotary International, the US Centers for Disease Control and Prevention, UNICEF, and WHO, with support from the Bill and Melinda Gates Foundation.

A can-do attitude was another reason for success, as witnessed by the unwavering dedication of millions of front-line workers. Vaccinators and religious leaders: I thank you for your service to your own people.

Let me illustrate the magnitude of this achievement with just a few statistics. In the 1970s, India was home to as many as 200 000 polio cases each year. Each nation-wide polio campaign involved the vaccination of nearly 170 million children by an army of 2.3 million vaccinators.

The reporting of suspected polio cases relied on a network of more than 39 000 health facilities from the public, private, and non-traditional sectors.

The need to reach every child meant that every nook and cranny of this vast country was criss-crossed by tireless polio workers. It also meant reaching every child in marginalized and migrant populations.

India, arguably facing the toughest challenges of any polio-endemic country, met each problem with creativity and innovation. In so doing, this country pioneered key operational and technical strategies as lessons for other countries.

India quickly took advantage of new technologies and served as a proving ground for their effectiveness. When better systems to support high-quality performance were needed, India built them. With support from the WHO country office, India built its world-class surveillance system. An efficient and reliable network of laboratories was established to support poliovirus testing and the rapid confirmation of cases.

Millions and millions of vaccinators were supervised and motivated. India also made very good use of another unique asset: its Bollywood film-stars and celebrities.

As the number of cases dwindled and the polio map began to shrink, independent monitoring of progress was introduced to provide a framework for accountability. Meticulous micro-plans were prepared to guide each and every vaccination team, on each and every day of an immunization campaign, ensuring logistical support down to the last detail.

Surveillance and monitoring generated high-quality data. Constant research produced the evidence for the fine-tuning of strategies, another strength of India’s polio programme.

Research improved understanding of the dynamics of transmission in different populations and environments, the effectiveness of different vaccines, and the reasons why some children were being missed. When research determined that vaccine efficacy was compromised in children with severe diarrhoea, social mobilization, led by UNICEF and supported by other partners, was used to educate households on diarrhoea prevention.

Pressure on the poliovirus increased each time a problem was uncovered and solved. In the end, it was the best of human creativity, ingenuity, determination, and perseverance that pushed the poliovirus out of India.

Ladies and gentlemen,

India has shown the world that there is no such thing as impossible. This is likely the greatest lesson, and the greatest inspiration for the rest of the world.

India’s leadership in polio eradication is widely appreciated and warmly welcomed, especially among the 194 Member States of WHO. The country has shared its experiences, best practices, lessons learned, and expert staff with the remaining endemic countries.

The defeat of polio in India paves the way for certification of the entire South-East Asia region as polio-free, possibly at the end of March. When this happens, nearly 80% of the world’s population will be living in countries that are certified polio-free.

The polio-free status of every country remains under threat as long as poliovirus is still circulating anywhere in the world. We still have some way to go. But India provides the decisive proof that eradication is feasible, technically and operationally.

India is fully aware of the need to safeguard its magnificent achievement. Immunization against polio remains high, and emergency preparedness and response plans are in place to respond urgently to any importations.

India will continue its role as a global leader as the Polio Endgame is implemented, including through the introduction of inactivated polio vaccine and the stepwise phasing out of oral polio vaccine.

Right now, the country is using the legacy of its polio success to intensify routine immunization, with a special emphasis on reaching underserved and marginalized populations. The elimination of measles will likely be the next permanent improvement for the health of India’s people.

The 13 January news that India had now gone 3 years without a polio case made headlines around the world. This is a monumental achievement that fully deserves today’s celebration.

Thank you.

Commentary: Science for the poor _ making Vaccines to combat poverty

Peter Hotez, M.D, Ph.D.
The Huffington Post | 11 February 2014

Is it possible to vaccinate against poverty?

According to the World Bank, an estimated 2.4 billion people live on less than $2 per day, while 1.2 billion live on less than $1.25 per day — a group often referred to as “the bottom billion”. We now know that almost all of the bottom billion and many of those living on less than $2 per day remain trapped in poverty because they are chronically debilitated by a group of afflictions known as the neglected tropical diseases, or ‘NTDs’.

NTDs are long-lasting parasitic and related infections such as ascariasis, trichuriasis, hookworm, schistosomiasis, lymphatic filariasis, onchocerciasis, trachoma, Chagas disease, and leishmaniasis. The major point is that these NTDs can actually cause poverty either because they make people too sick to go to work and limit agricultural productivity, or because they strike children at vulnerable times, thereby stunting their physical and intellectual development.    NTDs also disproportionately affect pregnant women, making them ill and causing them to produce low birth weight or premature infants.

Beyond their staggering public health impact, the economic losses from NTDs are also impressive: our studies with collaborators at Johns Hopkins University show that Chagas disease results in more than $7 billion lost annually, mostly in the Western Hemisphere. There are similar data available for many other NTDs.

Remember, the NTDs are not rare conditions — virtually every single person living in extreme poverty is infected with at least one of these conditions.

Science can offer a lot to prevent these infections, thereby making poor people well enough to   go back to work, children healthy and intellectually vibrant, and improving pregnancy outcomes. One approach now underway is annual mass treatment with a package of essential medicines that targets several NTDs at once, and costs only 50 cents per person. Although not a true vaccine, the World Health Organization uses the term “preventive chemotherapy” to describe this approach because when used over a period of time, together with other supportive measures, it is actually leading to the elimination of lymphatic filariasis and trachoma, and in some cases even river blindness in dozens of impoverished countries. In collaboration with several international organizations we organized a Global Network for NTDs that is raising awareness about the opportunity for these low-cost preventive chemotherapy approaches.

For other NTDs, however, we need new technologies. In 2011 the Sabin Vaccine Institute allied with Texas Children’s Hospital and Baylor College of Medicine to expand its development portfolio of new and novel vaccines to combat NTDs. The result is the expansion of a unique non-profit product development partnership that is located in Houston’s Texas Medical Center — a medical city of 100,000 people — to transition discoveries from the bench to the clinic and produce the next generation ‘antipoverty vaccines’, i.e. vaccines that would not only improve health but simultaneously also lift people out of poverty. For example, hookworm infection affects more than 400 million people in Africa, Asia, and the Americas, where it is a leading cause of anemia and childhood malnutrition, and has been shown to reduce future wage earnings. Our product development partnership, through activities led by Dr. Maria Elena Bottazzi, has developed, transitioned, and produced a prototype hookworm vaccine undergoing clinical trials in Brazil, and will soon undergo additional testing in Gabon through a so-called HOOKVAC consortium of European and African partners. We are also working to evaluate and modify the vaccine so it targets additional parasitic infections such as ascariasis and trichuriasis.
Finally, a new schistosomiasis vaccine is under development and will soon begin clinical trials.

Nor is poverty exclusive to developing countries or failed nations. Today, almost two million families in the United States live on less than $2 per day and poverty is rampant in southern states such as Texas and others along the Gulf Coast. We found that NTDs are also widespread among these impoverished Americans. For example 300,000 people in the United States suffer from Chagas disease, a cause of heart disease transmitted by kissing bugs — our group, which includes a consortium of Mexican institutions, is now working to develop one of the first Chagas disease vaccines for clinical trials.

Dr. Albert Sabin, whose name and legacy our Institute honors once said, “A scientist who is a human being cannot rest while knowledge which might reduce suffering rests on the shelf.” Our Sabin Vaccine Institute and Texas Children’s Hospital Center for Vaccine Development is one of six major international product development partnerships currently pioneering vaccine development in the non-profit sector. Together we are making the vaccines for diseases that affect millions if not billions but only those living in extreme poverty.

Almost thirty years ago I graduated from New York’s Rockefeller University, whose motto is Scientia pro bono humani generis – science for the benefit of humanity. Developing a new generation of antipoverty vaccines is a true expression of that concept.

Peter Hotez, M.D., Ph.D. is president of the Sabin Vaccine Institute and the founding dean of the National School of Tropical Medicine at Baylor College of Medicine, where he is also Professor of Pediatrics and Texas Children’s Hospital Endowed Chair of Tropical Pediatrics. Prof. Hotez is also the Fellow on Disease and Poverty at the James A. Baker Institute for Public Policy at Rice University. He is the author of Forgotten People, Forgotten Diseases (ASM Press).

Source: 

http://centerforvaccineethicsandpolicy.net/2014/02/15/commentary-science-for-the-poor-making-vaccines-to-combat-poverty/

New Oral Vaccines means No more needles

New oral vaccines are being developed to increase immunity against Tuberculosis (TB) and influenza, and prevent C. difficle, which will mean leaving needles behind, according to researchers from Royal Holloway, University of London. 

The new type of vaccinations were developed using probiotic spores by Professor Simon Cutting, lead researcher of the study, from the School of Biological Sciences at Royal Holloway.

The professor implemented trials to analyze the biology of the bacterium Bacillus subtilis, which caught the attention of microbiologists because it has the capability of making spores that live millions of years until they germinate in proper environmental conditions.

"The mechanisms by which this process occurs have fascinated microbiologists for decades making it one of the most intensively studied bacteria. Its simple life cycle and ease of use make it an ideal laboratory subject," said Cutting.Bacillus spores were found to be perfect for transporting antigens and boosting immune responses.

Cutting explained:

"Rather than requiring needle delivery, vaccines based on Bacillus spores can be delivered via a nasal spray, or as an oral liquid or capsule. Alternatively, they can be administered via a small soluble film placed under the tongue, in a similar way to modern breath fresheners. As spores are exceptionally stable, vaccines based on Bacillus do not require cold-chain storage alleviating a further issue with current vaccine approaches."

In addition to being less painful than vaccines given through jabs, oral vaccines also come with certain advantages, such as being safer to administer, particularly in nations where HIV is a major concern. Also, these types of vaccines will be more cost effective to make and easier to keep fresh, lowering the risk of adverse outcomes. 

Trials have been conducted, by Professor Cutting, to determine the effectiveness of Bacillus based vaccines for many different diseases, such as influenza, Tuberculosis, and tetanus. Now, he is is examining whether the vaccine can be used against Clostridium difficile, a disease extremely prevalent in the West.

C. difficile is a serious cause of diarrhea linked to antibiotics and can result in intense inflammation of the colon, or pseudomembranous colitis.

The professor said: "C. difficile, is a gastrointestinal infection that is commonly picked up following hospital stays and causes around 50,000 infections and 4,000 deaths per year in the UK, mostly in elderly patients. Currently, there is no vaccine against the disease, and although several approaches are currently undergoing clinical trials, none are expected to provide full protection, and new solutions are urgently needed."

Bacillus based vaccines offer distinct advantages as unlike other approaches, oral delivery can cause a more specific immune response in the gastrointestinal tract to fully eliminate C. difficile."

Cutting has been given private seed investment to continue his research and develop the new vaccine for Tuberculosis, C. difficile , and influenza.

Written by Christine Kearney

Source: http://www.medicalnewstoday.com/articles/251884.php

Copyright: Medical News Today
Not to be reproduced without the permission of Medical News Today.

Medical Cartoon

Impact of climate change and other factors on emerging arboviral diseases

Summary

While some sceptics remain unconvinced that global climate change is a reality, there is no doubt that during the past 50 years or so, patterns of emerging arbovirus diseases have changed significantly. Can this be attributed to climate change? Climate is a major factor in determining: (1) the geographic and temporal distribution of arthropods; (2) characteristics of arthropod life cycles; (3) dispersal patterns of associated arboviruses; (4) the evolution of arboviruses; and (5) the efficiency with which they are transmitted from arthropods to vertebrate hosts. Thus, under the influence of increasing temperatures and rainfall through warming of the oceans, and alteration of the natural cycles that stabilise climate, one is inevitably drawn to the conclusion that arboviruses will continue to emerge in new regions. For example, we cannot ignore the unexpected but successful establishment of chikungunya fever in northern Italy, the sudden appearance of West Nile virus in North America, the increasing frequency of Rift Valley fever epidemics in the Arabian Peninsula, and very recently, the emergence of Bluetongue virus in northern Europe. In this brief review we ask the question, are these diseases emerging because of climate change or do other factors play an equal or even more important role in their emergence?

Keywords

Climate change; 

Emerging diseases; 

Arboviruses; 

Chikungunya; 

Rift Valley fever; 

Bluetongue

Link: http://www.sciencedirect.com/science/article/pii/S0035920308003325

Benefits of Nanopatch

The inherent features of the Nanopatch™ delivery technology provide some key benefits that include:

Improved immunogenicity

By direct delivery of the vaccine to key immune cells, the Nanopatch™ can potentially either enhance the immune response generated by a vaccine, or allow the generation of an effective immune response with fraction of a full vaccine dose. Indeed, the Nanopatch™ has been shown in preclinical studies to result in a protective immunogenic response using as little as one hundredth of the dose required by conventional needle and syringe.

Comment: Need to study published literature & verify the statement

No cold chain
The coating formulations used to coat the patches can provide for ambient temperature stability of the vaccine. As a result, vaccine distribution would not need to rely on costly cold distribution chain that is otherwise required to prevent temperature damage which can render conventional vaccines ineffective or potentially harmful. Temperature stability also introduces the option of distributing vaccines to parts of the world where cold chain infrastructure is unreliable or non-existent.

Comment: Need to study published literature & verify the statement

Needle free

The array of Nanopatch™ microprojections rely on the use of an applicator to allow them to penetrate through the protective outer layer of the skin to deliver a vaccine. This contrasts the traditional needle and syringe where needle stick injuries are common and can lead to serious consequences due to the transmission of infectious diseases as a result. The Nanopatch™ projections are invisible to the naked eye and therefore are not anticipated to cause distress to people that dislike needles (around 10% of the population are considered to have a phobia against needles); this is expected to help improve patient compliance.

Comment: I agree

Pain free
The microprojection array of the Nanopatch™ has been designed to deliver vaccine directly to the key immune cells just below the skin surface. These projections do not reach a depth where they meet nerve endings, and so the Nanopatch™ delivery device is anticipated to be pain free.

Comment: I agree

Cost effective
The Nanopatch™ vaccine delivery system is being developed with high volume, low cost manufacture in mind, using well established manufacturing techniques. As a result of some of the other benefits listed above, there may be further cost savings due to using less vaccine to achieve an effective immunisation, elimination of cold chain costs and a significant reduction in the costs associated with needle stick injuries.

With its strong and unique benefits, we envisage this platform technology may be suitable for delivering a vast majority of vaccines.

Comment: I hope WHO / GAVI / UNICEF are in the same board

Source: http://www.vaxxas.com/nanopatch-technology/benefits

Bonnie Bassler: How bacteria "talk"

Transcript of TED talk

Bacteria are the oldest living organisms on the earth. They've been here for billions of years,and what they are are single-celled microscopic organisms. So they are one cell and they have this special property that they only have one piece of DNA. They have very few genes,and genetic information to encode all of the traits that they carry out. And the way bacteria make a living is that they consume nutrients from the environment, they grow to twice their size, they cut themselves down in the middle, and one cell becomes two, and so on and so on. They just grow and divide, and grow and divide -- so a kind of boring life, except that what I would argue is that you have an amazing interaction with these critters.

I know you guys think of yourself as humans, and this is sort of how I think of you. This man is supposed to represent a generic human being, and all of the circles in that man are all of the cells that make up your body. There is about a trillion human cells that make each one of us who we are and able to do all the things that we do, but you have 10 trillion bacterial cells in you or on you at any moment in your life. So, 10 times more bacterial cells than human cells on a human being. And of course it's the DNA that counts, so here's all the A, T, Gs and Cs that make up your genetic code, and give you all your charming characteristics. You have about 30,000 genes. Well it turns out you have 100 times more bacterial genes playing a role in you or on you all of your life. At the best, you're 10 percent human, but more likely about one percent human, depending on which of these metrics you like. I know you think of yourself as human beings, but I think of you as 90 or 99 percent bacterial.

These bacteria are not passive riders, these are incredibly important, they keep us alive.They cover us in an invisible body armor that keeps environmental insults out so that we stay healthy. They digest our food, they make our vitamins, they actually educate your immune system to keep bad microbes out. So they do all these amazing things that help us and are vital for keeping us alive, and they never get any press for that. But they get a lot of press because they do a lot of terrible things as well. So, there's all kinds of bacteria on the Earth that have no business being in you or on you at any time, and if they are, they make you incredibly sick.

And so, the question for my lab is whether you want to think about all the good things that bacteria do, or all the bad things that bacteria do. The question we had is how could they do anything at all? I mean they're incredibly small, you have to have a microscope to see one.They live this sort of boring life where they grow and divide, and they've always been considered to be these asocial reclusive organisms. And so it seemed to us that they are just too small to have an impact on the environment if they simply act as individuals. And so we wanted to think if there couldn't be a different way that bacteria live.

The clue to this came from another marine bacterium, and it's a bacterium called Vibrio fischeri. What you're looking at on this slide is just a person from my lab holding a flask of a liquid culture of a bacterium, a harmless beautiful bacterium that comes from the ocean,named Vibrio fischeri. This bacterium has the special property that it makes light, so it makes bioluminescence, like fireflies make light. We're not doing anything to the cells here.We just took the picture by turning the lights off in the room, and this is what we see.

What was actually interesting to us was not that the bacteria made light, but when the bacteria made light. What we noticed is when the bacteria were alone, so when they were in dilute suspension, they made no light. But when they grew to a certain cell number all the bacteria turned on light simultaneously. The question that we had is how can bacteria, these primitive organisms, tell the difference from times when they're alone, and times when they're in a community, and then all do something together. What we've figured out is that the way that they do that is that they talk to each other, and they talk with a chemical language.

This is now supposed to be my bacterial cell. When it's alone it doesn't make any light. But what it does do is to make and secrete small molecules that you can think of like hormones, and these are the red triangles, and when the bacteria is alone the molecules just float away and so no light. But when the bacteria grow and double and they're all participating in making these molecules, the molecule -- the extracellular amount of that molecule increases in proportion to cell number. And when the molecule hits a certain amount that tells the bacteria how many neighbors there are, they recognize that moleculeand all of the bacteria turn on light in synchrony. That's how bioluminescence works --they're talking with these chemical words.

The reason that Vibrio fischeri is doing that comes from the biology. Again, another plug for the animals in the ocean, Vibrio fischeri lives in this squid. What you are looking at is the Hawaiian Bobtail Squid, and it's been turned on its back, and what I hope you can see are these two glowing lobes and these house the Vibrio fischeri cells, they live in there, at high cell number that molecule is there, and they're making light. The reason the squid is willing to put up with these shenanigans is because it wants that light. The way that this symbiosis works is that this little squid lives just off the coast of Hawaii, just in sort of shallow knee-deep water. The squid is nocturnal, so during the day it buries itself in the sand and sleeps,but then at night it has to come out to hunt. On bright nights when there is lots of starlight or moonlight that light can penetrate the depth of the water the squid lives in, since it's just in those couple feet of water. What the squid has developed is a shutter that can open and close over this specialized light organ housing the bacteria. Then it has detectors on its back so it can sense how much starlight or moonlight is hitting its back. And it opens and closes the shutter so the amount of light coming out of the bottom -- which is made by the bacterium -- exactly matches how much light hits the squid's back, so the squid doesn't make a shadow. It actually uses the light from the bacteria to counter-illuminate itself in an anti-predation device so predators can't see its shadow, calculate its trajectory, and eat it.This is like the stealth bomber of the ocean.

But then if you think about it, the squid has this terrible problem because it's got this dying, thick culture of bacteria and it can't sustain that. And so what happens is every morning when the sun comes up the squid goes back to sleep, it buries itself in the sand, and it's got a pump that's attached to its circadian rhythm, and when the sun comes up it pumps out like 95 percent of the bacteria. Now the bacteria are dilute, that little hormone molecule is gone, so they're not making light -- but of course the squid doesn't care. It's asleep in the sand. And as the day goes by the bacteria double, they release the molecule, and then light comes on at night, exactly when the squid wants it.

First we figured out how this bacterium does this, but then we brought the tools of molecular biology to this to figure out really what's the mechanism. And what we found -- so this is now supposed to be, again, my bacterial cell -- is that Vibrio fischeri has a protein -- that's the red box -- it's an enzyme that makes that little hormone molecule, the red triangle. And then as the cells grow, they're all releasing that molecule into the environment, so there's lots of molecule there. And the bacteria also have a receptor on their cell surface that fits like a lock and key with that molecule. These are just like the receptors on the surfaces of your cells. When the molecule increases to a certain amount -- which says something about the number of cells -- it locks down into that receptor and information comes into the cells that tells the cells to turn on this collective behavior of making light.

Why this is interesting is because in the past decade we have found that this is not just some anomaly of this ridiculous, glow-in-the-dark bacterium that lives in the ocean -- all bacteria have systems like this. So now what we understand is that all bacteria can talk to each other. They make chemical words, they recognize those words, and they turn on group behaviors that are only successful when all of the cells participate in unison. We have a fancy name for this: we call it quorum sensing. They vote with these chemical votes, the vote gets counted, and then everybody responds to the vote.

What's important for today's talk is that we know that there are hundreds of behaviors that bacteria carry out in these collective fashions. But the one that's probably the most important to you is virulence. It's not like a couple bacteria get in you and they start secreting some toxins -- you're enormous, that would have no effect on you. You're huge.What they do, we now understand, is they get in you, they wait, they start growing, they count themselves with these little molecules, and they recognize when they have the right cell number that if all of the bacteria launch their virulence attack together, they are going to be successful at overcoming an enormous host. Bacteria always control pathogenicity with quorum sensing. That's how it works.

We also then went to look at what are these molecules -- these were the red triangles on my slides before. This is the Vibrio fischeri molecule. This is the word that it talks with. So then we started to look at other bacteria, and these are just a smattering of the molecules that we've discovered. What I hope you can see is that the molecules are related. The left-hand part of the molecule is identical in every single species of bacteria. But the right-hand part of the molecule is a little bit different in every single species. What that does is to confer exquisite species specificities to these languages. Each molecule fits into its partner receptor and no other. So these are private, secret conversations. These conversations are for intraspecies communication. Each bacteria uses a particular molecule that's its language that allows it to count its own siblings.

Once we got that far we thought we were starting to understand that bacteria have these social behaviors. But what we were really thinking about is that most of the time bacteria don't live by themselves, they live in incredible mixtures, with hundreds or thousands of other species of bacteria. And that's depicted on this slide. This is your skin. So this is just a picture -- a micrograph of your skin. Anywhere on your body, it looks pretty much like this, and what I hope you can see is that there's all kinds of bacteria there. And so we started to think if this really is about communication in bacteria, and it's about counting your neighbors, it's not enough to be able to only talk within your species. There has to be a way to take a census of the rest of the bacteria in the population.

So we went back to molecular biology and started studying different bacteria, and what we've found now is that in fact, bacteria are multilingual. They all have a species-specific system -- they have a molecule that says "me." But then, running in parallel to that is a second system that we've discovered, that's generic. So, they have a second enzyme that makes a second signal and it has its own receptor, and this molecule is the trade language of bacteria. It's used by all different bacteria and it's the language of interspecies communication. What happens is that bacteria are able to count how many of me and how many of you. They take that information inside, and they decide what tasks to carry outdepending on who's in the minority and who's in the majority of any given population.

Then again we turn to chemistry, and we figured out what this generic molecule is -- that was the pink ovals on my last slide, this is it. It's a very small, five-carbon molecule. What the important thing is that we learned is that every bacterium has exactly the same enzymeand makes exactly the same molecule. So they're all using this molecule for interspecies communication. This is the bacterial Esperanto.

Once we got that far, we started to learn that bacteria can talk to each other with this chemical language. But what we started to think is that maybe there is something practical that we can do here as well. I've told you that bacteria do have all these social behaviors,they communicate with these molecules. Of course, I've also told you that one of the important things they do is to initiate pathogenicity using quorum sensing. We thought, what if we made these bacteria so they can't talk or they can't hear? Couldn't these be new kinds of antibiotics?

Of course, you've just heard and you already know that we're running out of antibiotics.Bacteria are incredibly multi-drug-resistant right now, and that's because all of the antibiotics that we use kill bacteria. They either pop the bacterial membrane, they make the bacterium so it can't replicate its DNA. We kill bacteria with traditional antibiotics and that selects for resistant mutants. And so now of course we have this global problem in infectious diseases. We thought, well what if we could sort of do behavior modifications, just make these bacteria so they can't talk, they can't count, and they don't know to launch virulence.

And so that's exactly what we've done, and we've sort of taken two strategies. The first one is we've targeted the intraspecies communication system. So we made molecules that look kind of like the real molecules -- which you saw -- but they're a little bit different. And so they lock into those receptors, and they jam recognition of the real thing. By targeting the red system, what we are able to do is to make species-specific, or disease-specific, anti-quorum sensing molecules. We've also done the same thing with the pink system. We've taken that universal molecule and turned it around a little bit so that we've made antagonistsof the interspecies communication system. The hope is that these will be used as broad-spectrum antibiotics that work against all bacteria.

To finish I'll just show you the strategy. In this one I'm just using the interspecies molecule,but the logic is exactly the same. What you know is that when that bacterium gets into the animal, in this case, a mouse, it doesn't initiate virulence right away. It gets in, it starts growing, it starts secreting its quorum sensing molecules. It recognizes when it has enough bacteria that now they're going to launch their attack, and the animal dies. What we've been able to do is to give these virulent infections, but we give them in conjunction with our anti-quorum sensing molecules -- so these are molecules that look kind of like the real thing, but they're a little bit different which I've depicted on this slide. What we now know is that if we treat the animal with a pathogenic bacterium -- a multi-drug-resistant pathogenic bacterium -- in the same time we give our anti-quorum sensing molecule, in fact, the animal lives.

We think that this is the next generation of antibiotics and it's going to get us around, at least initially, this big problem of resistance. What I hope you think, is that bacteria can talk to each other, they use chemicals as their words, they have an incredibly complicated chemical lexicon that we're just now starting to learn about. Of course what that allows bacteria to do is to be multicellular. So in the spirit of TED they're doing things togetherbecause it makes a difference. What happens is that bacteria have these collective behaviors, and they can carry out tasks that they could never accomplish if they simply acted as individuals.

What I would hope that I could further argue to you is that this is the invention of multicellularity. Bacteria have been on the Earth for billions of years; humans, couple hundred thousand. We think bacteria made the rules for how multicellular organization works. We think, by studying bacteria, we're going to be able to have insight about multicellularity in the human body. We know that the principles and the rules, if we can figure them out in these sort of primitive organisms, the hope is that they will be applied to other human diseases and human behaviors as well. I hope that what you've learned is that bacteria can distinguish self from other. By using these two molecules they can say "me" and they can say "you." Again of course that's what we do, both in a molecular way, and also in an outward way, but I think about the molecular stuff.

This is exactly what happens in your body. It's not like your heart cells and your kidney cells get all mixed up every day, and that's because there's all of this chemistry going on,these molecules that say who each of these groups of cells is, and what their tasks should be. Again, we think that bacteria invented that, and you've just evolved a few more bells and whistles, but all of the ideas are in these simple systems that we can study.

The final thing is, again just to reiterate that there's this practical part, and so we've made these anti-quorum sensing molecules that are being developed as new kinds of therapeutics. But then, to finish with a plug for all the good and miraculous bacteria that live on the Earth, we've also made pro-quorum sensing molecules. So, we've targeted those systems to make the molecules work better. Remember you have these 10 times or more bacterial cells in you or on you, keeping you healthy. What we're also trying to do is to beef up the conversation of the bacteria that live as mutualists with you, in the hopes of making you more healthy, making those conversations better, so bacteria can do things that we want them to do better than they would be on their own.

Finally, I wanted to show you this is my gang at Princeton, New Jersey. Everything I told you about was discovered by someone in that picture. I hope when you learn things, like about how the natural world works -- I just want to say that whenever you read something in the newspaper or you get to hear some talk about something ridiculous in the natural worldit was done by a child. Science is done by that demographic. All of those people are between 20 and 30 years old, and they are the engine that drives scientific discovery in this country. It's a really lucky demographic to work with. I keep getting older and older and they're always the same age, and it's just a crazy delightful job. I want to thank you for inviting me here. It's a big treat for me to get to come to this conference.