Home » Bugs, Drugs and Guts: Pratik Shah at TEDxBeaconStreet (Full Transcript)

Bugs, Drugs and Guts: Pratik Shah at TEDxBeaconStreet (Full Transcript)

Pratik Shah – TRANSCRIPT

I’m going to talk about something we cannot see, and we’re going to visualize it today together. So let me start with a very simple question about who we are.

As a microbiologist and as a geneticist, as a biologist, when I look at all of you right now, I see one human, with 30 trillion bacteria inside you. That’s right, at this very moment, all of us are carrying 30 trillion bacteria. They are invisible, they are amazing, they do stupendous things for us. They help us digest our food, they help us act as sentinels of our immune system, but we never see them.

Ladies and gentlemen, meet your microbio. What we know about bacteria and infectious diseases is the dark side of this interaction we have with them, which is commonly known as disease, and we all are familiar with epidemics of plague, cholera, and right now the ongoing pandemic of Ebola that’s going on in Africa, and in our country a little bit, too. So how do these relationship shift from being 30 trillion harmless bacteria to making us sick? And what can we do? Throughout history we have been combating bugs in different ways, and in the 20th century we discovered something called antibiotics. Antibiotics are these small molecules of drugs that you take, you eat, or you inject to kill the bacteria in your body. Unfortunately, they end up killing both the good and the bad, and that’s a problem. While we were innovating, bacteria were innovating too.

They were like, “Oh, OK” So what they did is they became resistant to almost all the antibiotics that we have I had a shoulder surgery five years back, and when I talked to my physician after coming out of surgery, the list of antibiotics I was put on was crazy; I was like, “Wow!” Then he, or she, at that point, they both told me that this is the current state where many bugs that we have now are not treated with these antibiotics that we have.

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And the numbers are staggering: every year, 69 million kids die before they reach their fifth birthday. Out of these children, approximately 2 million kids die due to pneumonia and diarrhea, and these are infectious diseases. If you see, there is no Ebola on this slide. We need to start a conversation about managing infectious diseases better in our world that we live in.

President Barack Obama in September of this year issued an executive order, and the order states that scientists, innovators, community members like you, all of us should come together and brainstorm for a better way to manage infectious diseases because our current arsenal of drugs which can treat infections has been depleted. To solve these things, there are a couple of things we need to know. The first thing we need to know is that we will have access to a patient whom we will call John. John consistently falls ill because he drinks contaminated water, and gets diarrhea. And before we leave this room, we’re going to make sure John gets better.

That’s the task for today. Diarrhea is a serious disease. It kills approximately 2,000 kids every day. Let’s simulate a quick diarrheal infection in this room, quickly. If you were in John’s body right now, and these were the walls of John’s intestines, and all of you were bacteria, there were two things you did when you entered John’s body.

The first thing you did is you grabbed a seat; that’s what you did when you entered this room. The second thing you did as soon as you entered is you looked for food. And that’s exactly what infectious agents do: they get into our body, they find a place to park themselves, and they start eating. These are usually called dietary requirements of infectious agents. As a microbiologist, I am passionate to not kill bacteria first, before we understand what they do to us.

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Till now, we have been killing them without understanding what they do, so let’s change the approach a little bit here. So this is John, drinking contaminated water, and this is you in John’s guts, coming in, you grab a seat, and John’s body provides you with this amazing food that you love. The bugs eat these food molecules that John’s body naturally provides them, and they become virulent, pathogenic, and they cause John diarrhea, obviously I decided to intersect into this problem in a different way, I wanted to understand what other food sources our body provides to bacteria when they cause infection. The technology I used to understand that is called metabolomics.

What metabolomics does is that it basically allows you to take any biological sample, infected sample, from a patient, from an animal, and lets you understand, get a peek or eavesdrop into the conversation that’s happening between a patient and a bacterium, and understand what are the food sources that the body is producing when we are sick. These food sources are usually called metabolites. These are the food sources that the bugs get when we get infected. With this information, I was able to build a Google map of all the metabolites you get when you are sick, – in the context of diarrhea and a couple of other infectious diseases – and these are the metabolites your body produces once you get sick. Apparently, humans had been dealing with bacteria before we invented antibiotics, right? Antibiotics in the 20th century.

It turns out when you’re sick, your body produces two different kinds of metabolites. The first metabolite your body produces are these blue ones which are called pathogenic metabolites. These pathogenic metabolites, when the bugs eat them, produce millions of molecules of toxins, and these are the toxin molecules that the bugs produce, and you get sick.

On the other hand, your body also produces millions of molecules – small amounts or trace amounts, depending on the infection – and these are the green metabolites – just colored here for understanding – that the bugs have evolved not to eat, they’ve learned to ignore and not eat them, or learned to circumvent themselves from these metabolites. So I did an experiment in the lab: what if we make these bugs eat these non-pathogenic or these other metabolites which they usually don’t eat? The answer was: when they eat those metabolites, they basically become avirulent or nonpathogenic.

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In other words, they turn their toxin production down More toxin, disease; less toxin, less disease. So what we have is that nature has programmed us and bugs to have this conversation, and the conversation basically is: what do bacteria eat when they cause disease? Usually they eat the foods which make them pathogenic and make toxins. Sometimes, we can change these interactions by making the bugs eat things which sometimes make them nonpathogenic. So this is the handle we have on John.

Now let’s try and cure John, OK? So, John has diarrhea, and we’re going to see what we can do to help John. This is the second experiment I did in the lab. I reasoned if all of you are bacteria in John’s body, you come inside this room, you are expecting pathogenic metabolites, and this is what you’ve been eating, let’s assume that’s called steak. What if, when you walked into John’s body, we make John give you the other green, nonpathogenic metabolites? Let’s call them salad. So I said: “OK, let’s see what happens to John.” These are not steaks and salads, this is for the purpose of the talk, these are organic molecules. You guys are smarter than me, so I’m assuming you got that. So you did that, and basically what happens is – I was surprised – I failed miserably. The bugs wouldn’t eat them, they would not like them It’s like training a pet: they’re like, “No, No.”

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