Ending the arms race with infectious diseases | Janelle Ayres | TEDxSanDiego

Ending the arms race with infectious diseases | Janelle Ayres | TEDxSanDiego


Translator: Ilya Bychkov
Reviewer: Denise RQ “It is now time to close the book
on infectious diseases and declare the war
against pestilence won.” It is something we all want. We all want to live in a world
free of infectious diseases. Think about when you watch movies
like, “Contagion” or “Outbreak.” or when you watch the news coverage on the Ebola virus
or more recently, the Zika virus. How did seeing those things make you feel? They freaked you out, right? Infectious diseases
evoke legitimate feelings of fear in every single one of us, because none of us is free from the threat
of contracting an infection. The quote that I began with is from
the US Surgeon General from the 1960s. He made this statement in response
to the success of the early antibiotics. It is a statement that accurately reflects
the overall sentiment of the time: which is that because we had such great success
with the early generation of antibiotics, infectious diseases were soon
going to become a worry of the past. I want to tell you about one
person’s war against an infection that took place just last year. That is my dad’s. In January of 2015,
my dad became very sick. It took the doctors
a few weeks to figure it out, but they realized that he had gallstones, and he would have to have
his gallbladder removed. That diagnosis was actually
a relief to all of us, because gallstones are very common
in the United States, and gallbladder removal surgery is one of the most commonly performed
surgeries in the country. So this is basically standard
operating procedure for his doctors. We couldn’t imagine that anything
serious could possibly go wrong. Actually, nothing serious did go
wrong with his surgery. It went quite well.
He was discharged from the hospital, but 12 hours after his discharge,
my mum sent me a text. It said, “He can’t walk.
I have to call an ambulance. I don’t know what’s wrong.” My family is up in the Bay Area; I was down here in San Diego
when this happened. So my sister was communicating to me
from the ICU my dad’s symptoms. I’m the only biologist in my family, so you can imagine how confused they were. How could 12 hours ago
my dad be perfectly healthy, and discharged from the hospital, and now he is laying paralyzed
in a bed in the intensive care unit? But after I heard his symptoms,
I knew exactly what had happened. My dad had sepsis. If you don’t know what sepsis is this is a life-threatening condition that occurs when your body’s response
to an infection is so powerful that it begins damaging
its own tissues and organs. It’s pretty much a death sentence because it has mortality rates
greater than 80%. I dropped everything. I had to rush home. I had to get to the hospital
to be with him and to talk with his doctors. It felt like I couldn’t get there
fast enough. First, my flight was delayed. Then I had to battle Bay Area traffic
for over two hours. I was certain that he was going to be gone
by the time I got to the hospital. But he wasn’t. When I walked into his room in the ICU, my dad waived to me and gave me
one of his classic thumbs up that I had seen 1,000 times growing up. The doctors confirmed
that he did have sepsis. What happened is that his gallstones
went undetected for so long, that his gallbladder became infected. From there, the bacteria
spread into his bloodstream, and then infected his vertebrae,
and that caused his paralysis. It was his body’s response
to the bacteria being in the blood that caused him to have sepsis. The treatment strategy
proposed by his doctors was really the only option
they had available for them: to administer broad spectrum antibiotics and to hope for the best. I sat there for a week with my dad, and I can remember obsessively
watching his vitals monitors, hoping the next blood pressure read
was going to be higher, or the next ventilator read
was going to be lower. I was looking for any indication that the infection was actually
responding to the antibiotics. But the numbers never got better, because he had
an antibiotic-resistant infection, making the only strategy that was
available to him completely useless. After nine days, my dad lost
his war against an infection and he passed away. It is because of the global spread
of the antibiotic resistance, and our current strategies
for treating infectious diseases that my dad died. We are further away than ever from closing
the book on infectious diseases. But why? If we really had such great success
with the early generation antibiotics, how is it possible
that we screw things up so badly that we now are in far worse condition
than we were 50 years ago? And the main issue is our perspective on
how we should be dealing with problems. When we are faced with the challenge, we think that in order to solve
that challenge, we have to annihilate
the source of the problem. If you have a mouse in your house,
you set traps to try to kill that mouse. If you have a weed in your yard, you spray toxic chemicals
all over your yard to try to kill that weed and prevent
new ones from coming in. Infectious diseases are
no exception to this mentality. All of our current strategies
to fight infectious diseases are based on the question: how do we fight infections? As a result, we declared a war
against infectious diseases. We put all our efforts
into developing weapons in the form of antibiotics and antivirals
in order to win this war. But bacteria and viruses
are incredibly slippery targets. They can evolve so quickly resistance
to our weapons, making them obsolete. So what do we do? Our solution has been
to just make more new weapons, make more antibiotics,
make more antivirals. It’s not surprising that the microbes have
evolved resistance to our new weapons. So our perspective is fueling
an ever escalating arms race between us and the infectious diseases. The scary fact is it’s
an arms race we can never win. The second issue, in addition
to driving drug resistance, is that there is a fundamental issue
with this perspective, if we actually want to develop therapies that will enable a patient
to survive an infectious disease. To help you understand
what I mean by this, I want to continue with the war analogy. In an actual war, there is
combat between soldiers. But that combat
does not occur in isolation. Something that can happen is what’s called
“the collateral damage of war,” which is the unintentional
or incidental damage that can occur to civilians,
property, economy, and the society. The same principle
can be applied to an infection that’s occurring in a patient’s body. So if we have a septic patient, there is going to be bacteria,
virus, or even fungus that has entered their bloodstream. Their immune system
is going to recognize that foreign invader and it’s going to mount a killing response
to try to fight that infection. But that fight
is not occurring in isolation. What happens is, basically, every other physiological system
in the patient’s body becomes damaged: the liver, the kidneys,
the intestine, lungs, the cardiovascular system,
all get damaged. You can give
a septic patient antimicrobials, and they might be effective
at killing the infection, but you are left with a patient that has suffered extreme
collateral damage to his body. For my dad, even if his infection
was sensitive to the antibiotics, the likelihood of him
to surviving was very low because he suffered so much physiological
damage from the infection. What he needed were therapies
that would fix that physiological damage. He wasn’t given any drugs that do that
because those drugs don’t exist; because we haven’t been approaching
infectious diseases from the right perspective. So if we’ve been asking
the wrong question, what is the question
that we should be asking? Instead of asking,
“How do we fight infections?”, we should be asking
“How do we survive infections?” I know that a single word change
from “fight” to “survive” seems simple, but by making the single change, we’ve completely changed
the meaning of the question. If we can understand
the answer to this question, we will completely change the way
we treat infectious diseases. We will be able to develop
drugs, therapies, strategies that will enable the patient
to survive an infection without driving drug resistance
in the microbial populations. Because these drugs will be
fixing the collateral damage that’s happened in the patient’s body rather than targeting the microbe
that’s causing the infection. I became very interested in this question,
“How do we survive infections?” when I was getting my PhD
at Stanford about ten years ago. We all know that our bodies
have an immune system, and this immune system is important for recognizing microbes
that are invading our body, and it is important for mounting
a killing response against these microbes to fight the infection. We found in addition to our immune system, our bodies encode
a distinct defense system that we call the tolerance defense system. This tolerance defense system
is absolutely necessary for our ability to survive infections. It protects us from mortality by preventing and fixing
the collateral damage that happens to our bodies
during infectious diseases. This is really exciting
because it means that if we can find out how this tolerance defense system
is working in our bodies, we can change the way
we treat infectious diseases, we will be able to develop therapies that overcome the limitations
of current strategies that are available, we can develop strategies
that promote survival without driving drug resistance. So then how do we go about doing this? This is actually a main goal
of my team at the Salk Institute. We’re committing to understanding
this tolerance defense system so that we can make this a reality. We take a variety of approaches
to address this goal, but one of our main approaches
that we’re really excited about, and that we have already
been successful with is we’re leveraging our interactions
with beneficial microbes. Right now all of you have
about three pounds of bacteria that are living on you body surfaces
exposed to the environment. If we sprinkle in some viruses
and some fungus, now you have your microbiome. Your microbiome is
absolutely essential for your health. We have an evolutionary theory,
that has lead us to predict that the microbiome has evolved mechanisms
to turn on our tolerance defense system. It can effectively manipulate
this defense system to promote our health. We are using the microbiome to teach us
how to turn tolerance defenses on, to teach us what they are,
how to manipulate them to promote health. We are using these microbes
as platforms for drug design so that we can move this into the clinic. For example,
we’ve recently identified an E. coli that lives in the intestines
of healthy individuals. This E. coli has taught us
that we can cure infectious diseases by mediating communication between the immune system,
our fat tissue, and our skeletal muscle, by preventing collateral damage
in the form of skeletal muscle wasting. In pre-clinical trials, just by orally administering
this E. coli to the model patients, we can cure sepsis, bacterial pneumonia,
typhoid fever, and infectious diarrhea without the need for a single antibiotic. I think that’s amazing. I think it’s exciting (Applause) I think it opens up a promising future for our ability to treat
and cure infectious diseases. My lab will continue to do this. We are committed to it,
but we can’t do it alone. We are all vulnerable to the threat
of contracting an infectious disease. We are all terrified of that threat. But if you leave here
with one thing today, I want you to leave here
believing that there is hope to get us out of the mess
that we got ourselves into. The first step to this
is really changing our perspective going from “How do we fight infections?”
to “How do we survive infections?” All of you: doctors, scientists,
health care officials, drug companies need to make
that perspective shift. We have the technology
and knowledge to do it. We have to make that shift,
because it’s only then when we’ll truly be able to close
the door on infectious diseases and end the war against pestilence. Thank you. (Applause)

3 Replies to “Ending the arms race with infectious diseases | Janelle Ayres | TEDxSanDiego”

  1. What an inspiring presentation! Changing the perspectives changes everything. The mentality of war and fight got us in the trenches and we've been stuck there. Now we need to realize that the world may evolve through wars and fights, but it exists by peace and coexistence. We can only live by surviving infection, not by fighting it. If we understand that, as Ayres said, then we would have hope and be able to close the books on infections. Let this be the final chapter. Thank you so much for your work and inspiration!

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