And my first question is a point that several of you hit on.

But we have spent very little time talking about this week and which is anti microbial resistance.

Um, it as an issue comes right up to the issues that we have been talking about around outbreaks.

I would argue that it's sort of belongs and inside the tent of this conversation.

But reasonable people can disagree, given the focus on pandemic influenza that we've had, but really just as a model for threats that can quickly harm human health.

I'd love it if we could all just comment on anti microbial resistance, how big a threat it is and how big of a challenge it is and whether the tools that we are thinking about from surveillance systems, building better vaccines, all of the stuff we've been talking about to what extent is that helpful in this conversation or does am our need a different set of strategies, and I know several of you talked touched on it and Hillary, as you thought about that the national global health security strategy by the security strategy to what extent has am are played into that conversation and then most vocal.

When we get to you, as you guys have thought about your surveillance systems for these very classic diseases, what about a M R.

As a threat to the population of library, so I won't ask anymore?

I think I've laid out the question.

I'll start with Mike, and then if we could just go down the road.

Well, first, I think we have to just really come to grips with the reality that, like earthquakes, hurricanes and tsunamis and recover resistance occurs.

Um, a very fascinating study that was done in a few years ago when a group of researchers went back into one of most distant areas that calls bad caverns an area that had not ever seen human contact before.

400 million years back in time, and when they sampled the walls accepted Clea, they not only recovered a whole number of bacteria, but they found that the bacteria resistant to 14 of our current leading antibiotics we have today and say, Well, how did that happen?

Well, they were all along competing for space and food as bacteria and they had their own evolutionary pressure that brought them to develop similar resistance issues to what we today capture relative to our modern antibiotics.

So this has been happening.

What we've done is we've put it on steroids, in a sense, by the dumping of the amount of of antibiotic into the environment that we have, whether it's through humans, whether it's through animals, whatever and so we have to understand is from an evolutionary standpoint, this is going to happen.

It is happening and it's only gonna get worse.

It's accelerating.

And I think that to the extent that we for a long time have predicted severe challenges around and local resistance, we're now just really beginning to realize in depth the extent to which it's impacting treatment of disease, clinical outcome, how it's being used to cover for poor sanitation, et cetera, which then just accelerates the problem and the roll with the food supply plays, I just would add one last piece.

I think one of the areas that's going to come back and be a real challenge for us also is, and I think this clearly has been well described recently in the Microbiome Studies Animal Crow bills have a lot of downsized to humans that we never appreciated.

Clearly they've had a lot of upsides.

They have been lifesaving in so many ways.

But the relationship between those gut bacteria the skin vector that we've evolved with over the last hundreds of thousands of years, were very critical in terms of the human physiologic response and the signaling that goes on between them.

And when we came in and started altering that with Anna McRobie ALS, we've actually created a whole nother other set of Helmand health problems.

And I think that that we're gonna learn one day that how we use anima crow Bealls to reduce the risk of infection disease is gonna be critical.

Just very briefly say to your question, Yes.

We need whole new strategies.

We, anyway, say we it's the world, you know, if we don't take this on globally and to follow up on the point just made, if there's a disease anywhere, it will be everywhere.

We're seeing that with chemical resistance.

You know, the Chinese introduced Colistin into the odd population four years ago, and before we knew it overnight Colistin resistant bacteria around the world and So I think that to the extent that we also deal with this, it can't be a coalition of the willing.

It has to be a complete worldwide effort because otherwise we'll just continue accelerated.

Great.

And Dennis says, You answer this.

I'm gonna put one more a little spin on it, which is so as a practicing physician, I feel like I get bombarded with antibiotic stewardship.

And yet I hear 1990% of antibiotics.

My weight is in the farming sector.

And so whose fault is it?

Is it mine, or is it?

There's like, How do we apportion blame between me, uh, versus our food supply in our food industry and our farming industry?

And I'm not really trying to apportion blame, but I'm trying to get a sense of from your perspective, as you think about, you know, seizes you Think about, um Am are where are the major sources of that evolutionary stress that are creating these problems?

Well, it's unfortunately in both categories, and they do accelerate different kinds of problems.

Uh, the animal husbandry industry clearly has contributed a substantial amount, and there's been a defensive posture there that has made it very difficult for us to try to deal with that issue, but humans have contributed their own.

I would also add, though, that what we don't understand is on the global level, whether it's animals or humans.

Antibiotics are like candy.

They are basically the 1st 2nd and third line of medical care is to go to your local quote unquote store because frankly they don't have except health care.

And because of the diseases, particularly of low and middle income countries, this becomes by default what you do so that house to also be added.

Let me just add one last piece because I was involved with this and some of the people know about this.

Just last week, we made an announcement.

There turns out that there is a very major trade in dogs being sold in pet stores throughout the United States and as a result of the exchange of goes on between these animal breeders and so forth, we now have bred a strain of campylobacter that we have no antibiotics for.

If you get infected with this thing, good luck and we have seen numerous infections, particularly young Children that have been very severe and acute that we don't have anything to treat it with, and it's now part of the dog breeding industry in the United States.

So there's an example where it wasn't even livestock.

It was pets and and the concern that we have with it, let me first bring the discussion back to 1918 because what's the difference between 1918?

And if it's similar viruses to emerge in 2018 this upcoming spring of 2019 and in 1918 What didn't we have?

We didn't have antibiotics.

We didn't have antivirals.

We didn't have vaccines.

Uh, if we were to have a similar event for as long as it takes to get the vaccine, we would still have antivirals and antibiotics.

And that's significant because when you look retrospectively at 1918 you know half or so of the deaths were due to the virus.

Half were secondary bacterial infections, so anti virals antibiotics will be a very fast frontline response.

If we move into a you know, a post antibiotic world, we're moving back to 1918.

And so just to tie the circle back, you know the vulnerabilities are extraordinary.

Thea, other about you know what's the relative balance of influence at livestock, aquaculture?

Human environmental?

We don't know.

And largely because we've spent a lot of our effort over the last two decades really zeroing in on clinical practices, right prescriber users.

This is a big black hole out there in terms of what's the contributing factors around animal husbandry, aquaculture and environmental contamination in an environment where, as Mike said, you already have just a natural dynamic of evolution within bacteria we don't know.

And that's one of the really important one health agendas, which is to bring a much deeper evidence based understanding.

What are the relative contributions?

Because it talks about risk mitigation.

And you really need to be smart about that because Mother Nature is doing her own independent of us evolution as well.

Hillary, have you got sad about this in the national strategies?

Yes.

So I will add a just a few things to the comments my colleagues made, and that is when I, from my perspective, we think of things in terms of policy.

How do we put in place policies?

How do we mobilize either the U.

S government or the global community towards specific actions and Aymar will certainly continue to be a critically important issue.

Um and so from the vantage point of organizing actions, one of the effective ones has been the global health security agenda, which you heard Osaka mentioned in terms of a group of over 60 countries working together towards specific technical actions as defined in the joint external evaluation.

And a M R is one of the action packages under G.

H s A.

There is a working group that is it's a global working group that is very active and they're trying to identify different new solutions and trying thio put in place actions to counter this problem.

But it certainly will continue to be a, um a critical issue.

And I'll just take a moment since you asked about the global health security strategy which I didn't have time to mention in my previous remarks.

We've been the National Security Council in particular, has been tasked with coordinating the development of a global health security strategy.

This was in the F 18 omnibus and so we're working on that.

There are specific things that it asks the U.

S government to dio, but we're taking a comprehensive approach similar to what we did with bio defense toe.

Look at how do we define global health security?

What does it include on doesn't go beyond some of the things that we've traditionally thought of.

So it's all I can say at this point.

But it's a really great opportunity to think through these issues and specific to global security.

Right, Thank you.

Respect to surveillance for antimicrobial resistance Within a rough analysis off the total number off a cute free brocades illnesses in Liberia For one year, we found out there were 2.5 million cases of fever off the 2.5 million cases, one million off those cases where confirmed to be malaria and what they're calling it.

The rest of the one confined really know what to tell antibiotics.

Be some touch this.

So basically there were no positive agenda skull where they were giving antibiotics, so that's telling the low off the lack of stewardship for anti politics in the country.

The second child is that there is a lack of data, and so because we have like that, it's hard to convince this.

Take orders, I think.

Yes, it will get us in an email.

But because I'm trying to commission a research to look at underpowered, it's a susceptibilities and want to run a five without real diseases has even in traction.

We have the guys from initial discussion, with glass conceding to begin attractions of.

Basically, this is like a beautiful in many off the African countries until about extortion on the treatment.

Be some trust Lee, but doctors doctors like our hospital doesn't have a microbiology lot.

For now, we're old train doctors, so it's not taking a serious as it should be taking.

And so that's a big trick that is gonna happen all across Africa if our lastly is issue off fit drop.

We lack off active substance that comes into this country, and these are being controlled and regulated.

And so we're just starting.

We would know that dressed there, we know that there is abuse of antibiotics, there's no prescription, and I want to talk to any drug store and guess because anti politics off their own choice.

And so the last one is that we have a test in that year.

That is the water test that test for typhoid Optimus sensitivity should be around 40% or 30%.

But as I was using right now, not everybody gets die for and everybody is put on our three super flexing on Terek and deal issue off very sensitive diagnostics.

We're going to be abusing antibiotics and not bring the rest of Africa.

Mike Regan and I just had a quick appoint you had asked us and would notice.

Really Address it head on is the tools for dealing with the M R.

Let me just say right now that I think that the future for animal crow burial research and development and bringing products to the market is gonna be very challenging.

And the reason is again the business model.

We keep talking about that.

Think about the car salesman who has the best damn car that anyone had ever want.

But you got to tell the people by taking only drive it from 10 to 11 on Sunday mornings.

That's it.

Who's gonna buy that car?

Well, part of the problem is we're trying to get new animal Crow Bill agents for very serious issues around drug resistant infections.

We want you to hardly ever use it, okay?

And so trying to incorporate that into the business model is a challenge Thio site To get people to want to get into that business.

So it's gonna happen, but it's going to be challenging.

But the second piece of this is I last night laid out categories of vaccines we have.

I'm predicting that in the next five years we're gonna see a new category of vaccines.

It's called Vaccines for Preventing and Recover Resistance Infections, meaning that we're gonna actually start targeting diseases for which we don't have any other really good, eh?

McRobie all treatment options.

Or at least they're very limited.

And we are going to make these high priority.

Staph aureus is one as an example.

The second thing is we're going to see unconventional treatments, I predicted.

Within 5 to 10 years we will see major emphasis on father's treatment for antibiotic resistant infections, which is going to be a whole new area that, you know, the Russians are way ahead of us on this one on have been working on it for some time, but I think we're also going to see that as a Newman.

You want to get one liner on the father's treatment stuff because I think it's really interesting guys, you know, viruses that infect bacteria.

And we've already had some wonderful clinical successes with very, very serious resistant infections where we can match up a virus.

And actually, you treat the patient with the virus that is very specific to that infectious agent.

And the Russians did it for a long time before, Uh, you know, we heard about it or got into it.

And, ah, there's been several really highly noted treatment.

Success is where people literally were on their last leg with a total resistant infection, and the fathers are actually in.

The work was being done.

Saved him.

It's really a arms race between us and the bacteria and were actually playing on both sides of the battlefield, which makes it a bit more challenging.

If people have questions, please come on up, amassed one more question of the of the panel, and then again, there's a microphone up there.

So please come on up and ask questions.

The glass question I want to ask before we open it up is something miss okay, Just mentioned at the end, I'm so we spend and when we think about our response tools.