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As drug-resistant infections proliferate, financial barriers are preventing the pharmaceutical industry from investing in new drugs to fight off superbugs. Economics correspondent Paul Solman, in a series of reports with science correspondent Miles O'Brien, explores how researchers could be incentivized to develop new antibiotics.
Now to our series on the hunt for new antibiotics, as superbugs and bacteria are building more resistance to the current line of drugs.
It is a joint project from our correspondents Paul Solman and Miles O'Brien.
Last night, Paul looked at why the market for developing new drugs is simply no longer working. But, as one expert warned, antibiotics are a class of drugs that could be lost for treatment if there's no new investment.
As part of his series Making Sense, Paul looks at some new options for solving that problem.
Northeastern University biologist Slava Epstein has traveled the world on the hunt for hitherto undiscovered microbes. Some trips are shorter than others.
We are five minutes from your lab, right in the heart of Boston, and this soil is as good as any?
DR. SLAVA EPSTEIN, Co-founder, Novobiotic Pharmaceuticals:
This soil is as good as any.
As Professor Epstein told my NewsHour counterpart on the science beat, Miles O'Brien, just about any handful of soil contains tens of thousands of different microbial species, 99 percent of which remain utterly unexamined, in part because they refuse to grow in petri dishes.
Epstein's breakthrough was figuring out how to cultivate them, inventing a gizmo that isolates individual bacteria, then grows them back into teeming colonies.
So, you can kind of see through them there.
AMY SPOERING, Research Director, NovoBiotic Pharmaceuticals:
That's right. So, in each one of those individual holes, in theory, there is a single cell. And by capturing single cells and putting them back out into the environment that they came from, you can cultivate microorganisms no one has ever cultured before.
Amy Spoering is research director at NovoBiotic, the company Slava Epstein co-founded to study newfound bacteria, now up to 60,000 strains, and counting, as potential sources of new antibiotics. And how does that work?
Antibiotics are produced by microorganisms to kill their neighbors, so the enemies, the competitors. This is an exercise that the microorganisms have been going through for the past four billion years.
And that humans have exploited for the past century or so, with chemicals from microorganisms like penicillium, the mold that makes penicillin.
The trick is finding chemicals that kill infections in people without killing the people too.
So, I don't mind interviewing movers and shakers, but it's actually making me slightly dizzy, so I'm just going to look at you.
Just look at me. That's fine.
So, what is this?
So, what this is, is, this is where we grow all of the novel microorganisms that we cultivate. They need a large amount of air in order to grow well, in order to produce the antibiotics.
So you're aerating them?
That's right. That's why they're shaking.
So far, they have identified 33 novel compounds here, one of which may be a breakthrough: a new antibiotic that kills bacteria in two completely different ways, making resistance much less likely.
So, this is making our lead compound, teixobactin.
And the cost, if all goes well, of eventually getting it to market?
That's big money.
Big money that investors would be tripping over one another to provide, right, to get in on the ground floor of the next Z-Pak.
The payout will be huge, if we are successful.
But it's a long lug, says Spoering, between bug and drug.
This is 30 liters of it growing to produce the compound that we need to do the next set of pre-clinical tests.
And then, after you have done those animal trials, the toxicology trials…
… then, and only then, do you do trials on humans?
First, an initial set of studies that is just for safety, and then you move on to the efficacy studies, which is phase two, and then much larger efficacy studies, which are phase three, clinical trials.
DALLAS HUGHES, President, NovoBiotic Pharmaceuticals:
Drug discovery is a very long process.
Dallas Hughes is NovoBiotic's president.
We are talking with venture capitalists now, but venture capitalists aren't going to become interested until we discover a compound like teixobactin and move it forward a bit farther than it is now. And we're hoping to raise some financing soon.
But, for now, they're relying on government and foundation grants.
Promising something that may or may not happen 10 years from now doesn't make people as excited as if you were promising the results like here.
But, hey, every drug costs a fortune to bring to market. That can't be the reason antibiotic firms like this one have such a tough time raising private capital.
So, what's the story? As we explained in a prior report, there just isn't enough profit soon enough. You buy a week's worth of an antibiotic, not three months, say, of Harvoni for hepatitis C.
That's one pill, once a day, for 12 weeks.
And it costs about $30,000 a month.
Moreover, when a company comes up with a new superbug slayer, the medical community wants to keep it off the market as long as possible to delay toxic microorganisms developing resistance to it. Meanwhile, the patent runs out. Small wonder that even big pharma has said no mas.
DR. JOHN REX, Former Pharmaceutical Industry Executive:
Most of the companies that were really doing the large-scale development work backed away from the area.
Like AstraZeneca, where infectious disease Dr. John Rex used to head antibiotic development. What did he learn from his tenure?
DR. JOHN REX:
It's a good way to destroy $50 million to $100 million worth of net present value after 30 years of really hard work.
But ever-hopeful startups like this one, Tetraphase, outside Boston, have popped up. And a new public-private partnership called CARB-X has stepped in to help fund their trek from test tube to clinical trials.
KEVIN OUTTERSON, Executive Director, CARB-X:
We have, at CARB-X, $455 million over the next five years, but what we need globally across all countries is about $2 billion per year for antibiotic R&D, supported by public and charitable funds.
So, says executive director Kevin Outterson.
This is an infrastructure investment that has to be made in order to keep this drug class alive. I think antibiotics is the most valuable drug class in human history. It's done more to save lives than any other drug class. It's incredibly powerful. But it's the only one that, if you don't keep investing, you lose it.
Every other invention of modern medical science is still going to work in 100 years. Antibiotics, we know they won't.
Because bugs resistant to the antibiotic will evolve. But what cure can economics possibly come up with, when the market itself fails?
The model that people are coalescing around is some sort of a significant prize, a significant billion-dollar payment, that rewards them for the innovation, and then we can still use that antibiotic sparingly for the next 10 or 20 years.
Rich prizes, they have motivated everything from discovering a way to determine longitude at sea, to Charles Lindbergh's transatlantic solo flight in 1927, to private space flight today.
DR. PETER DIAMANDIS, XPRIZE Foundation:
We have got $50 million of prizes on the table right now, and $200 million of prizes in development at different stages in the pipeline.
DANIEL BERMAN, Longitude Prize:
Prizes can be the answer when you're trying to motivate people beyond the normal suspects.
Daniel Berman is in charge of today's so-called longitude prize, 10 million British pounds for a quickie test to see if you need antibiotics at all.
One of the main reasons why drug resistant infections occur is that antibiotics are used inappropriately, such as people taking the wrong ones or not needing them in the first place.
We need a rapid diagnostic test because we need to make sure that we don't burn through the few antibiotics that are left. And when new antibiotics come on, we have to make sure that we dramatically use them in a more rational way.
Without such a test, doctors are under constant pressure to prescribe.
DR. LINDSEY BADEN, Brigham and Women's Hospital: Often, acute infections are viral, and without the ability to specifically diagnose you at the point that you're in the office, it's very hard to know that an antibiotic won't help.
Boston infectious disease expert Lindsey Baden.
But to just distinguish between a virus and a bacterium, that would be a big deal.
DR. LINDSEY BADEN:
A virus and bacterium would be very important.
And even more so in developing nations.
For example, in India, you can still purchase antibiotics without a prescription in a lot of places. And people are dying because, for some pathologies, there are simply no antibiotics that work anymore.
But look, says Slava Epstein:
Can you use antibiotics smarter? Absolutely. But that will not prevent antimicrobial resistance. It will delay it.
That's why, he says, we must ramp up the efforts and investments in new ones.
This is economics correspondent Paul Solman, reporting for the PBS NewsHour.
And I'm still dizzy from the shaking.
Join us next week as Paul and Miles continue their series.
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