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Matt McCarthy, MD, graduated from Harvard Medical School and went on to complete his internal medicine residency at Columbia University Medical Center. He is the author of two national bestsellers,[…]

MATT MCCARTHY: Yeah, the discovery of antibiotics is one of the most remarkable stories in medicine. There was this young military physician named Alexander Fleming who was taking care of injured soldiers in 1914 at a makeshift military hospital in France. And he noticed that many of the soldiers had infections that were not getting better with the tools that he had to treat them, which was largely his surgical scalpel and also antiseptic fluid. And he was just 34 years old at the time, but Fleming recognized that there had to be a better way. And after the war was over, he went back to his laboratory at St. Mary's Hospital and started tinkering around. And it wasn't until nearly 15 years later that he stumbled upon this fungus that was producing a chemical that was so extraordinary that it could kill almost every bacteria in its path. And the chemical that that fungus was producing is what we now know is penicillin.

What's interesting about that story is that the discovery did not lead to a commercially available drug right away. In fact, Alexander Fleming didn't realize that he was on the cusp of some incredible discovery. It took another World War, and teaming up with the burgeoning pharmaceutical industry and a number of other researchers at Oxford University, before everyone fully recognized what he had stumbled upon in his laboratory in the late 1920s. And that discovery of penicillin ushered in what we now know of as the golden era of antibiotic development. The 1950s was a period when there was a new drug being discovered seemingly every few months. And the life expectancy of humans shot up because of all of these fantastic discoveries. But then there was a problem, which is that we were so successful finding new antibiotics, that a number of prominent physicians and scientists came out and said, we got this infectious disease issue kicked. It's time to look for more pressing issues like heart disease and cancer.

And so we started focusing our attention on treating those diseases just as the bacteria were being exposed to our precious arsenal of antibiotics. And that set up a very difficult situation, which is that the bacteria were mutating when we took our eye off the ball. And we didn't recognize the scope of the problem until the 1990s. And that's when we first recognized that there were all of these drug resistant bacteria around us, which we now think of as superbugs. Yeah, so when we talk about bacteria evolving into superbugs, what we mean is that they are mutating to develop machinery and enzymes that can evade even our most powerful antibiotics. My favorite one is something called an efflux pump. And it's a microscopic vacuum cleaner that bacteria have developed that can suck up an antibiotic and spit it out. One of the other things I really like are these enzymes that they have created that chew up antibiotics. And they scavenge for metals, like zinc. And they can chop up even the most complex or nuanced medication that we throw at them.

And so bacteria are constantly doing this whether we recognize it or not. And so what's been fascinating to see is how quickly they can evolve. This is a remarkable insight that we can now discover this. But it also sets up a very perilous situation for the companies that want to create new antibiotics. They know that, if they make a new drug, the bacteria will eventually figure out a way to outfox them and become resistant to it. And that's a problem. We count on the pharmaceutical industry to help us make new drugs. And increasingly, they're saying it's simply not worth it. It's too risky. And the reason for that is, if you compare an antibiotic to, say, a blood pressure medication, a blood pressure medication is prescribed by a doctor like me. And I say, "Take this every day." And you may take it the rest of your life. That's a great business model. Now compare that to an antibiotic where doctors are stingy about doling them out. We only prescribe them in short courses. And eventually, even that best new antibiotic is going to wear out its welcome when the bacteria become resistant.

So this has created a crisis really, which is that at a time when we desperately need new antibiotics, the companies that make them are saying no thanks. Well, some antibiotics are economically viable. If you happen to hit on a broad spectrum antibiotic that has minimal side effects, you're going to make your money back. But the problem is most antibiotics, to go from discovery in a laboratory to a hospital somewhere, costs roughly $1 billion and takes at least 10 years of trials to show that it's safe and effective. The problem with that is that not all drugs succeed. And we have found that many of the companies are saying, it's simply not worth it for us to take this risk. And they point to a company called a Achaogen. Achaogen spent years and millions of dollars developing a new antibiotic called plazomicin, which was finally approved by the FDA in June of 2018. And it was approved to much fanfare. And in April of 2019, the company filed for bankruptcy. And that's because people like me weren't using the drug. And people like me weren't using the drug because it wasn't available in hospitals. Because the company got approval for urinary tract infections, but we don't really need a new drug for urinary tract infections. We need a new drug for ventilator acquired pneumonia or for bloodstream infections. And the company didn't receive that approval. And that was a disaster for them and for the whole enterprise.

And so when we talk about small companies developing new antibiotics, they're very nervous about doing so. And they point to Achaogen and say, we want to do something else with our time and our money and our resources because the risk is just so great. And this to me is the most important political issue that no one is talking about. There are a number of new incentives and financial enticements that are on the table that we're going to be hearing about in the coming months and years that are going to be brought up before Congress that we all should be informed on before we go and vote on them. And the two most common types of incentives are called push incentives and pull incentives. Now a push incentive is when you go to a company let's suppose, Merck, a large multinational pharmaceutical company and we say, hypothetically, your corporate tax rate is 20 percent. What if we cut that to 15% provided you promise to take a portion of the excess profits and invest in new antibiotics? So this is a surefire way to pump more money into the antibiotic pipeline.

The problem is that you're suddenly giving a tax break to a multibillion dollar pharmaceutical company. And when people look into the finances of how pharmaceutical companies are doing, they may not be enthusiastic to do that. My stomach turns when I look at some of the comments from pharmaceutical CEOs who jack up the prices of their drugs. One notably increased the price of an antibiotic for urinary tract infections by 5,000 percent. And he justified it by saying he had an ethical mandate to charge as much money as possible for antibiotics because he's ultimately accountable to shareholders and not patients. So the idea of giving a tax cut to a company like that is tough to stomach. On the other hand, it would give us more investment in something we desperately need. So those are called push incentives because it would push the company to do it. By contrast, there's something called a pull incentive. That is to say to a company, if you take on the risk of developing a new drug and it succeeds, rather than giving you five to seven years of market exclusivity, we'll give you 25 years, which means that generics can't challenge you.

That's a way that the company could charge more money for a longer time for their drug. Pull incentives are more popular among a lot of academics because it forces the companies to take the risk head first. And if they're successful, then they get to make money on the back end. Whether companies will go for this is unclear. But these push and pull incentives are the type of topics that we need to be talking to our politicians about. And then adding yet another layer to the complexity here is that, when an antibiotic is approved by the FDA, there's no guarantee that a hospital is going to use it. And in fact, I found that many top hospitals are not using the latest antibiotics that are approved. The reason for that is that the drugs take so long to get approved and are so expensive to produce that the companies are charging thousands of dollars per dose. And the hospitals are saying, no. We're not going to pay the ransom for these drugs. That leaves patients in the lurch. I've been in front of patients for whom there was no treatment option, knowing that there were antibiotics out there that would probably work. But they were not widely available because of dollars and cents, that the hospitals could not afford these drugs. And what make gives me pause is that we don't always see that with cardiovascular drugs or with chemotherapeutic drugs. We routinely give patients with cancer a chemotherapeutic drug that will cost tens of thousands of dollars that will extend their life by just a few weeks or months.

But we aren't taking that same kind of financial risk with infectious diseases, and that's got to change. So I've talked to people from across the political spectrum about this. People on the right who typically would be hesitant to have the government more involved in health care and making these financial deals are also open to tax cuts for corporations because they believe in the innovation of these companies. And they want to have antibiotics when they come to the hospital. And if a tax cut will get them there, that's fine with them. I've also talked to people on the left who are enthusiastic about coming up with these tax breaks as well because they recognize this is a problem. But on the left, there is also more interest for socializing the production of antibiotics. Now in England and in other parts of Europe, they've said, we recognize the antibiotic market is broken. Let's disentangle profits from the entire process. These are public goods, like electricity or water. We shouldn't think about them in terms of dollars and cents and that the key here is that we should all invest in these drugs, meaning countries should pool together their resources. And when the drugs are approved, we should all use them, and we shouldn't be looking at profit margins. We should be thinking about patients' lives.

Anyone who's looked at this issue knows the market will not solve it strictly because we're producing a product that doctors try not to prescribe. So the traditional laws of supply and demand don't work here. And something has to be done. This is called a market failure. And with market failures, you need government intervention. The controversial part is how the government should intervene. Many people are fearful of nationalizing the production because they think it will stifle innovation that, if you have the government involved in investing, then the top people will not go into this will not go into drug discovery. Drug discovery is the most exciting part of this entire process that people aren't really talking about either, that many of the best new antibiotics that we're discovering are in the soil beneath our feet. And that's something that has been lost on the lay press. It turns out that there are bacteria in the soil all around us. And those bacteria, just like Fleming's fungus, are producing chemicals to kill the other organisms in the environment, the other microbes. And it turns out that those chemicals that are being produced everyday beneath our feet can be harnessed and turned into antibiotics.

The challenge is finding where those are. And not far from where I work in Prospect Park, they recently found that the soil under the park had antibiotics and other potential medications. And what we're doing now, the next frontier, is using big data and artificial intelligence to sift through the proverbial needle in the haystack to find the next life saving drugs. The challenge is, once we identify that molecule in the soil, it costs $1 billion and 10 years of research to make sure it is safe and effective for humans. And we have to find someone, whether it's the government or whether it's a private company, that's willing to take on the risk because often those trials fail. When you find something in the soil, you've got to test it in a test tube and in animals, in healthy human volunteers, and then in patients who are sick. And that's a high wire act that people don't recognize how challenging it can be. But the pharmaceutical industry recognizes that it is a very perilous business model to rely on, that lengthy process to turn a profit. Our current antibiotics are waning in efficacy.

And we have an opportunity to invest in the future and to invest in the next generation of lifesaving antibiotics. But we cannot expect that this will take care of itself. And in fact, many people compare this to something like global warming, where there are things that people can do on a small scale, individuals, and there are things that countries and that corporations can do on a large scale. And even comparing that is fraught with controversy. But on a small scale, what we can do is that doctors like me cannot overprescribe antibiotics. And in fact, we found that dentists too are overprescribing antibiotics. Up to 80 percent of the antibiotics prescribed by dentists are inappropriate. So we can be better about prescribing. We can also be better as patients where, if a doctor says take seven days of antibiotics, you don't take two days and stop after you feel better. That gives the bacteria a whiff of the drug and gives them just enough of it to figure out how to evolve to escape it the next time around. So those are small things that we can do.

And then on a larger scale, we can make sure that we're not using antibiotics inappropriately in commercial agriculture and farming. For example, we're using some of our best tuberculosis and syphilis drugs in orange groves. We're using powerful antifungal drugs in tulip gardens. We're pumping meat producing animals full of antibiotics. We've gotten better about curbing that. But these are things that we have misused antibiotics for a generation. And that has allowed the bacteria to evolve in a way where they are now these superbugs.