Today I’m going to tell you a little bit about the development of new antibiotics. Now at this stage in the course you should be well aware that we have a crying need for new antibiotics so we can maintain a high standard of medical treatment. And you might be surprised to know that this isn’t actually happening, that over the last few decades there’s been a big innovation gap, very few new antibiotics have been brought into the clinic. And there’s been a huge drop off in investment by the big pharmaceutical companies.
Now you might ask how this has come about and why it has come about, and I suggest you look at a couple of the reviews I put on your reading list, Fischbach and Walsh, and Shlaes and Cooper, they’re going to give you some of this background. But essentially it comes down to issues of economics and science. In the ’60s, the big pharmaceutical companies thought we had more than enough antibiotics, they were not very profitable, and they could make more money from investing in other types of drugs. In addition, it turns out to be scientifically very challenging to develop new classes of antibiotics.
And I’m going to take you through a little bit of the economics, a little bit of the science, and then tell you what I think we need to be doing in the future. So if we take the economics firstly, it takes about 15 years from beginning a discovery project until you get a new antibiotic onto the market, and it costs an estimate of around about 1 billion Euros to do this. Now the pharmaceutical companies can make very little profit on this type of economic scheme because, as you know, we have resistance arising all the time, so the effective lifetime of these new drugs might turn out to be very short. Also, patients are treated for short periods of time.
Now, the economics is bad, what about the science? Well, antibiotics are very special drugs. They have to kill bacteria, or stop them growing, in the context of an infection in the human body. That means you have to chemicals that can distinguish between bacteria and human cells, this turns out to be very difficult. If you do a new drug development or a new drug discovery project you’ll easily find chemicals to kill bacteria. Many of them do it by disrupting the bacterial membrane, unfortunately these will also disrupt the human cell membrane, and so you get toxic chemicals. Another issue is that many of these small chemicals will bind to many different targets, not just the thing that you’re aiming at.
And many of these new drugs under development turn out to bind to human ion channels, like cardiac ion channels, and so you get a huge increase in the risk of a heart attack in patients. Again, toxic compounds that cannot be developed. Now you also have the issue of efficacy. How effective are they at inhibiting the growth of bacteria? Well, as you already know from this course, many of the pathogens that cause us medical problems are so-called gram-negatives. These have two different cell membranes, and unfortunately chemicals that can get through one of these membranes typically cannot get through the other. So the number of molecules that we can discover that inhibit gram-negatives is very, very small.
So these are the scientific challenges. Now what can we do about this? Well, there’s a lot of discussion going on at the moment about how to encourage big pharmaceutical companies to get back into the game. And one of the possible solutions, which is being developed, is to initiate so-called public-private partnerships where taxpayer money helps to reduce the risk for the big pharmaceutical companies, and where scientists, basic scientists, are brought into the development project to bring with them new types of expertise and new ideas.
Here in Uppsala we’re actually heavily involved in one of these, the European Union’s Innovative Medicines Initiative, New Drugs for Bad Bugs, a particular project called ENABLE, where we’re trying, with the collaboration of big and small pharmaceutical companies, research institutes and hospitals, over 30 different partners, trying to develop new drugs for gram-negative pathogens. Now in the future what do I think we need to do? Well, a big mistake was made in the ’60s when we thought we had enough antibiotics. So, in the future we need to encourage investment, whether it’s through public-private partnerships or some other means is not really important, but we have to have a continuous stream of investments.
Because we are going to need a continuous stream of new antibiotics, because resistance will keep coming up for all of the new drugs we develop. So, we have to think of this as a continuous process. And we need investment in basic science, because we realise now that we have very little idea of how to find drugs that will get into bacteria, and that will have low levels of toxicity. So, there’s a crying need for basic research and for continuous investment. The aim has to be to develop a continuous pipeline of new antibiotics into the future. So, thank you.