Drug discovery with a difference

Dr Mat Todd, University of Sydney, Australia
Dr Mat Todd, University of Sydney, Australia

In 2011, MMV launched an Open Source Drug Discovery (OSDD) programme. The programme differs from traditional drug discovery, as all research is reported openly, online and in real-time, allowing the best and the brightest to contribute and accelerate science and drug development. Dr Mat Todd, from the University of Sydney, leads one of these projects, Open Source Malaria; he explains how he got involved, how the project works and what he thinks the future holds for open science.

  1. How did you get involved in OSDD and particularly for malaria?
  2. What are the objectives of the Open Source Malaria project?
  3. How does it work? How can scientists get involved?
  4. What’s in it for contributors?
  5. What are the advantages of open source drug discovery?
  6. What are the challenges of open source drug discovery?
  7. What are the success stories so far for open source drug discovery?
  8. What is the advantage of working with MMV?
  9. What is the future of open source science in your view?

1. How did you get involved in OSDD and particularly for malaria?

It all began when I was approached by Piero Olliaro at the World Health Organization with the challenge of improving the synthesis of praziquantel, the drug used to treat schistosomiasis. Supply was only meeting approximately 10% of the demand and a more efficient method of synthesis of an improved version of the drug was needed. As schistosomiasis is a neglected disease, the price of the drug couldn’t go up. That was interesting to me because I thought, “I can solve the problem chemically but not without the price going through the roof.” All my clever little solutions were no good because of the issue of cost.

It occurred to me that I needed the input of other experts, but I didn’t know who. As I was looking into it, I saw that many software programmes have been developed using open source, things like Linux, Firefox and Google Chrome. It seemed like a great model and I thought why not apply the same model in a looser way to drug discovery? That’s what we did, and it worked really well. We solved the problem quickly with the aid of experts we didn’t know.

When I spoke with people about the project that year, many would say, “It’s easy to be open when there’s no IP, Praziquantel is off-patent and for a very neglected tropical disease…what if you were trying to discover a new drug, how would the economics work?” No one, myself included, really had a good answer. So I thought instead of talking about it let’s just try and do it. The first person I met that agreed with that was Tim Wells, MMV’s Chief Scientific Officer. We met by chance in Cape Town in 2011 and that’s when open source drug discovery for malaria all started.

2. What are the objectives of the Open Source Malaria project?

Scientifically, the objective is to start with a compound and end up with a preclinical candidate drug that can then be further developed in Phase I trials and beyond. There are always many risks in research and development, but if we produce such a candidate, we will be very happy. There is also the social side. We want to show that we can get a sizable number of contributions from people that we don’t know. The only limiting factor now is really how many people know about the project, which is why we have recently launched a new website to help get the word out and coordinate everything. We also feel it’s important that the work be published; we need to show that we are serious scientists making important contributions, albeit in an unorthodox way. 

3. How does it work? How can scientists get involved?

The day-to-day work is very similar to that with any research project. You have a lab book and the scientists jot down everything that is done. The key difference is that everything is in the public domain. It sounds quite trivial but it’s actually quite a big mind shift. In addition to describing everything that has happened, the project also makes clear what is planned for the weeks ahead. The idea is that no one is behind the curve; people can provide input ahead of time. We are also present on platforms such as Google plus and Facebook which really allow people to communicate with us in a way that works for them.

4. What’s in it for contributors?

Certainly some people are contributing for purely altruistic reasons, although, I don’t think that will always be enough to make people give up hours and hours. For the schistosomiasis project, the inputs came from industry, which may seem counterintuitive. There were people that did a lot of work in the lab for free. I think in this case, the reason was good PR, as it’s clearly a way of demonstrating to potential clients how good you are, especially as it’s in real time. There is also a good chance of being named on a publication, which is valuable. Academic scientists in particular live and die by publications. There will be about 30 names on the first open source malaria paper. You might think the authorship is diluted, but it’s going to be a bigger and better paper as a result.

5. What are the advantages of open source drug discovery?

You get to work with the best people even if you don’t know them. Whenever you look at a scientific problem, you think “I want to solve this problem but not if someone else already has or if someone else is better placed to do so”. Open source is not for the faint hearted though. It creates an extremely challenging environment for a scientist, if you make a mistake you are going to be caught out. Or, if someone is better at what you are doing they can take over. We must work in that kind of environment where you have the best people working on the right problems. Open source allows you to do that.

6. What are the challenges of open source drug discovery?

The main hurdle is the entrenched culture of secrecy we have in science. I do understand why that exists; there are obvious commercial pressures in industry and in academia there is a similar need to establish ownership. It’s a huge psychological barrier to overcome.
There are some really big questions that need to be discussed regarding whether patents are healthy. My own view is that they are quite stifling. I think that’s inevitable if you restrict the flow of information and prevent teams from working collaboratively. Even so, at this point, most people are not suggesting we take patents away. I think it’s too enshrined in the way we work, but we will see more and more discussion about them in the future. The open source software model has proven to be extremely powerful; the resulting products are incredibly robust. I think software developers are teaching us something we would be foolish to ignore.

7. What are the success stories so far for open source drug discovery?

The first one is praziquantel for schistosomiasis; we found a better way of making the molecule and the project progressed very quickly. For the malaria project, the consortium has had inputs and established collaborations with people around the world and people have even made molecules for the project. Experts from various fields have contributed and it does feel like the project is progressing faster as people are contributing at the same time. Also, we have built a platform that will live on even beyond this project. We haven’t found a drug yet but we have built something that will last. 

8. What is the advantage of working with MMV?

It’s amazing to have funders who have the courage to support an initiative that has never been attempted before. The second is the scientific expertise. Working with Paul Willis has been sensational. He is extremely knowledgeable about medicinal chemistry and is able to make contributions that drive the project forward. He is also happy to accept scientific questions live over the internet, something many scientists would be far more reticent to do.

9. What is the future of open source science in your view?

To my mind open source is where science came from; free enquiry where all data and ideas are shared. It feels as though structures have been placed on top of that, which reduce the flow of information and make science less interesting to be involved in. One thing is clear about the astonishing time we're living in – through the creation of the internet we can now work together in ways that are so efficient as to make obsolete many of the structures we're used to. An open culture is more competitive and yet more collaborative – a mixture that I think really can improve the way we go about solving hard problems. The future, then, will change the way we work together, perhaps ironically, back to a mechanism that is more human and intuitive, where we can ask and answer any questions that naturally interest us, without having to belong to an exclusive club to do so. Wouldn’t that be exciting?