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Inside one of New Zealand’s biggest quests to find the next breakthrough drug for brain disease. Not long ago, as recently as the 1990s, scientists searching for new drugs tested molecules one by one in the lab, looking for signs of disease-fighting potential and the next breakthrough medicine. These collections of molecules often ranged from a few hundred to a few million, representing naturally-occurring molecules as well as a growing ability to make molecules in a lab. Testing these compounds ranged from very manual efforts in small labs to highly automated systems in specialist labs called high throughput screening centres. This is howmany of our existing medicines were first discovered. Today, with global advances in chemistry, the scale of these collections has massively increased, moving into the billions, even knocking on the door of trillions of compounds. “Just to put that in perspective, the search space for newmedicines now contains many more molecules than there are stars in the MilkyWay. What those numbers mean is that we have to rethink howwe search for the molecules that could become our future medicines,” says Associate Professor Jack Flanagan, a pharmacologist from the University of Auckland’s Department of Pharmacology and the Centre for Brain Research. We also need to recognise that quality research takes a long time. Accordingly, there needs to be continuity of funding, i.e., there needs to be a reasonable chance that any promising programmes of research started by small one-to-three-year project grants can continue to attract funds in order to reach their potential. Sadly, the public research funding system in New Zealand over decades has not been up to the job, and not just in neuroscience. The level of research funding support by government and businesses is only a little more than half of the OECD average. To have rates of funding by government agencies sit at only 5 to 10%of applications coming in is dispiriting, while the levels of support for successful grants has deteriorated significantly due to inflation. And now, unfortunately, research priorities have been shifted towards technology development and economic outcomes, while basic research and even health research sit very much in the back seats. It is no wonder that research is stalling, that scientists are discouraged, and that many seek better opportunities elsewhere. Thank goodness, then, that private organisations such as the Neurological Foundation of New Zealand and other NGOs have been coming to the rescue. In my case, I have been immensely grateful for the support I’ve received. This funding has enabled such things as seeding of new ideas, keeping projects going in the lean years between government grants, supporting large projects in their own right, and, of course, the training of students and early career researchers. This is how it has so usefully played out for me, and I know for many others. We are all immensely grateful for the support of those donors who over decades have channelled the lifeblood of research, through donations and bequests, into the Foundation and thus us researchers. Fortunately, because of the Foundation’s continuing support, it’s not all doom and gloom. We actually live in an exciting time of opportunity for making progress toward solving some of the most difficult problems in brain science, most notably the treatment of brain diseases. We have the brainy workforce here, alongside colleagues in the international community, to achieve these goals. The tools now available for gathering and analysing data are just as amazing. Given our rapidly growing ability to detect biomarkers of neurological diseases in their early stages, and our growing understanding of molecules and mechanisms that can be targeted for treating those diseases, the future is increasingly bright for achieving the breakthroughs we are all hoping for. “We actually live in an exciting time of opportunity.” Distinguished Professor Cliff Abraham Cliff in the lab with colleagues Dr Bruce Mockett (left) and Dr Owen Jones. Left to right: Dr Rebecca Johnson, Dr Daniel Conole and Associate Professor Jack Flanagan. The billion-molecule question In instalment three of our four-part series on the Neurological Foundation’s new Platform and Programme Grants, we talk to the team behind New Zealand’s largest effort to find a new drug to treat neuroinflammation, a condition at the centre of many brain diseases and injuries. 10 Headlines 11 Headlines