Modern science, modern life

by Lila Landowski

LIKE MANY CHILDREN born in the 1980s, I grew up playing outside, catching lizards and feeding tadpoles. My parents were Polish immigrants to Australia who, like most immigrants, followed their vision of a better future. They gave up respected jobs in the government ministry and education to start new lives here, but unfortunately the grass wasn’t quite as green when they arrived on the other side. Australia seems to go through phases of ostracising specific minorities, and the slashed car tyres and rocks thrown on our roof were testament to that. As a child, I saw the aftermath of my dad’s brief time at home between shifts at the local fabric factory. The personal costs of moving to Australia and being outsiders haunted my family, hanging around us like a thick fog.

Concerned that I would face the same discrimination at school that they had encountered, my parents made sure I never appeared ‘different’, and I never spoke in their native tongue. They needn’t have worried; my class got along famously, oblivious to differences in heritage. Children are not inherently racist: racism is a learnt behaviour. In hindsight, the only person to blatantly discriminate against me was an adult: one of my Year 3 teachers. Generally speaking, school was a wonderful escape, full of adventures and learning opportunities.

To my teachers’ frustration, I had no answer to the question, ‘What do you want to be when you grow up?’ Then, at a school camp on Maria Island in Year 4, I caught my first fish. There I was, holding this fish – a banded morwong – with its thick cloying slime sticking to my fingers. It was the coolest thing I had ever seen. I’d heard that shark-liver oil could perform miracles for your health (apparently), and I wondered if the gunk on my hands possessed magical properties too. Then and there, I decided that when I grew up my mission would be to discover a new fish extract that could be used to cure something.

In the late 1990s, my dad picked up an old Commodore 64 computer. My brother and I would pore over the computer, learning to code and make simple programs. He was brilliant at it and eventually became a computer engineer. I just enjoyed experimenting with it and seeing what I could get it to do. My dad would occasionally take the computer off us to play chess against it. On the hardest setting, it would take over a day for the computer to process, calculate, and respond with the next move. That set the tone for the rest of my future. I never had the time to wait for someone to make a move. I much preferred to do things myself to make sure that things got done.

Fast forward fifteen years to a neuroscience lecture in the third year of my Bachelor of Medical Research. I saw something unusual in the research data that was presented, and my honours research project was born. This led to my discovery that the protein metallothionein could guide the growth of neurons and promote nerve regeneration in the skin. You know the best bit? Metallothionein exists in fish. My childhood curiosity had set me on the right path; I had started to contribute to the narrative of neuroscience research.

EVERYTHING WE DO, whether we are thinking about it or not, is controlled by the brain and the nerves that extend into our bodies. That is why injuries to the brain and nerves can be so devastating and why, for centuries, people have pursued ways to reverse the effects of this damage. My own research has focused on how to regenerate nerves and, more recently, understanding what goes wrong in the brain after a stroke.

Here’s what actually happens when a stroke occurs. Blood vessels in the brain are blocked by a clot, or less commonly a ruptured vessel, starving the downstream tissue of oxygen and nutrients. Toxic by-products start to accumulate, and the neighbouring nerve cells die.

Of the fifteen million people worldwide who suffer from stroke each year, about six million die and a third of the survivors are left with significant disabilities. Despite decades of research around the world, only one drug is licensed for clot-induced stroke: recombinant tissue plasminogen activator (rtPA). However, this drug is only helpful in a limited set of circumstances. For example, it can only be given within a narrow window of time after the stroke occurs – if it is administered after this window it may worsen outcomes. Approximately 7 percent of people in Australia who have suffered a stroke are eligible to use rtPA. Of those who do, half either die or remain dependent on others for care. There is huge scope to improve outcomes, but current research strategies are simply not delivering effective solutions.

A systematic review from the lab I work in has shown that, over the last forty years, more than a thousand novel drugs have appeared to show benefit in pre-clinical stroke research, yet only one of these has been sufficiently successful in further tests for it to now be used clinically. Clearly, something is going wrong. Science is flawed because humans do it. The introduction of bias into experiments and poor experimental planning are part of the problem, but there are also flaws in the way potential stroke therapies are tested pre-clinically. This worrying reality is not unique to stroke research and is true in most fields within neuroscience, if not most areas of biological science. Thankfully, these issues are recognised by the scientific community; and there are methods in place to reduce the pervasiveness of poor scientific practice. But the science is still far from perfect.

My role is addressing these flaws by helping to establish an innovative new model for testing potential stroke drug therapeutics. Challenging the status quo in any research field is hard, but taking the road less travelled has the potential to be so much more rewarding. Thanks to a generous project grant from the Royal Hobart Hospital Research Foundation, my research team at the University of Tasmania, led by Professor David Howells, may be able to overhaul the stroke research field within a few short years. This work would not be possible were it not building on the work of the research of thousands of others.

Science is ‘bitty’: we each contribute bits to a bigger picture. While this enables us to work from a body of accumulated knowledge, there are inherent restrictions on the freedom of individual ideas and the stiff competition for funding stifles creativity. Consequently, the breadth of our research-driven knowledge grows much more slowly than it could.

At a recent public lecture, Professor Brigid Heywood described a time when brilliant scientists had the creative freedom to tackle big ideas, when they were trusted with funds to explore different avenues, to attend all scientific meetings and conferences that would enhance their work, to collaborate with others and cross-pollinate ideas. Such a world no longer exists.

I am fortunate that Professor Howells, my supervisor and mentor, has endeavoured to recreate a version of this creative, supportive environment in our lab. He understands that science is about generating original ideas, asking big questions, chasing the unusual finding and even pursuing avenues of research that are risky in order to find the path that yields fruit. Sadly, this is not the norm. Research labs are generally very focussed, working on one specific part of a larger problem. I feel that a bit of creative license helps make for better science. Sometimes you need to think outside the box to find an answer to a problem. If you are constrained by a very specific way of thinking, it is easy to lose sight of the big picture.

RESEARCH UNDERPINNING FUNDAMENTAL concepts or mechanisms of disease is referred to as ‘basic science’. I detest the term. It conjures up images of mundane, uninteresting, simple lab work, but this is rarely the case. No two days are the same. And more importantly, basic science provides the crucial foundations for research pathways and is essential for identifying opportunities for innovation. Perhaps it should be called discovery science? You can’t always see the potential applications for basic research; indeed, the applications may not even exist in our lifetime. Isaac Newton surely did not anticipate his universal law of gravitation being involved in the implementation of satellite technology.

Unfortunately, basic science remains one of the least attractive kinds of science to fund, especially in Australia. Our country is lagging behind as a result. Australia is ranked seventeenth overall on the Global Innovation Index and just seventy-second for ‘innovation efficiency’, which compares how much research input, across all fields, is turned into commercial output. I wonder how much better we’d do if our National Health and Medical Research Council funded more than the current 15 per cent of submitted research proposals. Of this funding, basic science receives proportionately little. While investing in science that has more obvious and direct commercial outputs appears to make more economic sense than investing in basic science, you can’t take market logic and apply it to science. Some of its greatest achievements began with an accidental discovery or an unexpected result. This is the beauty of science.

For example, the discovery that stomach ulcers were caused by H. pylori was, in part, a beautiful accident. Australian Nobel laureates Barry Marshall and Robin Warren stumbled across the existence of this bacteria after their lab technician forgot to discard the experiment before the Easter holiday period. Marshall and Warren wanted to confirm their observations that bacteria were present in the location of the stomach ulcer, so they had been collecting samples from people with diagnosed ulcers. The lab technician had seeded those samples onto a culture plate with a nutritious jelly and left them to grow for two days (as per standard bacterium-growing protocols). Nothing grew, and they didn’t find the evidence they were hoping for. As it turns out, leaving them in the incubator for five days was key. It was the necessary step they didn’t know was missing.

THE PRESSURE TO perform and publish also stifles the research landscape. A scientist’s worth is apparently quantifiable. We are judged on the volume and impact of our work. The number of papers we write and the number of times those papers are cited are turned into a single number: an h-index. Technical skills, teaching and mentoring aptitude, passion, and experimental rigor don’t feature in the metrics. Some of the most brilliant scientists I have encountered exhibit all of these qualities, but do not have glowing h-indices to show for it. Scientists and funding bodies generally acknowledge that the h-index is imperfect; however, the score still carries considerable weight, and is key in deciding funding success, fellowships, promotions and, ultimately, a person’s ability to continue being a scientist. In my eyes, this definition of success is wrong. A scientist with a high h-index, but who performs poor-quality research, does not embody success.

Another problem is that scientific journals have an aversion for publishing negative results or minor findings, which, in turn, impacts researchers’ h-indices. A scientist who has spent years on an experiment that fails to yield a positive result may not have the opportunity to publish their work because journals want a juicy story: a new pathway discovered, a paradigm shift, something done with flashy new technology, or a potential cure. This can come at a huge cost when the perceived value of the headline usurps the quality of the data or its interpretation, and, after many failed attempts at replication, the data gets retracted. This pressure on scientists to report significant results, especially unusual or breakthrough findings, in turn exposes the research itself to bias.

The bias in scientific reporting also flows on to the public. Journalists trawl academic journals for articles they can turn into splashy headlines and too often report half truths, premature assumptions, and over-exaggerated extrapolations of data. According to the media, there’s a new ‘treatment’ reported for Alzheimer’s Disease every month. In reality, there is still no cure for Alzheimer’s Disease in humans.

Furthermore, if an experiment doesn’t have a positive result and therefore is not published, others are likely to waste time, money and resources repeating that work in the future. However, scientists are nothing if not problem solvers and pushed back against this tendency in recent years. For example, the journal PLOS ONE started a collection for all negative, null and inconclusive results, aptly titled The Missing Pieces. It is refreshing to see that the requirement for significant results is no longer the only path to publishing research, but there’s still a long way to go.

A YEAR AGO, I was treading a very lonely path through science. There were no funds for me to research full time in Hobart and I wasn’t able to move away for similar work elsewhere for family reasons, so I taught full time at a university while caring for my parents, and spent over a year doing neuroscience research for free. You could say that I made it hard for myself, but I was determined.

I received a small grant for the materials necessary to complete the work. A portion of the grant was intended as a stipend; however, with the increasing cost of materials, I forfeited this to buy what I needed to perform what I saw as essential research. I was also the only scientist working on peripheral nerves – in this case, nerves in the skin – in the institute’s laboratory at the time. I couldn’t benefit from collective knowledge, nor could I share the workload. Most weeks I worked around eighty hours, and often more. I didn’t resent this because I thought it was what I needed to do to keep up in the industry, but I later discovered that my efforts had instead disadvantaged my research career: taking time off work to be a carer or to have a child would have been accounted for in my research profile as a ‘career break’. Oblivious to this, I’d tried to do it all while the research clock kept ticking and my h-index was diluted. I could have easily dropped off the radar.

I had been fighting so hard for the career I love, but the seemingly endless setbacks left me heartbroken and demoralised. I lamented on social media, ‘If only we, as scientists, could be judged on our passion and enthusiasm, our zest for driving new lines of inquiry, on our ability to ask the challenging questions, and for our genuine scientific skills.’

Science is supremely beautiful, but I know it can be brutal and unforgiving if you stray from the well-worn pathways. Many people struggle, not fortunate enough to secure a job, a grant or a mentor to keep their passion alive. The issues with research practice and publication can be infuriating, particularly when the path you want to follow hasn’t been paved yet.

I am one of the lucky ones. Professor Howells is a true advocate for junior researchers and is both my hero and my mentor. Rather than beating my own passage through the challenges of research, we face them as a team. And it made all the difference: I’ve secured considerable funds to keep my research work going for the next three years. It’s safe to say that my heart is filled with hope.

From Griffith REVIEW Edition 56: Millennials Strike Back © Copyright Griffith University & the author.