Australasian Science: Australia's authority on science since 1938

Research in Practice

By Barry Leviny

What does a scientist do day-to-day? Barry Leviny talks to a biomedical researcher to find out.

I grew up reading about scientists. I know the story of Archimedes finding what the King’s crown was made of after an idea he had in his bath. I know the story of Newton’s inspiration about gravity after the apple fell and I know Gallileo saw ‘ears’ on Saturn when he looked through his telescope. I know all these things, and yet I didn’t know what a modern scientist actually does each day. I remember science at school, but I can’t imagine most scientists today getting to work, turning on their Bunsen burner and waiting for their first beaker of reagent to turn pink. How was I going to find out what a scientist did each day? I decided to gather some empirical data. I decided to ask one.

The one I chose was Dr Rob Medcalf. Dr Medcalf is a PhD, and an associate professor in the Department of Medicine at Monash University, although his position is based at a laboratory on the Alfred Hospital campus in Melbourne. How did he become a scientist? Did he just start sending applications to want ads? In Dr Medcalf’s case at least, it wasn’t that simple. He completed an Honours degree in Science at Monash University and then applied for a position as a ‘Research Assistant’ at Melbourne University, based at the Royal Melbourne Hospital. Dr. Medcalf remembers this as a happy time with, as he puts it, “no out of hours responsibility”. A research assistant, as the name implies, just assists with running experiments and doing ‘leg work’ for someone else’s research. After a year of this Dr Medcalf ‘got bored’ and decided to do a PhD.

A PhD is a ‘Doctor of Philosophy’, a postgraduate degree that involves approximately 4 years of work based on original research. A supervisor is appointed, and this person acts as a mentor, guiding, suggesting and encouraging amongst other things. In this case his mentor and PhD supervisor was the same person who employed him as a research assistant, a situation that is not uncommon. At the end of the 4 years the candidate writes up a ‘Thesis’ on his or her work, which is reviewed by scientists familiar with the area and published. Arguably, Dr Medcalf’s true scientific work began at this time. The subject he chose was pre-eclampsia. This is a condition in pregnant women where patients suffer high blood pressure, kidney problems and oedema (doctor talk for ‘puffiness’). After the PhD was finished, Dr Medcalf decided to move out of this area which had extensive clinical involvement. The clinical environment had too many decision makers, and his direction was reset to move into pure research, with little or no clinical involvement, yet with clinical implications. While still in Melbourne in the early 1980’s, Dr Medcalf moved into the area of “fibrinolysis and proteolysis”, a fancy way of saying the “removal of blood clots”. This period of research was very successful and productive. The essence of science is new frontiers and the development of new ideas, and contacts with peers is an important part of the life of most working scientists. For this reason also, many scientists seek work overseas to gain new perspectives and expand their networking contacts. In Dr Medcalf’s case, an opportunity came serendipitously, while he was visiting an Australian friend in Lausanne, Switzerland. Lausanne is a beautiful city on the shores of Lake Geneva and this idyllic setting Dr Medcalf met Professor Wolf-Dieter Schleuning, and it was Professor Schleuning who guided Dr Medcalf on the next phase of his career.

Prof Schleuning also was interested in the field of Fibrinolysis and Proteolysis, or rather the busting up of blood clots. Strokes are a serious medical event that affect thousands of people each year. What happens is that a blood clot forms in the blood stream and moves to the brain, depriving an area of blood and hence nutrients and oxygen. The effect is to ‘kill’ that part of the brain, so the body can no longer do what that part of the brain controlled, maybe speech or muscle control in part of the body. Dr. Medcalf studies the enzymes and mechanisms behind clot formation and dissolution, particularly how to extend the time after a stroke during which patients can be effectively treated. Part of this concerns not only the physical removal of a blood clot in the brain, but the ‘blood brain barrier’ and how this is modulated. It was quite a surprise that the very same enzyme that busts up the blood clot also had an unexpected affect on the brain itself, in part by modulating permeability of the blood brain barrier. In fact this enzyme was acting like a double edged sword, having good and not so good features. The mechanisms behind all this are not yet fully understood, and that’s why Dr Medcalf and his colleagues are studying it. The better the mechanisms are understood, the better treatments for stroke we will have, and we will improve the treatment and quality of life of thousands of people. Dr Medcalf isn’t practicing his Nobel Prize winning speech just yet however, at least not publicly. He knows the years of effort that will be required. For a career scientist, that consists at least in part of the following.

Provide the basics
After a 7 year stint in Switzerland, Dr Medcalf took an opportunity to return to Australia, and his home town of Melbourne. He brought a Swiss wife with him, and she quickly presented him with twin daughters. The return home presented him with many professional challenges as well. He had left as a newly graduated PhD student. Now he needed to re-invent himself in the local area as career researcher offering his new university a chance to be involved in worthwhile, internationally recognised research. A laboratory had to be established and built up. Most importantly, funding had to be sought and secured. Without a lab, awareness in the local environment and funding, nothing could be accomplished.

At length the hard slog of establishing a lab and a reputation was largely completed, though maintaining both is an ongoing task. With the lab established as a going concern, Dr. Medcalf could focus on the day to day business of scientific research. This consists at least in part of the following.

Setting the course, checking the progress
The department has postdoctoral researchers, PhD candidates and research assistants. Dr Medcalf meets regularly with each to discuss their progress and help set overall directions. He may discuss plans for the next day, week or month depending on who he is talking to. Results are discussed and future directions are set depending on whether a result looks promising or doesn’t seem to offer the chance of further progress. Of course researchers are people like everyone else and the uncertain nature of science, where progress may not follow from effort, can play on the nerves and confidence of the toughest mind. Researchers may find themselves in difficult personal situations, or have conflicts with their peers or supervisors and Dr. Medcalf must do what he can to help a researcher through. Dr. Medcalf is part mentor, part disciplinarian, part collaborator and probably part of a few other things in this area.

The broader scientific community
As was discussed earlier, science doesn’t just advance in a single lab. Each scientist has a responsibility to the other scientists in his field, and perhaps even to science more broadly. In Dr. Medcalf’s case he has a number of roles in this area. He is on the editorial board of several journals, and assists in the peer reviews of papers submitted for publication. He is a Member of the council of the International Society on Fribrinolysis and Proteolysis (ISFP), and has facilitated some of their annual or biannual meetings. He is currently arranging a large conference in Melbourne later this decade. The ISFP has members in about 30 countries, and Dr Medcalf was its chairperson for two terms each for two years.

Regular contact with other researchers in his field is a must for Dr. Medcalf. He regularly attends conferences, both presenting and being presented to. The conferences allow everyone to know what research is being undertaken and what results have been achieved. Everyone can build on what others are doing and all contribute to the field’s advancement. At a scientific conference the ‘coffee breaks’ are as or more important than the formal sessions. Informal contacts and discussions allow specific points or interests to be discovered in detail, and the all important “networks” can be developed and maintained. Dr Medcalf likes to take new researchers along to these conferences to introduce them and allow them to start to develop the contacts they will need throughout their career.

Publishing Papers
As Dr. Medcalf sometimes reviews papers, as a researcher he regularly writes them. How does he decide what a worthy subject of a paper is? “If a question is worthy, and the answer is likely to be important if taken to a conclusion, then it’s a question worthy of a paper” he says. Each paper starts with an idea, and the scientist asking, “What is my question?” Then the question needs to be stated clearly, and “trimmed’ if necessary so it is of a manageable size. Following that, experiments need to be devised, carried out and the results analysed. Experiments can last anywhere from hours to months, but experience will usually tell if an approach is productive or not. Experiments must be repeated until results can be stated with confidence. The process can be repetitious and involve statistical analysis of the resulting data. At the end of an exhaustive process, a result which does advance science is submitted for publication. As Dr Medcalf says “Science usually progresses incrementally”. Some ideas advance the field and extend knowledge. Some results may run counter to current thinking and move a field in a different direction. Not all experiments give an expected result, and when this happens it may be necessary to redesign a project and rethink where research is going.

Funding
In times past scientists were often supported by a wealthy patron, or were even wealthy themselves. Dr Medcalf comments that grants are “onerous, but a necessary evil”. He estimates that 30 to 40 % of his time is spent in applications to different granting bodies. Preparing a grant application focuses thought, but it can also be tedious and frustrating. Also, there is no guarantee that an applicant will get what they ask for. Nationally, the success rate is about 25% with only one application in 4 being successful. What makes for a successful grant application? Aiming to answer a relevant question that justifies the use of public monies, where that answer can ultimately be used for public benefits is probably the key. In more detail, a grant application should ‘set the scene’ for a particular line of research. When that is done key questions should be identified. What don’t we know? Why is it important to know it? What time, effort and resources would be needed to answer these questions? Once the purpose of the research has been clearly established, an application needs to ‘sell’ the lab of the applicant. A persuasive case needs to be made for why this lab in particular is suited to meet the stated aims of the research, and why this lab in particular is likely to succeed. As in most professions, a scientist too must be part salesman.

Hitting the jackpot
Australia has long lamented that while it seems to be able to produce a stream of world class researchers, the discoveries they make rarely go on to be developed to commercial success in the ‘Land of Oz’. One of Dr. Medcalf’s ideas is currently in commercial development. As stated earlier, a blood clot that forms and lodges in the brain can cause a stroke and permanent damage to some area of brain function. Dr. Medcalf and his collaborators went to a very logical source to find a way to clear clots, the vampire bat. Unlike the vampires in Bram Stoker’s “Dracula”, vampire bats don’t drink by sinking their fangs into their victim’s neck. They open a wound and just drink as the blood flows out. But why doesn’t it clot? It turns out that the bat’s saliva contains an enzyme which busts up the clots as soon as they are formed. By understanding this mechanism Dr. Medcalf and his associates hope to develop new treatments for stroke and to limit the amount of damage strokes do by offering different and better clinical treatments. Dr Medcalf is involved in this project, but has no financial or business interest or benefit.

While new scientific breakthroughs don’t happen every day, scientists wouldn’t be human if they didn’t hope to have an idea which brought fame, recognition and financial security for life. Each probably holds a secret hope that they will discover the next ‘penicillin’ or ’theory of relativity’. They might hope this, but each is also realistic enough to acknowledge that such breakthroughs come only rarely.

Conclusion
So what have we found that scientists do? They find a field that interests them and do the hard yards of gaining the knowledge and other resources they will need to work in this chosen field. They continually work to fund their research, clarifying ideas and competing with other scientists for the grant money to continue their work. They maintain constant contact with the colleagues in their lab, making sure that research is progressing by supervising and suggesting as necessary. They maintain networks of other scientists in their field and work at staying ‘current’ with developments. They hope for the breakthrough that may give them greatness in one form or other. In the meantime they do the hard work to advance our knowledge

Mostly, scientists like their work. Dr. Medcalf certainly likes his. He finds the questions and searching for answers ‘amazing’. “We have the capability and capacity to take on questions we couldn’t answer until recently, but have the possibility now”, he says. He says we are at a very exciting point. Maybe passion and that excitement is what drives most scientists. Perhaps we should add one other thing that scientists do, enjoy their work.

Barry Leviny is host of ‘The Uncertainty Principle’ on Vision Australia Radio in Victoria. The show consists of interviews with scientists and reading of scientific articles.