The research road to doctorate

Working hard for low pay, but Graeme O'Neill reports that the pursuit of a PhD could be the most rewarding time in a scientist's life.

They're the foot-soldiers of the biotechnology revolution, spending long hours of hard slog at the front, for salaries that barely allow a life beyond the lab. So who'd be a PhD? There's no supply problem, even in the age of Mammon, opportunity and a Beemer by age 25. For all the inevitable pain and poverty of the PhD experience, the prospect of intellectual adventure, peer respect, and of being in the right lab at a moment of discovery, retain an almost mystical allure for an inquiring mind. For a relatively modest investment in Australia's higher education system, PhDs deliver enormous value to governments and taxpayers. Where else could you get a freshly minted, first-class mind, to work a dozen hours a day for three years, for just $20,000 year, no penalty rates?

Breakthrough discoveries In 1988, a young PhD student at the Walter and Eliza Hall Institute of Medical Research (WEHI), David Vaux, was the lead author on a seminal paper in Nature on apoptosis, for his discovery that a gene called Bcl-2 protects cells against apoptosis, or programmed cell death. Apoptosis was little more than a curiosity at the time; it is now one of the hottest fields in biomedical research, a phenomenon that is now known to be involved in embryogenesis, cancer, central nervous system disorders like Alzheimer's disease and motor neuron disease, and brain damage from stroke or head trauma. One of WEHI's current crop of PhDs, Vanessa Marsden, was lead author on another paper in Nature last year, describing a novel apoptosis pathway. And Ygal Haupt, a PhD student in Prof Gerry Adams' cancer research lab at WEHI, was lead author on a recent paper in Cell announcing the discovery of a new oncogene involved in lymphomas, called BMI-1.

Important contributions Dr Andreas Strasser, head of WEHI's Division of the Molecular Genetics of Cancer, and chair of the institute's education committee, describes the contribution of PhDs to modern medical research as "incredibly important". "It's the way the research system works -- senior researchers and laboratory heads rarely get time to do the practical work in research, so they usually don't appear as first authors on significant papers -- it's now most likely that the first author will be a postdoctoral researcher or a PhD student. Some labs employ postdocs, but Strasser says his personal preference is to work with PhDs. "There's a lot of joy teaching them, watching them grow into their projects -- they usually make very rapid progress in the first year, master many new techniques, so there's a lot of satisfaction on both sides." Strasser says that WEHI typically has about 70 PhDs and half-a-dozen Honours students working in its laboratories. Most are from the University of Melbourne; the institute is a department of the university. It's trendy for Honours students to take a year off at the end of their project to see the world, and perhaps earn enough money to help support themselves when they return and upgrade to a PhD. Some PhD students are medical graduates who have completed specialist degrees; others come from other Australian universities, and have trained in molecular genetics, microbiology, immunology, and biochemistry. In recent times, students in bioinformatics, mathematics or physics have been recruited to work in the Institute's new Division of Structural Biology. "In my case, I haven't had single PhD from Melbourne in the past seven years -- my students have all come from Adelaide, Hobart, Perth, Auckland and Auckland," Strasser says.

Job dedication Strasser says PhD students have to be "incredibly dedicated". "It can and should be the most worthwhile experience in a scientist's life, because it's the time when the learning curve is steepest, and the person grows the most. And it can be extremely satisfying when it works well, and there's a major paper and some glory at the end of it. "It tends to be a fairly rare occurrence, but we have labs in which 30 to 40 per cent of the PhDs have ended up with a paper in a top class journal like Nature, Science or Cell." For second-tier journals like Nature Genetics, EMBO (Journal of the European Molecular Biology Organisation, and the Journal of Experimental Medicine, the strike rate is 50 to 70 per cent. Strasser says the Federal government has made life harder for PhDs by funding fellowships for only three years, with the possibility of one six-month extension -- in other industrialised nations, the norm is four years. "The government now has an expectation that a PhD will be completed in three years, when it should be four to four-and-a-half years, because there is an increasing amount that students must learn. There's a trade-off between the money saved, and the amount learned -- although in some ways, the technology has made research easier to do. "Australian PhDs are disadvantaged when they go looking for postdoctoral positions overseas -- they might come out of their PhD with one or two good papers in international journals, whereas a PhD from Holland or Germany might have four or five papers -- if they're competing, the European PhD will usually get the job. "Yet because Australian kids start school at an earlier age than most kids in Europe, they can really afford to have 4.5 years in the lab, without hindering their progress."

Young investigators The Adelaide Women's and Children's Hospital (WCH) is another prime training ground for PhDs -- most of them graduates of Adelaide University or Flinders University. Molecular geneticist Dr Jozef Gecz says the hospital has about 50 PhDs. The hospital tries to foster a strong sense of community and sponsors an annual Young Investigator Award for its top PhD, based on research excellence and skill in describing the research to a lay audience. Karen Lower, this year's winner, was recently lead author on a Nature Genetics paper announcing the discovery of a new zinc-finger regulatory gene that, in mutant form, causes a rare hereditary disorder, Borjeson-Forssman-Lehmann-Syndrome, involving severe intellectual disability, hypermetabolism and obesity. Another PhD, Marie Mangelsdorf, shared lead authorship of another Nature Genetics paper announcing the discovery of a mutant gene that causes severe intellectual disability and epilepsy -- it involves a novel Hox gene, one of a family of genes that have basic roles in embryogenesis. Different mutations of the same gene are associated with other hereditary disorders that have mild to severe effects on brain development. Like WEHI's Strasser, Gecz says the hospital values its PhDs' work "enormously." Of the PhD's garret salary, Gecz says, "We try to subsidise them. A PhD costs me half as much as a research assistant. They probably work twice as hard, and their work is very high quality.

Good value "They're usually self-motivated to pursue a career in science, and very responsible, with very good undergraduate records. We don't offer them much, and we get lots out of them." Don Roberton, Professor of Paediatrics at Adelaide University, and head of the WCH's Department of Paediatrics has about 20 of the 50 PhDs at WCH working in his department. Like Strasser, Roberton has concerns about the three-year PhD "squeeze". "I think the pressure to complete in three years constrains opportunities for students to think more broadly and laterally. "Learning is an ongoing process, and it can take one or two years to realize that a particular approach is not going to be productive, while an alternative is going to be spectacularly productive. "Students have to learn to be less adventurous in their thinking, and to learn to choose an optimal path, that is more rewarding in relation to the time and effort involved. That demands higher-order thinking that can be invaluable to their research careers." Roberton says Australia must understand the importance of higher levels of learning and experience to progress in medical science. He says the PhD process delivers community and economic benefits in terms of improved health care, disease prevention, and savings in health costs. He believes institutions should aim to develop two basic attributes in their PhDs -- the capacity for independent inquiry, and skills that will be of maximum utility in the research environment. "Our students work in areas of immediate, direct relevance to health and clinical practice. Patients' needs are very much to the fore, which helps students focus their research projects. "One of the things we emphasise with students commencing their research is that they need to think widely, even though they are likely to finish with expertise in a fairly narrow area. The need to consider how their skills might be useful in broader, rapidly changing environment. "In this country, and others, we need to recognise that support for a PhDs career development is often less than it should be -- we need to help our PhDs develop a sustainable career in research. "The NHMRC and other funding bodies are aware of the problem [of narrow specialisation limiting career prospects] but it's a tough area to address."

Local talent CSIRO Plant Industry is one of Australia's major graduate schools in plant science. It currently has 62 PhDs scattered around Australia, according to molecular geneticist Dr TJ Higgins, a senior researcher with the division. "We regard them as extremely important in our own research, but we also see their involvement as very important in training modern plant biologists." Higgins says the division's PhDs are usually recruited locally from universities in the cities and towns where the division's specialist laboratories are located. There are 20 PhDs at divisional HQ in Canberra, 15 in Adelaide (horticulture), 5 at Merbein (horticulture), eight in Brisbane (sugar cane, wheat, macadamias) five in Perth (Mediterranean crops), one in Narrabri (cotton), and two in Townsville (sugar cane). Students are encouraged to return to their affiliated universities for peer-group interaction and to avoid intellectual isolation, says Higgins -- the 20 PhDs in Canberra regularly interact with their peers at the Australian National University. The division funds some PhD fellowships from its own resources, in addition to those funded by CSIRO. A first-class Honours degree is a basic requirement "and we tend to take only the very top students," says Higgins. "They've usually had quite a bit of lab experience, but they usually take a year to find their feet, during which they need lot of individual supervision. Few PhDs return as postdoctoral researchers -- "We see them as learning what we've got to teach them, then we encourage them to go overseas to do postdoctoral research -- it's another important step in getting experience." When they return to Australia, they're usually recruited by other plant science agencies or private companies -- the PhD system has been integral in establishing research networks and collaborations between CSIRO, universities and other plant research agencies, and businesses across Australia, says Higgins. The division's PhDs are attracted by the prospect of one-on-one interaction with senior scientists, and its superb research facilities, which are more modern and comprehensive than most universities can afford, says Higgins. The division's PhDs make major contributions to research; Chinese student Ming Luo has had papers on apomixis -- seed formation without sex -- published in Proceedings of the National Academy of Science, while one of Higgins' own PhDs, Nick Hagan, a former Biology Olympiad silver medallist as a high school student in 1986, has also been lead author on papers in leading journals. It's not only research skills that PhDs acquire at Plant Industry, Higgins says the division is encouraging Hagan to develop his natural skills as a science communicator -- good science communicators are precious, especially in the controversial field of plant gene technology. Hagan tutors in gene technology in the division's Industry Link program for decision-makers in business, briefs politicians on the division's research, and is now an organiser for Australia's Biology Olympiad team. Croatian-born biochemistry graduate Jasmina Dedic, a PhD in Dr Peter Waterhouse's laboratory, has published papers on gene silencing by RNA interference n first-class journals, and in her spare time is an internationally-ranked skier. The division does not have as many overseas PhDs as it did in former years, because of the very high fees that overseas students must now pay -- "But we still have a few students from Asian countries, who are funded by Ausays -- we see this as part of Australia's responsibility to build the research capacity of our neighbours," says Higgins. Higgins has also used a Rockefeller Foundation grant to establish research collaborations with several universities in sub-Saharan Africa to transfer the division's expertise on pasture and crop legume genetics, "We've invited several PhD students already enrolled in these universities to spend part of their time with CSIRO, so they can get a feeling for what's going on."