Robyn Lindley’s Adventure Journey
A Lifelong Passion for Science
Robyn A. Lindley, we are proud to present you an overview on her career. Having educated herself multidisciplinary, she gained an extremely broad overview on several aspects of natural sciences. In the past years she increasingly worked on evolutionary questions.
Today, the mainstream view on evolution is based on paradigms grounded on Darwin's ideas on natural variation and subsequent selection of the most suitable genetic setup (survival of the fittest) and the paradigm of the Weismann barrier, a strongly mechanistic and static interpretation of Darwin's concepts, strictly excluding any influence of the experiences of an individual on its progeny.
Most evo-devo researchers still try to adjust an increasing body of evidence for acquired inheritance effects, more or less reasonable, to outdated concepts. But there are overwhelming evidences that there are mechanisms transferring acquired information to offspring of an individual, often condensed to the much too simple term "epigenetics".
An overview on Robyn's research you can find in G.I.T. Laboratory Journal 3-4 (2011).
Born strong willed and adventurous by nature in Australia's Snowy Mountains provided me with the furtive grounds to foster a lifelong love of nature and science. Much of my formative years were spent wondering about the physical laws that gave rise to the geological forms and life that surrounded me.
At around eleven I recall reading The Radium Woman by Eleanor Doorly: It immediately resonated with my rather naïve sense of scientific adventure, and it was this that ignited a lifelong passion for science. From this point on I considered no other possibility other than a life built around a scientific career.
A few years later and armed with the power of youth, I studied mathematics and physics at the University of Sydney. These were days full of hope, and the days that I loved best. I graduated with a BSc in physics from the University of Sydney in 1974.
Later I began research in nuclear physics in the Department of Physics at the Duntroon Royal Military College in Canberra. It was during this time, that I met and married Australian immunologist Ted Steele. I was greatly attracted to his fervor for scientific discovery that is still not diminished.
Following the birth of my third son, I took up a position as the Foundation General Manager of the Illawarra Information Technology Center which was sponsored by the University of Wollongong. There I became actively involved in the innovation community and I developed a research program around mobile telecommunications and smart card technologies. I spent a term as President of the Inventors' Association of Australia 1989-1990. Later, I established the Technology Innovation Research Center (TIRC) at the University of Wollongong.
After completing a Master's Degree in Telecommunications (1994) and a doctorate in smart card innovation (1996), I secured several large competitive research grants, as well as industry grants and government contracts. I also became actively involved in risk management in preparation for the Y2K bug for New South Wales Government Departments and its agencies. With an increasing number of students competing for my time, this was one of the busiest times of my life. It was also a time when Australian universities were yielding to political pressures to generate more funding. I questioned my own motives, and the ideological value of a system that demanded so much of my time to obtain grants to support short term research goals. I still lament the dichotomy.
As my career in IT blossomed, I continued to nurture an interest in evolution and understanding how our genes function. For me, many of the inbuilt logic functions are analogous to an object oriented program that has an inbuilt ability to learn to solve its own problems. Our own ability to solve problems has evolved using the same logic.
In 1996-1997, I co-authored Lamarck's Signature (1998). With a bottle of red, we spent many Friday evenings drafting another section. Our aim was to explain the Lamarckian nature of the process of updating the variable regions of antibody genes. At the time, it was believed that the Somatic Hypermutation (SHM) mechanism involved in updating antibody genes simply did not apply to other genes. So the wider implications were largely ignored.
Despite some protestation from Professor Robert Blandon (co-author), I introduced some of my early ideas on conscious evolution into the epilogue: the idea that we have the ability to consciously direct our evolution is one of the many consequences that flow quite naturally from an acceptance of an evolutionary paradigm based on natural selection and acquired inheritance phenomena.
After spending twelve years in a University environment, I resigned from my post as Associate Professor to accept a position as the Technology Product Development Manager, and later as the Business Intelligence Manager, at Vodafone Australia. These were very heady days for the mobile telecommunications industry. The demand for new mobile data services and the rapid global market growth seemed quite insatiable.
Late in 2003, I accepted a position as the Business Development Strategist at Silverbrook Research (SBR). These were also exciting years. While working at SBR, I continued to work on genomics. Thanks to a new generation of high throughput sequencing technologies, a massive amount of well curated new data was becoming publicly available for analysis. The only resource I required was a laptop with internet connectivity - and a few hours in the evening.
The first exciting insights came in early 2006. I recall going out to dinner with Ted. As usual we discussed the possible meanings of some of the data we had been mining. We were at a point where we knew that there was a key role for base modified RNA intermediates. But how could we use the available data sets to show that this is the case? We came home, and I immediately set up a simple algorithm to produce the first graphs showing that if an adenosine base is presented in the correct context of a double stranded RNA structure (emerging from a transcription bubble) and allowing the deamination of adenosine to inosine (i.e. A→G mutation) following reverse transcription, correlated strongly with the predicted hotspots for A→G transitions. These crude graphs provided the first tangible evidence of a role for base modified RNA intermediates as central to all strand biases at G:C and A:T base pairs in SHM.
A few days later we sent the data to Georg Weiller and Jiayu Wen at the Australian National University. Initially Georg had some difficulty coming to terms with our conclusions, but after using a different bioinformatics approach he was able to improve our analysis. The results were published several months later.
Shortly after publication, and while I was competing in the gruelling 2006 Sydney-Hobart yacht race on a Volvo 60, I decided that I must make plans to devote more time to genomic research. In late 2008, I resigned from my position at SBR. I had enough money to indulge my passion for at least 12 months. As my husband had been unemployed since 2000 and I needed to support my boys, I recall the trepidation I felt. I had no idea how I would be able to pay the bills after a year.
Each day I sat at my desk and went through the papers I had been carefully archiving for over a decade. What did they all mean? I began writing The Soma: How our genes really work and why that changes everything (2010). While this work was not immediately accepted for publication by a mainstream publishing house, the response to it has been far more welcoming than I had anticipated. For now, it exists as a record of the large number of scientific works that collectively provide a compelling argument in support of the ancient idea of pangenesis.
After my sojourn, I took up a temporary post as the Honorary CEO of the C.Y. O'Connor Research Foundation in Western Australia. This shift led to a quite unexpected discovery. One weekend in late January 2010 when the temperature outside reached a scorching 47 degrees centigrade, I decided to escape to a cool lab to analyse sample mutation data provided by the Cancer Genome Project (CGP). With Ted as my collaborator, we wondered just what it might reveal? Would each tissue type throw a different mutation signature? We were absolutely stunned to discover that the same SHM signature that was known to characterize the mutation patterns arising in the variable regions of the antibody genes, appeared to occur in most of the cancer groups. It was as if the same finger print was stamped over each data set we looked at. The results were statistically highly significant. We rechecked the data. The results were published in the form of a Letter to the Editor of DNA Repair a few months later.
Surprised by the implications for how we might view the genesis of cancer, we knew that the results would raise more questions than they answered. We concluded that whilst SHM is known to be a tightly regulated and beneficial process for B cells, the ‘switching on' of the SHM mechanism to produce aberrant mutations (or ‘crisis') in a range of normal somatic tissues could result in the genesis of cancer. RNA intermediaries appear to be involved in the genesis of sprays of mutation in all of the non-lymphatic cancer genomes we analyzed.
Now living back in the Snowy Mountains of Australia, we have since confirmed our conclusions using the TP53 data base. The central tenet is that whilst there are several other causes of somatic point mutations, there is an identifiable underlying "endogenous" strand biased signature that co-opts the SHM mutation machinery at both G:C and A:T base pairs. While Ted is continuing to work on the TP53 data base, I am adopting a different strategy. The basic premise upon which my current data analyses depends, is that the SHM mechanism can become activated in any somatic tissue, and that those genes that are actively transcribed will be the main targets for the SHM apparatus. I am currently analyzing the strand biased mutation signatures in relation to the chromatid structures for the different tissue types in which the major cancers arise.
Future research efforts will aim to determine whether or not the SHM appartus is co-opted as a ‘universal mutator' mechanism to induce genetic variability in actively transcribed genes (i.e. those that are required by an organism). Achieving this goal will continue to rely on a multidisciplinary approach.
I am fortunate in that I am now ‘free' to conduct research that is not restricted by mainstream thinking. I am also optimistic that further work and acceptance of the role of SHM will enable new drug targets for cancer to be developed such as AID, Pol-eta, ADAR1 and a range of modulators of the RNA Pol II transcription-coupled repair (TCR) apparatus. My hope is that the evolutionary implications will also not be lost.
 Lindley R.: The Soma (2010)
 Lindley R.: G.I.T. Laboratory Journal Europe 15, (3) 20-22 (2011)
 Lindley R.: EdgeScience 8 July-September (2011)
 Steele E., et al.: Lamarck's Signature (1988)
 Steele E. et al.: DNA Repair 5 1346-63 (2006)
 Steele E. Lindley R.: DNA Repair 9 600-603 (2010)