What’s in a Name: what MD really means for us

I feel like a dying breed. A dinosaur, if you will. At the outset of my studies I knew this and I still think about it occasionally, still wonder if I made the right decision at the naïve age of 17.

I’m talking of course about my name. Specifically, what’s going to appear after it in just a few years’ time — MBBS. That cultural UK tradition drawn from the fusion of Physicians (Bachelors of Medicine) and Surgeons (Bachelors of Surgery), who at some point decided it was all the same stuff, and that MBBS was more attractive than BM, BS.

In Australia, and in my university, we’re seeing a relatively new kid on the block — the Doctor of Medicine (typically MD). The roots of this seem to come from across the pond, where at some stage Americans decided to silently disagree once again with the conventions of England. In fact, I am the last cohort of MBBS in my university – many of the students below my year boast their superior would-be qualification, and I’ve heard it time and again from universities that already have it. But is MD a new degree, or just a new name? Is this really a new breed of Doc that will one day uniformly scoff at me, a dinosaur from the age of MBBS?

I set about this question in a number of ways. There are the facts and figures, the institutional requirements that fall under the Australian Qualifications Framework (AQF) and the Australian Medical Council. And then there are the perceptions — much more difficult to grasp, but no less important for a degree so public as medicine, where your qualifications guide your job opportunities, your patient trust, and ultimately the ability to help people.

So to the facts. The AQF guides the ability of universities and other tertiary providers to name programs. This is a 10-step ladder, available in an interactive website provided by the AQF [1]. It runs from Level 1 – a Certificate 1, through to Level 10 – a PhD. In Australia, universities are self-accrediting higher education providers, and are overseen by the Tertiary Education Quality and Standards Agency, a Commonwealth Government department. Although I can’t admit to knowing the exact process of application and oversight, the simple fact remains: In Australia, your primary medical degree can be Level 7, Level 8 or Level 9.

Level 7 is a Bachelor degree – there are several broad expectations of someone having attained this level of degree, which is summarised on the AQF website as the following:

“Graduates at this level will have broad and coherent knowledge and skills for professional work and/or further learning” [1].

That seems pretty good to me. Medicine is a profession that I want work in, and I’m very open to further learning – such as a specialty or a research higher degree.

Level 8 is a Bachelor degree with Honours, something provided by many of the universities that still offer MBBS. Although it must be noted that at some universities, Honours is given only to those who undergo extensive research on top of their studies, while at other universities, the requirements seem far less stringent. Level 9 qualification is where MD comes in — according to the AQF levels it is a single Masters degree. The summary of graduates of this level is:

“Graduates at this level will have specialised knowledge and skills for research, and/or professional practice and/or further learning” [1].

This doesn’t seem to mean much to me as a medical student. Surely “specialised knowledge” is gained in postgraduate vocational training, as per the system of Australian Specialist Medical Colleges, in turn overseen by the Confederation of Postgraduate Medical Councils and the AMC [2]? And in terms of research, does that mean I can’t complete useful medical research, with my measly BSc/MBBS?

Maybe the Australian Medical Council could straighten things out for me, and tell me how much I’m worth. The AMC is ultimately responsible for the training of all medical students and doctors in Australia, as dictated by the Medical Board of Australia [3]. This is a huge responsibility – and with medicine changing more and more rapidly over the past 50 years, it’s impressive that they could keep up!

In fact, there is no difference in the AMC accreditation level of university medical graduates. Quite the opposite – the AMC regards all medical students as having had a comparable experience in medical school to make them safe enough for an Australian internship. For the University of Melbourne, the first university to offer the MD in Australia, there was a re-accreditation process with the AMC before the degree could be offered [4]. Likewise, the University of Western Australia overhauled their program, entirely changing the number of years of medical school [5]. But every other medical school in Australia that has switched or is considering switching has not required extensive re-accreditation beyond the normal requirements that exist year-to-year [6][7].

On the ground, what is this meaning for students? Are students becoming better doctors and better scholars, or are they not? My personal feeling is the latter. I have peer-tutored at my university for the year below me, and they do not seem to be a new breed at all. Like me, they wish they started cramming a week earlier with each coming semester. Like me, they whinge when the School makes small program changes that they don’t agree with, or schedules lectures that they think are useless. Like me, they attend Evidence-Based Medicine with a somewhat silent resentment, not because it’s not important but because it’s not exciting.

The School has made some changes; I suppose to be in line with AQF standards. All MD students at my university now write a research protocol – as I understand it, a report on how they might do some research. It’s not revolutionary, it’s not PhD-worthy, and in fact, it’s a lot less than the research required to get an Honours in my current program.

But more than all the facts and figures, I do care about the perceptions. I do wonder if a patient one day will take a look at my name-tag and ask me what an MBBS is, and why they’re not being seen by a real doctor. I wonder if the applications office at RACP or RACS will one day look at my name and think less of me. I wonder if I should have chosen to be the last of the MBBS cohort at my university, or done an extra year of science and slipped into the first MD class. These are worries that can’t easily be put to rest – especially when my juniors already think themselves superior in some way. As though somehow, their research protocol made them able to pick the diagnosis when I would have missed it.

Many students at my university are from overseas, and eventually become fully registered doctors in countries like the US. There, MBBS means nothing, and MD sits in a strange qualifications level that we don’t have in Australia. In many states of America, you can, for a nominal fee, apply to legally change from MBBS to MD after your name, and many of my colleagues will do so [8]. This may be a potential solution to my worries down the track, should they ever really arise.

I decided at the end of the day, that MD is much more about business than health. It was attractive for the University of Melbourne to pioneer a new name, and now each new medical school that “gets the MD” can call themselves on par once again. Unfortunately, the restrictions for Domestic Full-Fee Places in universities do not apply to postgraduate courses such as Masters, which legitimately poses a financial threat to new students, and added strain to the internship crisis [4]. For now, I’m content in the hope that most people don’t care what’s in a name. A medical degree by any other name would doctor just as well. And after all, the Australian National University now provides their students an MChD and nobody seems to complain [9]!



The Australian Medical Students’ Association (AMSA) for inviting me to present policy related to this topic.


Conflict of interest declaration




[1] Australian Qualifications Framework [Internet]. Canberra ACT: Australian Government Department of Education and Training; 2015. AQF Levels; 2013 [cited 2016 Jul 24]. Available from:

[2] Confederation of Postgraduate Medical Education Councils [Internet]. Melbourne VIC: Confederation of Postgraduate Medical Education Councils; 2008. Postgraduate Medical Councils; 2008 [cited 2016 Jul 24]. Available from:

[3] Australian Medical Council Limited [Internet]. Kingston ACT: Australian Medical Council; 2016. About the AMC; 2016 [cited 2016 Jul 24]. Available from:

[4] Roberts-Thomson RL, Kirchner SD, Wong CX. MD: the new MB BS? Med J Aust [Internet]. 2010 Dec [cited 2016 Jul 24];193(11/12):660-661. Available from:

[5] Australian Medical Council [Internet]. Canberra ACT: Medical school accreditation program and status report; 2015 [cited 2016 Jul 24]. Available from:

[6] Australian Medical Council [Internet]. Canberra ACT: Changes to Primary Qualifications for Admission to Practise Medicine in Australia: Implications for AMC Accreditation; 2012 [updated October 2012; cited 2016 Jul 24]. Available from:

[7] University of Queensland [Internet]. Brisbane QLD: Doctor of Medicine (MD); 2016 [cited 2016 Jul 24]. Available from:

[8] New York State Education Department Office of the Professions [Internet]. New York NY: New York State Education Department; 2009. Conferral of M.D. Degree; 2009 [updated Dec 15 2009; cited 2016 Jul 24]. Available from:

[9] Australian Government Department of Industry, Innovation, Climate Change,

Science, Research and Tertiary Education. 2014-16 Mission-based Compact Between The Commonwealth of Australia and The Australian National University. Canberra ACT; 2014 [cited 2016 Jul 24]. 23. Available from:


Healthcare in Australia must continue to be freely available for all Australians

Universal healthcare is a privilege and a right that we must protect to ensure the healthy future of Australia. As medical students and doctors, we are more than simply practitioners of medicine. We hold more responsibility than solely the management of disease. A key responsibility of our profession is advocacy for the health of our patients, the health of our nation, and the protection of our public health system.

The recent election has highlighted the fragility of our public health funding, and the willingness of both sides of politics to use Medicare and public healthcare as a political tool to serve their own agenda. This short-term and selfish thinking has the potential to abolish equal and fair access to healthcare; this is something that is, and should continue to be, a universal right for every Australian. The opportunity to live a long and healthy life should not be decided by our wealth. As it stands, the health gap between those from upper and lower socioeconomic backgrounds is significant [1]. The ramifications of freezing or removing funding to Medicare and public healthcare will be widespread. The current policy of a “freeze” on Medicare will increase out-of-pocket costs to all patients, impacting patients from lower socioeconomic backgrounds significantly. The effect of this freeze will be two-fold, with the added effect of increased practice costs in areas where patients cannot afford to pay out-of-pocket fees [2]. In turn, this will impact practice viability, and in lower socioeconomic areas, some practices may be forced to close, leaving vulnerable groups with limited access to healthcare [2].

The result of increased out-of-pocket fees will be an increasingly privatised healthcare system, and one does not need to look far to see the detrimental effect of such a system. In America, the healthcare system screams of inequality. It is a system where doctors are often placed in tremendously difficult situations, and are often left with no option but to turn away patients who are unable to afford healthcare [3]. America has a per capita healthcare expenditure that far exceeds that of other developed nations, however, public spending only covers 34% of residents in the United States, compared to every resident in Australia and the UK [4]. What is most damning about these statistics is that despite exorbitant healthcare expenditure, predominantly at a cost to patients or their insurers, the life expectancy American citizens languishes at 31st in the world, well below that of Australia, which is ranked fifth [5]. But that is not where the inequality stops. The privatised, self-funded system in America also stakes claim to the highest infant mortality rate amongst all developed nations, and a higher prevalence of chronic disease than that in developed nations with a universal public healthcare system [4]. If we are to preserve the health of Australians, we must take on the responsibility to advocate for healthcare as a universal right for all Australians.

In the lead up to, and in the days following the recent election, the Australian Medical Association (AMA) and the Royal Australian College of General Practitioners (RACGP) have been highly outspoken regarding their concerns about the inequality of funding cuts to Medicare. This advocacy, along with campaign material centred on Medicare, led to a strong response from the Australian public at the election, making it evident that Australians value free universal healthcare. However, this has not led to a response from parliament about the freeze on Medicare funding. Without a change in this policy, 57% of GPs have said they will increase out-of-pocket expenses, and 30% have said they will stop bulk billing [2]. This will directly affect patient access to healthcare, and has the potential to have a detrimental impact on Australian health outcomes, similar to health outcomes seen in America. As medical students and doctors, we are on the frontline of these changes, and it is our responsibility to protect our universal healthcare system. It is an issue that needs all of our support.

As a highly educated and privileged group, we need to ensure that governments understand the ramifications of cutting funding to Medicare and public healthcare. Universal healthcare needs to remain a priority in Australia and a right for all Australians, young and old. The health of our nation reflects the spirit of our nation, and it is the role of all medical professionals to advocate for equality in healthcare. Our advocacy need not make headlines in newspapers or fill prime-time television slots. Through simple conversation we can raise awareness about the importance of universal healthcare. It is our role to ensure that Medicare and public healthcare remains a priority, not just for the next election cycle, but for the long-term, so that future generations of Australians can enjoy long, prosperous, and healthy lives, just like the Australians of today.


Conflicts of interest

None declared.


 [1]       World Health Organisation. Health Impact Assessment: The determinants of health [Internet]. World Health Organisation; 2016. Available from:

[2]       RACGP. Antifreeze campaign – fact sheet for GPs and practices [Internet]. RACGP; 2015. Available from:

[3]       Weiner S. I can’t afford that!: Dilemmas in the care of the uninsured and underinsured. J Gen Intern Med. 2001 Jun;16(6):412–8.

[4]       Squires D, Anderson C. U.S. health care from a global perspective: spending, use of services, prices, and health in 13 countries. The Commonwealth Fund; 2015.

[5]       World Health Organisation. Life expectancy 2015 [Internet]. World Health Organisation; 2015. Available from:


I am a medical student, and I am afraid to report bullying and harassment

The president of the Royal Australian College of Surgeons (RACS) has apologised on behalf of surgeons for discrimination, bullying, and sexual harassment [1]. The Australian Medical Association (AMA) has released a position statement on workplace bullying and harassment [2,3]. Despite this, Dr Caroline Tan still does not work in any major public hospitals and I, a final year medical student, am still afraid to report bullying and harassment.

“Suck Sarah*, suck” was what the consultant surgeon who was operating repeatedly instructed me to do with the suction device whilst I was assisting him as a medical student in theatre. After about the twentieth time he said this, the assisting registrar joked “I thought you’d be better at sucking than that Sarah”. Everyone in the theatre laughed aloud and despite feeling increasingly uncomfortable, I joined in. I was trying my best to please my superiors and laughing at their jokes was part of this attempt. It wasn’t until the casual discussion with my colleagues that evening that I realised how degrading and inappropriate these comments were. My uncomfortable feelings weren’t just part of being a medical student surrounded by intimidating seniors, but rather, were the result of sexual harassment. The very fact that I assumed what occurred was normal is testament to the fact that bullying and harassment is entrenched in the culture of medicine and its hierarchy. I never reported the incident, and none of my colleagues ever encouraged me to do so.

My story raises the issue of commonplace occurrences in medicine. Sydney surgeon, Dr Gabrielle McMullin, publically said Dr Caroline Tan’s career was ruined by a sexual harassment case that she won against her fellow neurosurgeon in 2008, and that she would have been better off giving him ‘a blow job’ [4]. Dr McMullin’s controversial comments attracted unprecedented media attention and were successful in exposing a silent epidemic of bullying and harassment in medicine.

Bullying is defined as repeated unreasonable behaviour that creates a risk to health and safety. Harassment is unwanted, unwelcome, or uninvited behaviour that makes a person feel humiliated, intimidated, or offended [5]. According to the AMA, medical students, doctors in training, female colleagues, and international medical graduates are the most common victims of bullying and harassment in the medical profession [2]. Up to 50% of doctors, doctors in training, and international medical graduates have been bullied or harassed, and the most common perpetrators are senior doctors [5-7]. This problem has persisted for many years because hospitals and professional associations have failed to act, discouraged change, and have thereby fostered a culture of bullying [8].

The sequelae of workplace bullying and harassment in medicine are serious. The continued erosion of confidence, skills, and initiative creates negative attitudes among medical staff. It directly leads to reduced employee physical and psychological health that manifests as anxiety and depression. This leads to diminishing performance, reduced quality of patient care, and subsequently deteriorating patient safety [9].

Most large medical organisations including the AMA and RACS have responded to the issue and identified bullying and harassment in medicine as a priority area for change. The AMA, on 9th March 2016, released ‘Setting the standard’, a strategy to overcome bullying, discrimination, and harassment in the medical profession [2]. The RACS Expert Advisory Group (EAG) has published its final report on the extent of discrimination, bullying, and sexual harassment in the practice of surgery [5]. However, despite these efforts and the extensive coverage in the media, bullying and harassment still occur and victims such as myself are still afraid to speak up. Barriers to victims making claims include the perception that nothing would change, not wanting to be seen as a trouble-maker, the seniority of the bully, fear of impact on future job prospects, and uncertainty over how cases would be managed and future policies implemented [5].

Efforts need to focus on ground-level interventions. Importantly, new policies from the AMA, RACS, and other leading organisations need to work towards creating safer and more effective complaints processes that people such as myself are more willing to use. A system that ensures we will not be punished as Dr Caroline Tan was. All members of the medical workforce need to normalise a zero-tolerance attitude to bullying and harassment so that it can be cultivated and adopted into the culture of medicine. Only then may the change be organic and not just another unread policy used by medical associations as medicolegal protection.

* A pseudonym has been used to protect the author’s privacy.


[1] RACS Media Release. RACS apologises for discrimination, bullying and sexual harassment. Canberra:RACS;2015 [cited 2016 Mar]. Available from:

[2] Australian Medical Association. AMA position statement: workplace bullying and harassment. Canberra:AMA;2015. Available from:

[3] Australian Medical Association. Setting the standard, AMA Victoria’s summit. Canberra:AMA;2016 Mar. Available from:

[4] Medew J. Surgeon Caroline Tan breaks silence over sexual harassment in hospitals. The Age [Internet]. 2015 Mar 12 [cited 2016 May]; Victoria. Available from:

[5] Expert Advisory Group. Survey of all college fellows, trainees and international medical graduates to find out the scope of discrimination, bullying and sexual harassment, 2015. Canberra:RACS;2015 Sep [cited 2016 Mar]. Available from:

[6] Rutherford A, Rissel C. A survey of workplace bullying in a health sector organisation. Aust Health Rev. 2004;28(1):65-72.

[7] Fnais N et al. Harassment and discrimination in medical training: a systematic review and meta-analysis. Acad Med. 2014;89(5):817-27.

[8] Watters DA, Hillis DJ. Discrimination, bullying and sexual harassment: where next for medical leadership? Surgeon. 2015;2015(001).

[9] Rosenstein AH. The quality and economic impact of disruptive behaviors on clinical outcomes of patient care. Am J Med Qual. 2011;26(5):372-9.


On the importance of regular reporting from governmental public health bodies

Despite the increasing importance of transparency and accountability in government, and the demonstrated efficacy of consultation, communication, and response to criticism in policy development, the last decade has seen a backwards step in the effective output of Australia’s governmental public health bodies.

The National Public Health Partnership (NPHP), a federal government organisation formed in 1996, was, and continues to be, widely celebrated by public health practitioners for its enduring contributions to Australian public health. The NPHP published quarterly newsletters and produced close to 100 publicly accessible reports in their relatively short tenure [1,2] covering a very broad set of issues. In 2006, the NPHP was dissolved and replaced by two advisory committees: the Australian Health Protection Principal Committee and the Australian Public Health Development Principal Committee (APHDPC). The former group exists in order to formulate strategies for response to public health emergencies and other large-scale heath threats, while the APHDPC was intended to “coordinate a national effort towards an integrated health development strategy” [3]. To rename, rebrand, divide, and unite government entities is a common process undertaken for a variety of reasons. Indeed, the APHDPC appears to have since been divided into five separate principal committees, all advising the Australian Health Ministers’ Advisory Council (AHMAC) [4]. However, these newer committees do not publicly report on their work, which is problematic in a number of dimensions.

Most governmental organisations communicate their work as a matter of principle (even ASIO releases yearly reports [5], and secrecy is their business). Accountability of governmental institutions is becoming an ever-more important factor in modern societies [6], and it is imperative that the public have some sense of the function of government departments. This is important for ensuring that public expenditure is well-targeted and produces meaningful results. In an ideal system, underperforming government entities will be subject to public pressure calling for internal change to either increase the efficacy of the entity in question, or remove it entirely. This is one of the key arguments for the importance of governmental transparency [6].

More importantly, the infrequency and inconsistency of publicly available reports emerging from the new principal committees are counterproductive to their stated aims. It is clear that consultation with the public is crucial to maximising the efficacy of emerging public health practices and policies [7]. As the peak groups responsible for advising governments on health policy, their work should be open to criticism, and therefore improvement, through as many avenues as possible.

Stifling the process of wider input into policy development restricts scrutiny to after-the-fact analysis. Australia has clear mechanisms to evaluate the progress of certain health outcomes and effectiveness of new policies – the Australian Institute of Health and Welfare and the Bureau of Statistics are responsible for this – so why is it that the evaluation of developing policies is not as open? Delaying consultation with academics and calls for public submissions on proposed policies until the implementation stage is not ideal; as with public health issues themselves, suboptimal policy decisions are best addressed upstream. It is critical for academics, non-government organisations, and the general public to have access to plans for developing public health programs, reports on current strengths and weaknesses, and other procedural documents. Helpful scrutiny can arise from such publicity and accelerate Australia’s advances towards a healthier society.

After the immensely public legacy of the NPHP, the sudden absence of regular reporting in the sphere of public health policy development is somewhat disarming, but the reasons underlying this sudden disappearance are unclear. The central issue here appears to be primarily one of communication. A small suite of reports is available for download on the Council of Australian Governments (COAG) Health Council website, which represents the recent work of the principal committees which comprise the AHMAC [8]. These are, however, poorly advertised, difficult to find, and infrequently accessed. In short, a number of issues conspire to ensure that the work that does emerge from the COAG Health Council goes relatively unnoticed.

Consultation is a cornerstone of policy development in any sector, and all government bodies should seek to interact with the public in order to promote their work and receive feedback. Australians have a right to know what ideas our governmental public health groups are proposing and developing, and the optimisation and implementation of these ideas depends on communication with clinicians, public health practitioners, and the wider community. If the COAG Health Council and its subsidiaries more regularly presented work for public criticism, our formulation and implementation of federal public health initiatives would inarguably be more successful. A strong collective public health partnership is vital for the effective dissemination of information, as well as discussion and improvement of developing public policy. The current widespread radio silence from our peak intergovernmental public health bodies is damaging to the future of Australian health, and these organisations should be expected to more frequently demonstrate interest in communicating with the community through both consultation and the release of public reports.


Conflicts of Interest
None declared.


[1] Victoria Health. NPHP News Archive [Internet]. Melbourne, Victoria: Victoria health; 2003 [updated 2005 July 1; cited 2016 March 4]. Available from:

[2] Victoria Health. NPHP Publications [Internet]. Melbourne, Victoria: Victoria health; 2003 [updated 2006 July 24; cited 2016 March 4]. Available from:

[3] Victoria Health. The National Public Health Partnership (NPHP) [Internet]. Melbourne, Victoria: Victoria Health; 2006 [updated 2010 February 22; cited 2016 March 4]. Available from:

[4] COAG Health Council. Principal Committees [Internet]. Adelaide, South Australia: COAG Health Council; 2014 [cited 2016 April 13]. Available from:

[5] Australian Security Intelligence Organisation. ASIO Report to Parliament 2014-15 [Internet]. Canberra ACT: Australian Security Intelligence Organisation; 2015 [cited 2016 March 4]. Available from:

[6] Bertot JC, Jaeger PT, Grimes JM. Promoting transparency and accountability through ICTs, social media, and collaborative e-government. Transforming Government: People, Process and Policy. 2012 Mar 16;6(1):78-91.

[7] Organisation for Economic Co-operation and Development (OECD). Citizens as Partners: OECD Handbook on Information, Consultation and Public Participation in Policy-Making. Paris: OECD; 2001.

[8] COAG Health Council. Reports [Internet]. Adelaide, South Australia: COAG Health Council; 2014 [cited 2016 April 13]. Available from:


Student surgical societies in Australia and New Zealand: do they play a role in early surgical exposure and streaming?

In recent years, there has been an increase in the number and activity of student surgical societies and interest groups in Australian and New Zealand medical schools. To remain competitive, the modern medical student seeks out opportunities for additional surgical research and takes on extra-curricular activities, in addition to their medical studies. This has occurred in the context of increasingly busy curricula and concerns about the reduction in time devoted to structured surgical teaching in medical schools. [1] Most recently the introduction of Doctor of Medicine (MD) programs at several Australian universities, where the qualification of the medical graduate no longer includes a Bachelor of Surgery, reflects a transition whereby surgical teaching now takes place largely in expensive postgraduate courses. Medical training in general is lengthening whilst the number of graduates is increasing and the competition for jobs continues to heighten. In this setting, student surgical societies are becoming more active, and will likely play an increasingly important role in facilitating early exposure to surgery during medical school. [2]

Discussion about the length of general medical and specialty training in Australia and New Zealand continues and several authors suggest there is room for reduction. [3,4,5] It has been proposed that early streaming of general practitioners and specialists from the senior medical student level, as seen in the US, should be considered as a way to potentially reduce the length of training without compromising its quality. [3,6,7] Development and implementation of change to training requires coordination and compromise between the various stakeholders, including universities, teaching hospitals, and medical colleges, which makes formal career streaming seem unlikely in the foreseeable future. But does this already happen informally at our medical schools? Throughout Australia, student surgical societies and interest groups help to facilitate early medical student exposure to both academic and clinical surgery. Already, medical students with an interest in surgery enrol in higher degrees by research in surgical areas, develop technical skills from an early level, complete extra professional courses, and take on leadership and advocacy roles in which they liaise with university faculties, Health Education and Training Institute (HETI), Royal Australasian College of Surgeons (RACS), and other professional bodies. Although there are no guarantees for these surgical-hopefuls, our surgical societies do help to facilitate early streaming albeit in an informal way and at the initiative of the student.

The Sydney University Surgical Society (SUSS) was established in 2006 with the aims of promoting the development of the nine surgical competencies outlined by the Royal Australasian College of Surgeons, facilitating communication between students and surgeons, and providing educational opportunities for students. [8] These goals are achieved by organising student grand rounds, surgical skills tutorials, a journal club, advocating at faculty meetings and working with academic surgeons to facilitate student research. SUSS attempts to ensure early exposure for all students by running surgical career events targeted particularly at students in years one and two, such as the annual ‘Introduction to Surgery: SET & Beyond’ lecture which consistently attracts over 200 students. Many students are enrolled in concurrent honours, masters, and PhDs programs in surgical areas and the academic output is high. Academic surgery is encouraged through a monthly journal club meeting and our relationship with the new Institute of Academic Surgery at Royal Prince Alfred Hospital, where the SUSS President sits on the advisory board. A RACS-accredited eight week intensive anatomy by whole body dissection course is run in the elective period at Sydney Medical School and has become an important way for surgically-inclined students to identify themselves and develop their skills at an early stage. [9] Most importantly, medical students who have been involved with SUSS and related activities can progress through medical school and graduate with a competitive set of skills, knowledge, and insight into the training that lies ahead.

The Surgical Interest Network (SurgIN) is a subcommittee of the Australian Medical Students’ Association that coordinates student surgical societies and interest groups across Australasia. Broadly most of these groups have a similar focus on extra-curricular skills sessions and seminars in clinical surgery, although approaches and philosophies vary. In addition to SUSS, other student surgical groups in New South Wales include the UNSW Surgical Society, Surgical Society of Notre Dame Sydney, Surgical Association of Western Sydney, University of Wollongong Surgical Interest Group, University of New England Surgical Society, and Newcastle University Surgical Society. There has been increasing cooperation and shared events between these NSW groups, most recently coming together to organise and compete in the Golden Scalpel Games Student Edition (previously the NSW Students’ Surgical Skills Competition) with sponsorship from RACS and HETI. [10] Organisational structure or models will necessarily vary, as surgical societies must be run within the confines of their University’s bylaws and regulations; particularly regarding whether they are part of their university’s student union, a sub-division of their medical society, or a stand-alone entity. However, communication and cooperation between surgical societies across Australasia has allowed them to learn from each other and gain access to innumerable opportunities such as conferences, seminars, skills workshops, and networking events to maximise engagement and exposure.

In the face of reduced surgical teaching at medical schools, surgical societies in Australia and New Zealand will play an increasingly important role in promoting and fostering surgery and it is critical that they are well run. A society must present themselves as a professionally oriented and academically productive group of students to ensure support from their medical faculty and input from surgeons.

Conflicts of Interest

None declared.


[1] Truskett P. Surgeons of the future: where will they come from? ANZ J Surg 2014; 84: 399–400

[2] Dolan-Evans E, Rogers GD. Barriers for students pursuing a surgical career and where the Surgical Interest Association can intervene. ANZ J Surg 2014; 84: 406–11.

[3] Dowton SB. Imperatives in medical education and training in response to demands for a sustainable workforce. MJA 2005; 183: 595-598

[4] McNamara S. Does it take too long to become a doctor? Part 1: Medical school and prevocational training. MJA 2012; 196: 528-530

[5] McNamara S. Does it take too long to become a doctor? Part 2: Vocational training. MJA 2012; 196: 595-597

[6] Taylor TKF. Changes to the University of Sydney medical curriculum. MJA 2008; 189: 414-415.

[7] Taylor TKF. Training doctors – too long in the cellar? MJA 2012;197 (6):328-329

[8] Sydney University Surgical Society (SUSS). About Us [Internet]. NSW (Australia) 2015. Available from:

[9] Ramsey-Stewart G, Burgess A, Hill D. Back to the future. Teaching anatomy by whole body dissection. MJA 2010; 193: 668-671

[10] Golden Scalpel Games Student Edition [Internet]. NSW (Australia) 2015. Available from:


Why should students write a global health case report?

We often see a case report about something absolutely fascinating – that one condition found on that page of Robbins [1] that we vaguely remember – but we don’t often hear about a global health case report. In this short piece, we offer a tangible definition of global health, discuss the concept of a global health case report, [2] and make the case for why we, as medical students, should be writing these.

Defining Global Health

Most medical students find global health quite nebulous and so overarching that it does not necessarily fit with our idea of treating the individual patient in front of us. Global health seems to be for health policy makers rather than doctors. It seems far-fetched that as medical students we could have any effect on how patients live and the determinants of health, especially when we hear that global health concerns only low-income countries. There are two main reasons for this perception: one, a single definition of global health is not universally accepted; and two, worldwide, there remain profound differences in global health education. [3,4]

We propose that the ‘global’ in global health does not refer so much to ‘overseas’ or ‘over there’, as it refers to ‘over here’; indeed, the real definition of ‘global’ in global health is ‘health everywhere’. Even if a doctor, or any health professional, trains and works in their home town, never travelling beyond the limits of what they see every day, they will inexorably meet and treat someone of a different socioeconomic group, ethnicity, religion, race or language. Dealing at an individual level with patients who have become ill because they do not have a safe and clean environment in which to live, have nowhere to sleep, are exploited at work, or vulnerable at home means that those international problems over there for doctors without borders who travel all over the world, are right here for all doctors whose routine practice is right at home. Global health has much in common with public health in that aspects of global health address populations and changes may be implemented at population levels through local, national, and international governments. However, ‘global’ also refers to all aspects of health, i.e. a holistic approach essential to exploring and taking on the real causes of disease, the social determinants of health. This focuses our attention and intervention on the patient in front of us and what we need to do to prevent them from becoming ill again. [5] Global health is, therefore, health that affects every patient we treat, and their families, at a very personal and individual level.

The British Medical Journal Case Reports has published several global health case reports. Here we summarise two examples. In one case, a 2 year-old boy with 40% burns to his head and arms presented to an eye clinic in Turkey one month after his injury. By then, he was blind. [6] The author was moved to write because of the severity of the burns, the preventable causes of house fires, the dire need for equitable access to medical care, and the devastating consequences for the child. Perhaps on their own, each of these global health problems is too large to contemplate and tempting to ignore, but no one can ignore the clinical history of this child, and the authors were moved to investigate the lack of health resources and the social circumstances responsible for this lamentable outcome. The authors offer solutions in healthcare that seem very practical. Certainly, they provide the evidence that these changes are necessary.

Another case report explores the link between HIV/AIDS and Jogini culture of sexual exploitation. [7] The case is of a 32 year-old woman who, since the age of seven, has worked as a Jogini. It’s a powerful story. We read of her first sexual encounter, teenage pregnancy, and total isolation. The global health issues discussed by the authors include the consequences to health of profound social inequalities, gender inequality, criminal prostitution, and the scourge of HIV/AIDS amongst the most vulnerable of society. The author remains focussed on the patient’s life and we read with dismay about her relationship with her son and the likelihood that his life will also be in poverty, without the education or opportunities to change a course that seems bitterly unfair. These global health problems, overwhelming and pervasive, are poignantly real and move us to act. The doctors and medical students submitting global health case reports are describing the lives of patients they see every day, and are moved to write because tackling these problems head-on is essential to making their patients healthy again, keeping them healthy, and helping people just like them.  Enormous, ethereal global health problems are now individual and personal; indeed, they are tangible and very much inside our consulting room or hospital ward.

Why are these case reports useful? Why should we write these?

  1. To look at the root causes of the illness. Let’s think about why our patient is really ill. While a discussion of the social determinants of health may switch off an audience overawed by the magnitude of these issues, with a patient in front of them no doctor or medical student can ignore the causes of illness and the factors limiting the effectiveness of medical therapy for that patient.
  2. To learn about society, economics, politics, cultures, and how they affect our patients. These help us understand our patients better and facilitate all contact with them. These case reports show how individuals deal with illness, how they seek out medical assistance, and what is available for them. By writing these case reports, we also understand better how healthcare priorities are set and decided.
  3. Global health is an in depth analysis of the causes of ill-health, perceptions of health and disease and how healthcare is provided. This is relevant not simply to general practice or public health, but to all medical specialties.
  4. To learn global health. Global health case reports help both the students and faculty discover together the global burdens of disease, the social determinants of health, and factors essential to equity in access to healthcare.
  5. To publish and share patient cases. Publishing an excellent piece of work that speaks for your patient and the general society, and promotes peer discussion of these issues.
  6. To create an evidence base. Every time a global health case is published, we provide more evidence of what our patients need, the reality of their lives, and the care that they received. No one is closer to patients than we are in the medical profession [3]; we have a responsibility to advocate for our patients, and we can do this by writing their stories. This builds evidence that these problems are real and that they cannot be neglected.
  7. To create change. We publish and keep publishing in order for the medical community and the public to read and demand change. Change is possible – doctors are responsible for seat-belts, helmets, and much legislation that has saved millions of lives. [8, 9]

For the audience reading these case reports, global health becomes personal and individual. The case reports are a call to action to work for our patients, and an inspiration to look beyond a pharmacological prescription to the underlying social determinants of health and disease. Ultimately, we must look through the global health lens because, as Virchow famously said:

Medicine is a social science and politics is nothing else but medicine on a large scale. Medicine as a social science, as the science of human beings, has the obligation to point out problems and to attempt their theoretical solution; the politician, the practical anthropologist, must find the means for their actual solution. [10]


[1] Robbins SL, Kumar V, Abbas AK, Fausto N, Cotran RS. Robbins and Cotran pathologic basis of disease. Philadelphia: Elsevier Saunders; 2005.

[2] BMJ case reports; (Journal, Electronic).

[3] Liu Y, Zhang Y, Liu Z, Wang J. Gaps in studies of global health education: an empirical literature review. Glob Health Action 2015;8(1):25709.

[4] Rowson M, Willott C, Hughes R, Maini A, Martin S, Miranda JJ, et al. Conceptualising global health: theoretical issues and their relevance for teaching. Global Health. 2012;8(36).

[5] Marmot MG. Status syndrome: a challenge to medicine. JAMA. 2006;295(11):1304-7.

[6] Istek, Ş. The devastating effects a fire burn in a child. BMJ Case Rep. 2015 Jun 8;2015. doi: 10.1136/bcr-2014-206663

[7] Borick J. HIV in India: the Jogini culture. BMJ Case Rep. 2014 Jul 11;2014. doi: 10.1136/bcr-2014-204635

[8] Bike helmets a no-brainer, say surgeons. The Australian Doctor [Internet]. 2015 Aug 13 [cited 2015 Oct 09]; Available from:

[9] Children’s doctors urge national 20mph limit in built-up areas. The Guardian [Internet]. 2014 Nov 19 [cited 2015 Oct 09]; Available from:

[10] Virchow R. Die medizinische reform 2. Medicine and Human Welfare. 1949.


2015 Australasian Students’ Surgical Conference research presentations

The Australasian Students’ Surgical Conference (ASSC) is the leading surgical conference for medical students in Australia and New Zealand. ASSC is designed to coincide yearly with the RACS Annual Scientific Conference and was held this year in Perth, Western Australia from 1-3 May 2015.

Organised each year by medical students, in 2015 it provided 250 delegates with a unique opportunity to be educated about, and inspired to pursue, a surgical career through a program of keynote addresses, research presentations and a full day of skills based workshops.

The ASSC committee encourages fellow medical students to develop and challenge themselves professionally. This is a major objective of ASSC, as reflected throughout our entire program. This year, in collaboration with the Australian Medical Student Journal (AMSJ), the winning abstract has been offered publication.

We received an overwhelming response to our call for abstracts, with many outstanding submissions. Abstracts were de-identified, checked for eligibility criteria, and the format standardised prior to consideration by our panel and being offered a podium presentation. Congratulations to our research prize winners:

  • Best Research Presentation – Cameron Iain Wells, University of Auckland
  • Runner up Research Presentation – Damian James Ianno, University of Melbourne
  • Best Poster Display – Omar Khan Bangash, University of Western Australia

With such a phenomenal response, the 2015 ASSC committee is delighted for other participants to also have their research presented in the AMSJ.

The ASSC committee look forward to seeing you at the next ASSC!

Please download the pdf to read the research presentions.


Surgical hand ties: a student guide

Surgical  hand  ties  are  a  procedural  skill commonly employed in surgery; however, student    exposure    to    practical    surgical experience  is  often  limited.  Students are therefore often excited at the opportunity to learn these skills to practise for themselves. Often the only opportunities to formally learn these skills come in the form of workshops presented at student conferences or run by university special interest groups.

Having attended such surgical skills workshops I have noticed the difficulty demonstrators and students have had in teaching and learning learn and master hand ties.

In addition to being an individual resource, this guide was also created for use in a workshop setting. Ideally, a demonstrator would show the students the basic steps involved in hand ties. The guide could then be used to reinforce this learning, where the student can practise with the sutures in their hands while following the steps using a combination of pictures, text, and memory aids. This would also have the benefit of letting the demonstrator help students with more specific questions on technique, rather  than  repeating  the  same the skill of surgical hand ties. I felt this was the product of two things: the difficulty the tutors had in demonstrating the small movements of the fingers to an audience; and the students’ difficulty with remembering each step later. Therefore, I combined an easy to follow graphic with some helpful memory aids into a simple resource to help medical students demonstration multiple times.

The overall aim of this guide is to make the process of learning and teaching surgical hand ties to students easier, and to improve recall and proficiency for students performing the skill through the use of simplified steps and diagrams.

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Conflict of interest

None declared.


J Ende:


About Helen Caldicott’s guest article

About Helen Caldicott’s guest articleAs a university academic whose professional interests include the chemistry of serious reactor accidents I disagree with many of
the statements made by Helen Caldicott in her recent article “The impact of the nuclear crisis on global health”. While she is an iconic figure for many people it is important that her statements are critically assessed, in the interests of public health neither statements made by the opponents or supporters of any technology should be accepted blindly. For reasons of brevity I am unable to address all my concerns about her article, so I will focus on a few of the errors I believe she has made. Helen claims that the low level exposure that the general public experienced caused symptoms of “radiation sickness”. This claim is at odds with what I have been taught during the radiological health and safety training I have had and I would like to point out that
to induce the acute radiation syndrome in humans a dose of at least 1 to 2 Gy needs to be delivered over a short time. The doses which the public had during the accident were far too small. If radiation is as able as she claims to induce the acute effects (blood and GI disturbances) then surely these effects would be commonly seen after moderate medical exposures such as CT scans and diagnostic nuclear medical procedures.

I would like to challenge her claim that all radioactive elements bioconcentrate as they pass through a food chain. While some
radionuclides can pass through food chains with ease, others do not do so, for example, the human digestive system is unable to
absorb into the blood more than a small fraction of any plutonium that is swallowed. A classic test to determine if a worker has
inhaled plutonium dust is to measure the plutonium content of their faeces. If the digestive system were a good absorber of this element then this test would be impossible.

It is noteworthy that the biokinetics of tritium and cesium are not compatible with the idea that it will bioconcentrate in all food chains; the biological half-life of cesium in humans and farmyard animals is in the range of one to three months. As a result, after a short exposure to cesium most of it will be gone in less than one year. During a protracted constant exposure to cesium-134 or 137 an equilibrium will be set up within months which will prevent the further accumulation of cesium; the majority of the cesium ingested will be excreted before it is able to undergo radioactive decay. The common form of tritium (HTO) has an even shorter biological half-life in humans, as a result it is one of the least toxic radioisotopes.

Helen claims that iodine-131 is a potent carcinogen in humans, while I advocate exercising great care when working with any radioactive substance I note that a Swedish medical scientist (L.E. Holm) was unable to find any evidence that this radionuclide is able to cause thyroid cancer in humans. He could see no excess of thyroid cancer in a population of people exposed during diagnostic medical procedures. However data associated with Chernobyl and atom bomb tests strongly indicates that radioactive iodine causes thyroid cancer. L.E. Holm suggested that the shorter lived higher beta energy iodine radioisotopes from bombs / Chernobyl may have been the main carcinogen. While I do not know if L.E. Holm’s short-lived iodine hypothesis is right, based on the current evidence it is not a certainty that iodine-131 is a potent carcinogen.

I hold the view that people are equally entitled to hold antinuclear or pronuclear views. However, any scientific argument either for or against nuclear power should be correct and good quality science.

Conflict of interest

None declared.


M Foreman:


Insights into the application of evolutionary and ecological concepts to cancer treatment via modelling approaches

Therapeutic resistance has been shown to result in poorer clinical outcomes in cancer treatment. It has been proposed that evolutionary adaptations of cancer cells to therapy result in the development of resistance with the rate of adaptive change correlating with the heterogeneity of the tumour. These concepts can help overcome therapeutic resistance and have been exploited by Gatenby and others in promising evolutionary double-bind simulations. It was further suggested that tumour vasculature contributes to intra-tumoural heterogeneity through the development of substrate gradients. Increasing analogy between natural ecosystems such as riparian habitats and the tumour environment may allow us to devise novel treatment strategies. This review will briefly examine some of these evolutionary and ecological concepts and how they can be applied to cancer treatment.


a7_0Carcinogenesis is the process by which normal cells in the body acquire mutations and form tumours. In the 1970s, Peter Nowell characterized this transformation in terms of evolutionary change and this concept has been well accepted by the scientific community. [1] He proposed that genetic instability and mutations form the basis for heritable changes required for natural selection and clonal growth of single cancer cells. Cells are selected for desirable characteristics such as survival and proliferation in response to changes in their immediate environment. [1] Surprisingly, evolutionary principles have seldom been used in the treatment of cancer. Aktipis and colleagues did an analysis of over 6000 papers focusing on therapeutic resistance and cancer relapse and revealed that ‘evolution’ has been used in only 1% of all papers. [2]

As evolution is influenced by changes in the environment, it is possible to view the tumour microenvironment as an ecosystem consisting of heterogeneous populations of cancer cells interacting with one another, and with other cells of the microenvironment. These complex interactions have much in common with ecosystems in nature and consist of analogous abiotic and biotic components which provide novel treatment targets to circumvent therapeutic failure.

Failure of chemotherapy can be attributed to cancer resistance which can be inherent or acquired. Inherent resistance may occur due to over-expression of drug metabolism pathways such as the excision repair cross-complementing 1 gene (ERCC1 — a nucleoside excision repair gene) in resistance against platinum agents while acquired resistance can be caused by altered membrane transport as in the case of the P-glycoprotein transport protein encoded by the multi-drug resistance-1 gene (MDR-1). [3]

Evolutionary game theory

Hypoxia and acidosis within the tumour can exert selective pressures on individual cancer cell populations. These populations may adapt to these conditions through different phenotypic strategies arising from genetic instability and genotypic variations. Gilles and colleagues proposed that these interactions can be understood through the evolutionary game theory. In this theory, the evolutionary rate of a phenotypic strategy is dependent on the amount of phenotypic diversity and the fitness of cancer cell populations. [4] Cancer cell populations will evolve rapidly in the presence of a harsh tumour environment or when cell populations are phenotypically diverse. Selective pressures originating from perturbations outside the tumour microenvironment can also promote further phenotypic diversity. [4,5] Alteration of the tumor environment by chemotherapy can potentially encourage cancer cell populations to diversify and become heterogeneous via de novo mutations arising from therapy or selection of existing chemotherapy-resistant cells in the tumour. [5]

The evolutionary game theory therefore predicts that the probability of the existence and/or emergence of resistant cells correlates with the level of tumour heterogeneity. It also suggests that chemotherapy will inadvertently lead to resistance if chemo-resistant cells (such as cancer stem cells) are already present in the tumour. [4,5] These predictions appear to correlate with clinical findings as advanced cancers which are less responsive to therapies usually exhibit high levels of heterogeneity while the use of high-dose chemotherapy improves survival but seldom cures epithelial cancers. [6]

High-dose chemotherapy regimens were first conceptualized mathematically through the Norton-Simon model. It is hypothesised that administering the maximum tolerated dose (MTD) over a short time period would achieve a high cancer cell kill rate and a low probability of therapy-induced evolution of resistant clones. [7] This model, however, does not account for pre-existing chemo-resistant cells which clonally proliferate and result in cancer relapse after initial treatment. By recognising that resistant cells potentially pre-exist in tumours and that they correlate positively with tumour heterogeneity, certain strategies can be devised. These include controlling the heterogeneity of the tumour to prevent the occurrence of chemo-resistance and, exploiting our ability to predictably alter the adaptive strategies of cancer cells through various treatment modalities.

Controlling tumour heterogeneity: induction of evolutionary bottlenecks and achieving an evolutionary ‘double-bind’

Intra-tumoural heterogeneity is minimal in early neoplasms and the use of low-dose chemotherapy may be sufficient to eliminate early cancers with less risk of resistance. [7] This formed the basis of metronomic chemotherapy where low doses of chemo-drugs were given in frequent intervals. [8] However, intricate strategies involving circumvention of therapeutic resistance would be required as a cancer progresses.

Resistant cells favour tumour progression in a treatment setting but many forms of resistance incur phenotypic costs. If the phenotypic cost is low, for example, due to the ability of the cancer cell to adapt to therapy through up-regulation of xenobiotic mechanisms or usage of a redundant signaling pathway, control of cancer cell proliferation will be less effective. [9] Conversely, if the phenotypic cost is high, for example, due to competition from co-existing cancer cell populations with different proliferative characteristics and biological therapies, robust and long-lasting control may be achieved because cancer cells can only survive by diverting resources away from proliferation. The latter creates an evolutionary double-bind where the only way tumour cells can evade the deleterious effects of treatment is by compromising its fitness attributes, thereby inhibiting its proliferation or ability to develop resistance. [9]

An evolutionary double-bind in a combination therapy setting would require anticipating the adaptation of cancer cell populations to a specific treatment and then targeting the adapted phenotype by a follow-up treatment. [4] In a study by Hunter et al., treatment of glioblastoma multiforme tumours with the alkylating agent temozolomide (TMZ) resulted in hypermutations in the MSH6 mismatch repair gene. [5,10] These mutations were not present in untreated tumours and suggest that chemotherapy selected for MSH6-mutant cells. A clonal selection process was thought to create an evolutionary bottleneck where the majority of the cells were MSH-6 mutants while cancer cells with the wild-type MSH6 gene were eliminated. [5,11]

The transient decrease in genetic heterogeneity following TMZ administration provides a therapeutic window when cancer cells are most susceptible to a secondary treatment. [5] An in vivo study investigating the effects of the oral poly(ADP-ribose) polymerase (PARP) inhibitor ABT-888 on xenograft models of human tumours found that this PARP inhibitor not only synergistically maintains and potentiates the cytotoxic effects of TMZ on different tumours but also overcomes TMZ resistance. [12] ABT-888 and other similar PARP inhibitors may therefore have a role as a secondary treatment in combination therapies as they can eliminate most of the residual chemo-resistant cell populations. A schematic diagram of a two-step evolutionary double-bind is shown in Figure 1.

Insights into the application of evolutionary and ecological concepts to cancer treatment via modelling approaches

Figure 1. Evolutionary double-bind. For simplicity, tumour cells can be sensitive (neutral or susceptible) or resistant to a treatment. A two-step setup would involve the first treatment reducing heterogeneity of the tumour by imposing a high phenotypic cost on tumour cells. The second treatment works synergistically with the first treatment, such as in the case of PARP inhibitors and TMZ, to eradicate initially resistant cell populations.

Chemotherapy-based combination therapies

The widespread use of chemotherapy necessitates a scrutinisation of its synergistic and antagonistic effects in cancer treatment. Basanta and colleagues examined the use of an evolutionary double-bind in a combination therapy consisting of the p53 vaccine and chemotherapy. [13] Using a mathematical framework derived from the evolutionary game theory, they found that the p53 vaccine and chemotherapy work synergistically to exert robust anti-tumour effects. Interestingly, depending on whether the p53 vaccine or chemotherapy was used as the first treatment, different effects were observed.

Application of chemotherapy before the p53 vaccine was found to be more effective than using the p53 vaccine initially followed by chemotherapy. [13] This was attributed to a commensalistic relationship between vaccine-resistant cells and other cell populations. Eliminating vaccine-resistant cells in the first instance disrupts the protective effect and results in other cell populations (e.g. chemo-resistant and fully susceptible) being susceptible to immune mechanisms mediated by the p53 vaccine. In other words, ecological interactions between different cell populations of a tumour appear to determine the effectiveness of an evolutionary double-bind.

Although application of the p53 vaccine before chemotherapy had a diminished anti-tumour effect, the effectiveness of this approach can be increased with longer exposure to the p53 vaccine. [13] Indeed, both approaches appeared to be most effective when the first treatment was applied for a longer period. This reflects the importance of the first treatment as a limiting factor in combination therapy. Prolonged exposure to the first treatment widened the therapeutic window and acted as a barrier against therapeutic resistance most likely by reducing tumour heterogeneity through the creation of an evolutionary bottleneck.

Ecological interactions (e.g. commensalism or competition) between cancer cell populations are important and we can further characterize these interactions by considering the fitness of different cancer cell populations through phenotypic costs. [4] In the absence of treatment, resistant cells are likely to be less fit and have a slower rate of proliferation as compared to sensitive cells since they have to devote more resources to surviving. [4] These cells are most often found in the inner regions of a solid tumour where harsh conditions such as hypoxia and acidosis cause necrosis of tumour cells but favour the selection of resistant clones. Conversely, sensitive cells will be located at the outer rim of the tumour where a close proximity to the vasculature and expression of pro-survival proteins allow them to proliferate easily. [14] We can therefore predict that sensitive cells will be more susceptible to chemotherapy due to their proximity to the blood supply whereas resistant cells are highly affected by metabolic changes.

Silva and Gatenby proposed an evolutionary double-bind strategy consisting of the glucose competitor 2-deoxyglucose (2-DG) and chemotherapy. This was an attempt to reduce the fitness of both sensitive and resistant cell populations as well as stabilize tumour growth through competition via in silico simulations. [15] Different combinations of 2-DG and chemotherapy were modeled mathematically and the combination of 2-DG→chemotherapy was suggested to have the most potent anti-tumour effect. Efficacy was predicted to be lower in chemotherapy→2-DG and lowest in the synchronous administration of 2-DG and chemotherapy. The results become intuitive when we consider tumour cell populations in terms of inner region and outer rim populations. For the 2-DG→chemotherapy approach, the inner region populations are ‘pulverized’ by 2-DG due to their sensitivity to glucose depletion and this increases the surface area for chemotherapy to eliminate the outer rim cells. [15] Furthermore, 2-DG created a ‘pulverized’ morphology where a barrier of cells exists between the outer rim and inner region cells. This potentiates glucose depletion because glucose cannot diffuse effectively from the outer rim to inner region.

Interestingly, 2DG→chemotherapy mirrors the effectiveness of the p53 vaccine→chemotherapy approach. [13] This is probably attributed to the initial targeting of chemo-resistant cells and also the maintenance of a higher proportion of sensitive (and presumably fitter) cells as compared to resistant cells. The latter implies that sensitive cells can impede proliferation of resistant cells via competition for resources. Indeed, the chemotherapy→2-DG approach most likely had a better anti-tumour effect than synchronous administration because, even though the chemo-sensitive outer rim cells were targeted first, the introduction of a break or ‘drug holiday’ between chemotherapy sessions in the study’s protocol allowed the sensitive cells to recover and maintain a sizeable numerical advantage over resistant cells. [16] A similar effect was also noted in previous studies with different treatments. The chemotherapy→2-DG approach fared worse than 2-DG→chemotherapy as glucose can readily diffuse from the outer rim to inner (i.e. allowing chemo-resistant cells to survive) while the synchronous approach was least effective as the outer-rim was readily destroyed by chemotherapy; therefore reducing competition between sensitive cells and resistant cells. [15] Moreover, poor diffusion of chemotherapeutic drugs to areas deeper within the tumour meant that the inner region cells only received sub-lethal doses which favour the development of chemo-resistance.

Out of the three strategies, only the 2DG→chemotherapy approach managed to achieve an almost complete eradication of cancer cells when a bolus of MTD chemotherapy was applied while the other two strategies resulted in chemo-resistance. This result has two implications: firstly, it reflects the point that eradication of tumour cells is possible if tumour heterogeneity is targeted in the first instance and, specifically here, the chemo-resistant population. Secondly, it also implies that delineation of tumour cell populations into sub-groups based on location and proximity to key tumour structures such as the vasculature may be therapeutically significant. In fact, there is evidence that populations of tumour cells often exhibit a convergent phenotype despite genotypic differences between individual cells. [17] Thus, targeting this phenotype may be a more practical option since natural selection acts on phenotypes rather than genotypes.

Riparian ecosystems as an ecological framework for human tumours

Tumour vasculature can contribute to intra-tumoural heterogeneity by creating disparities in substrates such as oxygen and glucose through blood flow gradients, which then select for different populations of cancer cells. [17,18] Alfarouk and colleagues proposed that growth of cancer cell populations can be understood in the context of plant species in a riparian habitat. [18] A riparian habitat is the interface between land and a river stream and two distinct regions of plants can be identified depending on their distance from a river. The mesic region contains lush, tall vegetation which are adjacent to and well nourished by the nutrients from the river. This is followed by an abrupt transition to a xeric region containing sparse, short vegetation which, due to their relatively long distance away from the river, develop adaptations that allow them to conserve water and survive in arid conditions. [19] The rivers and regions of vegetation in a riparian habit are analogous to the vasculature and cancer cells in a tumour respectively.

Tumour cell populations can be broadly separated into ‘mesic’ and ‘xeric’ cells depending if they are adjacent or distal to a blood vessel. [18] Mesic tumour cells and their proximity to blood vessels would render them highly susceptible to angiogenesis inhibitors by systemic administration. Since the ‘lush’ mesic region is expected to contain many tumor cells, a drastic reduction in tumour volume can be achieved. [18] However, the elimination of mesic tumour cells favours unprohibited proliferation of xeric tumour cells and an early treatment directed against the xeric region would be necessary. Phase I and II trials have shown that pro-drug carriers (containing chemotherapeutic drugs) based on 2-nitromidazoles can target hypoxic regions of a tumor and have shown strong anti-tumour effects. [20,21] Combining pro-drug carriers with an intra-tumoural route of administration may improve the accuracy of this approach. Considering the scarcity of xeric tumour cells, prolonged early treatment may be extremely effective. A summary of the different strategies described above is shown in Figure 2.

Insights into the application of evolutionary and ecological concepts to cancer treatment via modelling approaches

Figure 2. Best predicted outcomes in evolutionarily and ecologically enlightened strategies. (i) In silico studies suggest that p53-resistant cells and p53-sensitive cells exist in a state of commensalism. The initial introduction of p53 eliminates vaccine-resistant cells and predisposes all remaining cells to destruction by chemotherapy. A greater effect is seen with prolonged p53 administration. (ii) 2DG targets and ‘pulverizes’ resistant cells, creating physical barrier between resistant cells but retains an outer-rim chemo-sensitive cells that inhibits cancer spread. (iii) Riparian-based therapy may achieve maximal tumour cell death through a localized targeting of mesic cells by hypoxia-based strategies followed by targeting of xeric cells by angiogenesis inhibitors.

Discussion and conclusion

Tumours are resilient in nature because they consist of a heterogeneous system of cells locked in a constant state of feedback. [22] Any perturbations in the environment of these cells may simply reinforce tumourigenic processes which restore overall tumour fitness. Although all therapies inherently disturb this fragile equilibrium, in silico studies have demonstrated proof of principle that a well-designed strategy such as an evolutionary double-bind can control and potentially eradicate most tumour cells. While modelling methods may not translate to immediate clinical benefits, they are an inexpensive way of exploring theoretical concepts in a controlled situation and provide a sound framework for further in vivo studies and clinical trials. The models described here can also readily be modified to study other forms of combination therapy, illustrating their flexibility and broad applicability to the clinical environment. One limitation, though, is that the parameters used in models have to be as realistic as possible and this can only occur through close cooperation between experimentalists and clinicians.

Key features highlighted here such as the need for prolonged initial treatment to reduce intra-tumoural heterogeneity, enhancing competition between resistant and sensitive cells and combining systemic and localized approaches are intuitive and feasible options that can be readily applied to existing treatment protocols. High-dose chemotherapy is no longer considered as a first-line approach except occasionally as salvage treatment for relapsed disease. This is not surprising in light of possible selection for chemo-resistance and increasing preference for low-dose maintenance and adaptive regimens. [6] The examples discussed in this review focused primarily on solid tumours due to easy visualisation and amenability to mathematical modelling. However, treatment of haematological malignancies would also benefit from a double-bind approach as evident from the restoration of drug sensitivity by second-generation tyrosine kinase inhibitors in treatment-resistant chronic myelogenous leukemia. [23]

There are several potential areas for further research. Firstly, we need to understand why natural selection appears to control cancers but does not eliminate them. In fact, a parallel exists with infectious diseases and high fitness costs and the tendency for organisms to evolve tolerance mechanisms may account for this phenomenon. Secondly, we should consider maximising the potential of new treatment modalities such as immunotherapy in evolutionary double-binds. [24] The limited efficacy of immunotherapy appears to contradict observations in natural ecosystems which indicate that biological control incurs higher phenotypic costs and achieves robust control of pests. This implies that inappropriate immune targets are being selected and, therefore, a true double-bind cannot be achieved. [4,23]

In conclusion, therapeutic resistance is a major obstacle to the optimisation of cancer treatment. Evolutionary and ecological principles may appear far-fetched concepts with little direct relevance to oncology but a closer inspection of the evolutionary origins and the spatial organisation of cancer cells reveal strategies that can improve clinical outcomes. Under-utilisation of these concepts is most likely a reflection of an inability to change our mindset rather than an issue of practicality. These encouraging modelling results provide a sound foundation for further translational research.

Conflict of interest

None declared.




[1] Nowell PC. The clonal evolution of tumour cell populations. Science. 1976; 194: 23-28.

[2] Aktipis CA, Kwan VSY, Johnson KA, Neuberg SL, Maley CC. Overlooking evolution: a systemic analysis of cancer relapse and therapeutic resistance research. PLoS One. 2011;6(11): e26100. doi: 10.1371/journal.pone.0026100.

[3] Luqmani YA. Mechanisms of drug reistance in cancer chemotherapy. Med Princ Pract. 2005;14:35-48.

[4] Gillies RJ, Verduzco D, Gatenby RA. Evolutionary dynamics of carcinogenesis and why targeted therapy does not work. Nat Rev Cancer. 2012;12(7):487-93.

[5] Gerlinger M, Swanton C. How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine. BJC. 2010;103:1139-43.

[6] Gatenby RA, Silva AS, Gillies RJ, Frieden BR. Adaptive therapy. Cancer Res. 2009; 69(11):4894-903.

[7] Norton L, Simon R. Tumour size, sensitivity to therapy, and design of treatment schedules. Cancer Treat Rep. 1977;61(7):1307-17.

[8] Gately S, Kerbel R. Antiangiogenic scheduling of lower dose cancer chemotherapy. Cancer J. 2001;7(5):427-36.

[9] Gatenby RA, Brown J, Vincent T. Lessons from applied ecology: cancer control using an evolutionary double bind. Cancer Res. 2009;69:7499-502.

[10] Hunter C, Smith R, Cahill DP, Stephens P, Stephens C, Teague J, et al. A hypermutation phenotype and somatic MSH6 mutations in recent human malignant gliomas after alkylator chemotherapy. Cancer Res. 2006;66(8):3987-91.

[11] Merlo LMF, Pepper JW, Reid BJ, Maley CC. Cancer as an evolutionary and ecological process. Nat Rev. 2006;6:924-35.

[12] Palma JP, Wang YC, Rodriguez LE, Montgomery D, Ellis PA, Bukofzer G, et al. ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumours. Clin Cancer Res. 2009;15(23):7277-90.

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