The state of the union.

    In recent months, union movements (and the threat of mass resignations) have strongly influenced the perceptions of lobbying the Newman Government over the doctors’ contract debacle. Frequent strikes on behalf of teachers unions, police unions have also made significant changes to wage increases and structural reform. Every major profession has a union for employees. Accountants, retail, farmers, pilots, engineers, teachers, doctors and nurses. But who actually stands for scientists?  Despite increasing privatisation  of the science industry(http://cpsu-csiro.org.au/2013/05/21/big-choices-ahead-for-science-and-society/), regulatory bodies and funding agencies, why is it that scientists still get shelved among educators or medical technicians? 

Scientists in university labs have grounded reasons to be upset with the pressures associated with cramped lab space, institutional arrangements for IP claims and competitive projects, excessive hours, student duties and additional bureaucracy. Post-doctoral students are lucky to get a full 2 year contract in Australia and therefore move to the US to undertake additional training. Concerns have been raised also regarding the development and growth of a management culture of bullying and intimidation at CSIRO. Numerous scientists from the CSIRO are now going public about these practices (http://victimsofcsiro.com/)

   Of course, nobody can predict how a union movement would fair in the current political climate givenrecent examples of burocratic controversy. Instances of the ACTU scandals could bring debate and undesirable attention drawn on the scientific profession. But lets not forget that establishing a union would be a fundamental shift towards independence and self management. Presuming Australian science unions form with a balanced mix of of left and right we may see great changes to the way we tackle funding. Take for instance, the annual debate over poor funding from government agencies. A few years ago QLD scientists marched in the streets of Brisbane led by Professor Michael Good. The opposition to funding cuts was grounded on the fact that many labs had no future and the budget for science was unsustainable. At the time there was little support from health or education groups. The universities here also have a clear had a conflict of interest – so it’s down to the individual scientist to campaign among themselves. The exhausting campaign failed to maintain pressure once funding was announced – and the medical research community are back to square one.

Many unions back credit schemes and insurance for housing or investment purposes – the same approach could be used for reasonable projects. Labs can borrow for safe investment returns and setting achievable targets in a business plan. The Bill and Melinda Gates foundation have revolutionised charitable donations on these ideals alone. This would accelerate growth in the industry and facilitate for more freedom to innovate and research alternative, not popular science. By comparison, the NHMRC reviews spending plans for projects with the most credibility. This draconian approach is far from an equitable or sustainable cause. 

A scientific union ought to strive for scientific independence and autonomy from the current government, university and other institutions and tasked with resolving the crises in funding, support and working conditions for scientists at all levels of their career. 

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A bloody battle.

Since the first blood transfusion in 1628, blood donations have saved the lives of countless patients suffering severe trauma, disease or blood clotting illnesses. An entire industry has evolved and diversified towards the implementation of perfusion devices, separation and isolation of cells, monitoring the health of transfusions and isolating valuable products such as clotting factors or immunoglobulins. In recent years, improvements to the management of blood bank resources have led to some significant changes in the work of the administration to the technical staff.

For blood transfusions, time and storage of blood has a significiant effect on the survival of erythrocytes (Luten et al., 2008). Critical care patients are often administered fresh batches to reduce the likelihood of transfusion reactions and improved oxygen delivery in the patient (McLellan, Walsh, & McClellan, 2002). Furthermore, improved mapping of Rhesus Kell (K), Duffy, Cellano, Kidd and MNS erythrocyte antigens have also contributed to the improved specificity of blood group matching (Benahadi et al., 2014).

Accumulated stores of old blood are also becoming a problem. Long term >40 day storage of packed red blood ceslls (pRBC’s) have been associated with increased likelihood of hemolysis and exposure to plasma free Hb. Pretransfusion washing of allogenic RBC’s to remove the accumulation of dead cells and stabilise K+, Lactate, Glucose and pH levels before administering to patients may circumvent the issue of unused red blood cells (Bennett-Guerrero et al., 2014).

Screening for blood bourne diseases have eliminated the likelihood of contracting viral hepatitus and HIV-1. However many risks are still associated with the advent of unconventional infectious agents such as prions. Prions are ‘infectious’ misfolded aggregated proteins responsible for neurological wasting disorders such as Creutzfeldt-Jakob-Disease (CJD), Bovine spongiform encephalitus (BSE) and Kuru. It is now clearly established that transfusion of blood can transmit the disease and that this presents a major public health concern due to its difficulty to detect and the symptomatic latency of the disease (Andréoletti et al., 2012).  PrPSc ELISA – the gold standard bioassay is most sensitive to known isoforms transmitted within species. This is a critical shortfall because outbreaks such as BSE in the food chain are likely to have led to the spread of countless chimeric inter-species prion isotypes. The restriction of blood services in the UK has been justified by these findings (Hunter et al., 2002). Inevitably, in 2004 two transfusion-associated cases of vCJD were reported in individuals with a variety of pathological findings approximately 6-6.5 years after transfusion (Llewelyn et al., 2004; Peden, Head, Diane, Jeanne, & James, 2004). With the later reporting of a third prion infection the transfusion-transmission infection rate has been estimated at between 1/15,000 to 1/30,000 (Wroe et al., 2006).

Despite all efforts to improve the quality and efficiency of transfusion, transfusion medicine succumbs to perenial shortages. In Australia, this may be due to an ageing population and falling birth rate limiting the supply. Demand is also increased by a growing number of hematological, orthopedic and cardiovascular diseases among the elderly populations. A large study (n ~ 240,000) from the United States (Ottowa), found that these factors combined constitute 45.7% of blood products and approx 43.6 % total RBCs (Shehata et al., 2014). To address these shortages some countries like Japan have discussed insurance schemes that aim to promote the autologous donation (Makino, 2014). Private blood banks in the US have existed for a while where the donor is renumerated. However many aid organisations such as World Health Organisation and Red Cross remain in favour of non-renumerated blood donations as it support a safe blood supply. In Australia the emergence of private cord blood banks for emerging stem cell therapies have also attracted condemnation for their ‘fee for service’ approach (http://www.abc.net.au/news/2011-06-06/questions-raised-over-private-blood-banks/2748544).

The reprogramming (or induction) of pluripotent stem cells iPSC from adult ‘stem cells’ promises new applications towards regenerative tissue, transplant and transfusion.  The induction of stem cell factors by retroviral delivery can direct a distinct progression of cell fate more effectively than somatic cell nuclear transfer (Okita, Ichisaka, & Yamanaka, 2007).  Fibroblasts may even be directed towards multipotency in absence of Myc (Nakagawa et al., 2008) and utilising the micro-RNAse mIR-19a/b (He et al., 2014). These developments have piqued the interest of popular science writers (http://www.the-scientist.com/?articles.view/articleNo/39718/title/Artificial-Blood-Is-Patient-Ready/) and health technologists. It is now possible to impute specific human leukocyte antigen (HLA) types and strive towards the generation of thousands of specific blood lines. However significant shortcomings in infrastructure and the industry may pose a risk to the equitable and timely supply of this technology.

 

Andréoletti, O., Litaise, C., Simmons, H., Corbière, F., Lugan, S., Costes, P., . . . Lacroux, C. (2012). Highly efficient prion transmission by blood transfusion. PLoS pathogens, 8(6), e1002782.

Benahadi, A., Boulahdid, S., Adouani, B., Laouina, A., Mokhtari, A., Soulaymani, A., . . . Alami, R. (2014). Mapping Rare Erythrocyte Phenotypes in Morocco: A Tool to Overcome Transfusion Challenges. Journal of Blood Transfusion, 2014.

Bennett-Guerrero, E., Kirby, B. S., Zhu, H., Herman, A. E., Bandarenko, N., & McMahon, T. J. (2014). Randomized study of washing 40- to 42-day-stored red blood cells. Transfusion, n/a-n/a. doi: 10.1111/trf.12660

He, X., Cao, Y., Wang, L., Han, Y., Zhong, X., Zhou, G., . . . Gao, P. (2014). Human Fibroblast Reprogramming to Pluripotent Stem Cells Regulated by the miR19a/b-PTEN Axis. PloS one, 9(4), e95213. doi: 10.1371/journal.pone.0095213

Hunter, N., Foster, J., Chong, A., McCutcheon, S., Parnham, D., Eaton, S., . . . Houston, F. (2002). Transmission of prion diseases by blood transfusion. Journal of General Virology, 83(11), 2897-2905.

Llewelyn, C., Hewitt, P., Knight, R., Amar, K., Cousens, S., Mackenzie, J., & Will, R. (2004). Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion. The Lancet, 363(9407), 417-421.

Luten, M., Roerdinkholder‐Stoelwinder, B., Schaap, N. P., De Grip, W. J., Bos, H. J., & Bosman, G. J. (2008). Survival of red blood cells after transfusion: a comparison between red cells concentrates of different storage periods. Transfusion, 48(7), 1478-1485.

Makino, S. (2014). [The current state of transfusion medicine in Japan]. Gan To Kagaku Ryoho, 41(4), 410-415.

McLellan, S., Walsh, T., & McClellan, D. (2002). Editorial II Should we demand fresh red blood cells for perioperative and critically ill patients? British journal of anaesthesia, 89(4), 537-540.

Nakagawa, M., Koyanagi, M., Tanabe, K., Takahashi, K., Ichisaka, T., Aoi, T., . . . Yamanaka, S. (2008). Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nature biotechnology, 26(1), 101-106.

Okita, K., Ichisaka, T., & Yamanaka, S. (2007). Generation of germline-competent induced pluripotent stem cells. Nature, 448(7151), 313-317.

Peden, A. H., Head, M. W., Diane, L. R., Jeanne, E. B., & James, W. I. (2004). Preclinical vCJD after blood transfusion in a< i> PRNP</i> codon 129 heterozygous patient. The Lancet, 364(9433), 527-529.

Shehata, N., Forster, A., Lawrence, N., Rothwell, D. M., Fergusson, D., Tinmouth, A., & Wilson, K. (2014). Changing trends in blood transfusion: an analysis of 244,013 hospitalizations. Transfusion.

Wroe, S. J., Pal, S., Siddique, D., Hyare, H., Macfarlane, R., Joiner, S., . . . Hewitt, P. (2006). Clinical presentation and pre-mortem diagnosis of variant Creutzfeldt-Jakob disease associated with blood transfusion: a case report. The Lancet, 368(9552), 2061-2067.

 

Awkies.

A few years ago I scored an interview for med school at Monash University. I was thrilled about the offer as it was interstate, a new style of interview (multiple-stations) and had been based on a my competitive GAMSAT score and application lodged via ACER. I flew down to Melbourne for the weekend and on the day was ready for anything. Towards the end I thought I was doing okay, but then I had one scenario that completely stumped me…

Outside the interview room we were given a minute to read a brief introduction;

“You are in charge of a breast milk bank with a shortage of breast milk. What would be your approach to resolving this crisis”.

I was dumbfounded.  

The bell rang – and I walked in. I felt uncomfortable with the concept of a “Breast Milk Bank” nagging me. AIl wanted to do was ask if such a thing existed and for what good reason!? I did the best I could by discussing how dairy milk is processed for pharmaceutical companies, the need for batch testing and quality assurance and the distribution schemes to ensure year-round production. To an extent also how these relate to managing blood bank resources. My ignorance started to really show when I went on to say that “it’s probably not the end of the world” if babies are fed formulae by default when mothers can’t breastfeed – “I turned out just fine!”.
 I was receiving suspicious and doubtful looks at this point –  clearly any fumbled argument I wanted to make was going to be extraneous and not well received. I tried to develop a few ideas during the interview around the issues of formulae baby feed – like how there ought to be a synthetic milk that adequately substitutes the breast milk for the immune system. The same should be said of artificial blood. Also I questioned the moral significance of breast milk banks – as to whether it could be equated with vaccination or any other kind of public health debate (Fluoridation in QLD?)

I think that pretty much cooked my chances of med school that year. Clearly I felt embarrassed by my ignorance and handling of this – but most people agree that it was a fairly awkward situation to be in (Awkies). 

Progress or Perish

As I stand back and look at the trends and behaviors that exist in academic publishing in the science I’m both discouraged and a little saddened by my prospects of success in the academic world. It stands to reason as to whether this  is a reflection of my own poor performance or if it is just that I’m perhaps one of a growing number of junior researchers that that can’t progress further due to the inconsistencies in perceptions of academic worth, ethical and professional behavior most of which concern models for funding.

During my time in the lab, I used to conceptualised science’s main focus as rational problem solving developing of principles to ensure that under controlled experimental conditions we reduce error and discern expected signals from background noise. It later became inherently obvious that academic worth is judged more on the ideas you’ve contributed to your field. I am troubled that this is often times at odds with my initial concept of science when you consider that most breakthroughs and innovative ideas are largely brought about when one makes mistakes. All the while scientists do not intend to make mistakes and if mistakes are made we’re almost inclined to conceal or not admitted to them. There isn’t even a way we can document our mistakes or stand to be credited with making mistakes so that others don’t follow the same course. So in a sense; science merely strives for validity over novelty through inductive reasoning on consistent, sensible data.

Throughout scientific history, most ‘false positives’ are looked upon as misleading – that necessitates a persecution and mistrust of the researchers that worked to validate those old hypotheses. The virtuous image of moving through classical notions of hypothesis, selected method presented results and conclusions is a total misrepresentation. We only stand to determine that nature is not what we expect through a raw, unplanned process of poorly executed hypothesis, method and interpenetration of results an inconsistency serves to highlight. Despite this, papers are mechanistically constructed around a rigid objective framework that presents the idea as completely independent of the actual process that led to the discovery. An interesting post once cited that the Biosciences owed their exceptional progress in recent decades in part to spurious results…  http://simplystatistics.org/2013/08/01/the-roc-curves-of-science/ Why is this surprising?

The ‘Data age’ promises to move away from this traditional academic model of putting putative experts in charge of the publishing process. Tim Berners Lee rejects this ideology and demands a system of linked data that allows a multidimensional interpretation and utility of the data. The internet is already the right environment to foster the growth and dissemination of metadata. However, to most academics this may sound absurd, terribly idealistic and  myopic. This may be a reasonable stance to take if you consider that it would be the equivalent of asking researchers to relegate their obligations to a system which they’ve use to build a reputation and career upon. Great resistance also surrounds government research decisions to incorporate open-access to data and open-access publishing of academic literature. Underwhelming impact factors and instances of fringe worthy online journals have served to exacerbate the debate around the needs and virtues of being ‘open’.

Another source of frustration among academics stems from their inadequate funding for academic activities. Much of their work is either done on a low salary or entirely ‘pro-bono’. Consultations with students, the media, and professionals outside their field are not billed. Fulfilling a review on a paper this may also take up to 3-4 hours of careful consideration of the evidence, arguments, quality and quantity of work. Honest reviews are hard to come by and often the party who lodged the paper are met with unnecessary demands for extra work or extraneous cross-references. These unpaid hours that go in to reviewing or preparing an article for review go unrecognised by the university/research institutions. Once a paper is in press, academic researchers (either side of the peer review process) don’t see any proportion of the profits despite extra-ordinate profits incurred by paywalls upon the published works.

These widely held expectations, perspectives and the pressures underlying the ‘publish or perish’ mantra culminate in making public funding and academic employment for junior researchers improbable. Without junior researchers being funded, there will be a severe loss in the legitimacy of academic institutions. Senior researchers ought to recognise that the unsustainable growth of current research may also be a result of their own success. Progressive academics will be fostered by the internet to grow independent of the traditional academic and publishing systems. I see this as a ressolve to my dissillusionment with the academic life. In the public domain we ought to evolve new ways to merrit academic success, encourage the documentation of error, accident and mistakes, and demonstrate how data can be repurposed to generate new ideas.