A cameo week

Last week was one where a number of events occurred which illustrated the diversity of work and the activities at QIMR Berghofer. It started with my return from India following a scientific meeting, which is part of our Asian Strategy, and discussions with a major pharmaceutical company, which is part of our commercialisation strategy.  On Monday I attended meetings where the potential collaborations between the institute and others worldwide in the US led Moonshot Cancer Program started the day and continued with discussions with a team from BGI, the Chinese genomics company.

On Tuesday the Deputy Premier, the Minister for Health and another Minister attended a press conference to announce an agreement which establishes the BGI Headquarters in Australia within our building. This will be the start of an interesting phase of interactions with this very significant company.  The Minister for Science, Information Technology and Innovation then hosted an event to witness the formal signing of the agreement with BGI.

Almost simultaneously a very significant paper from Michelle Wykes from the Institute was published in a top ranked scientific journal; Immunity.  This describes a new immune checkpoint player. Interestingly, its discovery came from her work on malaria infection and included collaboration with James McCarthy who is carrying out human challenge studies where his team injects live malaria parasites into volunteers at our clinical trials company, Q-Pharm, then tests new drugs for consideration from the Bill & Melinda Gates Foundation (Medicines for Malaria Venture).

Michelle Wykes’ work holds great promise for the future. Molecules such as the one she described are already in the clinic and make a major indent on melanomas.  However, the drugs on the market do not work on every cancer or on every individual with melanoma so new therapies are needed and we continue to work with Michelle on that in our recently established SEEDBox®.

In another development during the week, we announced the outcome of the research carried out by Stuart MacGregor and colleagues worldwide on oesophageal cancer, identifying new genes that contribute to the onset of this cancer and again opening up pathways for future treatments.

A little earlier than this, my article on the impact of Brexit and researchers was published in EMBO Reports. To cap the week off I attended the Bangara dance performance which celebrates through dance and music the history and role of the indigenous people in Australia.

This was not quite a typical week but one that illustrates how research at QIMR Berhofer is giving rise to practical outcomes, how our commercialisation policies are kicking in, how our links with Asia are consolidating and how in the midst of all of that, it is possible to have balance and interesting life outside of work.

A formula for Formula 1

Not all would know that I am a keen follower of Formula 1 car racing.  That goes back many years starting in the 70s when I went from Strasbourg to Hockenheim to attend the German Grand Prix there. As the cycles of life turned I ended up living close to Hockenheim in Heidelberg and renewed the contact with the sport. Over the years I have had the pleasure of attending the GPs in Melbourne, Silverstone, Monaco and Singapore so I watch with interest the evolution of the sport.

At the moment, with viewing drifting down apparently, the promoters feel the  need to shake things up and attract viewers for the qualifying day (and eventually the practice sessions) to make it an exciting weekend that culminates with the race itself. For those that are not close to F1, a qualifying session defines the order of the cars on the grid with the fastest cars at the front. The order of the cars is decided by the lap times in a special qualifying hour on the day before the race itself.

The promoters decided to  try to get things a bit more mixed up as last year qualifying produced the same sequence of cars that were fastest at almost every GP They produced an idea to alter the process that is too complicated to describe correctly in a paragraph, but basically the aim was to have  one car eliminated every 90 secs instead of having three 10+ minutes where cars were eliminated at the end of each stint and the order defined by their lap times.

The new system was tried in Australia and was a disaster.  Everybody said it was rubbish as the contest for positions never materialised, the last session ended four minutes before the allocated time, and the outcome was the same old same old. Team leaders agreed (unusual) to revert to the old system…but  10 days later that decision was overturned in the sort of back room dealing that highlighted the lack of transparency of the sport.

So there will be no “shake up” of the grid and unless things change when the experiment is repeated in Bahrain next week the qualifying process will bring no extra excitement.

In the absence of a clear plan for the future I have outlined below my own suggestion. It has new elements and could make everybody get engaged. It covers the practice and the qualifying and has a new mini race.

In this plan

  1. The final grid is decided by computer making random selection. That will shake things up. See below in step 4 for a variation on this . Note that in horse racing the draw for the starting positions is standard and adds advantages and disadvantages that are part of that sport.
  2. Because of the process of computer selection, the qualifying session becomes irrelevant .So it will be replaced by a new 10 lap mini race  with no pit stops, with 1 car per team driven by the reserve drivers. That will showcase new talent. The scores (or perhaps 1/3)from this race will go to the constructors championship and a title will be given to the best driver at the end of the season
  3. The Practice will also be integrated into the new plan as the combined placing scores from P1,P2 and P3 will define the grid placings for the mini race. {An alternative would be to allow the best scores from 2 of the practice sessions-or randomly select one sessions for the ranking}
  4. The Practice sessions could also be used to give a ranking that could be converted into a score that would alter the random selection for the race proper. For example a car drawn 15th but that had been the top of the Practice sessions could get a 10 place advantage, second in the practice 9 place advantage etc.

Well those are my suggestions and I think they would change the inevitable grid ranking, add value to the Practice sessions (where frequently a car that is performing well does not convert that into the qualifying session), highlight reserve talent and new drivers and provide the fans with 2 different races (like Cricket tests and T20)

Interesting Week for Innovation

The analysis of the weakness in the Australian system in converting excellent research to economic benefit has been aired repeatedly over the last months.  Something has to be done about it and it is refreshing that a significant document was released by the Prime Minister on Monday addressing, in a holistic manner, various steps that can be taken, and hopefully will be taken, to pump up Australia’s performance in innovation.  In a recent blog I pointed to the dangers of excess pressure on moving away from the foundations of research-driven innovation. In this piece I would like to stress the real need to get better value from the investments that are being made at the federal and state levels.

The wealth of a nation ultimately depends on 3 major components as defined by the OECD in various studies: (1) its natural wealth (e.g. resources), (2) the utilisation of the natural resources (e.g. agriculture), and (3) generation of wealth from brain power.  Brain power does not mean PhD-driven research, it means all applications of intelligence by all members of society.  Australia has been very lucky to have great strengths in the first 2 categories and perhaps because of that has overlooked the third.  By converting the raw material that has been shown in research outputs, for example, there is a real opportunity for Australia to advance its economy even more than in its current healthy position.

The culture of innovation has to permeate right through the system, however.  Innovation is not compatible with excessive demands for totally non-productive administrative actions.  Government will have to accept this and in the process achieve one of its often stated goals of reducing red tape.  Delays in decision-making while every detail is covered can have a dampening effect on innovation and productivity.

Indeed, productivity is at the heart of the innovation initiatives as it really means getting from the system much more than it is at present. A great opportunity to increase productivity is to increase the conversion of discovery into economic benefit.  To address this gap the culture will have to be changed and a number of the measures that are outlined in the National Innovation and Science Agenda will do that and QIMR Berghofer looks forward to participating fully in this process.

However, it is not just at the federal level that innovation is receiving attention.  In Queensland, the Advanced Queensland plan has been rolled out over the last number of months ahead of NISA.  Perhaps not surprisingly ,the two plans align almost completely: the analysis of what needs to be done has been clear for some time and it is great that some actions are being taken to address these gaps.  As a member of the Advance Queensland Expert Panel, I attended the first formal meeting of that panel this week and heard of the progress in the operation of the multi-faceted program and also was part of discussions on many related topics.  It is up and running and hopefully NISA will be implemented with equal vigour.

It would appear that, subject to analysing all of the details which will emerge, the government has now put in place a pathway towards a new component of the Australian economy and we all have the responsibility to join in and do so.

This is a story about Australia but obviously it is one that is global with each country at a different stage of realising that the real riches of the future for society and the economy lies in the space above our shoulders.

Shaker of Trees or Counter of Leaves

I was a member of an interview panel recently.  As frequently occurs on those panels, the first question prior to seeing the candidates was ‘What are we looking for?’.  That’s when I came up with the aphorism ‘Are we looking for a shaker of trees or a counter of leaves?’.

For many positions the easy response is to say that we are looking for a shaker of trees, somebody who would shakes things up. But of course shaking things up does not mean getting things done.  So the shakers of trees although necessary are not sufficient.  Similarly if we look for a counter of leaves then that may ensure that everything is accounted for but does not necessarily mean that there is any forward movement as a result.  In both instances the person who is merely a shaker of trees or who is a counter leaves would be inadequate in order to make a true contribution at an effective level in an organisation.  There must be follow through from shaking trees and there must be a purpose in the counting of leaves.

Interestingly, having put that categorization on the table, it became easier to identify an individual who would shake the trees and ensure that when things were stirred  up they would be in a position to carry that through to get a productive result from the change that they had initiated.

Predicting unexpected consequences of proposed funding policy changes

The Sydney Morning Herald reported that the government is going to change the basis for funding university research.  With the aim of increasing collaborations between the universities and industry, the suggestion, based on questions at a public forum apparently, is that the government may remove publications in books, journals and conference papers as a criterion for a significant amount of the funding received by the universities.  A formal statement on the matter is expected early in December following a review of the government on its innovation program.

Although this relates to the mechanisms for university funding and hence does not have a direct impact on medical research institutes like QIMR Berghofer, there are some messages that underpin the opinions that are of great significance.  For many years I have been committed to the concept that excellent research should have consequences beyond publications.  The statistics in this respect in Australia are dire and need to be changed.  However the old adage of ‘Too far East is West’ may apply and there is a great possibility of unintended consequences if the more extreme view of ignoring publications prevails in decision making processes.

Research of relevance to industry and with the potential to generate economic and health benefits has its roots deep in research which may not, at the time of their initiation, pass the criterion on being relevant to society.  However without developing a profound understanding of an experimental system, there will be nothing of value that will come. Trying to take a shortcut directly to applications is similar to skipping the training part and expecting to win a marathon race.  As in all domains there is a difference in the quality of research which is generated in laboratories.  Only excellent research will provide insights, to the prepared minds, of useful and potentially useful outcomes.  It is dangerous therefore to totally ignore publications or their quality in defining where funds should go.

Having analysed the operations at this Institute, I categorised the research which is ongoing here (Gannon F, The steps from translatable to translational research, EMBO Reports 2014, Vol 15, 1107-1108). There are steps from discovery through to translation into health or commercialisation and it is important that the right mix is available in an institute or in a country such that a healthy pipeline is generated.  By defining the steps as basic research (D1), disease oriented research (D2), target identification (D3) and target modification (D4) prior to translation to procedures that can be tested in clinical trials, I established that 50 per cent  of our research was disease oriented and 47 per cent covered the steps that screen out discoveries and enrich to the point such that they can be applied.  The new funding proposals that are under discussion should take this pattern into consideration.  If the outcome is that all discovery projects are excluded then there is no doubt that the pipeline will dry up very quickly.  Already the NHMRC, that funds most Australian medical research, appears to look for impacts on health directly from the research that it supports and hence discovery research is harder to pursue.  The ARC funding provides an alternative that may cover some of those areas closer to basic research but unfortunately researchers from the medical research institutes are, bizarrely, excluded from applying for such funds.

The overall message from the government is totally in line with the needs of the country and the demand for change such that there is better return for investment in research is timely.  However it is important to avoid an excessive swing towards to practical outcomes or there will be outcomes that I see as predictable but will be classified as unexpected consequences.

The Walk, The Ride

Recently, I participated in the Weekend to Ends Women’s Cancers to benefit the QIMR Berghofer Medical Research Institute.  This was the third and final two-day 60 kilometre walk event.  I have participated in all three of them, but my feet and legs could only manage to do day one on each occasion.  Still, 30 kilometres is a good ramble.  The best part of the event is the opportunity to talk to people (mostly women) about women’s cancers, their motivation for engaging in the walk and sharing with them the research progress at QIMR Berghofer and elsewhere, that speaks to the continuing need for better prevention, detection and treatment of these cancers.

In August we had the fifth and final Rio Tinto Ride to Conquer Cancer.  This was an equally challenging event—riding 200 kilometres in two days.  I participated in this for the first three years, and again my lack of training or skill meant that I completed only day one of the event riding more than 100 kilometres. Again it was a big demand to go all day up and down hill. In the second year, the wind was in the wrong direction and we had to pedal downhill. I have previously blogged about that event and lessons learned. I have recognised that those participating were doing so for love of somebody close to them, to have a cathartic release of anger against cancer and to obtain hope from the research we would perform using their dollars.

But of course, cancer has not been cured (the implicit message of the Rio Tinto Ride to Conquer Cancer), nor have women’s cancers ended (the implicit message of The Weekend to End Women’s Cancers). This being said, we have seen some great advances, for example: it used to be that 80 per cent of women diagnosed with breast cancer did not survive five years—now 80 per cent do.  But there remains much more to be done. We at QIMR Berghofer and other researchers have to continue in our quest to move towards achieving these goals.  The funding that came to QIMR Berghofer has made an enormous difference.  Some of this is in the form of providing the best infrastructure and equipment that can be available that helps all researchers.  It also has allowed us to initiate programs to attract PhD students to the Institute, thereby looking towards the future.  It has helped us to recruit and retain crucial researchers that are part of our very strong team in the area of cancer in particular.  But most visibly it has allowed research projects to commence that would have otherwise not been possible.  It’s also allowed us to leverage funding from external agencies. Over the years, more than 30 such projects have been initiated.

One conundrum with working in Australia is that unless you have preliminary data you cannot get funding, and of course you need to have funding to get preliminary data.  The Ride and the Walk provided this, and so much more.

Although these high visibility events have come to an end, our need for funding, especially for those stimulatory projects, remains.  It is hoped the community we have bonded with over the years through their participation and support of the Ride and the Walk will stay with us and become regular donors. And you can do so also! Those who are participating in other community events can do so and raise money for QIMR Berghofer at the same time through Team Eureka.  Finally we will be communicating a series of specific projects in need of funding and sharing them with the community that we have grown close to.  Hopefully you/they will identify in this menu of opportunities, topics that they will particularly like to support.  Information on this will be provided very soon.  In the meantime, it is very appropriate to say a major thank you to all of those who directly or indirectly were engaged in the Ride and the Walk.  It is strange that the end of the challenge of participating in these events brings more sadness at the fact that they will not continue than relief at the fact that the pain will not have to be incurred every year.

Bench to Biotech to Bedside with Big Pharma

As a medical research Institute, QIMR Berghofer works hard to ensure that the insights gained from research get translated into the community or the clinic. Sometimes this is a long and slow haul, but when we make progress in transferring mature work from the laboratory, there is a great sense of satisfaction. Treatments to address diseases in patients have to be made robust and their safety tested by thorough evaluation in clinical trials. That is why we talk at QIMR Berghofer of our new paradigm of Bench to Biotech to Bedside (B2B2B). This is in contrast to Bench to Bedside or the other more classical B2B2B which is business to business to business. There is an essential step where industry nous and finances are essential and that is found in Biotech companies and Big Pharma – but B2B2B is easier to promote than variations that would include all industries.

In the recent past we have had two major developments that attest to the quality and relevance of our work. In August 2015 we announced that Bristol-Myers Squibb (BMS) a world leading pharmaceutical giant had selected us for a very significant research partnering agreement. This is in the area of Immuno-Oncology (IO) which is one of the most promising sources of potential new treatments for cancer. There are treatments that are based on an understanding of the interplay between the tumour cells and the immune system. A small but growing number of them have moved into clinical use. Clinically significant improvements in survival for melanoma patients have been recorded and the data are consolidating to a major boost for those with this difficult cancer. Our insights will add to the products that are being brought forward and hopefully will help to extend the range of cancers that can be targeted successfully.

Then last week we announced another agreement – this time with Atara Biotherapeutics, a biopharmaceutical company with a focus on developing meaningful therapies for patients with unmet medical needs in diseases that have seen limited therapeutic innovation. This company have identified opportunities to treat some cancers and autoimmune diseases by targeting viruses that are associated with them and by training the immune system to attack the associated tumour or affected cells. We have a leading track record in these approaches having completed clinical trials where we targeted Epstein Barr Virus (EBV) that drives Naso-Pharyngeal cancers and Cytomegalovirus (CMV) that accompanies brain tumours (Glioblastomas). Because of that, Atara have chosen us to partner with them in developing new and improved means of delivering these and other therapies.  Again this is the first part of B2B2B. We look forward completing the pathway in the next years.

So it is a time to recognise, again, that quality research carried out with an eye on the endpoint of translation can and does characterise QIMR Berghofer. Two significant agreements that arrive at almost the same time is unusual. In each case we hope that the patients will be the beneficiaries of success. Inspiration comes to all at the Institute when projects that had benefitted from years of work end up as part of a pipeline to the clinic. Now we have to re-focus on other research developments that we hope will add to these successes in due course.