Fourth Annual Hawke Lecture
Medical Science and Human Goals: a challenge for Australian research
delivered by Sir Gustav Nossal
4 September 2001 at Brookman Hall, University of South Australia
It
is a singular honour to deliver the 2001 Annual Hawke Lecture, and to be the
fourth in such an extremely distinguished series of orators. It is most
appropriate to pay tribute to the Hon R J L Hawke, AC, in this year when
Australia is celebrating the Centenary of Federation, for few politicians in
our short history have enjoyed such widespread popularity, achieved such
repeated electoral success or presided over such an ambitious social and
economic agenda. It has been my good fortune to know Mr Hawke for over a
quarter of a century, but I shall only pause to relate briefly three points
of contact.
While he was still President of the Australian Council of Trade Unions, I unexpectedly bumped into our hero in the foyer of the World Bank building in Washington, USA, and we had a spirited brief chat. He had been promoting Australia's interests within that powerful forum and discussing the Labor party's economic and industrial agenda. I was seeking a greater involvement of the Bank in world health, particularly in the field of communicable diseases. The point of the story is that, as two then much younger men, neither of us doubted his legitimacy as a significant player on the world stage, a situation which many Australian scientists enjoy.
The next interface was when Bob Hawke was a new Labor Prime Minister, Barry Jones was Minister for Science and Ralph Slatyer was Chief Scientist. Hugely significant steps were taken, including the initiation of the Prime Minister's Science Council and the launching of the Co-operative Research Centres' scheme. It was my good fortune to serve on this Council under three Prime Ministers, but I very well remember the keen interest and great pride that Bob Hawke took in the nation's research and development achievements. It was a heady feeling to have half a dozen or more senior Ministers present in the Cabinet room together with science and industry leaders and the Prime Minister in the Chair.
Finally, in 1985 the Prime Minister did me the great honour of opening
the splendid new building of The Walter and Eliza Hall Institute of Medical
Research in Melbourne. I well recall the zest he displayed in interacting
with the 5 or so Nobel Laureates who had come for the event, and the
thorough knowledge of the Institute's history and mission which his speech
revealed. It is indeed a joyous thing that the Hawke Centre, in a
politically non-partisan way, promotes understanding of the democratic
processes and civic obligations to which Bob Hawke has devoted his life.
Before launching into my main theme, a word about your Chair, the Hon Dr
Basil Hetzel. By a curious coincidence this good professional colleague of
mine over a forty year period shares two dominant interests with me, namely
health in developing countries and aboriginal welfare, but in the latter
instance the relationship is not symmetrical. It was in fact Basil Hetzel
who persuaded me to join the Australian Medical Association-Public Health
Association of Australia's group on aboriginal health, and through our
strong lobbying efforts with several Ministers, I re-met John Herron after a
gap of a good few years. I am sure that those contacts led to my appointment
as Deputy Chair of the Council of Aboriginal Reconciliation, so indirectly
Basil Hetzel is responsible! I strongly salute his continuing efforts, and
particularly his largely successful struggle to ensure that no child suffers
brain damage as a result of iodine deficiency.
Medical Science and Human Goals
This brings me to the subject of medical science and human goals. As Edelman puts it, "The idea of progress sweeps through Western history over twenty-eight centuries, from Hesiod to St. Augustine, and from the reformation to the post-Newtonian age in which we find ourselves." It is the dominant paradigm of our democratic age. As Nisbet has pointed out in his book "History of the Idea of progress", there are two basic ingredients in progress, namely the gradual, definite increase in human knowledge; and hope or belief in the continued improvement of the moral or spiritual state of humanity (cited by Edelman, 1986). On the face of it, the equation for medical science is simple. Society makes a major investment in medical research as a result of which the valid human goal of achieving better health and longer life is reached. But within that umbrella, two dilemmas must be explored. The first is unequal access to the fruits of research, at both national and international levels. The second is the tension between the pure flame of the search for knowledge and the practical problems associated with commercialisation. Before entering these turbulent waters, let us look at the extent of recent progress in biomedical science.
Recent Progress in Medical Biology and Biotechnology
By any measure, the progress over the last 10-15 years has been
breathtaking. Any analysis must begin with DNA and the remarkable triumphs
of genomics. Discovery of the DNA double helix was followed by the cracking
of the genetic code, universal for all life on the planet, and then the
capacity to move genes around at will. This recombinant DNA technology, or
genetic engineering as it is called, not only enormously speeded up basic
biological research but also allowed the manufacture of precious human
proteins by harmless bacteria or yeasts, which thus opened up new
therapeutic vistas. At the same time, techniques for sequencing the building
blocks of genes, and of the proteins for which they code, advanced
tremendously. Automation, robotics, miniaturisation and advanced information
technology made gene sequencing fast and cheap, so much so that the first
draft of the human genome project was finished years earlier than planned.
Knowing the full sequence of the human genome provides a dictionary of all
genes, allows these to be grouped into functional families, permits a
penetrating analysis of human diversity and creates a whole new range of
targets for drug discovery. All prescription pharmaceuticals modulate some
biochemical reaction. As the functions of the proteins for which the genes
code are gradually unravelled, it will become clearer which metabolic
pathway has gone wrong in a particular disease and which biochemical
checkpoint needs to be inhibited or enhanced by the new pharmaceutical. In
time, the new genomic knowledge will also make diagnosis more precise and
will allow a more sophisticated analysis of diseases to which a particular
person's genes predispose. Truly, things will never be the same again!
Genes code for proteins, the molecular machines of life, and knowledge of
protein structure has also proceeded apace. It is now possible to create
three dimensional images of proteins magnified 10 million fold, permitting
analysis of critical functional sites within the protein such that drugs can
be tailor-made to modulate (usually to inhibit) their function. This era of
"designer drugs" will be very much facilitated by an instrument known as a
synchrotron, which essentially is designed to accelerate electrons to very
nearly the speed of light, at which they emit a beam of photons of
incredible intensity. This allows the exact and rapid analysis of protein
crystals, making structural biology faster, easier and more user-friendly.
Victoria, with some help from the Commonwealth Government, has recently
decided to build a synchrotron adjacent to Monash University, at a cost of
over 150 million dollars. It will be a National Facility available to
scientists throughout Australia.
Another area of remarkable advance is in our capacity to grow and manipulate
cells in the culture dish. In vitro fertilisation, identifying and growing
human stem cells and "cloning" Sheep Dolly are all by now familiar examples
of advances in cell biology. Equally major strides have been made in the
neurosciences, in immunology and in endocrinology. At the same time, the
older, conventional medical sciences have not been left out of the race. For
example, pharmacology or the study of the mode of action of drugs, and
medicinal chemistry, the science of making new drugs, have benefitted from
what is known as combinatorial chemistry. Here, a huge range of new chemical
entities is synthesised more or less at random, creating libraries. Samples
of these libraries are then screened in appropriate biochemical tests, and
when a "hit" is obtained, the pool of compounds which gave the hit is
rapidly "deconvoluted" to reveal the single active drug. I hope this quick
gallop through modern biotechnology has given you some glimmer of the
exciting vistas which are opening up.
Australia's Potential in Biotechnology
It is frequently stated that Australia has a proud tradition in discovery and innovation but has not been good at reaping the commercial and economic benefits. I believe that this is changing, and quite rapidly. Let us begin right here in Adelaide and work our way anticlockwise around the country, and have a somewhat random, certainly not comprehensive look at the practical developments in progress. Here we have Bob Symons and his pathbreaking work which made the gene shears discovery possible; we have Peter Rathjen and his wonderful work on stem cells; we have Bresagen, the first Australian biotech company to spin out of a University, with a rich suite of innovations. In Melbourne, one can cite Don Metcalf's team and the discovery of the so-called CSF's, major drugs used to combat the bone marrow depressive effects of cancer chemotherapy and radiotherapy, marvellous adjuncts to bone marrow transplantation. A team led by Peter Colman pioneered the influenza remedy, Relenza, and now has an entirely new suite of drugs under development based on novel structures called dendrimers. We also see the great triumph of Graeme Clark's discovery of the cochlear implant, the bionic ear for the profoundly deaf which has captured 80% of a growing world market. In Canberra, Ian Ramshaw and the company Virax is looking at advanced and novel techniques for a possible vaccine against HIV/AIDS. In Sydney, Professor Sullivan's group and the company ResMed have successfully launched a treatment for sleep apnoea, and their device is a major export earner. In Brisbane, Ian Frazer is leading in the race to develop a vaccine against the human papilloma virus, the causative organism of cancer of the cervix uteri and of genital warts. In Perth, Fiona Stanley's group cemented the link between folate deficiency and neural tube defects, leading to folic acid supplementation of women about to become pregnant or in very early pregnancy. Such treatment virtually eliminates spina bifida in the offspring. In Perth also we have the stunning discovery of Robin Warren and Barry Marshall that a bacterium, Helicobacter pylori, is the cause of peptic ulcers and of chronic gastritis and many stomach cancers a swell. Simple antibiotic treatment cures the ulcers and gastritis. All of these discoveries span the research spectrum from basic to applied all have added significantly and definitively to the burgeoning global explosion. The challenge now is to maintain reasonable balance between continued fundamental research and the disciplined, focussed effort needed for development and commercialisation. Younger academics, on the whole, have readily embraced the challenge of viewing their research in a more entrepreneurial light, for example by taking out patents before publishing. It is important that this trend does not go too far - you cannot instantly create a business genius out of a research whiz-kid. We have to build teams to cover the spectrum of expertise required to launch new companies. The scientists should stick to science, and a new generation of entrepreneurs is required to work in partnership with them. I am encouraged by the developments over the last decade in this regard.
The Increasing Gap between Have and Have Nots: Indigenous Australians
Given the interest of the Hawke Centre in global equity, we must now examine the gap between rich and poor in access to the fruits of all these advances. At the national level, life-saving drugs are heavily subsidised and public hospitals are free, so in theory there should be no gap. In practice, however, the strategies aimed at prevention rather than cure show a distinct white collar:blue collar divide. Anti-smoking campaigns, cancer prevention such as Pap smears or mammographic screening and lifestyle changes for cardiovascular health show significant socio-economic stratification. Still, when it comes to the advanced therapeutic innovations, the duchess and the dustman get equal treatment in Australia, a cause for some satisfaction. There is one signal exception, and it relates to the health of the Aboriginal and Torres Strait Islander peoples. The statistics show an appalling 18-year gap in expected lifespan, a six-fold higher death rate in the prime of adult life, and a vast excess of diseases such as diabetes, kidney failure and a variety of severe infections. The causes of this health gap are multiple and complex. In the remote communities, small population size makes the provision of any kind of infrastructure difficult and expensive, and medical facilities are often at a rather primitive level. Overcrowded housing, poor sanitation and poverty all play a role. Undoubtedly the alienation and despair of people deprived of their culture and lifestyle make their contribution, particularly in respect of substance abuse and violence. It is impossible to isolate health from the total social framework. In terms of indigenous people living in country towns or in the cities, it is not so much the availability of services but a failure to access them optimally. Unfamiliarity, fear of rejection or discrimination and ignorance as to what is available all play a role. Our AMA-PHA group were convinced that extra resources will have to be devoted to indigenous health. At present, the total spending per man, woman and child within the indigenous population is $1.08 for every $1.00 spent on other Australians. Given the much poorer status of health, and the extra costs of working in remote areas, this differential is not nearly enough. Strenuous efforts are being made at Commonwealth Government level to bring a better balance, with particular emphasis on primary health care. Major community input into service design and delivery is also required, as is a major effort in the education of indigenous health professionals. More indigenous doctors, nurses, therapists and Aboriginal health workers are urgently required. Heartening progress has been made in immunisation, in eye health, in maternal and child health and in selected health programmes but much more needs to be done.
The Increasing Gap between Haves and Have-Nots: Programmes in International Health
From a global viewpoint, the problem of bringing health advances to the five-sixths of people who live in developing countries is even greater, in particular to the 2.8 billion people who are still living in poverty. The twin problems of insufficient funds and poor infrastructure make working in this area quite daunting. Even more depressing is the realisation that a single disease, HIV-AIDS, can negate the health gains of several decades. Nevertheless, pockets of bright promise can be found and I want to describe one of these. In overseas development assistance, cost-benefit considerations come to centre stage: what intervention will "buy" the most life-years saved for a given dollar spent? Not surprisingly, it turns out that prevention of disease is not only better than cure, it is also much cheaper. So vaccines come very high in the priority list. Since 1993, I have been the Chair of the Strategic Advisory Group of Experts guiding the World Health Organization's effort in global immunisation. The 1980s had been a good decade for WHO in this regard. Following smallpox eradication in 1977, the 80s saw routine infant immunisation rates rise from 5% of children in developing countries to 80%, though some claim that this figure is slightly exaggerated through inaccurate reporting. As a result, at least 3 million lives per year are being saved. A good beginning had been made in global eradication of poliomyelitis. Yet, by 1993 some serious constraints were becoming apparent. Donor fatigue was manifesting itself for routine immunisation. Infrastructure, such as refrigerators for maintenance of the cold chain, was deteriorating. Rates of coverage were dropping in the poorest countries. Newer important vaccines such as those for hepatitis B, a major cause of liver cancer, and Haemophilus influenzae B, which leads to meningitis, pneumonia and septicaemia, were too costly to include in programmes. Research into vaccines of interest chiefly to developing countries was being inadequately supported. It was time for a new initiative.
GAVI: The Global Alliance for Vaccines and Immunization
I am fortunate to have been friends with the Australian-born President of
The World Bank, Mr James D Wolfensohn, for 50 years, since Sydney University
days. Within weeks of his appointment in 1995, I briefed him on the promise
of vaccines, and he was readily sympathetic to helping the cause, because he
soon realised that "soft" infrastructure such as health and educational
services and programmes encouraging better governance were more important
for economic development than "hard" infrastructure such as roads, dams and
tourist hotels, important thought the latter undoubtedly are. He beefed up
the immunology expertise within the Bank and by 1997 we were able to plan a
World Bank "summit" meeting on global immunisation. With Wolfensohn as host,
it was easy to attract other leaders. In 1998, the summit duly took place
with the heads of WHO and UNICEF, key academic and industry leaders and
important foundations also present. It was decided to launch a new global
alliance, and later in 1998 fate took a hand. WHO had approached the Gates
Foundation, initially for a fairly modest grant. Bill Gates, the chairman of
Microsoft, and his wife Melinda became so impressed with the gravity of the
problem of 3rd World infectious diseases, and with the promise of vaccines,
that they decided to make a series of quite extraordinary donations, now
totalling $1,300 million US. The centrepiece was a Global Children's Vaccine
Fund for improving infrastructure in, and purchasing newer vaccines for, the
74 poorest countries of the world. I have the great honour but also the
daunting task of chairing the Strategic Advisory Council of the Bill and
Melinda Gates Children's Vaccine Program.
So in January, 2000, the Global Alliance for Vaccines and Immunization was
formally launched as a major public sector-private sector partnership. GAVI
has four linked aims. It seeks to increase coverage with the six standard
older vaccines against diphtheria, whooping cough, tetanus, poliomyelitis,
measles and tuberculosis. It is committed to the final eradication of
polymyelitis. It will introduce more expensive vaccines such as hepatitis B,
Hib and other meningitis vaccines as well as newer vaccines against
diarrhoeal and acute respiratory diseases. Already 36 countries are
beginning to benefit. Finally, it hopes to accelerate the research towards
new and improved vaccines for 3rd World diseases. The Gates benefaction has
already been augmented by funds from Norway, the US, The Netherlands,
Sweden, Canada and hopefully soon other countries. Still, it is already
evident that resources will finally be a limiting factor. Industry has
pledged to make vaccines available at sharply discounted prices. The costs
of GAVI are high but so are the benefits. The glittering prize for success
would be 30 million lives saved over the next 10 years.
A word or two about polio eradication: High infant immunisation rates are
necessary but not sufficient. It is also important to have massive campaigns
where all children under 5 are assembled in a day with the help of
governments, the media and voluntary organisations. On these so-called
National Immunization Days it is possible to reach children missed by the
less dramatic and unsynchronised routine infant immunisations. Rotary
International has been absolutely fantastic in supporting this "Polio Plus"
campaign financially and with extensive volunteer human resources. As a
country gradually gets on top of its polio problems, it is vital to have a
good surveillance system for case detection. Then intensive "mop-up"
operations, where the vaccine is actually brought to the dwellings in the
areas where the index case was found, obviate the need for children to go
anywhere at all, the vaccine comes to them rather than they going to the
vaccine. This quadruple strategy of infant immunisation, national
immunisations days, good surveillance and mop-up campaigns really works. As
a result, Europe, North, Central and South America, the Western Pacific
region including China, South East Asia and Oceania, are all now polio-free.
Even in India, formerly a great reservoir of polio, new cases are
essentially confined to two northern states. Of the 20 or so countries where
polio persists, chiefly in Sub-Saharan Africa and South and Central Asia,
the greatest effort is going into countries suffering from war or civil
strife, and countries like Nigeria or Bangladesh where high population
density is combined with great poverty. In the warring countries, so-calls
"days of tranquility" are called, where the guns are put down for a day so
that the National Immunization Day can proceed. It is hoped that by 2002
polio will be confined to a very few pockets, and by 2005 it should be gone
from the world.
As far as extra vaccines are concerned, GAVI is moving quickly with respect
to hepatitis B, yellow fever and the Hib meningitis/pneumonia vaccine.
Targets well in view include pneumococcal and rotavirus diarrhoea vaccines.
Of monumental significance to the world, but still some distance from being
a reality, are vaccines for HIV/AIDS, for malaria and a better tuberculosis
vaccine. In all 3 areas, research is making very rapid strides.
GAVI as a Model
Three features of GAVI require examination. The first is a careful planning process spanning two years or more with all stakeholders being fully consulted and coming as close as possible to a consensus about policies and priorities. The second is true commitment to a partnership with clarity about who is expected to do what. The third is the availability of resources which, for the first time, are measured in the billions rather than the millions. There are already plans to imitate GAVI. Potentially the most exciting is the pledge by the G8 Group of leading nations to create a global AIDS and Health Fund to tackle the three great communicable disease problems, HIV-AIDS, malaria and tuberculosis. To date, US $1.8 billion has been pledged. The fund has the personal backing of the Secretary-General of The United Nations, Kofi Annan. The difference from GAVI is that no detailed work has been done about the structure of the fund, its modus operandi or even its goals, except in the most general of terms. The UN itself has determined that the fund will require $8-9 billion a year, a sum deemed quite unrealistic by the donor community but well within the capacity of the world to deliver if there is the will. As a matter of fact, we spend three times this amount on pet food or on perfume. The private sector partner in this new Global Fund for Health is The World Economic Forum, which has its headquarters in Coligny near Geneva. The World Economic Forum is the powerful body backed by all the major multinational corporations, most famous for its conferences held in Davos each January. A few days ago, a young Australian doctor, Dr Kate Taylor, was appointed the chief medical strategist to develop the World Economic Forum's response to the G8 challenge. She will be one of a small group to flesh out the business plan for the fund, following which she will be seeking major private sector resources from the world's largest companies. I wonder whether the anti-globalisation activists will target her work for their next series of confused protests?
Education, Innovation, Research and Development as National Political Issues
Given the global nature of health research and consequent health
advances, we must now return to Australia's role in this 21st century
adventure. There is no doubt that our record in fundamental research is
proud, with our four Nobel Prizes in Medicine and perhaps as many as 5 more
possible over the next decade. These are just the tip of the iceberg as even
a casual study of other international prizes - Lasker Awards, Japan Prizes,
Paul Ehrlich Prizes, Royal Society Medals - would show. But we are late
entrants in the increasingly competitive biotechnology and pharmaceutical
industries. To be more than a "bit" player, Australia must lift its game
across the whole innovation spectrum, starting from secondary and tertiary
education, moving to university and other academic research (still the
crucible for generation of ideas and truly novel concepts), and ending with
the nurturing and growth of a high technology industry sector. From that
viewpoint, it is encouraging that innovation, research and development, as
well as the educational underpinning thereof, have for the first time in
Australia's history, moved to the centre of the national political agenda.
We are witnessing the beginning of an interesting auction in the run-up to
the forthcoming federal election.
The opening bid was by Prime Minister John Howard, Following a number of
Government Inquiries and Task Forces, earlier this year he issued the
"Backing Australia's Abilities" statement, which foreshadowed $2.9 billion
of extra government spending in the R&D area over the next 5 years. The
initiatives, all welcome, were heavily concentrated in the research and
academic sectors, but some modest industry incentives, directed chiefly to
early stage companies, were also included. Next, the stakes were raised by
Mr Kim Beazley in the Knowledge Nation Package. The most powerful elements
of this proposal were the symbolic ones. It calls for deep cultural change,
with a whole-of-government approach to the creation and commercialisation of
knowledge. This would be achieved by aggressive and sustained leadership at
the highest level. The current Prime Minister's Science, Engineering and
Innovation Council would be restyled the Prime Minister's Knowledge Nation
Council and would be a fully-fledged policy unit within the Department of
Prime Minister and Cabinet. It was significant that Mr Beazley nailed his
colours to the mast in respect of Knowledge Nation. Recognising that it
would take a decade for the changes to have major effect, he stated that he
wished his political career to be judged by the success or otherwise of the
initiative. In time, the proposal aims at a major increase in R&D
expenditure, bringing Australia to the top of the OECD league table by
doubling R&D as a percentage of GDP by 2010. There would also be additional
industry support especially for greater public sector-private sector
collaboration in research. Unsurprisingly, the paper did not go into detail
about how the university sector would be rescued from its present situation
of declining funding on a per-student basis, and from the low staff morale
resulting from overcrowded classrooms, uncompetitive salaries and rampant
formula-driven managerialism. These will represent major challenges,
whichever party wins government.
Beazley has called for a Knowledge Nation Summit after the election. Without
a great deal of hope, I will outline my preferred solution. I think the
election campaign should see the auction continue, with further new
proposals being revealed by both major parties. Then, in the kind of
leadership exercised so effectively by Bob Hawke, I believe a true
bipartisan approach to the knowledge century should be forged soon after the
election, and the summit should fully involve opposition parties. The stakes
are simply too high for continued partisanship.
We should not forget the States in this debate. Now in possession of a true
growth tax through GST, the States are already beginning to be significant
players in innovation, with Queensland and Victoria to the fore. Here, also,
one can hope, perhaps a little forlornly, for extra Federal-State
collaboration after the election.
Conclusions
Being a guest of the Bob Hawke Prime Ministerial Centre occasions reflections on society and development; on leadership in ideas and knowledge generation; on Australia's role in the world in the search for global social justice. It is easy to be gloomy about the trajectory of spaceship earth since the end of the cold war, humanity's darker side being manifest in so many parts of the world including our own. In our cynicism about the political process, we must not succumb to the temptation of democracy fatigue. There is a legitimate major role for governments but this requires leadership. The fact that leadership in a country like Australia is diffused is a source of strength, not weakness, and our tall poppies in so many fields must be cherished, not cut down. In asking whether science can be a tool for achieving human goals, I am buoyed up by the excellence of Australia's youth - so many seeds of hope. Well-trained, courageous, ambitious, pragmatic, they punch beyond their weight in international circles. If leadership can harness their collective wills, the lucky country's future is bright. Bob Hawke has a unique gift of distilling and reflecting what it means to be Australian. In his darkest moments, he never doubted that he could help to make Australia and the world a better place. Neither should we.