The Kenneth Myer Lecture for 2001 was presented by Professor Peter Doherty, on 8 August at the National Library of Australia, Canberra
'The Biomedical Revolution:What may we become?' It is a great honour to be asked to give this address. I see some old friends in the audience and it is great to see those faces again. Why is it that I am aging and they're not? It is great being a living national treasure. I actually have described myself in the field, when I talk to young people, as part of the living fossil record, which bears a little on the subject of this talk. The Nobel Prize was a very wealthy prize. Zinkernagel did not have to pay tax on it and I did. Ronald Reagan brought that in actually. It is one of the reasons I love him so much.
We know what we are, but what may we become? I have tried to deal with the question of the implications of what is happening now in biology, for what is going to happen to us as people and our societies, and our perceptions of ourselves and the way our future will be. So the questions that I am asking are the old ones that belong really, to some extent, to the soap operas—Who are we? Where do we come from? What does it all mean, mate?
Biological scientists like me have a few insights on the first two, but are generally content to leave the last one of, what does it all mean?, to the visionaries and the philosophers and the Hollywood fantasy machine, who make a lot of it of course. But the big excitement in science at the moment or in biological science is that the, 'who we are' question is being opened out really in the most extraordinary way and very recently in fact.
What is being uncovered now stands to have a major impact on human society, and is already changing the way that thinking people perceive the world and perceive our place in the world. I would like to convey to you some sense of that excitement and some sense of what has happened and what is happening now. What happens in the future is really up to us, and I think there are going to be some very interesting debates and some very difficult decisions to make.
Through the course of the 20th century we came to understand that physically, at least, we are the most extraordinary and wonderful chemical machines. Biological organisms like us are constructed from a small number of molecular building blocks, the proteins, the carbohydrates (sugars), the lipids (fats) and minerals, like calcium that builds the bones. So basically all the major food groups, except alcohol and chocolate, are in there somewhere.
These are the basic components of the cells that assemble to make the tissues, muscle and cartilage and brain, and organs like liver and kidney, and ultimately, a person or a puppy dog. Over the years we learned a great deal about the structure of these molecules—how they fit together, how they interact—but what remained hidden was the nature of the organising principle. The other great unknown, until the second half of the last century was the mechanism of inheritance. The Augustinian abbot, Gregor Mendel, working with sweet peas in a monastery garden, had laid out the basic principles of heredity in the 19th century. I think it was very hard to get a research scholarship in the 19th century. Unless you had independent means, you became a monk if you wanted to do research.
The scientific discipline of genetics is based on his observations and emerged after Mendel's discoveries. But still we did not understand for many years the basic nature of the hereditary material—the genes. We mapped those genes, we studied them, and genetics was a very substantial subject with some tremendously good scientists working on it, but we didn't know what the genetic material really was. This puzzle was broken open in 1953 when Jim Watson and Francis Crick published their discovery, that base pairing of DNA in a double helix allowed, when the double helix was separated into single strands, the replication of a faithful copy. This was the basic mechanism of inheritance and immediately it became blindingly obvious to people how things work. Now that has been refined in various ways, but it is still the basic story.
Their insight was recognised by the 1962 Nobel Prize for Medicine and it marked the birth date of the new science of molecular biology. Watson, at the stage that he did this work was just 23 years old, so he was really a very young man. As I talk about the human genome project, it was Jim Watson, in fact, who was one of the people that really pushed this through, because it was an enormously expensive project, and it was his getting behind it with his prestige and his contacts that really got it to happen.
Now, the language of inheritance is written in four base pairs or nucleic acids, adenine and thymine, guanine and cytosine—the four letter code ATGC. The code is determined by the way that these four letters are organised in sequence. The total genetic material, or genome, that is present in a single nucleated cell of each and every one of us consists of about three billion base pairs, that in turn code for about 30 000 functional genes. In fact, only about 1.5 per cent of our genetic material codes for functional genes. The measure of a functional gene is that it can provide the instructions, via an intermediate called the messenger RNA or MRNA, to make a protein.
The genes in turn are located on 46 chromosomes, which are paired structures in the cell nucleus. At conception, we receive one half of each chromosome from our mother and half from our father. The maternal ovum, or egg, also contains a small amount of mitochondrial DNA. The mitochondrial DNA has been highly conserved through evolution. The mitochondria are sub-cellular organelles that are largely concerned with things like the provision of energy and, more recently, we have also realised they are very much involved in cell death pathways.
Analysing this mitochondrial DNA through a spectrum of racial types has led to the conclusion that the current human family may be descended from, mitochondrial Eve, who lived in Africa about 200 000 years ago. There is also a chromosome Adam who has come along a bit more recently, and it turns out that he also lived in Africa about 200 000 years ago. So it is a fortunate coincidence that we are all descended from them.
Watson and Crick's 1951 model of the double helix provided the Rosetta stone that cracked the DNA code. The problems then were essentially technical. Fred Sanger from Cambridge, England, and Wally Gilbert from Cambridge, Massachusetts were awarded the 1980 Chemistry Nobel Prize for working out how to determine the DNA base pair sequences in a particular gene. Then the group led by Leroy Hood at CalTech played a prominent part in building the first automated DNA sequences.
The next 20 years or so saw developments in machines, computing, robotics, and a spectrum of related innovations. Scientific advances often depend just as much on the skills of computer wonks, technologists and engineers, as on the discoveries and ideas of the research chemists and biologists! Technology is a very powerful force in all modern research.
So what I have been talking about is a period of less than 50 years. During the 1990s high throughput DNA sequencing efforts were set up in Washington, USA under the leadership of Francis Collins, the publicly funded GNA project with Craig Venter. Complementary programs were established at a number of other sites, including the Sanger Centre in the United Kingdom, named for Fred Sanger, and a consortium that involves the larger Australian biomedical research institutes.
A major milestone was the publication, in the year 2000, of the whole human genome sequence. There are still refinements of that, but basically the total human genome sequence is out. There were two publications of the major journal Science and Nature, that had the map and so forth in them.
The genomes of a variety of other species have also been completed, or are in progress. And as a consequence of knowing basically this dictionary of life, though it is a fact that we only know what about a third of the words in that dictionary actually mean, in fact, we only know the function of about a third of the genes—but as a consequence of that, our perception of who we are in the physical sense, has been irrevocably changed and it will change more as time goes by. What it has told us about, of course, is our place in the natural world and the reality of Darwinian evolution.
Darwinian evolution and our place in the natural world
In the last part of the 19th century there was a ferocious fight between the established Church of England and the proponents of Darwinian evolution. The most famous episode was the debate between Darwin's bulldog, T.H. Huxley (Thomas Huxley) and Archbishop 'Soapy Sam' Wilberforce.
Huxley had actually been to Australia very early on. He came here in the survey ship, 'The Rattlesnake' and spent some time here and liked it, unlike Darwin who also spent some time in Australia and loathed it and couldn't get out of the place quickly enough. Huxley met Henrietta Heathorn and he later brought her back to England and married her. The Huxley family is actually a British scientific dynasty.
Darwin himself, was a devout Anglican and it is interesting to realise why his seminal work, On the Origin of Species was considered such a threat by the established church. The reason was, of course, that if life evolved by a very gradual process over the millennia as a consequence of natural selection, then the Biblical story of creation that is laid out in Genesis could not be literally true.
Some religious fundamentalists still continue this battle, believing that any acceptance of the book of Genesis as allegory throws doubt on the whole of revealed religion. But most of the major churches have avoided this issue by arguing that natural selection simply describes the mechanism used by the deity to create life on this planet. So I don't really feel that the confrontation that the fundamentalists feel is quite as serious for religion as they might expect.
Not surprisingly the whole sequence of the human genome gives us no insight into the realm of the spiritual and the divine. The aspects of the human condition addressed by religion and science, to me are really quite different, though cognitive neuroscientists may well have explanations for some of the more euphoric states that are associated with the extremes of religious experience. What the comparison of the human and other genomes does show us beyond any reasonable doubt is the validity of Darwinian natural selection. We are part of nature and have evolved with nature, and that really can be in no doubt.
The case for natural selection in the past has largely been based on the fossil record and on observing the effects of various evolutionary pressures on animals, plants, insects and micro-organisms. We can make micro?organisms evolve very quickly in a test tube by applying inappropriate selective pressure, like an antibody.
Archaeologists have made, and still make, enormous efforts to find bones that could identify 'missing links' between humans and other primates. Any discovery made of such bones is widely publicised, as are the debates on the significance of a particular find and the details of some of the extraordinary frauds that have been perpetrated in that area. Scientists have always been ambitious and some scientists—there are always some rogues in any area of science—do perpetrate frauds.
The fact of the matter is, however, that the most powerful argument for Darwinian selection does not rest in bones, but in genomics. Many genomes are yet to be sequenced, and the available maps are still being refined. However, we already know that the overall DNA sequence similarity between humans, chimpanzees and white mice is 99 per cent and 83 per cent respectively. We have about the same number of genes as white mice.
Humans have some 30 000 protein coding genes, compared with 6000 in baker's yeast, 13 000 in the fruit fly, 18 000 in a worm and 26 000 in a plant. Some 60 per cent of the predicted proteins from the fruit fly, 43 per cent from the little worm Celera elegans, and 46 per cent from yeast have human equivalents. That explains why research work on these organisms has often told us a great deal about the way we function. A lot of very important basic biomedical research has actually been done in the past, not just with mice, which is sort of obvious, but with yeast and fruit fly and little worms—we are very closely related to them. Complexity is not necessarily a function of size. We learnt at the Australian Academy earlier this year that the grasshopper genome is nine times bigger than the human genome. I really do not know what to make of that. Probably not much I suspect, because it depends on the utilisation of these genomes really and that's what we have to be interested in.
The inescapable conclusion is that all species, including us, stem from ancient common ancestors. The next decade or so will see clearer lineages emerge as the 'molecular archaeologists', sort through the spectra of genome sequences that will progressively become available from the 'factories', the sequencing 'factories' in Washington and elsewhere.
We are already seeing the reclassification of some species, relationships that we did not really recognise before. For instance, the hippo and the whale are very close. Species are being redefined and a great deal of biology will actually be rewritten. And that is the nature of science, of course, we progress from a level of understanding, from a level of hypothesis, from theory, to further hypothesis, further theory and further refinement. We rarely deal with absolutes.
Does the knowledge that we are inescapably part of nature in any sense diminish us? I don't believe it does. We have to accept our evolutionary heritage, while simultaneously taking due note of the adaptive mechanisms and patterns of behaviour that have made us what we are. Like all life, we depend on an energy web that requires the consumption of other species. Should we eat meat if we have so many genes in common with cattle, pigs and sheep? Well, we also share genetic similarities with potatoes. If we did not eat our more distant relatives we would starve to death. Could human beings have ever moved off the African veldt to inhabit the colder parts of Europe without access to the portable high energy source provided by meat and animal fat? In fact, I believe that it is worth asking very seriously, whether any useful moral or ethical system can operate in denial of either our place in the natural world or the part played by our evolutionary history in determining what we are.
Darwinian selection has nothing in common with Social Darwinism
I was talking in somewhat these terms recently in Canberra, at a meeting in Old Parliament House, a Cranlana symposium, and I realised that as I was talking about Darwinian selection, there was a certain measure of hostility from some people in the room. What I realised, in fact, was that we were talking at cross purposes. This is a common fault of scientists, we use a jargon, we use language, and we do not realise that other people use similar language in a similar way but that it means something really quite different. And we don't listen of course, my wife is always telling me that.
For us as scientists, natural selection and Darwinism are essentially synonymous. We have to be clear that contemporary human societies are not undergoing natural selection at the moment. The rule of law, social support systems, vaccination and the practice of modern medicine, all serve to neutralise possible selective forces. We are not likely to be subjected to the voices of natural selection. The only situation where I could envisage that we might see Darwinian selection operating in a modern western society is if we suddenly experienced a massive epidemic caused by some extraordinary lethal infectious agent that spread with tremendous speed, before we could develop vaccines or preventative medicine effects.
The survivors from that epidemic could well be selected for a particular genetic makeup that might be resistant to that disease. This actually may be happening to some extent with the terrible AIDS pandemic that is occurring in Africa. We know that the absence of certain gene products, absence of certain proteins, confers a degree of resistance to the AIDS virus. And we may see, with the very large numbers of people that were infected, some selective effect on those populations. But what we have to distinguish between is natural selection and Darwinian selection in the biological sense, and the philosophical or political concept of Social Darwinism.
Social Darwinism does not belong in biology, it belongs to the world of political extremists and opportunists. It has nothing to do with natural selection. The idea that the 'survival of the fittest' should be the operative mode in modern, industrialised societies is essentially absurd. What does 'fitness' mean in this context? Does 'fitness' imply the capacity to accumulate great wealth by the unscrupulous exploitation and manipulation of others? One could argue that the fitness of a wealthy person really reflects in what they do with their wealth, not how they accumulated it. The proposal that humanity will advance by embracing such behaviour is to me quite ridiculous. It is worth noting that in natural evolution, where you have predator-prey relationships, if the predators eat all the prey, the predators die also. Perhaps that could be put out there for the economic rationalists. Evolutionary biologists are most emphatically not advocating Social Darwinism as a political philosophy, and this was the reason that I was getting hostility back from some of the people I was talking with, because they thought that is what I was talking about—the idea of Social Darwinism. All human beings are likely to be 99.9 per cent genetically identical. Knowing the sequence of the human genome provides no useful information for the Social Darwinists or for that matter, for racists. But knowing the genome gives us much more insight into the nature of genetic abnormalities and disease susceptibility genes. It also makes us think about the whole area of eugenics.
Genetic abnormalities, disease susceptibility genes and eugenics
As the basic principles of inheritance became generally understood in the early part of the 20th century, it became quite fashionable for well-intentioned and responsible people to argue that society could and should progressively breed out the genetically unfit. This wasn't just an argument of extremists, it was an argument of many people who were well grounded in biology. This practice, of course, is known as eugenics. Sterilisation of those who were judged to be of very low intelligence was legally sanctioned and even aggressively pursued in some regions of the United States. There is a famous statement from one of the Supreme Court Justices, Hamberger J, I think it was, justifying legal sterilisation with the statement, 'Three generations of idiots are enough'. Some school teachers might feel like that at times, but I think it is not really justified by taking biological intervention.
The reason that eugenics and this type of approach became so discredited was really what happened in Nazi Germany. The horror of that era has been very ably documented in a recent account by the historian, Michael Burleigh who looked very closely at the social practices in the Third Reich. It is well worth reading. With few exceptions, the medical and legal professionals in Nazi Germany aided and abetted in the systematic killing of the mentally and physically defective. When they had finished with those, they got on to people they thought were racially inferior. They even, in the end, killed off their own wounded war veterans because they were a drain on the society.
Many religious leaders stood aside and ignored what was happening, though there were notable courageous exceptions in both the Protestant and Catholic clergy. The reason I read this stuff is that I am very interested in how good people act and behave in a situation where there is an evil society and the tensions that operate in that sort of situation. One often wonders how one would behave oneself.
Some societies have already initiated programs that seek to limit the incidence of genetic disease. In Iran, for instance, the gene thalassemia, or sickle cell anaemia causes very major problems, especially in the south, as it does in many Mediterranean countries. The Iranians conducted a large scale survey, more than 10 000 people, and used that to counsel prospective marital partners. Social practices in Iran are such that marriage tends to be an agreement between families. The net consequence of that is that many people did not marry, as a consequence of knowing that they carried these thalassemia genes and that they each had a rogue zygote and would actually transmit it and had a fair chance of having a child with thalassemia. And of course the same sort of thing happens in our society. We test for genetic abnormalities, in the foetus especially, from a family that has had some form of genetically defective child.
Talking recently to one of the geneticists who does this testing and is responsible for talking to parents and so forth, about this issue, I was told that in families with one particular genetic abnormality, if they had had a child with that genetic abnormality and there was a second child on the way, the decision 100 per cent, was to terminate the pregnancy, which was interesting. It didn't matter what their religious background was or anything else, they just would not go ahead with that. And of course, we must protect the right to make that decision. In some societies, particularly in the United States, there are elements that would try to stop or to remove from parents, the right to make such decisions, and of course I think that would be disastrous.
Now though, the question of genetic disease has moved on way beyond genetic disease that leads to major abnormality. That is what we have always thought of when we think about human genetics, unless we think about population genetics, the broader studies of whole populations. But in the medical area we thought of human genetics, particularly about abnormality and the abnormal child.
But what we can do now is, we now have the whole human genome, the whole 30 000 genes printed on three little chips, three tiny little chips. With the right sort of equipment and the sort of know-how that exists in any good biology laboratory—and there are plenty of laboratories at the National University that can do these sorts of experiments—these chips can be used to determine which genes are being expressed (or used) in any particular situation. Such analyses will inevitably lead to the identification of DNA sequences that confer susceptibility to a range of conditions that inflict us as we age. So now we are not just looking at gene abnormalities that lead to some sort of disastrous situation in a grossly deformed and sick child, we are looking at gene abnormalities that may well affect everyone at one level or another.
We know there are genes that predispose towards early onset of Alzheimer's disease. There are genes that predispose towards colon cancer. There are genes that predispose towards breast cancer. What is starting to emerge is that there are genes that predispose towards heroin addiction. Out of five people who use heroin, only two perhaps may become addicted. There may be a genetic basis for that.
So what we are seeing is that we are all going to have a sort of genetic 'fate map', if you like, that could tell us what particular types of disease, what particular problems we are likely to be afflicted with in the future, and what particular sorts of situations we could seek to avoid. One can envisage taking a small amount of blood from a foetus and simply doing this type of analysis. There would be a chip set up with all these susceptibility genes, and you would have a genetic 'fate map' for life. Now, the implications of that, obviously, are very considerable.
The reason for doing this, of course, would be to practise preventive medicine, to be able to tell people to avoid disastrous situations or to do something else about their genetic profile. But the question then will become, how far should one go down the road of trying to decrease the prevalence of those genes? For instance, the genes that can spur high levels of blood cholesterol and early death from coronary artery disease. Many of us have this situation, that we have a genetic inheritance that makes us susceptible to coronary artery disease. We have a high blood cholesterol, bad HDL/LDL ratios—I do, I got it from my father who died young from coronary artery disease. Now, this can be treated by long-term expensive drugs and/or by coronary by-pass surgery. It is possible that the genes that are associated with high blood cholesterol are there because they are linked with some other desirable trait. Perhaps people with high blood cholesterol have great personalities—winning smiles. Would we lose a valuable component of our human capital if the numbers of such people decline?
As the cost of long-term treatment and the potential for long-term treatment becomes much more obvious in societies, could we envisage, for instance, a political process that gives tax credits to prospective couples who first have their gene profiles validated before they embark on reproduction? Maybe we will see computer dating services that match genetically compatible people. We could have our chip data and we could feed it into the computer, go into a chat room and match it with someone else's chip data and then the screen would light up and you could send an email.
Maybe those seeking partners will wear DNA code rings—you know these rings that Americans wear as a college graduation thing—that will signal when they approach a similarly equipped, 'suitable' individual. Even now it is quite possible, when you're out for dinner, to sneak some DNA from the wine glass or table napkin used by a potential partner and have it checked before proceeding further with the relationship. I am really quite surprised, in our entrepreneurial business driven society, someone hasn't actually set up a service for that. Maybe they have and I am just not aware of it. Worse still, an insurance company—and this is serious—could have the DNA analysed from the form that you signed, or from the blood that you gave at a medical check-up and deny you cover on that basis. This, of course, is a tremendous concern. On the one hand there is the concern that if we have a genetic fate map that will show that we are going to develop some chronic debilitating and expensive disease at, say, age 45, then of course people will not want to insure us. On the other hand, if the insurance company doesn't know, we'll want to race out and get some very expensive insurance cover. So it cuts both ways, both from the point of the individual and from the point of the industry, because obviously insurance can only operate if there's enough money in it to pay back the people. So it has to operate in both directions.
So what we have to have is a spectrum of accepted practices, laws and penalties to protect people from invasion of their privacy and basic rights. This was recognised from the outset, when the human genome project was established. There was a major ethical legal component built into the genome project and funded from the genome project, and substantial resources were set aside for that. And, of course, if you know anything about the way biomedical research operates or research institutes operate, you will know that there are ethics committees in all biomedical research situations, particularly to do with human experimentation, which will involve people from a variety of backgrounds.
We have people from the religious community, the legal community, people who are in the community generally. One of the people on one of the committees I sat on in our institution, for instance, had a company that laid concrete driveways—we need to have general input from the community. If scientists and science have made one very serious mistake in the past, it is not involving the community in where it is going and what is happening. And all scientific organisations, all major scientific organisations, including the Australian Academy of Science are very aware of that and we are trying to address it. There are going to be a lot of legal questions about this, and I would bet that if your child is going to university, encourage them to do a joint science-law degree with a focus on genetics and they will do okay and be able to look after you in your old age.
Medical advances, costs and the necessity to set social priorities
This whole business of genetics and knowing susceptibility patterns and possibly being able to do something about them has enormous cost implications. Let me describe the sort of experiment that is being done in a lot of labs right now. Remember we are in Australia and the United States is 15 hours behind us. Cells are taken from, say, a tumour and from the adjacent normal tissue. These experiments are being done here, as well as in the United States and in Europe. You extract the messenger RNA from the two and then you 'interrogate' the gene chips. 'Interrogate' has become a big word in science. Science is like everything else. Suddenly a word becomes very prominent and now we are 'interrogating' everything. So we are interrogating the gene chips.
After some sophisticated computer analysis and the help from people who are specialising in a new science, which is called 'informatics', we learn which elements of the DNA are expressed in the cancer but not in the normal cell. This may lead us to the identification of a defective protein or protein pathway. Something has broken. Maybe the capacity of a regulatory protein to bind to another protein that regulates cell division. If we are thinking about cancer, what cancer is is basically a disease of unregulated cell division. We can't stop the cells dividing, they keep dividing, they get bigger and bigger and so forth. If we found that defect, if we could identify the protein that is defective, then we could take the normal protein and the other protein and make large quantities of them—see how they fit together.
Once the defect is found, we would then ask the protein chemists to produce reasonable quantities of the two proteins so that we can see how they fit together. Analysing the 'fit' will require the involvement of crystallographers, who will probably use a synchrotron to define the physical nature of the interaction. When the structure is known, the synthetic chemists may then be able to make a small molecule, or drug, that does the job of the defective protein and either kills the tumour or blocks its further growth. What will happen then is, after we've gone through this process, the project will go back to the biologists who will test for the effectiveness and toxicity of our new drug in animals, mice, primates even, and see whether it is a useful one. So far, our research effort has involved people with training in biology, mathematics, physics, chemistry. This is why most significant advances are now made in large, multi-disciplinary centres, which generally focus around one or more major research universities.
We tend to see drug companies setting up in the ambit of these universities. For instance, the research triangle area in North Carolina. If anyone has been to North Carolina, you will realise, if you go into rural North Carolina, that it is hardly an intellectual place. But the research triangle area in Raleigh-Durham is a tremendously powerful research focus. And it is a powerful research focus because the state of North Carolina, in its wisdom—they have something like 16 public universities—has decided that two universities are going to get the research resources. They are the University of North Carolina, which tends to do more with biology, medicine and liberal arts, and North Carolina State University, which is more on the engineering, agricultural side. They are both in Raleigh-Durham. And you've got a third university, the sort of thing we do not have much in Australia, a large private university, Duke University. These three institutions are the anchor for a focus where much major drug company investment is going. It is coming from Britain, from Europe and it goes into that focus. And you have got similar foci around Boston—I just realised this the other day. I have known for a long time that Boston has some 500 000 university students but I didn't realise that Harvard University has 8000 faculty. You take all the affiliated institutions, the hospitals, that are all part of Harvard University and you've got 8000 faculty. It is pretty scary when you think of the scale of what we can do in our country. So centres are very important, and we have to convince politicians of this. It smacks of elitism that you have major centres and, of course, politicians in Australia are very sensitive to this sort of suggestion. I don't think it is elitist, I think it is reality.
The next steps after we've got our drug and we've tested it are to seek patent protection, scale of the manufacture of the product and obtain regulatory approval from the various authorities and do a phase one (or safety) trial in normal human subjects. Of course it has been tested very carefully for safety before you get to that stage, but you have to have that safety trial.
If successful, the next thing is a phase two trial where you will actually test it in patients who have got the disease—the problem you are trying to do something about. A very much bigger phase three trial will then be necessary before the chemical can be licensed and marketed. You have to do a really big study to make sure it truly is safe and truly does the job. The opinion here is, on the whole, that we can do phase one and phase two trials in Australia without too much trouble—it is not that expensive. And we need all these people, we need the help of venture capitalists, lawyers, people with managerial and business skills as we get through these sort of stages.
So again, we need centres that have not just got the scientific expertise. We need centres that have got the business and legal and regulatory expertise as well, if we are going to really think about developing some sort of drug industry here. By the time you have done all that, by the time you have got through your phrase three trial, you have actually probably expended hundreds of millions of dollars. Whether we can afford to do that in Australia is a good question. We can certainly get through phase two, according to the people I've talked to about this question. After that it may be necessary to form a partnership with a large international company or to sell off the drug completely.
People have talked about trying to free up some of the resources here from superannuation funds to allow that sort of development to go ahead. Whether that will actually happen, of course, is another matter. But even the less desirable scenario where we actually sold it off after phase two, could lead to net yields of hundreds of millions of dollars, so it is still worth pursuing even at that level.
So genomics opens the way to the development of whole new families of drugs. The downside is that those drugs are likely to be expensive, both to develop and to deliver. No commercial operation can, in the end analysis, afford to develop products that will not return a substantial profit—this is a fact of life. They cannot develop products simply for altruism if it involves that sort of money, or not many such products, only some.
We face this in the institution where I work, St Jude Children's Research Hospital, which is a children's cancer hospital. Children's cancers, though they are terribly distressing and absolutely horrible, are really low incidence diseases. And so if we have to develop specifically targeted drugs for specific paediatric cancers, how will we afford to do it? How will we do it? Well, with our institution we have decided we are going to have to do a lot of that ourselves, but it is a real problem. It is also a real problem when you are considering diseases that are very prevalent and very important in the poor countries that do not have the resources to pay for drug treatment.
What we are likely to see though is the development of a range of products that actually have the potential to prolong life, and the statins, the cholesterol lowering drugs are a case in point. We saw the major battle that occurred recently here about the statins, when the Federal Minister of Health, seeking to control costs, was saying these things are being used too extensively. At the same time, other people in the United States were saying that they are not being used enough. There was an angry reaction from the Australian Medical Association and I guess you all watched it through the newspapers and so forth.
Also, it is a fact that lengthening the productive life span does not necessarily cut health costs. There is a recently leaked report that was commissioned by the Phillip Morris company, that provides very compelling data that smoking and consequent early death had operated to save health care dollars in the Czech Republic. So one solution would be for the government to get everyone to smoke like crazy. That would bring in revenue from taxes on cigarettes, but of course our government is more responsible and would not do that.
It is also true that the last stages of life consume enormous amounts of health resources. It is generally the last year or so of life that consumes up to 50 per cent or more of the total health care costs of an individual. And maybe we have to think, as time goes by, more in terms of hospice rather than hospital type models for terminal health care rather than the idea that life at that stage has to be saved at all costs. And even as I get older, I still think this is probably true. Whether, as I continue to age I still think it is true, is another matter.
Australian society generally pursues a more-or-less collectivist agenda that allows reasonable equality of access to preventive and interventional medicine. It will be necessary in the future to achieve some sort of broad consensus on just how much of the natural resource will be allocated to health because health, with the new advances, has the capacity or the potential to consume just about everything we produce. The possibilities are enormous, but there is only so much money to go around. A dollar that is spent on drugs that prolong what may be a very low quality of life in the elderly, is not available to support the costs of providing better water quality, educating a child or building a dynamic university sector. And so there are some difficult choices ahead of us and all societies.
Though the application of genomics clearly has enormous potential to increase human wellbeing, I do not personally believe that we will see a great increase in longevity beyond what we currently think of as the maximum normal lifespan. While you may see a lot more people living in a reasonably good state of health, up to even 100, I do not think we will see a lot of spry 110-year-olds dancing around. Even so, it is of some concern that the interests of the young and the elderly could come into even greater conflict. With much of the political power and the wealth in society in the hands of older people, it is essential that we continue to recognise that the future rests with the young and that we provide resources accordingly. We are seeing this tension, particularly in the United States where schools are funded from the local tax base. What we are seeing is older people who are no longer interested in investing in children, refusing to see tax rates increased to provide better schools. Of course that dynamic doesn't happen here, but one can envisage similar dynamics developing.
A great deal of hype has been focused recently on the linked possibilities that we can clone human beings and correct genetic defects in fertilised embryos prior to implantation in the womb. There are applications where gene therapy is likely to work, particularly for the modification of bone marrow stem cells to treat some human immuno-deficiency diseases and cancers that arise from the haematological system. There are many other sorts of applications like that. However, the error rate in genetically modified (or cloned) concepts is potentially so high that such applications should never be approved by any science ethics committee. I am not so much concerned about the chance that some crazy person is going to do this, and there is some crazy guy trying to do it right now—but what we shouldn't do is let these extremist scenarios confuse us and distract attention from issues that do require substantial public attention and public debate, like the conflict between health care costs, drug development and all those things.
Knowing the complete sequence of the human and other genomes establishes very clearly that we are, at least in the physical sense, part of the natural world. Our latter evolution as human beings has been driven by our unique capacity for conceptual thought. In my opinion, the enormous challenges that face us and our close and distant relatives can only be dealt with by the human mind. Reason, science and the rule of law are the best weapons that we have, as we grapple with the necessity to ensure a sustainable future for this planet and its biosystems.
I think a regrettable feature of some aspects of the environmental movement is that it turns its back on technology. I think many of the problems we face are only going to be solved by the environmentally sensitive and thoughtful application of advanced technology, and I believe that quite seriously.
We cannot afford to take an essentially anthropocentric short-term view of the future. Australia is a relatively pristine place and Australians are, in the main, a sensible and pragmatic people. I think we have, with our small population, a unique opportunity to influence affairs and to help shape the world of the future. What we become is to some extent in our hands.
© Peter Charles Doherty
Kenneth Baillieu Myer was a good friend of the Library and Chairman of the National Library of Australia Council for eight years. As most of you know Ken and his wife Yasuko died tragically in an aircraft crash in 1992.
He was born in 1921 in the United States, the eldest son of the Australian based family of Sidney Myer, which had established the Myer department store in Melbourne.
Ken Myer’s philanthropic interests ranged across the performing arts, libraries and museums, visual arts, scientific and medical research, international relations and the environment. He served on many boards and committees in pursuit of these interests.
Ken Myer’s association with the National Library commenced in 1960 when he accepted membership of the Library’s Interim Council. Following passage of the National Library Act 1960 he became a member of the full Council and was Chairman from 1974 until 1982. His association with the Library was marked by his strong encouragement of the Library to adopt for the future, new technology and the opportunities that this offered.
His other great contributions to this Library, as to many other institutions and causes were his infectious enthusiasm and unstinting generosity.
In 1976 Kenneth Myer was created a companion of the order of Australia and, in 1989, the Australian Library and Information Association gave him its Redmond Barry Award, which goes to a lay person not employed in a Library who had rendered outstanding service to the promotion of a Library and to the practice of Librarianship.
In April 1990 the National Library launched a library support group called Friends of the National Library. Friends now have more than a thousand members from all over Australia and even some from overseas.
One of the most important activities established by the friends is this lecture series, named to honour Kenneth Myer. It was conceived as an opportunity for invited lecturers to make a significant statement on a broad subject of particular interest to them which may also relate to their background and career interests.
The Hon Gough Whitlam delivered the inaugural Kenneth Myer lecture in April 1990. Nugget Coombs, Elizabeth Reid, David McCaughey and John Mulvaney have presented other lectures.