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The biomedical revolution: what may we become? - Part One

By Peter Doherty - posted Wednesday, 15 August 2001

We know what we are, but what may we become? Who are we? Where do we come from? What does it all mean? Biological scientists like me have a few insights on the first two, but are generally content to leave the last one to the visionaries, the philosophers, and the Hollywood fantasy machine. The big excitement in science is that the "who are we" question is in the process of being opened out in the most extraordinary way. What is being uncovered stands to have major impact on human society, and is already changing how thinking people perceive themselves and their place in the natural world. I would like to convey to you some sense of what has happened and is happening now. What happens next is up to us.

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 bones. These are the basic components of the cells that assemble to make the tissues (muscle, cartilage), the organs (liver, kidney) and, ultimately, a person or a puppy dog. Over the years we learned a great deal about the structure of these molecules and how they fit together. 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. The scientific discipline of genetics emerged as many built on his observations. Still, we did not understand the basic nature of the hereditary material, the genes. 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 separated into single strands, the replication of a faithful copy. Their insight, which was recognised by the 1962 Nobel Prize for Medicine, marked the birth date of another new science, molecular biology.


The language of inheritance is written in 4 base pairs, or nucleic acids, adenine and thymine, guanine and cytosine, ATGC. The code is determined by the way these 4 letters are organised in sequence. The total genetic material, or genome, that is present in a single nucleated cell from each and every one of us consists of about 3 billion base pairs that in turn code for some 30,000 functional genes. The measure of a functional gene is that it can provide the instructions, via an intermediate called the messenger RNA, to make a protein. The genes are located on 46 paired structures, or chromosomes, 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 that has been highly conserved through evolution. The mitochondria are sub-cellular organelles that are largely concerned with the provision of energy. Analysing this mitochondrial DNA through a spectrum of racial types has led to the conclusion that the current human family is descended from "mitochondrial Eve" who lived in Africa some 200,000 or so years ago.

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 sequence of the DNA base pairs in any particular gene. The group led by Leroy Hood at CalTech played a prominent part in building the first automated DNA sequencers. The next 20 years saw developments in machines, computing, robotics and a spectrum of related innovations. Scientific advances often depend as much on the skills of computer wonks, technologists and engineers as on the discoveries and ideas of the research chemists and biologists!

During the 1990s high throughput DNA sequencing efforts were set up in the Washington, USA, area under the leadership of Francis Collins and Craig Venter. Complementary programs were established at a number of other sites, including the Sanger Centre in the UK, 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. The genomes of a variety of other organisms have also been completed, or are in progress. Our perception of who we are in the physical sense has been irrevocably changed.

Darwinian evolution and our place in the natural world

The last part of the 19th century witnessed a ferocious fight between the established Church of England and the proponents of Darwinian evolution. Perhaps the most famous episode was the debate between "Darwin's bulldog", T.H. Huxley and Archbishop "soapy Sam" Wilberforce. Charles Darwin was, in fact, a devout Anglican. Why did the ideas laid out in his book, "The Origin of Species", seem so threatening? The problem is that the Biblical story of creation is untenable as a literal account if biological species have evolved over millennia by a slow process of environmentally induced genetic change. 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. Most of the major churches have ducked the issue by arguing that natural selection simply describes the mechanism used by the Deity to create life on this planet.

Not surprisingly, knowing the 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 are different, though cognitive neuroscientists may well have explanations for some of the euphoric states 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.

The case for natural selection has, in the past, been based largely on the fossil record and on observing the effects of various evolutionary pressures on animals, plants, insects, and micro-organisms, both under experimental conditions and in their natural environments. Archaeologists have made, and still make, enormous efforts to find bones that could identify "missing links" between humans and other primates. Any discovery 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.


The fact of the matter is, however, that the most powerful argument for Darwinian selection rests 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 in the order of 99% and 83% respectively. Humans have some 30,000 protein coding genes, compared with 6,000 in baker's yeast, 13,000 in the fruit fly, 18,000 in a worm and 26,000 in a plant. Some 60% of predicted proteins from the fruit fly, 43% from the worm and 46% from the yeast have human equivalents. Complexity is not necessarily a function of size: the grasshopper genome is about 9 times bigger than the human genome.

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" in Washington and elsewhere. We are already seeing the re-classification of some species, with unexpected relationships (eg the hippo and the whale) emerging. Species are being redefined and a great deal of biology will be re-written.

Does the knowledge that we are inescapably part of nature diminish us? I do not believe so. We must 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? It is worth asking 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.

A big problem for scientists is that we often fail to appreciate that the words we use mean something else to people with different training and experience. Natural selection and Darwinism are essentially synonymous terms for biologists. We should be absolutely clear that natural selection belongs to history for contemporary human societies. The rule of law, social support systems, vaccination and the practice of modern medicine all serve to neutralise the operation of possible selective forces. The only situation that I could envisage where we might see Darwinian selection operating in western society is if we suddenly experienced a massive epidemic caused by some highly lethal, rapidly spreading, novel infectious agent. The survivors, ie the selected population, would be those that have some natural resistance gene.

Social Darwinism belongs to the world of political extremists and opportunists. It has nothing to do with natural selection. The idea that "survival of the fittest" should be the operative mode in modern, industrialised societies is essentially ridiculous. What does "fitness" mean in this context? Does "fitness" imply the capacity to accumulate great wealth by the unscrupulous exploitation and manipulation of others? The proposal that humanity will advance by embracing such behaviour is as ludicrous as the idea that Hitler and Himmler were superb examples of the blonde Nordic, Aryan master race that they considered to be the pinnacle of human evolution. Evolutionary biologists are most emphatically not advocating social Darwinism as a political philosophy. All human beings are likely to be 99.9% genetically identical. Knowing the sequence of the human genome provides no useful information for the social Darwinists or, for that matter, for racists.

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This is part one of an edited extract from Professor Doherty's Kenneth Myer Lecture, sponsored by the Friends of the National Library of Australia on August 8, 2001. Click here for the full text of this speech.

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About the Author

Professor Peter C. Doherty won the 1996 Nobel Prize for Medicine. He is the Michael F. Tamer Chair of Biomedical Research at St Jude Children's Research Hospital, Memphis, Tennessee.

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