I wasn’t interested in biology at all when I was young because it seemed like there was so much to learn, and no rules. It wasn’t until I got introduced to genetics that I realised there are rules. And they’re really interesting.
So I studied genetics at the University of Adelaide and then went on to Berkeley, California, to do a PhD in molecular and cell biology back in the early 1970s. And that turned into a way of mapping genes. When I came back to Australia, a friend suggested I use this technology – somatic cell genetics – to map genes in kangaroos. I think I was quite rude and said, “Why would anybody want to do that?” But just to be friendly, I did.
That turned out to be so interesting because it told us how our human genome, and particularly sex chromosomes, evolved. This has turned into a real obsession.
I became a gene-mapping person very, very early. Everybody else was looking at the mouse genome, but I was looking at kangaroos and platypuses, and even fish. So I think I was sort of an early adopter, and that turned out to be absolutely fascinating.
By the 1990s we were trying to clone the sex gene in kangaroos after we’d been involved in the discovery of the male-determining gene in humans. Back then we had little teeny-weeny bits of DNA that we laboriously sequenced on these great big sheets of X-ray film, counting them out – it took such a long time to do just a couple of hundred bases. These days, you can do a couple of billion bases and a computer gives you your results straight to your desktop. It’s really another world.
A lot of my interest has been on sex chromosomes. Back then, we were using very primitive methods, looking down the microscope and trying to figure out where genes were and where they’d all gone to. The Y chromosome is so weird – it hardly has any genes on it and it is disappearing fast. Then it was very, very difficult to get a whole sequence. But now, with new technology, people are getting from one end of the Y chromosome to the other. So we’re able to test a lot of the theories that we’ve come up with in the last 20 years.
You still have to make the DNA, but that’s not very hard. In the old days, we would have to get enormous amounts of DNA that you could actually see in the bottom of the test tube. But that’s not necessary anymore. Now you just get some blood or cells from anywhere in the body and you put it on one of these machines that can actually read the base sequence along a long molecule – it is just amazing.
I don’t have a lab myself any more, but I’ve had collaborations that I’ve built up over the years with ex-students and postdocs who are doing exciting work on sex determination. I work with one group in Adelaide on platypus sex chromosomes and another in Canberra looking at sex determination in dragon lizards. That turns out to be absolutely fascinating because dragons usually do it with genes and chromosomes, but when the weather gets hot they all hatch as girls. So we have an environment interacting with genes there, and this is really where we need a lot more information – how does the environment influence the way the genes are expressed?
Knowing about other mammals and vertebrates helps us to figure out how the human genome works. The next big thing is what they call epigenetics, the modification of genes. Epigenetics means “on top” of the genes – all those factors that are turning genes on and off. That’s what we really need to know about, not just for interest’s sake, but because that’s how a lot of diseases are caused, not by mutations in the gene itself, but by mutations in some of these signals that turn genes on and off. We have a lot to learn about that.
We’ve all got the same genes basically. Of course, elephants and mice are a bit different, and that’s largely because the genes are on or off at different times in different places. So what’s turning these genes on and off? That’s where epigenetic factors come in.
There are some enzymes that modify the proteins that are bound to DNA. And those enzymes have a huge effect on whether the gene is expressed or when it’s expressed or what tissue it’s expressed in. In the next few years, it’s all going to be about epigenetics.
You arrive at some very profound truths when you compare genomes – sharks, humans, even fruit flies. They’re not that different. We have essentially the same genes and they’re doing the same thing. And they’ve been shaped by the same evolutionary forces. Understanding them gives you a very profound look at life, and how life evolved on our planet, and what it means to be human, and to accept our place in the universe, which I don’t think we’re very good at doing.
My other next big thing? I’ve had an idea brewing away for 20 years that’s about to come alive on stage. I’ve been choral singing for 65 years, but I kept on thinking, “Why are we still singing about Adam and Eve? Somebody ought to write Haydn’s The Creation from the point of view of science!” And I thought, well, maybe I could do it . . .
Our first performance of “Origins of the Universe, of Life, of Species, of Humanity” is at Melbourne Recital Centre on July 18. It involves a full orchestra, a huge choir, and fabulous soloists.
I’ve got fantastic help! One of the other choristers is a poet and she helped write the libretto. Our conductor realised that this could be something very big for our 100-voice Heidelberg Choral Society. And a young Australian composer jumped at the chance to write the music for such a blockbuster.
It starts with the Big Bang and then tells the story of the origin of the molecules of life, then the origin of species. We meet Charles Darwin and his hysterical hecklers. In the end it becomes a bit dark when we talk about the “third chimpanzee”, which is us, of course. And what a mess we’ve made of the world. But I’ve finished up with what I hope is a strong message of hope. The finale is called, “Man is the astronomer.” I love the thought that we may be puny and insignificant in the vastness of the universe, but we have the power to understand it, and us, and maybe we can do something to save ourselves and the world.
As told to Graem Sims for Cosmos Weekly.