Well, Michael West, of course, was talking in the film there about the yin and the yang
and maintaining that balance.
What is it that, in terms of telomeres, that maintains that balance, that it doesn't go
too much or too little?
So surprisingly, we know very little about it.
So it's an active area of research, but we've learned very little so far about how telomerase
levels are actually controlled in normal cells.
What we do know is that you need some of it, and if you don't have enough, you have problems.
But normal cells manage to control the levels in such a way that there isn't enough for
them to be immortal.
How they actually do that, we've got years of research ahead.
So you're able to take human cells in the laboratory and add telomerase?
Yes.
Okay.
How do you do that?
It turns out to be surprisingly simple, and we don't quite understand how it works, because
Scott Cohen, working in my lab at the Children's Medical Research Institute just three years
ago, showed that human telomerase has three molecular subunits.
Each of those subunits is coded for by a separate gene.
But it turns out, and this was work that was first done in 1999, you can turn up the production
of just one of those subunits, and that's enough to give you an increase in the overall
telomerase level, even though it's only one of the three subunits.
How that actually works is a matter for further research, but experimentally, we can do it.
I was remiss, of course, in not pointing out that Roger is the Laura Madod's professor
and director of the Children's Medical Research Institute in Sydney, which I should have done
at the beginning of the program.
So you can do this in the lab, but what's the difficulty with doing that in normal human
beings?
At the moment, we don't really have the technology to do that reliably in a way that we would
be confident doesn't predispose those cells to cancer.
So there have been lots of advances with gene therapy in recent years.
Not many of them have really made their way effectively to the bedside yet, but it is
something that I think will become increasingly adopted into medicine over the years ahead,
and that is being able to take a normal copy of a gene, put it into certain cells and put
them back into the body, or use a vector, so something that carries the gene and targets
particular target cells within tissues in the body.
That can be done in the experimental animals.
It hasn't been widely applied in clinical medicine yet, but that's coming.
But there are technical issues there as to how you exert fine control over what we call
the expression level.
So how much of the gene product is being made in those cells that have not yet been solved.
That will come.
These are technical issues that can be sorted out.
So you foresee a time when we can introduce telomerase in a way that addresses the problem
that Sonya was raising about, you might have the precancerous cells that might accelerate
them straight into cancer, which probably wouldn't have happened if you didn't introduce
the enzyme.
That's speculative, but in principle I think the answer is yes.
There was a very interesting experiment done in Professor Jerry Shae's lab in Texas quite
a few years ago, and it really hasn't got the attention that it deserves.
What he did was take some normal human cells, so this is just in the lab, so it's not in
people, but he took some normal human cells.
He used a genetic trick that allows telomerase to be expressed for a short period of time
and then to be removed from those cells.
So he did this in cells that were getting to the end of their lifespan, so they're aging.
Just by turning telomerase on for a short period of time, these cells became rejuvenated
and proliferated for far longer than they would have otherwise.
As I say, that's something that can be done in the lab, and that's a proof of principle
experiment I guess.
But if that, when that can be done in the human body, then some of those issues can be
addressed.
Richard, how long have you been working with telomeres?
I've been working with telomeres since 1994.
So that was when a graduate student in my lab, Tracy Bryan, took on telomeres as a project
to understand cellular immortalization.
And Tracy actually discovered a non-telomerase mechanism for maintaining telomeres that we
call alternative lengthening of telomeres.
And it turns out that 85% of all cancers use telomerase.
The other 10% or 15% use alternative lengthening of telomeres.
What is that exactly?
So that's a different mechanism for synthesizing new telomeric DNA.
So instead of using the telomerase enzyme, there's a DNA replication process where DNA
copies DNA.
And would healthy cells do that as well or not?
So that's a very active area of experimentation in our lab at the moment, and we believe the
answer is yes.
So again, it's highly analogous to telomerase though, that there is a low level of this
alternative lengthening of telomeres activity going on in normal cells, but not enough to
immortalize them.
And I'll just get back to you in a moment, but how would you describe, Roger, the development
of research in the sort of telomere area in Australia?
How's it come along?
Oh, in Australia?
So it's a growing area of interest.
We hold a telomere conference every two years in Australia, and typically there are 50 or
so people who come along, and there are more than that who work on telomere biology in
some shape or form, including some people in the audience here tonight who are telomere
researchers.
And yeah, it's a growing area.
What about funding?
How's that going?
Never enough, I think.
Yes, of course there's never enough, but yes, I have been extremely fortunate that
my research on immortalization has been funded continuously by Cancer Council in New South
Wales.
So ever since I started on this in Sydney in 1988, they've funded me continuously, and
I've had the support of the Children's Medical Research Institute, and it's Genes for Genes
Campaign, so the public have been directly supporting this research for many years.
So there could always be more, but we're very grateful for what we get.
