Welcome everybody, it's very nice to be here.
This is a talk that is very difficult to give because the cell cycle is extremely complicated,
cancer is even more complicated and the two together would really require several weeks to discuss fully.
So what I'm going to do is start off by talking a little bit about cancer
and then I'm going to talk a little bit about the cell cycle
and if we can get to the end we'll try and put the two depressing subjects together.
Cancer is largely a disease of old age.
Anders was criticizing me because this graph should be a little bit higher, perhaps at the origin.
And it was Richard Doll who postulated that the reason for this is
that something like six or maybe seven things have to go wrong in order to generate a tumour.
And over the years we don't really know quite how many things have to go wrong or in what order they have to go wrong.
But the good news is that the youngsters among you are not very likely to get cancer,
the bad news is that if you live to a ripe old age you're extremely likely.
And about probably one in three of the people in this room will die of cancer when they get old.
Also good news is that quite a lot of cancers are going away, mostly cancers of the digestive system.
I think the reason for this is not advances in medicine but advances in refrigeration technology.
We don't eat so many preserved foods, fresh strawberries are now available year-round in our supermarket in London etc, etc.
And so the bad news is that some cancers are on the increase and those are largely cancer of the lung,
fortunately in men is now beginning to tail off but in women it's still going up.
A very shocking statistic is that more young women now die of lung cancer than die of ovarian, breast cancer put together.
That is absolutely amazing. And of course wholly preventable.
This again is a Japanese slide, this is a cigarette machine I found, I love it.
"The infinite skies reflect the innocence in your eyes, your greenish hair flows as the wind blows from the ocean,
waves and bubbles speak in riddle" and so on.
So if that doesn't want to make you smoke, you know.
I don't know what it's like here but I was just in Vienna and it was amazing on the street, so many young women smoking.
And those of you who smoke, and I'm sure there will be some among you,
please, please, please stop because we don't want to waste young talent.
But from now on I want to concentrate on this little tiny yellow box over here,
if you can read it at the back, probably not, called cell proliferation and the cell cycle.
Because all of these arrows eventually come into that place.
And the one caveat I should say that one really does need to distinguish between cell growth and the cell cycle,
the two go hand in hand and traditionally have been very, very hard to disentangle.
And what we understand very well is the control of the cell cycle.
And I want to explain how we know that.
What we don't understand so well is what makes the cells actually grow.
When my mother, who was dying of cancer, was in her final stages, she had an amazing amount of ascites in her belly.
So her belly was swelling up, she couldn't eat because everything was gone by then.
And what happened was that her muscles, her limbs-she looked like a concentration camp victim,
the tumour cells were growing at the expense of the rest of her body.
But interestingly mostly at the expense of her muscles and not of her brain for example.
And that again is something very mysterious, you know.
How is it that these cells, they behave totally selfishly, they can suck the goodness out of you.
And that again is a really, really important problem about which we know very little
and on which very, very few people actually work.
So I think actually, going back to the question, obviously either removing cells or killing cells is what's needed to cure cancer.
And we've known how to do that in one way for quite a long time,
for example Taxol is a relative recent addition to the armamentarium.
And Taxol stabilizes microtubules, it arrests cells in mitosis, susceptible cells die in mitosis.
But you know we don't know why, we actually haven't a clue.
So there's still an awful lot of work to be done.
Thanks very much.
I am also delighted to be here and have this opportunity to speak to all of you.
We know today that, as you probably know, the immune response depends on a lots of Src-type kinases.
And as I had told you before, those enzymes are repressed by interaction of the SH2 domain with a phosphate.
Well, it is known that CD45 is one of those tyrosine phosphatase particular dephosphorylate,
p56lck activate the system and then triggers a whole cascade of tyrosine phosphorylation.
So what you see here is that you need a tyrosine phosphatase to activate a tyrosine kinase.
And this is why, when you express that enzyme we have or other tyrosine phosphatases in animals injected with an oncogene, increases oncogenicity.
So you can't use that.
Any case, since then a whole bunch of transmembrane tyrosine phosphatase have been cloned and characterized
and they all have a structure very similar to that of CD45,
they have a single transmembrane segment, catalytic domain inside and then a variety of different structures on the outside.
From what Tim told you a moment ago, obviously cancer is much more complicated than that.
And we know well today that it results from a series of genetic changes, mutations that occur over a period of many years,
clonel mutation that have been selected because presumably they provide a proliferative advantage to the cell.
And of course in turn those mutations will result in a number of oncogenic events
that cumulatively will contribute to the advance stage of the disease.
Thank you for your attention.
I have a comment to Craig's remark that in the United States health care is really not solved
and it has been the problem of several administrations.
And here you have an example of a very wealthy country, that hasn't solved this and one has to be very careful about,
scientists cannot solve everything, I mean this is a political problem.
That's a problem that the politicians have to solve and as scientists we can only help to educate politicians.
And the problem in the United States is that the gap between the politicians and their education
and the science that is being done in the United States is huge, it is getting bigger.
We have presidential candidates, not to speak about the president sitting in office at the moment, who are creationists.
And we have to defend principles that came out of the last century or the century before that.
And so a very important aspect of scientists, of you, of the next generation is to communicate with the public,
not in a descending way but trying to inform the public about what progress has been made in science.
And this is not only in the biological science, in the physical sciences and everywhere else.
And that is a huge, huge gap.
And this is what we should do and what we should learn how to do.
And you have seen in the lectures today that you have heard, and also yesterday,
that scientists can do that and can effectively communicate with the public.
And I think that is a very, very important task for the future because otherwise ignorance will increase.
It is an opportunity I think to try to talk about issues that I could never feel that I could make a difference in beforehand.
I've always been very concerned for sort of the path we seem to be on as a species.
I think humanity is amazing, you know the human condition is fascinating to me.
We have a great potential as a species to go on.
I like to tell people, like in my talk that RNA Interference, the thing that Andrew and I shared the prize for,
arose in the common ancestor of plants and animals.
And if you think about how long ago that was, it was about, at least a billion years.
The entire galaxy that we're in has rotated on its axis 4 times since the RNA Interference mechanism arose.
That is amazing, if you really think about that.
Living things like ourselves can go on and on and I'd like people to realize that.
I think we have, as human beings we have so much in common,
you know we need to embrace our common history and start planning for a really bright future,
otherwise we may have to suffer for many years to come before we're able to really make a breakthrough.
This goes to all the major issues, sustainable living, high quality medical care for everyone,
we can do these things, we just need to work together.
You know, the idea that you see in old movies where the fellow has a test tube with white fumes coming out,
I have the solution of cancer, this is of course nonsense.
As I mentioned and as Tim mentioned cancers are very complicated, we don't have one form of cancer, we have many different forms.
And I think we have already made some considerable progresses.
He mentioned Gleevec, which is a drug against chronic myelogenous leukemia.
It has been a very successful drug.
So, slowly by slowly we will get there.
But in science you never know where the next discovery will come from and when it will come from, you never know.
And you cannot buy a discovery, governments who throw millions of dollars to projects cannot buy a discovery,
you don't know where it will come from.
So, this is why I cannot predict and nobody can predict when those advances will occur and from where,
it might be something having nothing to do, think of Röntgen with the discovery of X-ray,
he was interested in what happens to electrons going in a vacuum tube,
until he found out that he could activate something at a distance and then it went through solid object,
probably the greatest discovery ever made in the field of medicine.
But if you had a NIH like we have at that time and he had applied for a grant
or Mendel, you know who looks at what happens with peas, there's not a chance in a million that it would have been approved.
This is what I wanted to say.