Professor Norman Maitland Director of Y.C.R. Cancer Research Unit and Professor of Molecular Biology, The University of York
Vivienne Parry: I'm delighted to welcome our next speaker, who is Professor Norman Maitland, Director of the Yorkshire Cancer Research Unit, and a Professor of Molecular Biology, who's going to take us through the significance of Research: Hope or Hype?
Professor Norman Maitland: Thank you very much. I am very grateful to be given the opportunity to speak here today. I've come a long way, I've come from Prague , via Denver , Colorado , although I actually live in York. I‘m going to tell you today a molecular biologist's point of view of prostate cancer. And one thing I want to say, and perhaps bearing in mind what's gone before, is that I don't treat patients, but I do see patients - because one of the things we set out to do is get patient groups involved in the basic research that we do. We have open days in our laboratory, and that's not because the patients come to see our researchers, but because my researchers see the patients and that's very important too because if you see the people that you are working for then hopefully your motivation will increase.
Now if we move on to my first slide. This is a very important slide, some of you may know John and Diana Robinson from York. Sadly, John Robinson died a couple of days ago from prostate cancer. Diana has been very vocal in the needs of men with prostate cancer, and John had visited out lab on no fewer than four occasions. I think it's very appropriate to remember him today.
Let's get it straight from the start. I exist here, but I want things to move from here down into here, and that's why the National Cancer Research Institute are funding so called “translational research” and I am one arm of that effort. I very rarely interact down here but I am very keen that this should happen and happen as quickly as possible.
And this is the sort of timescale that you've got to think about. The great danger is that people think they can jump from here, which is me sitting in my lab in the morning, through to here, where there is real benefit for patients. This takes time. First, with the research grant, then with pre-clinical testing because you really don't want to rush something into the clinic and have a set back, as happened for some of the newer therapies. And then it takes clinical trials properly conducted, extensive clinical trials.
So going from the idea to the patient I would normally say, would take 10 years. We are starting to see some of those efforts paying fruit in breast cancer research now. But the other thing you have to be aware of is the sheer cost of carrying these things forward. Modern therapies cost a lot of money – and from a research grant of perhaps a few hundred thousand pounds, up to the cost of a drug, which you're talking perhaps one hundred million pounds or more. That is the challenge we face and the big challenge lies in here, in actually getting the ideas across what is actually a modest funding barrier into these very large cost trials. And that's where we need to pressurise government from my point of view.
So is there hope? Well, this I think is probably one of the great stories of the year. This I would count as “hope”. I worked in cervical cancer when I was a PhD student and we always knew it was caused by a virus but we didn't know how to treat it. But now we have a way of preventing cervical cancer. Not treating it with a vaccine but preventing it. If we can implement this, then we can eradicate another cancer.
For the ladies in the audience there is also hope. In breast cancer we now have a drug that will effectively treat 20% of ladies with breast cancer. But we have to apply it at the right stage of breast cancer. Wouldn't it be lovely if even 20% of men with prostate cancer had something similar?
We are now getting into an era of patient specific medicine. Every man in this room is different genetically and, because I am a geneticist, I would want to stress that. We now have drugs like Herceptin which work in a proportion of men, but we have a whole slew of other potentially drugable targets which will only work if we treat each person as an individual. And that's expensive, again. But expense shouldn't matter at the end of the day as long as it works.
With prostate cancer we have androgen therapy. We can almost define the way the person is going to respond. How many times is that done? How many times is a man told his genetic profile before he is treated? I think I could count that on the fingers of probably one hand in percentages.
There were a number of other treatments where we can sub-stratify patients we need to find out. Who are the men who are going to respond to Docetaxel? Not every man will. Wouldn't it be lovely if you had a certainty that you were going to respond? And there are clues as to how we can do that. We should be trying to stratify men along those genetic guidelines, so why don't we?
And that's the message. Not all prostate cancer patients are the same. We must try to treat them more individually.
And here is the reality check. The Royal Society did a survey on personalised genetic medicine and this appeared in The Guardian. It's going to be 15 to 20 years before this happens. I think that's wrong. And I want to prove that to be wrong, I think we can take this much faster and much better for men with prostate cancer and we can do it in the next 5 to 10 years, if not sooner.
So does a solution in mice translate to human disease? You'll notice I've been drawing freely from the BBC website, because I think for many of you, that is a very common point of contact with the facts. The danger is that a discovery or perhaps even a breakthrough is over-hyped, and this one is a case in point. In mice, where there are some beautiful science being done by Pier Paulo Pandolfi's group in the Sloan-Kettering in New York , they are looking at genetically modified mice. These mice get prostate cancer, which I'll show you, it quite difficult to equate a man to a mouse. This is how their chromosomes line up, the mouse's is similar but most definitely not identical. For one thing, it probably has a more frequent sex life than men.
Here is the big difference - the mouse has got a completely different shaped prostate from a man. The mouse prostate looks like this and the human prostate looks like this. So it will tell us some things but it won't tell us everything. And there is a bit of good news about that. Some of you may well be taking green tea. I know I do, but it gives me terrible wind, so I stopped. But if you give a mouse green tea he can't complain, and if you give a mouse who's going to get prostate cancer - this is another genetic modification of mouse, a tramp mouse - you can virtually prevent the prostate cancer developing. So it seems logical to try this out in men, and there has been a small survey and there is now going to be a big survey, of the progression from PIN, the pre-malignant disease, to carcinoma. And you can reduce that in 12 months from the normal 30% to 3% if you take green tea capsules. This is not treating prostate cancer, this is preventing prostate cancer.
So this is good news for people who sell green tea. But we have to trial it. If we get the numbers in the trial, then we have a perfectly acceptable way to prevent prostate cancer occurring.
And here it is right up to date. When I refused to send John Neate my slides, I said that is because I wanted to keep this updated. And I'm just back from Denver as I say, but I also was visiting the University of Michigan the day that this paper was publicised last week. In some ways this is, I hesitate to use the word breakthrough, but it is a step forward in our understanding of prostate cancer if it's confirmed. But it's not a test for prostate cancer, and it's not a potential treatment and it won't be a potential treatment for at least 10 years hence, and for anyone to publicise it that way is hype. It's misleading and it's self publicity.
The same, to some extent, is true for this. “A new test for prostate cancer”. It doesn't spot prostate cancer, it tells you whether a cancer is going to respond to a particular type of therapy. So I think the media bear a great burden of responsibility to report these things accurately to the people who matter.
So on to the learning part. One of my other duties is obviously to teach biology and we had Prince Andrew visit our new laboratory to open it. And he said he learnt more in his two hours with us than he had in 7 years of school from biology. This is the prostate and you can think of the prostate as a little factory. The product is prostatic fluid, the workers are these cells right here, and the office workers are the ones at the bottom just underneath them. And that's what it looks like in section. That's a cancer and that's a bit of normal prostate, over there.
So where does all this come from?
Well, we believe that these derive from a very complex bit of biology called stem cells. You've probably all heard of stem cells, but these are not the stem cells that go on to make a person. These are adult stem cells and they occur in the prostate. And we believe that this is the target for cancer, and it's this target which goes on to develop the cancer that we see down the microscope.
Now why haven't we found this before? I've been growing prostate for 16 years and I've been working on cancer for 31 years. Well, it's difficult and when I have a difficult problem I consult the literature. This is one of my little boy's books, this is called “Where's Wally?”. Some of you who have grandchildren or children may have seen this. And what you have to do is find a particular character in this. Now in this case all the Wally's look the same but Wally is in there, he's about there. It took me three days to find him. It's taken me 16 years to find a stem cell. Now you can distinguish these stem cells if the Wally's are dressed differently. And in this case the Wally's are dressed in 17 th and 18 th century clothing, but Wally still has his bobble hat on. Anyone spot it?
I showed this to a set of pathologists, and said this is how long you've got to review a slide - can you see the stem cell? Because strangely the frequency of Wally here is the same as the frequency of a stem cell in a prostate cancer, so it's a very good teaching aid. Let's look closer. There he is right there. Ok, I'm not lying, and there's the prostate stem cells, right there, because we've found a way to tag them. This is the work of a very talented lady in my laboratory, Anne Collins. So what can we do with these? How can they help us to help patients with prostate cancer? Well, up until now, prostate cancers have been treated as if all the cells and the cancer are growing like mad and are the same. We didn't believe that was true. If you look down the microscope those cells don't all look the same.
So we believe that the stem cell model can answer many of the questions about cancer recurrence, and also focus us on new ways to treat cancer. And we found a way to grow them. We can grow stem cells from 99% of (without hyping it) of the prostate cancers that arise in York. We have 70 cultures - 69 successes in the last 2 years. This allows us to maintain and grow the tumour and then watch it try to differentiate into little prostate buds. But we can go more than that. We can get a genetic fingerprint of these and the methods describing this are going to be published next month. So this allows us to pull out new targets for therapy. So this a new target cell which hopefully will change the way we treat it.
Why do we think that's important? Because prostate cancer comes back - not every case and we've heard some encouraging cases today - but the properties of these stem cells suggest that they are completely resistant to anti-androgen therapy. They are relatively resistant to radiotherapy, they have drug pumps so they pump out chemotherapeutic drugs. They don't express the same targets for immunotherapy and gene therapy against prostate specific targets won't work either because they have a very special type of cell which can hide from these therapies. And that's what they are programmed to do. That's what stem cells should do. They should survive.
So when the treatment fails, the stem cell is in a new environment and it changes and it develops and the cancer comes right back again. Now that's a hard concept to get over and the way to explain it is my other obsession which is growing vegetables. I live in a farmhouse out in the Yorkshire countryside and the bane of my existence are the weeds that blow in from the inconsiderate farmers roundabout. And we think of cancer therapy at the moment as a conventional therapy - the ones you've heard about. And they kill the bulk of the cancer which are the leaves of my weeds. But in extremists, if the weeds get so bad, I get in there with ‘Roundup' and that kills the roots of the weeds. So stem cell therapy should be able to kill the roots of the cancer.
So my conclusions today are - I think we all bear some responsibility for over-hyping scientific process. As a scientist, I want people to give me money to do research, the news media want to sell newspapers - so we have to be realistic in what we say. However, hope is a vital part of any therapeutic process so I think that's the other side we have to mention. And these scientific discoveries, they will take time to work through.
Because I am a scientist I have to have more than one conclusion. You can think in terms of there being relatively few major advances since the 1940s in prostate cancer, the taxol derivatives that we've heard about most recently have a limited extension to lifespan, but are an improvement - but not what you'd call a breakthrough. Perhaps now we're in a new era where we can take target therapies and, I hope as quickly as possible, into the treatment of prostate cancer.
I've got three conclusions, right, stem cell theory in practice. This is our small bit of hype. We believe this is going to happen. We are not alone. My trip to the States revealed that they are putting billions of dollars into this as a potential new target for therapy. This has not happened to the same extent in this country where a lot of our efforts have been focused on embryonic stem cells and not cancerous stem cells.
And here is a slide I prepared earlier. This was actually prepared by my young son. This is meant to be me - he obviously doesn't see me often enough - and I'm delivering a wonderful new therapy to the oncologist and urologist over here. The bad news is this resembles a very famous Dutch urologist, who some of you may know and got me into terrible trouble. And here's our prostate cancer patient. And as we've all heard today they are very positive people but sadly in many cases their PSA is continuing to rise until I can hand that over to this gentleman, I don't think I'll be doing my job properly.
So this is my wish list. The sad thing in Prague was the Christmas lights were out, so if I had to get anything for Christmas this is what I'd get:
• I would love to discover what actually causes prostate cancer. You have two risk factors: a Y chromosome and getting old. If we can develop effective prevention measures then perhaps we can change the landscape.
• If we could develop a more reliable discriminatory test for invasive cancer before it invades then we'll be one step ahead of things
• And then lastly, in memory of John Robinson, we need to find an affective treatment, long term treatment, and a cure for metastatic cancer.
So if I were to have all of these, I would be a very happy man this Christmas. I want to thank the people who do this work for me: Anne Collins is the lady who's driven our stem cell efforts, Steve Bryce has genotyped all these, Yorkshire Cancer Research grows them. And the most important person in our team, well one of them, is our local urologist who talks to patients and has bonded, I think, the patients with my research group in terms of provision of material for study. We work in people, not mice. Yorkshire Cancer Research have been incredibly generous at a time when other people were very reluctant to fund anything on prostate cancer. They took a risk on me in 1991. And lots of people around the UK and in other countries who've helped me out. So thank you very much for bearing with my dreams today, I hope some of them will become reality.
Vivienne Parry: Thank you very much indeed Professor Maitland. I think we've got some time for a few brief questions and I'll go into the audience to gather them for you. But how would you suggest that men, when they see a piece in the newspaper, what are the question they should ask themselves to discover whether it is “hype” or “hope”?
Professor Norman Maitland: We live in an information rich age. The first thing you should do is not just read, and goodness I am going to offend someone now, but you should not just read the Daily Mail. Probably go and read another newspaper because different newspapers sometimes take different points of view given the press release. You should then try to go perhaps to the website of the journal in which these discoveries have been published because there is often a commentary by experts on it and it does not normally contain the same degree of hype. So read everything. Don't just read the headline. Look behind the headline if you really want to find out what's going on.
Audience: Do you know the website Phoenix Five? It is a source of a lot of information.
Professor Norman Maitland: This is a patient driven website?
Audience: Yes, very much more so than you seem to find over here. Phoenix Five.
Vivienne Parry: There's a question just behind you there.
Audience: Is there a really a more reliable genetic test than the PSA test in the pipeline?
Professor Norman Maitland: There are several studies that are developing. The problem with the new test is that it's got to be better than the one we have at the moment. Some people would say anything was better than PSA. I'd like to think that hugestudies coming out of both the US and Pan–European studies are going to give us these new markers. They need to be tested - they are at the intermediate stage now. I would hate to say there was a better one at the moment. I have my misgivings about the PSA test which I have vocalised to various people, but I'll keep my opinions to myself. The PSA test is a terrific way to monitor disease. What we need to do is have those studies which tell us how we can predict disease occurring and that's the long and slow process - some of the studies won't mature for another 5 years probably.
Vivienne Parry: Let's go to this gentleman over here.
Audience: Is your work being done elsewhere in the UK and is there any way patients can access it to know what is happening in their own bodies, their own genes and their own susceptibility to cancer?
Professor Norman Maitland: In terms of the stem cells studies we've translated that to the other National Cancer Research Institute Centre of Excellence at the Institute for Cancer Research before publication and we've done the same to some of our partners in the Pan-European study as well. There's no point in sitting on something which people agree is important, just waiting for publication and glory. You've actually got to try and make it used, get it used.
Audience: Can patients make use of it?
Professor Norman Maitland: In terms of accessing the data at this stage we are still at the £1 sign at the left.
Audience: I like your definition of the risk factor of basically being a man or growing old! Do you scan the (unable to hear rest of question)
Professor Norman Maitland: I visited Japan a few years ago and before I went I did some ground work with the Japanese Cancer Institute in Tokyo. In fact, if you look at the rate of increase in prostate cancer, it's probably higher in Japan than it is in the UK. So I'm not going to mention any particular risk factors, but I suspect diet has something to do with it. There was another item on the website last night, so I am right up to date, from a cancer prevention meeting in the American Association of Cancer Research, which is talking about calcium intake - your mothers always told you to drink lots of milk - as a risk factor as well. So diet is almost certainly important but it has not yet reached statistical significance in any of the studies.
Audience: What is the link between genetics, prostate cancer and black men?
Professor Norman Maitland: This is something I believe to be true. It's not always politically correct to say it, but black men have probably got a 2 to 3 fold higher risk of prostate cancer. That is enormous. One of the links here could well be the genetics of their androgen receptor gene. The androgen receptor mediates the effects of the male sex hormone. And there is a polymorphism, a specific feature of black men's androgen receptor, that actually makes it a much more powerful receptor. This could have something to do with the musculature in black male sprinters and things like this, and that may well influence their ability to develop prostate cancer. So that's probably the strongest genetic link at the moment. The human genome is a very, very information rich source - that picture I showed you was 30,000 genes analysed down to 400 - so that's the complexity that we have to deal with and I think it will happen because we now have the tools to do it.
Audience: I've just come back from ECHO13 - the European Cancer Conference - but as a patient I wasn't allowed in to the AstraZeneca presentation, where they claimed some very startling results for a new drug called Bicalutamide. Do you have any comment on that, because it was of interest to those of us who went over, but we couldn't get in?
Professor Norman Maitland: Was this because it was packed out or because there was a restriction I wonder?
Audience: I'm a patient.
Professor Norman Maitland: That shouldn't make a difference in my opinion. Bicalutamide is something you will know about, it's called Casodex - it's the chemical name for Casodex, and I think what AstraZeneca have been doing is refining the use of Casodex.
Audience: Have you considered the shark? The shark allegedly does not get cancer at all, and this is research many years ago in Sweden by Doctor Rolph. I myself take shark liver oil capsules and my PSA started increasing from 6 up to 20 until I doubled the dose I take. I now take 2000mg of the capsules a day and my PSA is going down. I think there must be something in the shark?
Vivienne Parry: I think Norman , it's a myth that sharks don't get cancer, because actually, speaking as a zoologist, they do get cancer.
Professor Norman Maitland: They get different forms of cancer. One thing we can be certain of is that sharks don't get prostate cancer. That's because they don't have a prostate. Interestingly the only other animal that really gets prostate cancer is the dog. These things are very hard to explain. I think if it works, then you should continue with it. To make it a treatment and something that we would believe in we would have to do a study and it takes it beyond that, so I'm not knocking it because if something works, then you go with it.
Audience: Today prostate cancer is affecting men much younger than in the past. Have you a suggestion as to what age the PSA test should be given to men as a general practice?
Professor Norman Maitland: You are beginning to push me towards the boundary of what I am allowed to say really, because I don't do clinical tests. I'll tell you my opinion, it's a personal opinion. If you have a first degree relative, your father, uncle, brother, who has either died or has prostate cancer then you should think very hard about being treated probably at the age of 40, perhaps 45. If it has gone through two generations, the cancer and the age of incidence will be dropping - we know that for genetic breast cancer. Those are the number one people. At one of the meetings I spoke at for the Prostate Support Association, there were two brothers there and one had prostate cancer, when they heard me say that the other brother went off to be tested and was found to have a raised PSA as well. That's the number one message.
Number two message is - When in the general population you should be tested? And that's where it begins to get tricky. You can be tested at the age of 50, and that's not a problem. And I think many private health schemes do that. I am now over the age of 50, he says modestly, and I haven't been tested yet, because I heard of a epidemiologist who I greatly respect at the National Cancer Conference in Birmingham speak in September, and he said he could cut the incidence of prostate cancer at a stroke and everybody gasped, and he said ban the PSA test.
Vivienne Parry: I think on that controversial note, I think we'll break for some coffee. If you would you like to be back here for 11.55, when we have Professors Kirby and Mason, the dynamic duo.