SUNCOAST DAILY NEWS,
Sarasota, Florida, February 24, 2003.
Dr. Donald Coffey

“The James F. Mullen Distinguished Lecturer Series has two primary puposes.”  So stated Peter Stults, President of the James F. Mullen Memorial Fund, Inc. as he opened today’s meeting.  “ One is to honor Jim, whom many of you knew when he lived here in Sarasota.  After he was diagnosed with prostate cancer, he was frustrated by his inability to find the type of information and support that he felt he needed.  As a result of that, he founded the Man To Man prostate cancer education and support program in 1989.  His vision, commitment and perseverance resulted not only in the benefits of that program being available to those of us here in this auditorium, but to literally thousands and thousands of men and their families and caregivers across the country.  Although he is no longer with us, we wish to honor him.  He was, truly, an inspiring individual.

                “The second purpose of our Distinguished Lecturer Series is to continue his efforts.  To him, providing prostate cancer information to diagnosed patients was of paramount importance and that is what we are doing today.  Periodically, we bring to Sarasota outstanding professionals in the field of prostate cancer to have them share with us their knowledge and experience.  We know that you will find both of these purposes are being met in the program that you are about to hear.. 

                “Now, I would like ask Dr. Alan Treiman, the medical advisor to the James F. Mullen Memorial Fund, and also a staunch supporter of the Man To Man program since its inception, to introduce to you the speaker we have chosen for the 2003 edition of the Distinguished Lecturer Series.”

                 “Thank you, Peter and welcome to all of you who have assembled here today.  This is an amazing privilege to have someone like Dr. Coffey here in Sarasota.  It’s like having Tiger Woods here to give us putting lessons and then make us actually understand what we’re doing.  I had the pleasure of spending the morning with Dr. Coffey and his lively wife, Ula.  This was the first time I have spoken to him, but I have heard him lecture in rooms 50 times the size of this one, to as many as 10,000 people at the American Urologic Association meetings.  At those meetings, he is on stage and I have to watch him, like a rock star, on a television screen.  That is the caliber of lecture we’re going to hear today.

                “I found out something very interesting this morning about Dr. Coffey.  He is a professor at Johns Hopkins in multiple disciplines, none of which he ever studied.  We got on the  subject  of   success   and  concluded  that  it  takes  some problem, some adversity, to inspire people to greatness.  In his case, he was burdened by dyslexia and has had to overcome that not only to become educated, but to rise to the position he has.   I think Jim Mullen was this type of person too.  I knew him well.

                I am a little wistful right now that I left academics, because today Don Coffey has made me exercise a part of my brain that has not been exercised in a while, just listening to him.  He  has almost total recall on any subject.  Name a topic, he’ll lecture on it.  I want you all to welcome this remarkable man to Sarasota.  Here’s Dr. Donald Coffey.”

                [Editor’s note:  I’ve been writing the Man To Man - Sarasota newsletter, on and off, for more than ten years.  Over that period I’ve had to correct speakers grammar, improve their logic, straighten out their disjointed thoughts, you name it.  I thought I was pretty good at making doctor’s sound presentable, but when I tackled Dr. Coffey’s transcript I found I had met my match.  What you are about to read below is, for the most part, Dr. Coffey as he speaks.  To try to embellish his syntax I felt was like painting a mustache on the Mona Lisa.  Read on for his slide / graphics presentation.]

                I’m sure everybody always says, thank you for having me here, but when you’ve just left Baltimore and 26 inches of snow and the water main is broken,  I am truly thankful to be here.  You folks here have two things to be supremely grateful for.  One, it’s just too beautiful here for me to imagine, but you see it every day.  The other thing is the Tampa Bay Buccaneers.  I will try to forgive you for that as I’m a staunch Ravens fan, and you “whooped” us, as they say.

                One of your members told me earlier that I would be audio taped and I asked him if he knew what Barium was?  If he doesn’t know that’s what you do in the South when someone dies, then he’s in trouble, because I am a hillbilly.  I’m from Bristol, Tennessee near where such notables as Tennessee Ernie Ford and Dolly Parton hail from -- need I say more?

                       Who I Am, Where I Come From

                The situation is as follows:  I was dyslexic, as Dr. Treiman said, so I failed the fifth grade.  No one knew why I couldn’t spell or remember dates and names.  I couldn’t use good English.  No one in my family had ever finished high school and when I failed the eleventh grade too, I didn’t think I would.  You’ve got to make some terrible academics to fail the fifth and eleventh grades in Bristol, Tennessee.  Later, I got  thrown  out of  King  College, a little Presbyterian school, and I did graduate, with a “C” average, from East Tennessee State Teachers College at Johnson City after going six years full time.

                The next thing I knew, I was a chemist for a large textile mill and then I started meditating and got this overwhelming feeling that I should work on cancer. I didn’t know a doctor and had seen one only once or twice in my life.  I never knew anyone who had cancer, and I didn’t really know what the word meant.  I looked it up and it said “uncontrolled growth” which didn’t sound so bad to me.  Someone told me I should go to Johns Hopkins.  I said I never heard of it.  They said, it’s in Baltimore.  I said I never heard of that either.  When I found out it was near Washington, I said that’s Yankee country, I can’t go there.  But I did, and they took me in, “C” average and all.

                To help out with expenses I took a job at Westinghouse as an engineer.  I had never had an engineering course in my life and the next thing you know, I was working with a group of engineers and we were putting up some satellites and things.  Then, I volunteered to wash glassware and sweep the floors to get into the chemistry department at night at Hopkins.  That went along smoothly for a while.  Then I saw a notice on the bulletin board that said Johns Hopkins was looking for someone to work on “17 ketosteroid in the urine of hypophysectomized patients with prostate cancer”.  I didn’t know what a 17 ketosteroid was.  I had never heard of hypophysectomy and I had never heard of the “prostrate” gland.  But, it did say cancer and I applied for the job and got it.

                That was 42 years ago, when I started out as a technician, and I have remained there.  I hold five professorships.  I have been the Chairman of Pharmacology and once was a professor of pharmacology and molecular science although I never had a course in either one.  I am a professor of pathology although I never had a course in that either.  I am a professor of urology but I’m not a surgeon or even an MD  I’m also on the Applied Physics staff, but never had a physics course.  There are other functions that I serve but I have forgotten, for the moment, what they are.  So, either b.s. baffles the brains, or I do something different.  What I do is ask, “If this is true, what does it imply?”  That is all I do.  I guarantee that I could become a professor of ophthalmology doing that, because most people don’t ask the question “what does this mean?”.

                                A Quick Quiz

                Let me give you a bunch of questions real fast.  Everybody gets old; I am 70, you are old, so you are going to get prostate cancer. Not true!  If you age in the Orient, you don’t get prostate cancer.  It is rare, extremely rare in China.  I spend a lot of time with the Chinese physicians on this.  They do not get prostate or breast cancer.  BUT, when they move to the United States, they do.  And the next generation does too.  Does that sound like genetics to you?  No.  What does it sound like?  For fifty years we have known about that and for fifty years we haven’t answered that question.

                Second question:  No other animal (other than man) gets prostate cancer.  Why?  All mammals have a prostate, but the only animal that gets prostate cancer is man.  Apes and chimpanzees, who have 98% of the same DNA as we do, don’t die of prostate cancer.  Aging cats don’t; aging bulls don’t.  No horse or bull ever died of this.  They have prostates and things like PSA in them.  But, dogs do get prostate cancer and when they do his PSA goes up and the cancer goes to the bone.  I want to know why that is true.  I worry about these things.

                I want to show you how this one guy from Bristol, Tennessee, who does a lot on the nucleus and DNA organization, looks at these and asks questions.  I have five people in my laboratory so I let somebody else do the experiments for me.  The people I let do the experiments for me love nature.  Because, nature has spent 3.5 billion years, that’s 3.5 times x 1,000 million years, and it is only favoring the winners.  Every time there is a winner, nature takes it.  And what happens to the losers?  How did you get here when the dinosaur didn’t make it?  So, I go back and apply those principles of evolution to prostate cancer to see what it can tell me.

                         A Trip Into DNA Land

                The picture on the screen now is my little daughter.  She is grown up now and has her own little boy.  Here she is now, a nurse, one of the great nurses at Johns Hopkins.  But, she is going to age.  Why does she age, and why is she more susceptible to autoimmune diseases than men?  It is exactly the same DNA in her body as it is in the falcon she holds on her arm.  The same DNA as it is in a lily and the aerobacter (a bacterium) living in the soil and the E-coli in her intestines.  In fact, there are about 500 different types of bacteria growing in her intestines.  I want to show you a little later that it might have something to do with prostate cancer.

                It was  hard for me  to have imagined, when she was born, that what made up the difference between a cockroach and my daughter is the sequence of these simple compounds.  That is DNA. A-T-G-C, dot, dash, dash, dot, dot, dot.  Caucasian, female, 5’8”, propensity for diabetes...dot, dot, dot, dot, dot, dash, dot, dot.  It is hard to believe that it is that simple, but it is.  But, it is a   little   more   complicated that all life forms, human, viruses, trees and insects, are figured by  just A-T-G-C.  This is DNA we purified.  This DNA could make you, it could make a lily, it could make a hummingbird, and it could make a virus that could kill everybody in this room.  It could make a smallpox virus, or Adolph Hitler or a wino.  What is going on here?  How could something that simple do that?  It has the ability to Xerox itself.  Every time it doubles, one, two, four, eight, sixteen, it places a true copy---unless it makes an error!.

                You started out as one cell; just one little cell.  Now, let me show you how amazing this is.  I’m going to crudely scrape the inside of my mouth with my fingernail.  Under that fingernail there are now 10,000 of these cells.  Isn’t that amazing?  If one of those goes berserk and becomes a bioterrorist, it can wipe you out.  It can also make that little girl you saw or a hummingbird.  This is why we are so excited about it.  It can make a human; it can make a cancer; it can make a prostate.  They are called stem cells and we are spending a lot of time on them.  We’re not cloning humans, just trying to find out how that worked and how that works and can we make things heal like superman.

                        What Makes DNA Tick?

                The way to look at DNA is that it is exactly like a compact disc or like a record.  That is the software.  The hardware is the cell in which the DNA resides and it reads out what it wants to play.  The computer doesn’t work without a CD because all the information is on it.  Both are important and they need each other.  That’s why we now think it is time to pay attention to the cell as well as the DNA.

                Take one of the 10,000 cells under my fingernail and you’ll find it has a nucleus in it; like a cassette with a DNA in it.  This little cell, that you cannot see, has 30 inches of DNA in it; almost a yard of DNA in that little sucker.  It has more ATGCs than 30 complete sets of the Encyclopedia Britannica and it cannot make an error in any of these.  What a magnificent proofreading capability this beautiful system is.

                So, here we go.  You take one cell and fertilize an egg and you have a zygote, that is one cell.  That is how you started out.  And then one cell makes two, four, eight, and then sixteen.  When it gets to sixteen, one of them is going to start becoming the head, one is going to become the tail.  But, if I pull this cell loose and left it in a woman’s womb, it would make two people and they would be identical twins. 

                Those cells start dividing and they make a human.  They make a spinal cord and they make an esophagus, nerves, blood vessels, breasts.  A little baby can be made from some of these cells.

                But, then sometimes in this breast, some cells start dividing.  They don’t stop when they make the baby and they eventually show up as a mass.  It shows up in her breast and shows up in your prostate.  I’ll tell you that 90% of these masses are benign.  They will not hurt that woman, but 10% she is threatened by.  90% of the growth in your prostate is benign hyperplasia, BPH, enlarged prostate.  10% can be something else and only a pathologist can tell you whether it is cancer or not.

                Here’s a simple drawing showing normal cells piling up.  We don’t know what that is yet; it could be benign.  But, when they start breaking through and getting into the blood vessels, then they are cancer.  Let me show you how pathologists can look at one cell in your body, like from a PAP smear, and tell whether it is cancer.  That is how I started out in cancer, working in biochemistry at Johns Hopkins, and I didn’t know any more about cancer than anybody in this room.  But, I went over to a pathologist and said my wife had had a PAP smear, and I want to know how you know she doesn’t have cancer.  He said, OK, and I will show you what he showed me.

                      Through The Microscope

                This is a normal prostate cell, or a normal cell lining the breast, or lung or bladder; it doesn’t matter which.  They are stacked up and look like a row of soldiers.  But, the minute you see them starting to stack up and there are too many of them, that is a tumor.  It can be benign or malignant.  When the pathologist sees abnormal growth, abnormal shapes and they don’t look uniform, he knows that is cancer.  The more disorganized the cells, the higher the Gleason grade. 

                What would I ask about this?  What causes the shape of a cell?  Isn’t that a good question?  What causes the shape of a cell is the scaffolding inside of it.  Some of it is called actin, some is called keratin like in our hair and skin, and some of it is called microtubules.  Most of the drugs that are affecting cancer now affect the skeleton.  One of the biggest ones that affect the skeleton is called Taxol, Taxotere or Taxine.  Others are Vincristine, Estramustine phosphate or Estrocet.  I am now into what affects the skeleton and I am into what affects the nucleus, which is the tape deck inside that screws up the DNA.

                The next thing that happened was there was a guy working upstairs at Hopkins that found a pair of scissors (metaphorically speaking) that cut through the DNA.  That allowed them to cut the tape in your tape recorder for the first time.  Next we went and cut up a cancer  cell and  zipped back into the DNA.  They want to find out what gene it is that is in a cancer cell that isn’t in a normal person.   Wow, this is going to be simple.  We are going to take all these cancers that we’ve collected, cut them up and find out what the gene is that causes cancer.  It didn’t turn out that simple.  Because the genetics of prostate and breast cancer are highly complicated.  Let me give you an example.  Can you inherit the ability to play center in the NBA?  Oh, yes you can.  You are 5’4” so you have a suppressor gene.  There is no way you’re going to play center.

                I didn’t say you couldn’t play ball, but you won’t play center.  If I give you a Y-chromosome and make you a male, your chances skyrocket, don’t they?  Not many women play in the NBA, right?  We don’t know why this is so, but it is true.  Guess what?  If you inherit a gene that makes you 7’5”, your chances go way up.  It doesn’t guarantee anything, but you have a propensity if are a 7’5” male to play center in the NBA.

                We are finding a whole bunch of genes in families that we are tracing down to see which ones of these might be involved in what.  We can cut the gene from the cancer and put it back in (scotch tape back into the tape deck) and we play the record.  It works so well that a woman in our laboratory took the firefly gene that makes the firefly glow, and put it into a tobacco plant.  The leaves of the plant absolutely glowed!  Isn’t this amazing stuff?  With this powerful system we’re using you can see why we’re so excited.

                      Genes That Do Bad Things

                What do those genes that cause cancer do?  Well, there are some of them that are accelerators and some of them that are brakes, like in an automobile.  The cancer cells that make the cancer grow faster, the accelerators, are called oncogenes.  The ones that are brakes, slowing down the automobile, are called suppressor genes.  There are a lot of both of these types of genes.  Then we find that there  are maintenance genes that proofread the manuscript and take care of any misspelled words.  They are called DNA repair genes and the BRCA1s and 2s begin to look like that.  Next are genes that make the wheels go round called cell mobility genes or metastasis genes.  We’ve identified all these genes and been working with them for twenty years and everybody asks, “What causes prostate cancer?”, and we still don’t know.  But, I will show you that we are gaining knowledge in some areas. 

                I want to show you two things.  One, that there is something in the United States that promotes prostate cancer and something in China that inhibits it.  So, when he moves here he loses the Chinese protection and gains the hurt from America.  We are not sure what this means, but we’ll show you how the work is done.

                When I was born, the number one cancer in the United States, by far, was stomach cancer.  It stopped; well, it went way down.  Why?  When I was born, lung cancer wasn’t very prevalent.  Then WWII.  Smoking began in earnest with men, and it went up.  Is this genetic?  It doesn’t look it, but you are affecting the genes, so it is genetic.  It is genetic/environment interaction, but it is not like inheritance.  Understand the difference?  You inherit a trait or you get your DNA damaged.

                Look at breast and prostate, they go hand in hand.  What does that tell me?  It implies to me that whatever caused stomach cancer didn’t have anything to do with breast and prostate.  Would you agree?  It also shows me that cigarette smoking is not a major factor in prostate cancer.  Agree?  Right now in China, prostate cancer is way down and stomach cancer is right up near the top.  What do we think this is due to?  We think it may be caused by things we used to do a long time ago like smoking meat, salting meat, nitrates, nitrites and canning.  As refrigeration is coming in China, the stomach cancer rate is beginning to drop.

                Here’s a chart of various cancer rates around the world.  Notice please, that in every country breast and prostate cancer go hand in hand.  Where one is up, the other is up.  Where one is down, the other is down.  Other cancers like stomach, colon and lung do not go hand in hand, but breast and prostate do.  I thought I had better go figure this out.

                    Correlating Prostate & Breast

                First I go and look for a solution.  I say, when did you get a prostate and when did you get a breast?  When man got a breast, he got a prostate.  Did you hear him right?  Did he say man got a breast?  Yes, every man in this room has a breast.  Can you get breast cancer?  You bet you can.  Is it as prevalent as it is the female?  No way.  So, why do you have a breast?  Because the dominant form of the human is female.  The male is superimposed on it.  I will show you in a minute how that works.  When a woman got a breast, she began feeding her children.  Those are called mammals.  Every mammal on this planet has a prostate.  But, alligators don’t breast feed, chickens don’t breast feed and they don’t have prostates.  But, dogs, cats, bulls, anything that has breasts has a prostate.  All these animals have breasts and prostates but only we Americans get all this prostate and breast cancer.  What the heck is that due to?

                It gets even more interesting when we go inside the human -- here is one opened up.  Up here are the kidneys, then the bladder so urine is coming down the urethra  into  the  bladder.  This is the prostate, right here, your prostate,  about the size of a walnut.  Here is the seminal vesicle, the bulbourethral gland, the penis, the testes, the epididymis and the vas deferens. 

                Guess what?  Lots of cancers in the prostate.  How many?  One out of about ten.  How many prostate cancers have there been?  Millions.  Right now are there 180,000 diagnosed each year; in ten years that’s 1.8 million.  How many seminal vesicle cancers have ever been diagnosed in this world of 6 billion people?  40!  With all those billions of people, only 40?  What about bulbourethral cancer?  Never had a cancer, never had an infection, never had a benign growth.  You never heard of it because it never gets sick.  What about the epididymis here?  A big gland and it never had a cancer in the history of the  world  that  we  know  of.  No vas deferens cancer has ever been reported.  Why don’t these get cancer?  That is something I am working on.  We have some suspicions.

                Let me show you what happens if you’re a male; a full X - Y male.  Here’s what happens:  You make testosterone (T) with the testes and then 5-a reductase converses into dihydrotestosterone (DHT), then it pops onto an androgen receptor.  The glands you have, as a male, are breast, prostate and seminal vesicle.  If you have T, DHT and androgen receptor, your breast will not develop.  On the other hand, if you are loaded with T, but lack the androgen receptor, you actually look like a beautiful female.  You have a vagina and breasts.  There are people like that who, when they are born, are classified as females and when they get to be pubertic, it becomes apparent that up in their body they have testes.  They have normal testosterone levels and are every bit a male except in appearance.  That is called androgen insensitivity syndrome or testicular feminization; a well-known phenomenon.  I believe Mae West was of this type and there is a current movie star too, although it is being kept private.  What I am trying to tell you here is the culprits are T, DHT and androgen, and something we are going to call estrogen in a moment.  T plus the androgen receptor inhibits the breast and induces the seminal vesicles, and DHT induces the prostate.

                Let’s take a dog and add a new twist to it.  We’ll remove the dogs testes, then restore that dog’s testosterone and DHT and see what happens.  It makes a normal prostate!  But, if we put estrogens in it, WHOOM!, we get a four times bigger prostate, a big tumor.  So, estrogens synergize DHT.  I believe, personally, that estrogens play a major role in abnormal growth of the prostate.  Later, we are going to show you what that could mean.

                           Inflammation As A Factor

                There is a new discovery at Hopkins that puts a change in the picture.  That is that inflammation may be involved in the making of prostate cancer.  If I opened up every prostate in this audience, about 70 to 80 per cent of them would have cells that come from the immune system:   eosinophiles, microphages, T-cells, etc.  It looks like there’s inflammation, they don’t have any infection that we know of.  We did, however, find that these areas of  “inflammation” make reactive oxygen, which damages the DNA.  One of our bright young students found there were little islands of cells in the prostate which look shrunken and turned off.  They were not -- if fact, they were dividing like crazy.  He named this proliferative inflammatory atrophy (PIA).  It can be induced with estrogens, but we don’t know whether it is an autoimmune disease.  He found this near something we already knew was an early marker for cancer, PIN, prostate intraepithelial neoplasia.  All of these are premalignant lesions on the way to making cancer and metastasis.

                Next we asked ourselves, “If estrogens induce this, can we prevent this?”  One of the bright new faces in prostate cancer research, Angelo De Marzo, has proposed that proliferative inflammatory atrophy is an early lesion in prostate carcinogenesis.  In a paper that I read, but not paid much attention to, I remembered that estrogens did something to the rat prostate under some conditions.  I didn’t know about PIA then, but as soon as it was shown to be in the human prostate by Angelo, I could say, “Oh, I have seen that.”  We will show you some data we hadn’t paid much attention to then which is very interesting now.

                Can we prevent the formation of PIA?  What if we were able to block estrogens, like antiestrogens?  Would it work?  In food there are weak estrogens that work as antiestrogens; they are called phytoestrogens.  What are they in?  Soy, as well as other foods.  Could that possibly block PIA?  We did an experiment and the answer was “yes”.  What happens is when you take soy and certain grains, they make the compound phytoestrogens.  But, guess what?  They have to be worked on by the bacteria in your intestines.  When you move from China to the United States, you change your intestinal bacteria because of a change in your diet.  It is not as simple as looking up who takes soy, it is what is in your flora.  We have a lot to learn, don’t we?

                Next, we ran an experiment on some rats by feeding them a diet with no soy in it.  We couldn’t use our regular feed because Purina Chow is now loaded with soy, that is the protein they use.  So, we had to find a feed that was soy-free.  The final results were tabulated between three diets: one was soy-free, one had moderate soy and the other had high soy.  If we took all the soy out of the feed, 80% of the rats had inflammation of the prostate; those with high soy had no inflammation.  Would adding soy to your diet help you if you already had prostate cancer?  We don’t know.  Some claim that it will slow progression, but I don’t know about that.  But, certainly we’re getting down  to the fundamentals of what is going on.

                            What Else Is In Our Diet?

                Is there something in our diet that could be a causative factor in getting prostate and breast cancers -- a carcinogen?  Lo and behold, I got a shocker.  The shocker was that I couldn’t make a rat get prostate cancer.  I tried and I tried.  I sewed carcinogens into their little prostates by taking little sutures and soaking them in ether that is loaded with methyl cholanthrene, a know cancer producer.  Later, after opening them up I couldn’t get one prostate cancer, even with the head start I gave them.  I was really depressed.  And then, all of a sudden, someone changed their diet, and did they get prostate cancer!  Wow, did they!  And, what was it that was fed to them this time?  It was burnt meat!  I will show you that in a minute, but I skipped too fast to the burnt meat.  First, let’s talk about estrogens and fat.

                It has long been suspected that there is something in our diet with estrogens that seems to cause breast and prostate cancer.  This is a complicated slide so let me walk you through it.  If you walked up to me now and said, “Tell me what you know about obesity, fat, diet, meat, estrogens and prostate cancer”, I would summarize as follows:  Androgens effect the prostate and breast; they suppress the breast and stimulate the prostate.   Androgens  are  the  way estrogens are made in females.  Females make their estrogens from male androgens.  Males make estrogens from the androgens.  Where does this take place?  In fat tissue.  You don’t have to be fat for this to happen, but if you have a lot of fat it happens more.  Diet can affect this too.  You can get oxidative damage from fats directly to the prostate and breast.

                I was getting ready to tell something that is exciting.  Earlier I told you that  prostate cancer is rare in animals.  Why is this so?  Why would only the dog and the human be susceptible?  At the end, I’m going to tell you that it has something to do with burnt meat.  But, now let’s look at the evolutionary tree of how primates became humans.  Right here, where we split off from gibbons, orangutans, etc. are the chimps and the bonobos.  I want to show you the bonobo who is most interesting.  This animal eats no meat, but eats fruits and vegetables like vegetarians.  Scientific American points out that this animal is so close to us, it’s amazing.  They practice sex in the missionary position and they exhibit jealousy.  The magazine further adds that after they have sex, the female leaves with male’s two oranges; they swap food for sex.  This activity is very similar to our own.

                Now, coming down the evolutionary tree, way down several million years, there were as many as 3,000 fresh vegetables that came into season and man ate.  Today we have 20 and we say eat vegetables.  Then about 15,000 years ago we began cooking, processing, salting and preserving our meat so we could stop chasing animals every day.  We could store it.  And, it was about this time that man domesticated the dog. 

                Only the dog’s evolution changed the way the human’s did.  Why?  Because the dog became domesticated.  Throw it a piece of meat and you become the alpha dog.  If you want to go rabbit hunting, get a dog.  Bird hunting, get a dog.  All dogs are descended from the Siberian wolf over a period of 10,000 years.  Want a poodle?  Just keep saving the little one, you will eventually get a poodle.  Keep saving the big one, you get a Great Dane.  Dogs can be manipulated that way.  At one time I had both a beagle and Chesapeake Bay Retriever and the retriever had never seen water.  I took them both to the bay and I threw a stick into the water, Shung!  The retriever went whoomp, right into the water and brought back the stick.  The beagle couldn’t give a damn about Chesapeake Bay, he was up there in the bushes running around trying to find rabbits.  A rabbit could run across the back of my retriever and he would pay no attention.  This is  evolving and choosing properties.  Dogs have become our friends because we share our food with them.  Throw a piece of bread into the fat and toss it to the dogs to keep them quiet.  That’s a hush puppy.

          Getting To Know Your Food Friends & Enemies

                We now have special ways to find out what it is in food that helps us and hurts us.  This is one of the famous experiments done out in Stanford that was done on broccoli.  They found out  what is in broccoli that keeps you from getting cancer is sulforaphane.  They put this on cells and they then paint all of the genes being expressed green.  They put it on cells that do not have sulforaphane on them and paint their cells red.  If both of them are on it, they paint it yellow.  The green turned out to be cells that defend our DNA.  The red were some genes that activate carcinogens by turning them off.

                Let me give you an example.  Every person who has prostate cancer has this change in their disease.  There is a gene named glutathion S-transferase, GSTp.  The way to look at this is as if it were a Patriot Missile.  The reactive oxygen that rains down on your DNA and prostate are Scud Missiles.  On the roof I have all these Patriot Missiles guarding this room - (pretend it’s your prostate you’re sitting in).  What I do when the Scuds start falling (reactive oxygen - burnt meat), I flip the light switch over here and the Patriot Missiles knock out the burnt meat (Scuds).  So, the thing that turns on the Patriot Missile is this little switch, or promoter, here.  When this gets a methyl group put on it, called methylation of DNA, it is like putting your hand over the light switch.  It keeps the Patriot Missile from being fired.  One of the main defense systems in your prostate has been turned off by DNA methylation.  We are just now finding out what methylates are. We are finding out that diet. and other things, can affect methylation of DNA.  Big mystery!

                      The Case Of The Jumping Genes        

                Let me show you the last two or three things.  This is a lot of data here.  It’s important to note that your DNA is changed in cancer.  The structure of the cell is variable.  The functions of the cells and whether they express PSA or not, are changed.  The resistance to cancer changes.  How they age changes.  If you walked up to me and, “Coffey, explain cancer to me”, there it is.  Here’s a picture of an ear of corn, all nice and yellow with smooth rows.  Here’s a picture of an ear called Indian Corn with all different colored seeds on it.  There was a lady named Barbara McClintock that asked, “How can you plant a yellow seed and get an ear of corn with all these different seeds on it?”  It didn’t make sense to her.  (This is why we have to do basic science.)  She went to USDA and they weren’t interested.  This stuff just hangs on the front door during the Fall, right?  It’s useless corn.

                Then she went to National Institute of Health and they told her that nobody comes into the Emergency Room with this.  Why do you want to pursue this silliness?  They weren’t interested either.  She said it didn’t make sense and continued to pursue her experiments until one day, Whoomp!  The chromosomes were jumping around and mixing themselves up.  It was like a deck of cards, shuffling themselves hither and yon.  Holy mackerel!  Jumping genes!  All of  a sudden she became very popular and she was awarded a Nobel Prize.

                Meanwhile, a scientist looked at small child with leukemia and said, “Look!  In this patient the 9 chromosome jumped over to the 22 and the 22 jumped to the 9!”  He called that the 9-22 shuffle and named it after Philadelphia, his city.  We can cure those.  But, we looked at prostate cancer from patients who had died, and their genes and chromosomes were shuffled like crazy.

                Here is my punch line.  The ones we can cure, leukemia   and   lymphomas,  have  balanced   rearrangements.

Part of  9 goes over on a 22, and part of the 22 comes up on a 9.  This is a balanced rearrangement.  But, unbalanced rearrangements is when you mix them up every which way you can imagine; not balanced, not reciprocal.  Here is what it looks like.  Here are some chromosomes and look how the colors are all mixed up.  We went in and looked at the LNCAP cell (a prostate cancer cell).  It has too many chromosomes to begin with, but it has four balanced and no unbalanced.  Then we found out that there is a gene in here that we can make become unbalanced.  We can put a gene that is expressed here, into this one, and it will turn on the unbalanced one. 

                    Accomplishments And Future Targets

                Why are we so darn interested in this balance/unbalance?  We can now cure leukemia.  50 years ago, no one survived that.  When a child came into our hospital then, he went out 90 days later in a coffin.  Then somebody up in St. Jude’s found out that the cells we were trying to kill were growing back in the spinal fluid.  I was against injecting some vicious cytotoxic drug into the spinal fluid.  They went ahead and did it and the children were saved.  I am going to show you a picture of what I am talking about.  This won’t be easy to take, but trust me, it has a good ending.  This is a child at Johns Hopkins Hospital with leukemia.  He is bleeding under the skin because he has no platelets for clotting.  Sores jump out all over him, even his hair.  If this kid hits anything, he is bruised with no immune system left.  If we administer drugs in the normal manner and send him back to school, the disease will come right back.  Put it in his spinal fluid and it works.  This next picture is the same child twenty years later.  Folks, we can do that in 80 to 90% of these kids who have a balanced rearrangement.

                There is another cancer that we can do that to and that is lung cancer.  Sometimes when the metastases are so full and an xray shows not much lining left, we can treat them and they go back to playing golf.   Another example is testicular cancer and Lance Armstrong.  You know the story.  He had three golf ball size lesions in his brain from metastasis from the testes.  He was eaten up with this disease and then he wins the Tour de France.  I’m asking, if this is true, why is it true?  I want to find out so I can see whether we can do that for breast and prostate cancer.

                Here we go, Lance Armstrong.  We have got to find out how we were able to do this on those big, solid tumors.  How much money do you think the US Government is paying to find out if this true?  None, nothing.  And, here I am running around saying, “If this is true, what does it imply?  Let’s get all those people together.  Let’s find out what kind of chromosome changes are here?” 

                Is this making some sense to you?  This is what I came to talk to you about -- science.  The thing that makes me want to go crazy is on the last two slides.  This is what makes me so damn mad I can’t stand it, but I will try to be calm.  My program usually runs 2 ½ hours (a little shorter today because I have a plane to catch in Tampa), and in that time span 161 people will die of cancer.  11 will die of AIDS and 7 will be murdered.  We are all worried about terrorism, but forget that compared to the bioterrorism of cancer cells.  If you extend the cancer death rate to a full day it’s 1,500!  One thousand five hundred people die of cancer every day.  That’s the equivalent of three huge, jumbo jets going down every 24 hours. 

           What We Need Now.  Money - Money - Money

                The amount of money that the US Government is willing to pay for research is so little.  I am ashamed to ask young scientists to go into the field.  What am I talking about?  I’m talking about men and women in laboratories who have been in school 12 years after college.  They have $100,000 in loans, and they make less than half of what people in private practice do.  Their budgets don’t balance and if they do get a great idea, there’s only a 25% chance that it will ever get funded.  This is not right.  Our divorce rate has skyrocketed among our very best scientists who work hard, but can’t take anything back to the family. 

                Every time you pay $10 worth of taxes, one penny goes for cancer research.  Cancer is going to hit one out of every three people in this audience and one out of every four will die of cancer.  The National Cancer Institute gets $4.7 billion and Turkey wants $30 billion just for use of their runways.  What are we talking about here?  This is a serious problem. 

                What can make a difference is you.  I never talked to a cancer patient in my life, never saw them.  I am hunkered down in my lab, working, for gosh sakes.  Then, all of a sudden the patients started getting behind the idea of more funding and contacting their Washington representatives.  There was Man To Man, and others, and people started talking to each other and getting information.  They began squeezing on their Congress, squeezing on the American Cancer Society and squeezing on everybody and then next thing you know, activity begins to pick up.  Right now, of every 10 microscopes that could be turned on, funding allows us to turn on only 2 ½! When I started out in the cancer field, there were only eight scientists in the whole US that I could say were seriously working on cancer research.  There are several hundred now.  There should be several thousand really top flight scientists.

                Thank you very much.  God bless you.  Keep doing whatever you are doing.  Keep getting information and don’t start letting the water drip on your head until it is torture.  Keep looking forward.  I don’t know what is around the corner, but I can tell you it has already turned out ten times better than  I would have ever believed up to now.  The death rates are starting to drop; PSA has come on the scene; there are new surgical techniques; new ways to do radiotherapy, and for the first time, some interesting drugs are beginning to come down the road.  We are going to get this sucker.  We need your help to fund all the bright young people who are willing to work and sacrifice.  Thank you very much.

                        A Few Questions And Answers

I believe you said burnt meat has a chemical in it, right?

                What it looks like is we pay a price for using oxygen.  Reactive oxygen strikes, but you have a system within you which protects against that, the GSTPp.  Those are the Patriot Missiles.  That missile will not only knock out the reactive oxygen, it will also attack the carcinogen made from the burnt meat.  Let me assure you this is not a simple story, but here’s an example.  If you have a sausage patty and a link sausage with the same amount of meat, and cook them, which one has the most carcinogen in it?  The link, and here’s why.  The link only touches the heat in one place whereas the patty is spread - the link will have a black (burnt) line where the heat is in contact and that’s where the carcinogen is.  In fact, the link will have as much as ten times the carcinogen as the patty.  If you cook a patty and keep turning it so it doesn’t burn so bad, the carcinogen goes way down. 

                Some places like to put those black stripes on their cooked meat, to show it’s been grilled, but McDonalds, for one is trying to get away from that by turning their meat more frequently.  It is a little complicated, but basically when we scrape that black stuff off and feed it to a rat, we get prostate cancer and breast cancer.

Will soy protect against prostate cancer and breast cancer?

                There have been no scientific studies run yet.  There are, however, indications that it is beneficial.  Can I protect against inflammation with soy?  Yes.  Does inflammation damage DNA in the prostate?  Yes.  Does the damage lead to cancer?  We believe so.  We are doing a lot of basic, fundamental work trying to figure out how it works and what the mechanisms are.  The people who do the epidemiological studies are the ones who have to figure out the real answer. 

                One of my best young scientists found out (I told you about this) that it’s the bacteria in the gut that makes the soy work.  He was going to make it his life’s work and then died, very young, of a heart attack.  We need some scientists to go after this bacteria in the gut story.  That’s the best answer I have.

What can you tell us about selenium?

                Those Patriot Missiles that I mentioned absolutely require selenium to fire.  It is one of the lipid peroxidases that guards against things.  Personally, what do I do?  Well, I’m not crazy.  I am 70 years old and I take vitamin E and I take selenium and I take a multivitamin.  I mean, I’m not playing around. 

                I think these antioxidants are going to be very beneficial.  Has that been proven yet?  No.  Is the government going to pay hundreds of millions of dollars for the SELECT trial, now going on, which is selenium and vitamin E?  Yes.  I have seen enough of  selenium to think that it is very, very important.  And, so is vitamin E.  You do have to be careful not to overdose on selenium; 200 mcg is the recommended dose.  Will it prevent cancer is one question.  Will it help a cancer that is already there is a different question.  I don’t know the answers for sure, but I suspect it will prevent it.

                This transcript was brought to you as a courtesy by the James F. Mullen Memorial Fund, Inc.  Responsible comments may be sent to 910 Contento Street, Sarasota, Florida  34242.