cc  >> Cassie Immel: Thank you  for watching Wednesday Nite  at the Lab.  Tonight, we'll be having  Dr. Kurt Saupe.  He is a Madison native.  He completed his Bachelor's  and PhD here.  He did get his Master's  at Penn State.  Tonight, he will be discussing  his general interest in using  interventions, including aging,  diet, exercise and injury, to  investigate the cellular and  molecular underpinnings of  pathophysiological processes.  He will tell you more about  this tonight.  If you would, please join me  in welcoming Dr. Saupe.  (applause)  >> Kurt Saupe: Thank you very  much.  It's a pleasure to be here  before this audience. 

 I've never spoken to a Wednesday  Nite group before.  It's very interesting for me to  prepare a talk like this,  because usually, I'm preparing a  talk, thinking, how can I  impress all these other  scientists about what a great  scientist I am.  And I was told not to do that,  not to try to do that, which is  good, because that doesn't  really play to my strengths  as well as I wish it did.  So, my name rhymes with copy.  It's very difficult to  pronounce.  No one ever gets it right the  first time.  It's pronounced Saupe.  And it took me 45 years to  realize that it's very simple.  Just tell people it rhymes with  copy.  And the reason I mention this is  that it will fit into the first  story I'm going to tell about  stem cells. 

 It's kind of an important thing  about how to pronounce my name.  The title of my talk is "Three  Short Stories About Stem Cells."  I'm very anxious to take  your questions as I go along, so  please don't hesitate to raise  your hand or shout out a  question.  My interest in stem cells comes  from several factors.  First, I'm a faculty member in  the Department of Medicine.  I'm in the Cardiovascular  Medicine Division at the UW  here.  I'm a member of the UW Stem Cell  and Regenerative Medicine Center  on campus here.  And maybe the most interesting,  I'm a stem cell transplant  recipient, where in May, 2008,  May 9, a Friday afternoon,  a very memorable day for me, I  received a stem cell transplant  for reasons that I'll tell you  about in a minute.  This was the first and maybe the  most interesting short story  about stem cells that I have to  tell, in my personal experience  as a recipient of stem cells.  So the second story I'll tell,  the first story will be about me  and about my experience as a  recipient.  The second story I'll tell is  about some of the research that  we do in my laboratory,  coincidentally, on stem cells,  where we look at how age, how  getting older, and how a diet,  in particular, a diet that's low  in calories, how those two  factors can affect your stem  cells in the heart and in what  we call your white adipose  tissue. 

 Most of us would just call it,  in your fat.  The third story I'll be telling,  very briefly at the end, is the  idea of using brown adipose  tissue.  So there's two kinds of adipose  tissue.  There's the white stuff, that we  all know about and are very  familiar with.  Then there's brown adipose  tissue, that has some very  unique properties.  And we're interested in studying  the stem cells in the brown  adipose tissue.  I hope to get to that at the  very end of my talk today.  But first, I will be talking  about stem cells not really as a  science fiction treatment.  We hear a lot of things that are  maybe two years away, and in  five years, we'll have a vaccine  for this, we'll have a treatment  for that.  Stem cells is something that,  although it's growing in its  utility clinically, it's also,  if you work backwards, has been  used for decades. 

 Stem cell transplants, for  people like myself, have been  used for many decades.  So stem cell transplant, in a  way, in some applications, is  very mature therapy.  It's what we call the standard  of care, where it's what a  normal sick person would  receive, is a stem cell  transplant.  To give you a little bit of a  background about stem cells,  there's really three major types  of stem cells.  There's embryonic stem cells,  which I imagine you've all heard  about in different contexts.  They're very interesting cells.  We call them totipotent.  You can see here, totipotent  meaning they can become any  tissue in the body.  And because of that, they're  very powerful, potentially as  therapeutic re-agents, because  you can make a nerve cell out of  them; you can make a heart  muscle cell out of them; you can  make a bone cell out of them;  whatever you need to treat a  disease.  The second kind of stem cell  are the adult stem cells. 

 Now, you may not realize this,  because when you hear the words  stem cell, you might just think  about embryonic stem cells.  But all of us, most of the  tissues in our body have stem  cells.  In your liver, you have stem  cells.  In your heart, you have stem  cells.  In your fat, you have stem  cells.  And these are what we call  adult, or resident stem cells,  because they're living in your  body right now.  They're probably helping with  repair of tissues that are  damaged.  And finally, we have a third  type, the induced pluripotent  stem cells, or IPS.  These have only been discovered  or invented, actually, in the  last couple of years, done at  Wisconsin and in Japan at the  same time.  These are cells that, and I'm  getting ahead of myself. 

 The adult stem cells, as I  mentioned, have been used for  many decades, at least 40 years,  for the treatment of people with  diseases, like myself.  The induced pluripotent stem  cells, like I said, have only  been around for about two years.  They're not something that  is indigenous, or naturally  occurring in your body.  It's something that was invented  in the lab, and now is being  tested to see if it has  applications.  I hope you can see this.  Basically, what you do, is you  take a skin biopsy.  You just take a little piece of  skin from a person.  You culture it, divide it out,  and get all the cells out of  that tissue, identify what are  called fibroblasts, and culture  them in a special medium, and  insert three or four genes.  Using what's called a molecular  vector, you transport the genes  into those cells.  And if you do the right three or  four genes, you can convert  these fibroblasts, which are  pretty boring cells, into stem  cells, into, not embryonic stem  cells, but cells with very  similar properties to embryonic  stem cells. 

 These IPS cells, then you can  grow in culture, and depending  on what chemicals you put in  with them, you can push them  towards a given lineage.  You can push them into becoming  heart and muscle cells, brain  cells, liver cells.  So, there's a tremendous amount  of potential in these IPS cells.  But that's not my area of  expertise.  I'm just giving a little  background.  Yes?  (inaudible)  Yeah, I wish it had been me who  had discovered the three genes.  This took huge research teams  probably close to a decade to  do.  And I won't go into the details  of the work, mostly because I  don't understand them.  But it was quite amazing.  When you think of how different  a fibroblast is, just a skin  cell, from a cell that's in the  embryo, how different they are,  that you could convert that skin  cell, just by modifying three or  four different genes, you can  make that cell de-differentiate,  which is walk backwards, work  upstream, and become a very  primitive cell. 

 It's really a remarkable  discovery.  I'm not going to go into the  details, because I don't really  understand them.  (inaudible)  Sure, thank you very much.  The question is about these  potentially cancer causing  genes.  That's an issue.  Any time you manipulate a cell  outside of the body in culture,  you wonder, are you doing  anything really dangerous to  that cell.  If you implant that cell back in  the body, is it going to become  a cancerous cell.  And as I mentioned, you're  inserting genes into this, and  using a viral vector, which are  usually very safe and are made  so they're not going to cause  cancer or induce these cells to  replicate out of control.  So a lot of care is always paid  to that issue of, are the cells  we think are like embryonic stem  cells, are they really safe, are  they going to be under control,  where they won't replicate and  become a cancerous lesion.  All right, well now, I'm going  to get to story number one,  which is the use of stem cells  as a standard of care therapy. 

 My story starts back the day  after Christmas, in 2007.  We had a Christmas party at our  house.  My wife is a cardiologist, and a  very good one.  And also a very good wife,  because she noticed the day  before that I was having a lot  of trouble walking up stairs.  Any time I'd walk up one flight  of stairs, I would be completely  exhausted, and short of breath.  And this was something that I  had sort of been in denial  about.  I thought, well, maybe I've got  a little lung infection or  pneumonia, or something.  She said no, you're going to  Urgent Care tomorrow, and you're  going to get seen by someone who  will look at you.  So, the next day, the day after  Christmas, I went to Urgent  Care.  And a resident walked in and  said, "Hi, Dr. Saupe."  I'm like, how do you know how  to pronounce my name correctly?  You know, something's very  strange here. 

 And he said, "Well, about three  years ago, I was a first-year  medical student here,  and you were teaching  a pulmonary physiology course  to the medical students.  I'm one of those medical  students who was in your class.  I learned pulmonary physiology  from you."  I said, "Oh, no,  we're in trouble now."  (laughter)  But, I apologized to him, and he  said, no, that's okay.  So, he took a history and he  said it looks like you've earned  yourself an X-ray.  He sent me down to the basement  to get an X-ray.  And what came out was this  picture of my chest, my right  lung and left lung.  And as you might know if you've  ever looked at an X-ray, this  isn't at all normal.  When he showed it to me, the  attending had come up by now,  the attending physician.  When he showed it to me, I  thought, great, at least they  don't think I'm a faker.  This is something tangible. 

 That's sad to say, but that's  the mentality I had.  Well, you've got a pleural  effusion.  You've got a lot of liquid on  the outside of your lung.  And all we have to do is bring  you in tomorrow and we'll stick  a needle between your ribs, and  we'll drain that out.  I said, that's great.  It sounds fine.  You know what I have and you're  going to treat me, and you're  going to make me better.  What more could you hope for?  So, two days later, I come back  and have my lung drained twice.  And you can see it looks much  more normal.  A lot of air is in that left  lung, where there had been  fluid. 

 They took out three liters of  fluid, so about three-quarters  of a gallon of fluid, I was  carrying around, compressing my  lung.  So no great surprise, I felt  much better on December 28, than  I did on December 26.  But this was a Friday.  And one disadvantage of having  your wife be a physician is that  you can look up your own medical  records on the computer.  So it was Friday night.  And one thing they had done when  they had sampled all this fluid,  was they had sent it to the  pathology lab to see if there  was anything abnormal about this  fluid.  And about 6:00 on Friday night,  it came up on the computer that  there were cells in this fluid  that they had removed that were  consistent with leukemia, which  was quite a blow.  And it was a bad time to find it  out, because it was a Friday  night.  There was no one we could call,  no one we could talk to.  And it was also right before, it  was the weekend, and New Year's  Day was coming up. 

 So everything was shut down for  about four days.  So it's probably the worst four  days of my life, because all I  had to depend on was the  Internet for information.  And what I could find on the  Internet was not at all  promising.  But I was diagnosed.  They said it was consistent with  what's called Acute  Lymphoblastic Leukemia, or ALL.  What I found on the Internet, I  mentioned, was not very  encouraging.  They talked about a five-year  survival, of about 25%.  Within a year, it's a 50-50  survival.  And five years, probably 25%  survival.  As I mentioned, some very bad  days. 

 But I got in to see an  oncologist a few days later.  They started me on chemotherapy.  I went through the first cycle.  I felt much better.  The chemotherapy didn't seem to  bother me, for some reason.  And I felt better.  And I went into remission.  So it looked like the cancer was  shrinking, that the chemo was  doing what it was supposed to be  doing, which is great.  But in the second month, the  chemo started hitting me harder.  And they also had time then to  do a molecular analysis of my  cancer cells. 

 And they got the bad news that  there was a lot of indications  in those cells that were bad  prognostic indicators, meaning  that not only did I have  acute lymphoblastic leukemia,  but it looked like the variation  I have of it is one that's  particularly bad to have, a  particularly high mortality  rate.  So, maybe the 25% was on the  optimistic side.  So that was the point at which  the doctors started talking to  me about getting a stem cell  transplant.  A stem cell transplant is, of  course, dependent on a donor.  I'm going to be the recipient,  but I need a donor.  I need someone with an immune  system.  I need to find someone with an  immune system that's similar  enough to mine, that I can get  that immune system into my body,  and it won't see my body as a  foreign object, and attack all  of my body.  So, we have to have a good  matching of immune systems here  in order for this to work.  And so, we went to the  international registry of stem  cell donors.  And I was very fortunate,  extremely fortunate, in that I  was able to find seven people  who were considered perfect  matches for me. 

 It was quite a happy day for us  when that news came out.  So, they could go to those seven  people and look at the secondary  characteristics to see of those  seven perfect matches, which is  even better than perfect.  They ended up deciding to use,  they're all anonymous donors,  but a young female from Europe.  That's all I know.  Now, I've figured out that she's  from Germany, but that's really  all I know about her at this  point.  (inaudible)  The question is why couldn't  they use my own stem cells.  They couldn't because this is  going to be a bone marrow  transplant.  And my bone marrow has cancer.  So, it would've been going  around in circles.  My body is polluted. 

 They can't use anything from me.  I can't give blood.  I can't be an organ donor,  because I've had cancer.  So, donating to myself wouldn't  have gotten me anywhere.  We did try my siblings.  My two sisters weren't good  matches at all for me.  And they looked at the genetics  of my sisters, and my immune  system, and all three of them  were so different that my  father said there's some issue  of paternity probably going on  here.  (laughter)  My 82-year-old father and mother  have a good chuckle  over that one from time to time.  (inaudible)  Yeah, they did.  It's a good sign that, like 80%  of the people in my position  will go into remission with one  or two cycles of chemo. 

 So the fact that I went into  remission was a necessary thing  to proceed to a bone marrow  transplant.  But it wasn't really sufficient  that I was cured, in any way,  shape or form.  It was a very good sign.  If I hadn't gone into remission  with chemo, I would've been in  terrible shape.  There wouldn't have been any  hope for me.  (inaudible)  The question is, was when I was  in remission, was the cancer  totally out of my bone?  I'm not sure.  The problem is, if you have  a billion cancer cells in your  body, in your bone marrow, even  if you kill 99.999% of them,  you've still got thousands of  cells left.  And any one of those cells can  become a new tumor, and can  repopulate and kill you.  So, even getting an extremely  high percentage of those cells  killed with chemo is not enough.  They go to extreme lengths,  including damaging the rest of  my body, which I'll tell you  about, in order to get every  last immune system cell that  they can. 

 I don't have numbers on how  many, the two cycles of chemo,  what percentage of the cells  that they had killed, just  whatever they looked at, they  couldn't see any more, so  they're optimistic that they  killed a lot of them.  (inaudible)  Yep, just doing a spinal tap.  There's two separate things.  Once is a spinal tap, where you  get a tube of spinal fluid out  of your spinal cord.  And they did that to look for  cancer in my central nervous  system, which they thankfully  never found.  And they also do what's called a  bone marrow biopsy, where they  stick a needle into your pelvis  and suck out some bone marrow.  That's the real test to find  out.  They can look at those cells and  see if there's any cancer in  them.  They didn't do that when I was  getting the chemo.  They just were looking in my  blood for cancer cells. 

 They weren't doing, I don't  think they did a bone marrow  biopsy at that point to see how  much cancer I had left.  But they probably wouldn't have  been able to see much, if any,  after my two cycles of chemo.  So, now it's time to get primed  for my stem cell transplant.  So, I go through a third cycle  of chemo.  They give me a month off, just  to sort of rebuild my strength.  And I realize how important that  is, because the stem cell  transplant is very difficult,  very hard to tolerate.  You need to be as strong going  into it as you can.  So, just for example, when this  started, I weighed about 185  pounds.  Right before I had my stem cell  transplant, I got back up to  about 185 pounds, but I lost,  essentially, 40 pounds in that  month that I was in the  hospital.  I was down to about 145 pounds. 

 So, what really is a stem cell  transplant in the context of  treating leukemia?  As I mentioned, you of course  need a donor, a donor who's well  matched, who has an immune  system like yours.  Now, one big misconception about  stem cell or bone marrow  transplant is the terminology.  People have called it, for  decades, a bone marrow  transplant.  What I think a more  scientifically, medically  accurate way to describe it is a  stem cell transplant.  Because none of that woman in  Germany's bone marrow made it  into me.  All they take from the donor is  blood.  The way this type of stem cell  transplant works is the donor is  given injections into a muscle  of a drug that will mobilize  stem cells from the bone marrow.  So, you give this drug, and the  bone marrow starts dumping out  stem cells into the blood.  So, all they have to do with the  donor is basically a blood  donation.  They take out a pint of blood,  spin it down and process it, and  give it right back to the  person. 

 All they do is take out what  they believe are the stem cells,  the CD-34 cells.  So, actually, being a bone  marrow donor, or stem cell  donor, is just about like giving  blood.  In the old days, they had to  stick a needle in your pelvis  and do lots of injections  and suck out every last bit of  marrow they could get.  Thankfully, they don't have to  do that anymore.  Yes?  (inaudible)  No, the initial test to get onto  the registry, and thank you for  asking, because I'm a big  advocate on being on the  registry, is just a cotton swab.  It's like a Q-tip on the inside  of your mouth.  And they mail that in, and do an  analysis of the cells on it.  From that, they can look at your  immune system and see where you  are, what markers you have on  your cells.  Then, if someone needs a person  like you, then you're contacted  and you can decide.  So, the initial test to get on  the registry isn't even a blood  draw. 

 It's just a cotton swab in the  mouth.  (inaudible)  Very interesting question.  Who do you contact, and is there  an age limit?  I've got a Web site that I'll  show you in a minute, for the  registry.  There is an age limit, although  as my research is showing, I'm  not sure that the age limit is  valid.  I think, I know for me, they  were talking about my aunts and  uncles, they didn't want to test  them who were in their 70s and  80s, for matching me.  They said, if they're that old,  and my parents are that old,  they don't see them as viable  donors.  But I'm not sure exactly what  the absolute age limit is.  One of the aspects to my  research is looking at how age  affects stem cells, and whether  there really is a decrease in  the ability for your stem cells  to function as you get older or  not.  (inaudible)  The question is, why would you  be rejected for a cord blood  donor if you've had asthma?  I know, well, what I can tell  you may give you some insight  into that.  My donor was a young woman who'd  never had children before. 

 And they said that if you've had  children, your immune system  gets very, very complicated and  unpredictable.  And that you're not likely to be  an acceptable donor if you've  had children.  Now, I'm not sure with chronic  asthma, if there might be some  of that too, where your immune  system might be altered in a way  that they're not really  comfortable with.  (inaudible)  Yeah, I really can't  address that.  So here, they've got about five  million of these cells that  they're going to inject into me,  injecting IV, over the course of  about two hours.  So, for the stem cell  transplant, I'm there in the  hospital.  And I've gotten high-dose chemo.  I've gotten radiation.  And I've got about three  different IV bags hanging.  They come in with another bag  and they say, well, these are  your stem cells. 

 And it's very anticlimactic.  People had warned me that you  know, that lights aren't going  to flash, nothing big is going  to happen.  It's just one more bag they're  going to hang.  And your life is hanging in the  balance in that bag,  essentially.  Because if those stem cells  decide that they don't want to  go into your bone marrow and  make a new immune system for  you, you're not going to make it  out of the hospital alive.  You're going to be there for six  or eight weeks while they try to  do something else.  But if that transplant doesn't  work, you're essentially out of  luck.  They go into the patient.  And it's sort of a black box as  to what happens then.  Maybe some physicians would  argue with me if they understand  what's happening. 

 But to me, it's sort of a black  box.  They inject these cells into me,  IV.  Somehow the cells can home, have  a homing device where they go to  the bone marrow, and they can  start repopulating with the  correct cell types and start  producing white blood cells, red  blood cells, and platelets,  which are the three major cells  that your bone marrow produces.  And there's some sort of a  clinical outcome here, depending  on how well your donor matches,  and how well you accept that  transplant.  (inaudible)  Yeah, I'll show that on my  timeline a little bit later.  I should've mentioned it.  Right in the nine days before  I got these cells into my arm,  I was in the hospital.  And they tried to wipe out  everything that's left in your  immune system.  They try to kill every cell in  your bone marrow.  So, they give you a really  high-dose chemotherapy, as much  as essentially they think you  can stand without having  permanent damage elsewhere in  your body. 

 Then they also give you four  sessions of high-dose radiation  therapy, where you sit and they  give you a beam of high-dose  radiation to your whole body, to  try to kill every cell that they  can, without killing you,  essentially.  (inaudible)  I don't remember.  It's sort of hazy, what were the  different drugs I received right  before.  The question is, what are the   different drugs I received right  before my high-dose radiation  and my stem cell transplant.  I don't remember what drugs they  were.  I've gotten so many chemo drugs,  a defense mechanism, I think I  don't remember them.  Yes?  (inaudible)  No, that's a very good question,  about how immunocompromised am  I, then, if they've killed my  immune system, before my new  immune system revs up and starts  taking control.  In that window of time, in that  two to three weeks, and I was  very vulnerable to infections.  And 20 years ago, as you said,  they'd have you live in a  bubble.  They were very, very concerned  about it, about getting any kind  of infection. 

 That has sort of, they've shown  that that doesn't really matter.  You're sort of in an isolated  ward in the hospital.  But there wasn't a single day  when my kids couldn't come visit  me, my wife couldn't visit me.  You know, they'd have to wash  their hands.  But just very basic precautions  because my immune system is  weak, and it was essentially  disappeared and gone.  But now they have such good  drugs to treat infections.  That's one of the major reasons  survival rates have increased in  people like me.  They have such good drugs that  when I do get infections, they  can treat those much more  effectively.  So, getting an infection while  you're immunocompromised isn't  necessarily a death sentence  anymore, like it used to be.  So, now, they've found that  precautions don't really help. 

 They just make everyone  miserable, as one of my nurses  said.  They make everyone miserable and  they don't really help.  So in a way, if you remember the  old TV show, Let's Make A Deal,  really, getting a stem cell  transplant is very much like  Let's Make A Deal.  Do you want to trade in your old  immune system for a brand new  one?  Well, the old one, like I said,  after two or three cycles of  chemo, I was in remission.  They couldn't find cancer  anywhere in me.  Although, they didn't use their  best tools to look, necessarily,  but they couldn't find any  cancer in me after two or three  cycles of chemo.  Wow.  Maybe I don't need a stem cell  transplant.  Maybe they cured me.  I don't know. 

 That's a tough decision you have  to make at that point.  Or, would you like to trade your  old immune system in?  And that's one of the ironies,  is that in order to be eligible  for a stem cell transplant, they  essentially have to have  "cured," on some level, your  cancer.  So it's sort of like a mortgage  or a loan that a bank gives you.  The only people they give it to  are people who don't need it.  They had to, on some level, cure  my cancer, at least send me way  into remission, in order for me  to be eligible.  If I had had any traces of  cancer that they could see after  my chemo sessions, they never  would've let me get a stem cell  transplant.  Yes?  (inaudible)  So, why would anyone say I don't  want...?  (inaudible)  That's a very good question,  why would anyone go ahead  with the stem cell transplant?  And it's really a cost-benefit  analysis that the physician and  the patient, and the patient's  family, do.  I'll get to that.  I'll get to that cost-benefit  analysis in a moment, because  stem cell transplant is not a  trivial matter.  It has pretty severe risks in  the short term, and also in the  long term. 

 So, deciding that you want a new  immune system isn't just trading  all your old problems in and  having a great immune system.  You're trading one set of  problems for another set of  problems.  You have to judge whether or not  that's wise in your case.  So, here I am getting my stem  cell transplant.  I should mention, for the seven,  eight or nine days before I  actually got the stem cells,  that's when I got the high-dose  chemo, a different form of chemo  than I got back here.  I got the high-dose chemo and  the radiation therapy to destroy  my immune system.  So, I was an inpatient then in  the hospital for about four  weeks.  I was very fortunate.  It only took four weeks until I  could be discharged.  I think a lot of that is because  my wife is a physician, and I  wasn't really discharged from  the hospital, as much as I was  transferred to my home hospital,  because I could have IV drugs  and things. 

 She was quite happy to get me  home.  And she could help me with some  of the medical aspects that they  probably wouldn't have let me  get away with at home if I  didn't have a physician wife.  So side effects.  Why would anyone not want to get  a stem cell transplant?  Well, here are some of the side  effects of the stem cell  transplant, that I've  experienced, I'm experiencing  yesterday, I'm experiencing  today, and I'll undoubtedly  experience tomorrow, and  probably some of them for the  rest of my life.  Graft versus host syndrome.  So, with a heart transplant,  you're worried about your body's  native immune system rejecting  that new organ.  But with a stem cell bone marrow  transplant, it's just the  opposite.  Think about it.  I've got a brand new immune  system.  I'm worried that my immune  system is going to reject  everything else in my body. 

 So, every tissue in my body is  vulnerable to that new immune  system, saying, hey, that's not  a normal tissue, I'm going to  attack it.  I've been relatively fortunate  in that I haven't had it too  bad.  But every day, I do have  symptoms of graft versus host  disease, related to my GI  system.  I hope it's getting better over  the years, but no guarantees.  (inaudible)  Loss of appetite, nausea,  cramping, indigestion.  I should've mentioned that right  before my stem cell transplant,  when you get that high-dose  chemo and high-dose radiation,  those are very imprecise tools.  And all that chemo and radiation  is doing is killing a lot of  cells.  They kill the cells that are  replicating rapidly, which are  tumor cells and cancer cells,  but also the endothelial lining.  So, everything from your mouth  down to your other end, where  the food comes out when it's  processed, everything there, the  endothelial cells, are killed.  So, for two, three or four  weeks, essentially your gut has  been stripped of anything  meaningful that absorbs  nutrients. 

 And that's the unpleasant part,  the worst part of getting the  stem cell transplant, is being  in the hospital and having your  GI system completely torn apart  from the inside out, because  these cells have been killed.  And until they start  replenishing themselves, you're  not normal at all.  Irritability and other  miscellaneous things.  But now I can blame pretty much  any problem I have on my stem  cell transplant.  (light laughter)  And the other part is, I'm on 16  medications currently, even  today, from A to Z, I'm on  medications.  So, I have to take lots and lots  of pills.  As I mentioned, my wife is a  cardiologist.  She does a lot of heart  transplant work.  I've heard her say for years, I  tell these people, when you get  a heart transplant, you're not  getting rid of your problems.  You're trading in one set of  problems for another set of  problems. 

 That's exactly the situation I  was in.  I traded in one set of problems  for another set of problems, but  as I'll mention in a minute, I'm  thrilled with the trade-off that  I made.  Yes?  (inaudible)  Sure, I'm on a blood thinner,  because some of these other  drugs cause me to coagulate.  I had a big blood clot go to my  lungs about six months ago that  almost killed me.  It was completely out of the  blue.  I didn't have any symptoms.  I just had a chest CT and they  saw I had a big blood clot, so  they said, you better be on  blood thinners.  I'm on Warfarin, or coumadin, a  blood thinner.  A lot of steroids to try to  control my graft versus host  disease.  I'm also on some direct  immunosuppressants. 

 They don't want to let my new  immune system rev up too much,  too fast.  So, a lot of these drugs, we're  tapering off of, as we go.  But I'm still taking several  drugs to keep my new immune  system under control, and  relatively, the brakes on it  somewhat.  Anti-virals.  They really don't want me to get  an infection, so anti-virals,  antibiotics, among other things.  (inaudible)  So the question is, is my bone  density being monitored?  Yeah, part of my symptoms are a  tremendous amount of muscle  weakness.  And you know, muscular activity  is the best way to keep your  bones dense and healthy.  And also, I do a lot of falling.  I haven't fallen in about three  months now, but for a while, I  was falling once or twice a  week, just because I've got  numbness in my feet, nerve  damage, and I've also got very  weak muscles.  I can barely climb up a set of  stairs now, without using the  railing. 

 So, actually, what my doctors  said, between the falling and  the not using your muscles much,  we're going to look at your bone  density.  And fortunately, my bone density  came out fine.  That's one thing I don't seem to  have to worry about too much  these days.  So the happy news, this is a  short story.  They all live happily ever  after, at least at one year  after my bone marrow transplant,  they did a biopsy.  They did a bone marrow biopsy.  They looked in my spinal cord.  They looked in my blood.  They did a very, very detailed  analysis.  Everything they could, they used  all the tools they had to try to  find cancer, and they couldn't  find anything. 

 And if you can make it to that  one year point, your survival  goes, like when I got the bone  marrow transplant, my survival  went up to about 50%, and now,  it went up to about 80% after  one year, 85%-90%, actually,  being clean for a year.  >> Good for you.  >> Saupe: Good for my doctors.  Thank you.  (applause)  It's good for me, good for my  family.  But I give the credit to the  medical researchers,  oncologists, the people who have  come up with these treatments  that are really science fiction.  The good thing is, you know, 30  years from now, we're going to  look back on this treatment that  I got, and we're going to say,  how primitive was that?  That was awful.  But I prefer that situation to  saying, you know, this was the  pinnacle.  This is as good as it got.  I'd much rather have the medical  improvements keep going, and  people look back at my treatment  as something barbaric, like  leeches and giving mercury, like  they did 200 years ago. 

 I put this XX here to remind  myself to tell you, that one of  the reasons they used a female  donor for me was the XX  chromosome versus XY chromosome  being a male.  So, when they did this detailed  analysis of me a year after my  transplant, they could look at  the cells in my bone marrow and  in my immune system and see if  they were XX or if there were  any XY cells left.  And isn't that clever?  Aren't they smart people to do  this?  Yeah, I think so.  And they were very, very excited  to see that everything about my  immune system is female.  All the cells are XX.  So, there's no traces of my old  immune system, which my friends  give me a hard time, as you  might imagine.  (laughter)  They've asked me about  personality changes.  And they try to pick up some  subtle things about how I might  be different now that I have a  female immune system.  And there's even more fun, when  all I knew was that it was an  anonymous donor.  I told them I was getting this  transplant, and then lying in  bed for four weeks. 

 My friend would say, well, let's  think about who this woman is,  what kind of woman do you want  to get your stem cells from?  Well, I know she's young.  I know she hasn't had children.  I know she's from Europe.  Well, my first thing was a  Swedish model.  I want a Swedish model.  (laughter)  I was very superficial on this.  Then I had friends from New  York, who said, no, no, what you  want is a former Soviet Block  weightlifter.  (laughter)  You want a Bulgarian  weightlifter.  You want her immune system.  And then I had a friend from  Spain, you now, who advocated  for a Spanish woman. 

 You want her immune system.  It's been a lot of fun.  And I don't mind jokes at my own  expense, because I'm ultimately  incredibly grateful to her.  And I don't know if I'll ever  have contact with her or meet  her.  After a year, I could send an  email to her, through channels,  an email got to her from me.  But in Germany, I think it's  very strict.  I think they have to wait two  years before they can have any  contact with the recipient.  I think they want to make sure  that the story has a happy  ending before they start  exchanging phone numbers, and  things.  So, I look forward to contacting  her and finding out more about  her some day.  And there's a good chance she  might be very, very-- I might be  a little disappointed if she's  not a, you know, super athlete  or something. 

 But she's probably going to be  very disappointed when she finds  out her cells went into a middle  aged college professor in the  middle of the United States.  She's probably imagining Brad  Pitt or Tom Cruise, so we'll see  about that.  Yes?  (inaudible)  Any estimate of cost of all  this?  You know, just very, very  vaguely.  We've had great insurance.  I have Unity Insurance, and from  the get go, they've said it's  all covered.  And whoa, okay, it's all  covered, great.  And it has been, except for some  of the drug co-pays on drugs.  My estimate is in the range of  $300,000, what I've received so  far in medical treatment in the  last year and a half for this.  I could be off by $100,000 each  way.  So, to all you who are paying  your insurance premiums to  Unity, I thank you all so very  much. 

 So, hundreds of thousands of  dollars that this has cost.  (inaudible)  The question is, is this recent  treatment or not, what I  received?  And I would say that what I've  been getting is pretty standard  for the last five or ten years,  with some minor tweaking.  It's very interesting, leukemia,  this ALL form of leukemia, is  very common.  It's one of the most common  childhood forms of cancer that  there is.  And 40 years ago, it was about  90% fatal in the kids, and 90%  fatal in the few adults who got  it.  It's very rare in adults.  But because of better  chemotherapy for the kids, kids  now have about a 90% survival  rate.  It went from 10% 40 or 50 years  ago, to 90% survival rate in the  pediatric population with Acute  Lymphoblastic Leukemia.  And that's without stem cell  transplant.  That's just getting chemo. 

 Now, 90% of those kids alive,  so tremendous advance with  pediatrics.  With the adult population, it  hasn't worked out quite that  way.  For some reason, the adult  disease is much different and  has a much worse prognosis, and  doesn't seem to respond to the  same drugs as it does in kids.  (inaudible)  Is it different from lymphocytic  leukemia?  Um, yes.  It's the difference between a  lymphoblast and a lymphocyte.  A blast is a more primitive cell  than a cyte.  So you asked about a lymphocyte.  And that means the lymphocytes  are what has become cancerous.  Unfortunately, with mine, the  lymphoblast, it's a more  primitive cell, and so you go  back further in the lineage, and  that's what has become  cancerous.  So it's different in a subtle  but probably very important way  in terms of treatment and  prognosis. 

 But I don't know much more about  lymphocytic leukemia than that.  I'm not an oncologist, by the  way.  I have learned it all on the  street, and by necessity, what I  know about cancer.  So, someone asked was the stem  cell transplant worth it.  And as I mentioned, a  cost-benefit analysis.  Costs, there's about a 2%-10%  chance of mortality, that I  would never make it out of the  hospital if those cells would  not have grafted, and I would  expire in the hospital within a  month or two.  As I mentioned, 4-6 weeks is  typical to be inpatient in the  hospital.  It's a miserable time.  And then there's long term side  effects, which you never know  what they're going to be for you  in particular.  So that's an unknown. 

 But they have a pretty good idea  of what some of them are going  to be.  The benefits, potentially a long  increase in life span.  You know, I have two little  kids.  So to me, the costs were  relatively small when I thought  about the fact that I could  essentially double my chances of  survival by going through the  stem cell transplant.  So, for my wife and I deciding,  this, it was a 30-second  decision.  We knew that this was something  that we needed to do.  And this is a benefit I didn't  even know about at the time.  A couple months ago, I got  invited to throw out the first  pitch at a Madison Mallard's  game.  (laughter)  Yeah, because I was a transplant  recipient.  This is Dotty Dot, who is a  state mascot, I guess, for organ  donation. 

 You put an orange dot on your  driver's license and that  signifies that you're willing to  be an organ donor.  So, I got to throw out the first  pitch at a Mallard's game, which  to me, is one of the few  benefits of getting a stem cell  transplant.  But my kids thought it was  great.  They were more impressed about  this than when I found out I got  tenure.  They just couldn't care about  tenure at all.  Throw out a first pitch at a  baseball game, that's cool.  Okay, so the two plugs I put in,  this is for if you want to look  and learn more about yourself or  someone you know getting on the  registry, that's the best Web  site to go to.  And the other Web site I'm going  to put a plug in for is called a  Care Page.  Are any of you familiar with  what a Care Page is?  Have you ever come across this  before?  It's essentially like what I  guess they call a blog now.  It's a way of interacting with  lots of your friends and  exchanging information. 

 My wife set this up for me on my  first day in the hospital.  I was like, I'm a late adopter  of technology.  I don't have a cell phone.  And she said, I'm going to set  this up for you.  It'll be great.  And I'm like, whatever.  But what it is, it's a Web page  that people can access.  You can send it out to your  friends and say, hey, I've got  this Web page now.  If you want to know updates on  my condition, I'll post an  update every week or every  month, depending on how things  are changing.  And you can look in to this Web  page. 

 It's a secure Web page run by  this Care Page organization.  And you can see how I'm doing.  Look at my posting, and you can  then give me a comment and say  something nice to me, say  something sarcastic, say  something mean, whatever you're  feeling.  You can interact with me.  It was really, really  interesting, because we sent  this out.  We posted it and told a few  friends about it, and people  would email in and say, sorry to  hear about this, and hope you're  feeling better, and keep us  informed.  And then, the next week, it was  like concentric circles moving  out.  It was people who were more and  more distant from me  geographically and temporally.  So, within a month, I'm getting  emails from people, I'm getting  hits on my Care Page and  messages from people I hadn't  talked to in ten or 20 years.  It was very, very gratifying,  and a tremendous source of  support for me to have this Care  Page where I could turn to and  know that people were reading  about what I was going through,  and then writing back in to me. 

 It's very efficient.  When you're sick, you don't have  a lot of time to send emails,  write letters and take phone  calls, that can be very taxing.  So, I was very appreciative of  this system that they have.  And I would encourage any of  you, if you're ever in this kind  of situation, or know of someone  who is, to get a Care Page.  And you're welcome to look at  mine.  I post something every couple of  weeks, probably on average, for  the last year and a half, to  update people on what I've done.  You're more than welcome to  register.  You can register.  There's no cost to look and see  what I've said.  So these go for two hours?  (laughter)  I'm usually on the other side,  sitting in the chair saying,  when is this going to end?  So, I'll wrap it up very quickly  here, as I go through my short  stories number two and three. 

 One of our questions is,  scientifically in my lab, is  what happens to stem cells as  you get older?  As you can imagine, stem cells  are important for wound healing.  And if you take someone like he,  whose name must not be named,  (laughter)  and you realize he's in his late  30s, and he maybe doesn't heal  as well, some of that might be  due to stem cell function, and  stem cells getting older, not  being as many, or as able to do  what they need to do, in terms  of tissue repair.  And that's really what we're  looking at in my lab, and how we  might alter that rate of aging  of these stem cells.  There's two things that really  alter the rate of aging,  genetics and environment.  Does anybody recognize this guy?  >> You?  >> Saupe: No, not me.  Bob Dylan, very good.  Bob Dylan when he was 17.  And this is when he was 62.  (laughter)  On the surface, anyway, he looks  all of 62, I'd have to say.  This is him in his younger days,  which is how I like to think of  him more often. 

 All right, a tougher one.  What about this?  It's not Arnold Schwarzenegger.  He's 35 years old here,  not even young.  Not Lou Ferrigno.  Looks a little like him, though.  Here he is at 83.  Jack Lalanne.  Jack Lalanne, probably an  example of someone who ages  about as well as any of us could  ever imagine or hope for.  So, on a little more serious  note, what happens as we age is  the prevalence of heart disease  goes way, way up.  It goes up exponentially. 

 This is a percentage of people  who have cardiovascular disease.  Something intrinsically is  changing about the heart muscle  and the blood vessels that  predisposes, or makes us more  likely to get heart disease as  we get older.  And I like to think about  schematics, sort of like this.  If this is cardiovascular  functioning here, and this is  pretty stable, good  cardiovascular functioning in  your 20s, 30s, 40s.  It starts to drop off a little  bit and eventually, many people  hit a threshold where it falls  off so much that they develop  symptomatic heart disease.  And there are things we can do  to accelerate that, not  accelerate the aging, but  accelerate the deterioration of  cardiac function, like diabetes,  smoking, hypertension.  But there may be some things we  can do to retard that decline in  cardiovascular function.  Actually, retard the aging.  And it has to do with nutrition.  I'll go through this, because I  want to talk just a little bit  about this nutritional  intervention called caloric  restriction. 

 You may have heard something  about this.  This has been in the popular  press quite a bit lately.  And it's not, what I'm talking  about in scientific terms, it  isn't treating obesity.  It's not the health benefits you  get from going from obese to a  normal weight.  And it's not going on a diet to  lose ten pounds.  What this is, this form of  caloric restriction, we did in  laboratory animals, is very  severe.  We give them a third to half the  calories they would like.  You give them micro nutrients,  vitamins and minerals, so that  they're not malnourished.  And remarkably, it makes them  live longer.  It makes them healthier. 

 It delays the aging.  It's the one physiological  intervention that we have that  actually slows the aging  process.  So these are survival curves  from four different groups of  rats.  You can see the ones that ate  whatever they wanted, 100% of  them are alive, and they die  off.  Half of them are dead about 29  months.  The oldest ones live maybe 36  months, or three years.  The more you restrict their  calories, the longer they live.  Fewer die.  The mean survival goes out more  than a year from what it was.  The maximum survival also goes  out, from 36 months out to 55  months. 

 So there's a response to it.  The more severe the caloric  restriction, the longer they  live.  And it's not just living in a  decrepit state, it's actually  living in a youthful state.  Every measure of youthfulness we  have in these animals is  improved by caloric restriction.  No hearing loss.  No graying hair.  Other physiological things are  just attenuated with this diet.  Here are some of the animals  it's been tried on.  And you can see a lot of them,  30% to 40%  increase in maximal life span.  (inaudible)  Yeah, activity levels. 

 That's one very interesting sort  of confounding principle, is  that with mice and rats, if you  don't give them enough food,  they tend to be more active.  They tend to have food searching  behavior.  So you've got an increased  exercise component and the diet  component.  There might be some synergism,  but the best studies show it's  really the low energy intake,  it's the semi-starvation state  that they're in chronically, not  the increased activity that's  causing the anti-aging.  Yes?  (inaudible)  I've never heard of that before,  of injecting air into rat food  to make it higher volume,  to improve their digestion and  nutrient.  (inaudible)  No, it's new to me.  (inaudible)  Very interesting.  Well, if it's on Science Friday,  then I believe it, it must be  good.  But no, it's interesting.  And the other aspect of this is,  if you give them feeding every  other day, so instead of caloric  restricting them by 50%, if you  give them no food one day, let  them eat whatever they want the  next day, you still get some of  these benefits. 

 And even though their body  weight will stay pretty much  normal, so there isn't a loss of  body weight, because on the days  when they can eat, they'll eat a  ton, and they'll get back up to  their normal body weight.  So it isn't the weight loss  per se, you can even get benefit  from intermittent fasting.  So, many of us scientists are  interested in figuring out  molecular mechanisms for this,  what's causing this extension of  life span and this slowing of  aging.  Because none of us want to cut  our food intake, well, most of  us don't, by a third or a half.  What would be the point of  living longer if we were hungry  and crabby all the time?  That's a question for the  philosophers maybe.  Yes?  (inaudible)  Well, that's a point I sometimes  like to make.  This isn't my work.  This is work from Rick Weinrich  here at the UW, one of my  colleagues.  If you extrapolate this out, you  take them down to zero food  intake, they'll live forever.  (laughter)  That's where we started, you  know, defying common sense a  little bit. 

 And I'll tell you, one reason  why you probably can't restrict  the calories any more than this,  is animal rights, animal care  and use protocols.  There's a balance between making  animals suffer, even if they're  living longer and being  healthier, where you can't get  anything by an animal care  committee.  You can't say you're going to  restrict their food by you know,  more than you need to, even  though it'd be interesting to  know.  I don't think scientifically,  we're going to learn much from  where this turns around, and the  animals start actually living  shorter lives with less food.  But yeah, it's quite amazing.  Sort of like dumping nitrogen  fertilizer on a corn field.  The more you dump on, the more  corn you get, to a point.  Diminishing returns.  Animals.  So, this is Ponce de Leon  looking for the fountain of  youth. 

 We need a pipetter.  That's in the lab.  We're trying to find the  molecular reasons for aging and  for youthfulness, and so we do  our biochemical experiments.  Not quite as daring or as famous  as Ponce de Leon.  But then, well, we have desk  jobs.  We don't have to go out there  looking and dressing like that  every day, either.  (laughter)  I think I'm going to wrap up  here, and not show you the data  on what happens to our stem  cells in the heart.  This is where I'm trying to  impress you on what a good  scientist I am, and show you all  the detailed stuff.  I'll just get to my conclusions  and summary.  An aging mouse heart, contrary  to what we had hypothesized,  that the number of cardiac stem  cells actually increases with  aging. 

 Whether they're functional stem  cells, whether they maintain  their functionality, we don't  know.  (inaudible)  The number of adult stem cells.  What increases, is the question.  The number of adult stem cells  in your heart, or in a mouse's  heart.  As they get older, the cells  that are in charge of repair,  increases.  (inaudible)  It appears to be both.  Well, it's the absolute number.  The percentage of them that are  the real good kind of cells  stays about the same.  That's one thing we looked at.  We thought maybe the number of  stem cells goes up, but they're  of a low quality variety. 

 That hasn't been the case.  (inaudible)  These are mice.  I should've made that clear.  These are mice that we've  studied in my lab in the last  couple of years.  (inaudible)  Are these the caloric restricted  ones?  Yes and no.  We studied, we compared the  caloric restricted ones to the  normal ones.  And our hypothesis was that  whatever bad happens with age to  those cells in the heart,  caloric restriction is then  going to rejuvenate them and fix  them.  But in fact, age didn't do  anything.  We haven't been able to find age  doing anything bad to the stem  cells in the heart.  So there's really nothing for  caloric restriction to fix about  it. 

 So our results have been  largely negative with caloric  restriction, in terms of how  they affect the stem cells in  the heart.  And we've done similar studies  looking at fat in these same  mice.  Our hypothesis being that the  stem cells in the fat might  improve in number and/or  therapeutic usage, or efficacy.  But we found, very similar to  what we saw with the heart, that  in the fat, you actually do get  fewer stem cells as you age, but  those stem cells seem to be very  robust and able to do everything  they need to do.  (inaudible)  All right, story three,  I'll give you in one minute.  Brown fat is another kind of fat  that's mostly located in your  shoulder blades.  It's very energy-utilizing.  It's a very unique tissue, in  that it burns off calories and  converts them into heat.  So, instead of burning off  calories by exercising, if you  just rev up your brown adipose  tissue, you can generate heat  and burn off a lot of calories.  And it used to be thought that  this is only important in  rodents that hibernate, and in  infants, neonatal, because  newborn babies can't shiver. 

 So they need to protect their  body temperature by activating  their brown adipose tissue.  But a dogma has always been as  you get older, here's my little  guy out playing in the snow, as  you get to his age, you don't  really have much brown adipose  tissue, and it doesn't do much.  But three papers came out in the  New England Journal of Medicine  showing that adult humans do  have a lot of brown adipose  tissue.  Yes?  (inaudible)  Yep, it's the mitochondria that  make it brown.  And the mitochondria have a  special protein in it called an  uncoupling protein that allows  you to generate heat from your  calories you burn instead of  storing them, basically, as fat.  But this idea that you can burn  off more calories with brown  adipose tissue, a paper came out  last year showing that if you  use cells from brown adipose  tissue, they can become  cardiomyocytes.  And not only can they become  cardiomyocytes, but you can use  them, brown adipose cells, to  convert other cell types into  cardiomyocytes.  So, that's work we're doing in  our lab right now that's related  to stem cells, looking to see if  we can convert blood borne stem  cells, or fat, the white adipose  tissue stem cells, convert those  into heart muscle cells, using  brown adipocytes.  So, the brown adipose-derived  stem cells, if you incubate them  with this kind of cell, someone  published that yes, they become  heart muscle cells.  So we're looking now, we found  that the same cells, these CD133  positive cells, exist in the  white adipose tissue. 

 And white adipose tissue,  you have a lot more of it.  It's a lot more accessible.  It's a much better reagent,  a much more viable candidate  if you're going to use it  therapeutically.  So, we're very excited to see  these certain magical claims of  cells CD133 in white adipose  tissue.  We want to find out if we can  convert other cell types into  cardiomyocytes with these white  adipose tissue derived  stem cells.  All right.  Well, the famous Statue of  Liberty in Lake Mendota  a few decades ago.  I always like to think of as a  reason we don't always see the  connections in science or in  life, but we know that  underneath there, there's got to  be a connection somewhere.  Thank the people who work in my  lab, and also my wife, Nancy  Sweitzer, who's a cardiologist,  who's gotten me through all of  this, and my oncologist,  Dr. Natalie Callander, who has  tremendous empathy, wisdom and  knowledge, and an incredibly  smart woman.  I appreciate their efforts at  keeping me alive for the last  year and a half. 

 Thank you very much for your  time.  (applause)