Ritsuko Komaki

Christopher Rose, MD, FASTRO and Arjun Sahgal, MD

The following interview of Ritsuko Komaki, MD, FASTRO was conducted on January 23, 2018, by Christopher Rose, MD, FASTRO and Arjun Sahgal, MD.

Christopher Rose:  So, why don’t you tell us something about your background, where were you born and where did you grow up?

Ritsuko Komaki:  I was born in Amagasaki, just outside of Osaka. My father was working in Osaka, although, my parents, they came from Hiroshima.  And Amagasaki is about 200 miles away from Hiroshima.  I grew up in Hiroshima City after the atomic bomb was dropped in Hiroshima.  My parents decided to go back to Hiroshima where they came from to live with any relatives who survived through the atomic bomb (A-B).  So I grew up in Hiroshima.

Christopher Rose:  So, in the article in the Red Journal that you wrote on your memories it was very, very pointed and important, I think, to everybody to know, you experienced this personally yourself and maybe for this, you could let us know what your memories were actually of, of that experience.

Ritsuko Komaki:  Yes.  When we went back to Hiroshima to live and my father decided to work at Hiroshima Bank and I met with all those people who were exposed to atomic bomb.  Some of them had the keloids.  Well, my grandmother, she was my maternal mother, was in the city.  Her house was collapsed and she had a total body radiation.  She had bone marrow suppression causing nose bleeding, gastrointestinal toxicities causing severe diarrhea and other acute total body side effects.  But she survived.  And she was taken away from the city about six months.  And then, she came back and she lived in Hiroshima.  But amazingly, she never had any malignancy or anything other than osteoporosis and Alzheimer’s.  But when I did stay in Hiroshima with her and I went to the school where I met with a friend of mine, Sadako, who was there, just after she was born.  Her house was in the suburb of Hiroshima and she developed leukemia, acute granulocytic leukemia when she was ten years old.  And then, she died one year after due to leukemia although she tried to fold origami birds.

You know, in Japan we say, if we could fold 1,000 origami cranes, you could recover from illness and live happily afterwards.  But she had folded maybe 440 after she took medication, which was wrapped by wax paper.  Those origami cranes have been displayed in the Peace Memorial Museum now.  But she could not make one thousand origami cranes and she died.  And she had registered to go to junior high school, but she could not attend to the junior high school due to her death.

And when I went to the junior high school, I became the president of the junior high school.  So with Sadako’s older brother, two years older than her and also her classmates, we decided to create a memorial statue for Sadako and other children who died due to A-B because I just wanted to make sure nobody will forget about this A-B in Hiroshima, caused death of Sadako and many other children and adults including my relatives.

My father went in to Hiroshima the day after of A-B to look for any relatives who was alive or dead.  And he was exposed to high doses of radiation.  They called it black rain.  And my father died of bladder cancer although he smoked.  I was worried about his lung cancer, but he died of bladder cancer.  I assume that the cause of his bladder cancer was a combination with both.  But amazingly, my grandmother who had the acute radiation effect from total body radiation, she survived without any malignancy.  She developed terrible osteoporosis.  She eventually died of Alzheimer’s at the age of 72.

So I saw all those people with no houses.  We just lived in almost a shack, you know, small houses.  My grandmother had a huge, big samurai house which was totally destroyed.  But she was given a very small house just outside of Hiroshima where we moved in from Osaka.  Well, she didn’t like us to live in that small house.  But we didn’t have any other place.  So we lived in Hiroshima with her.

And my aunt, my mother’s younger sister, at that time she was 19 years old when the atomic bomb was dropped because she was living with my grandmother.  She was working in Hiroshima University as a secretary.  And she survived but the memory of coming from Hiroshima University going back to her house, she saw all those kids burned and children and the people asking for water.  And that nightmare, she never, ever forgot.  And she always had the fears to get married and to get pregnant because she never had any, you know, kind of information or nobody said what will happen to those people who are exposed to atomic bomb, to get pregnant.  And that she overheard some people telling about the baby who had microcephaly and so on.  So she never got married until she was like 45 years old and she never had any children.  But she died of overdose of medication.  She had to take tranquilizer to sleep.

All these are kind of not only physical problem, but also the mental problem which was never really explained to that generation.  Even when I was at school, the teachers never said anything.  We were kind of told we started a second war, and so this is the way we had to end that second war.  But it was kind of blinded.  When Sadako died, I really decided to become maybe a researcher for leukemia or maybe I should be some physician to treat the leukemia or malignancy.  And that’s why I became an oncologist.  But at the beginning I started to do hematology-oncology.

When I went to medical school, well, before that, we decided to create her memorial statue at the Peace Memorial Park.  I decided to do a fundraising for this and within two years we collected the money.  Also we created with some help Sadako’s documentary movie 1,000 Cranes and we collected the money.  That atomic bomb statue, they called it atomic bomb children’s statue.  That’s at Peace Memorial Park.  It’s standing on the top.  It’s about 10 feet tall, the bomb shell statue, and on the top Sadako is holding origami bird.  This is the kind of memorial statue for the peace, for the children.

When we did that, I never thought about this statue become such a famous statue.  But even now, all those children around 11 or 12 years old, they fold origami birds.  One string has 1,000 origami cranes and this comes from all over the world, you know, from San Francisco, Boston and Houston.  I was so touched when I went back to see these origami birds coming from all over the world.  When we created this statue, I had just to make sure this atomic bomb was not dropped like in Hiroshima or Nagasaki or any other place.  But now it is becoming a kind of fear because of this North Korea thing.

But anyhow, that’s the way I decided to become oncologist.  I went to Hiroshima University Medical School.  Two years pre-medical school, I did Bachelor of Science, then went to medical school.  My interest was to check the people who are exposed to atomic bomb, and so I volunteered during summertime at the ABCC.  They call it Atomic Bomb Casualty Commission.  And then now they call it Radiation Effects Research Foundation, RERF.  That was 15 years ago.  American and the Japanese government, they decided to share the support of this foundation 50:50.

Originally in 1946, when the ABCC started, that was 100 percent supported by United States in that they have incredible resources from the people exposed to atomic bomb and chromosomal abnormality.  The people who are interested in effects of the human beings - that’s all documented.  The people from Yale and different places, they came and they checked the thyroid dysfunction or the malignancy, the hematologic malignancy, thyroid cancer, breast cancer, stomach cancer, later on for Multiple Myeloma and colon cancer.  They were all studied.

I checked all those patients, the people who were exposed to atomic bomb - their blood pressure and blood count and so on - during summertime.  When I graduated from Hiroshima University, unfortunately all our university hospitals were closed because we went on strike.  All the medical students and the interns and the residents, we had to walk out from the university hospitals because we were demanding to the government to pay internship, which was free.  We had to work without any payments.  And also better medical education system we requested.  We had to walk out - entire nationwide.

I worked at the RERF one year, and then I met Dr. Walter Russell who was a friend of Dr. James E. Youker at Milwaukee, Wisconsin.  That’s the way I came to Wisconsin.  Then I started to do a fellowship at the VA hospital in Milwaukee.  And then I did my general internship at the St. Mary’s Hospital in Milwaukee.  Then I decided to go to radiation oncology because around that time all those patients in hematology-oncology of VA Hospital and St. Mary’s Hospital, some testicular cancer patients were cured cancer patients not really curable by chemotherapy other than testicular cancer, Hodgkin’s Lymphoma or early stage Lymphoma or Acute Lymphocytic Leukemia and I was very disappointed.  But I saw some patients having laryngeal cancer who were treated by radiation and they were cured, and I thought this is very interesting.  And then coming from Hiroshima, I became more interested in radiation oncology.

While I was doing my general internship at the St. Mary’s, I met Dr. Anthony Gueninger who was board certified in internal medicine and also radiation oncology.  He was respected by surgeons and the medical oncologists.  He had incredible knowledge about cancer.  So I became more interested in radiation oncology.  Then when, Jim Cox, came to medical oncology in Wisconsin and became the first chair, separated from diagnostic radiology.  I was the first resident under him.  So I became a radiation oncologist there.

Arjun Sahgal:  Basically, you’ve had an amazing experience and also an experience that’s quite tragic that ultimately led you through your education to become a radiation oncologist.

Ritsuko Komaki:  Right.

Arjun Sahgal:  So I wanted to just pick it up.  You went through your medical school and your education along the way.  At which point in your career, when you started your employment, where did you really pick up that passion?  Predominantly for lung cancer research, right?

Ritsuko Komaki:  That’s correct.  When I did the residency program under Jim Cox, Frank Wilson, Don Eisert, Roger Byhart and Larry Kun, I was very interested in GYN.
Then I went to MD Anderson to do a fellowship.  I wanted to learn everything GYN under Dr. Fletcher.  It was a very interesting time at the MD Anderson Cancer Center.  I met Eleanor Montague, and Norah Tapley and David Hussey - incredible people - Lillian Fuller and all those people who were there.  I have learned a lot from Dr. Fletcher who let me examine patients at the GYN joint clinic when I asked him why you were giving one large dose of radiotherapy to stage IIIB cervical cancer patients. The patient I examined with him had bilateral para-metrial nodal metastasis (frozen pelvis). Dr. Fletcher asked me if I could cure this patient. I said that it would be rare to cure this patient but some of them survive to manifest late effects due to one large dose of radiation treatment in the pelvis. He decided to start twice daily treatment for patients with bilateral para-metrial nodal involvement. Nobody could argue with him.  He decided everything - this patient should be treated by which machine and the dose and all of those treatment fields.  I think that Rodney Withers was the only one person who could ask questions to Dr. Fletcher such as “Why are you treating twice a day rather than once daily for inflammatory breast cancer.  But, otherwise, it was a very interesting time.

And Lester Peters, he was a fellow under I think David Hussey.  They were treating GYN, Head/Neck, Prostate and selected Lung Cancer patients such as superior sulcus tumors with neutrons.  And I went to the neutron facility at the A&M, College Station.  One person who was remarkable at MDACC was Eleanor Montague.  She was treating the breast cancer by radiation therapy.  When she was 60 years old, she said I’m going to retire.  Then the next thing she said, oh, it was wonderful to retire, I should have retired a little bit earlier.  She was just a wonderful person.

I had met other people at the MD Anderson.  Some people left MD Anderson but it was a great, great experience for me to meet with Gilbert Fletcher and all those – Norah Tapley and Lester Peters.  He taught us alpha-beta ratio and radiation effects to the tumor and normal tissue.  It was a great time at MD Anderson and I have learned so much.

Then I went back to medical oncology in Wisconsin, and there I became an assistant professor.  I was mainly treating patients with GYN malignancies.  But Jim Cox was always out of town, I had to cover lung cancer, because he gave the head and neck patients and the pediatric including Lymphoma patients to Larry Kun.  So he ended up treating lung cancer which none of Radiation Oncologists wanted to treat them. However he was always out of town.  He was very busy at the RTOG and I had to cover for him, and I became very interested in lung cancer as well as GYN.

We got married in 1980, and then we went to Columbia/Presbyterian Medical Center where I did lung cancer, GYN, as well as breast cancer.  It was a very interesting experience for me because I met very famous breast surgeons who were, Dr. Haagensen’s students.  They asked me, “When did you change your specialty to radiation oncology?  You used to be a radiation therapist.  And I said, well, a therapist took a radiation therapist’s name so we became a radiation oncologist.

They just wanted to do radical mastectomy or modified mastectomy rather than conservative for the early stage breast cancer.  Even the stage 1 patient, they said, “What are you talking about conservative surgery? Then the radiation treatment after limited surgery, it will cause more breast cancer in the opposite side or in the same side breast.”  I said I cannot believe that you are totally behind here on breast cancer treatment. I quoted many articles published from Europe, Boston and California. I just tried to do all the clinical research with them, but there was not much information at the tumor registry and I said this is not the place I could do all those prospective study or collaborative study here.

And then Jim Cox was appointed to be the physician-in-chief and the vice president of patient care at the MD Anderson.  And then Lester Peters he asked me to do lung cancer at the MD Anderson Cancer Center because my predecessor, Tom Barkley, he died of eosinophilic granuloma arising from the lung.  He was waiting for the lung transplant, but he eventually died.

So I started to be a section chief of the thoracic radiation oncology in 1988.  The first thing I had to stop was that split course of thoracic radiation treatment (TRT). All lung cancer patients were treated 3Gy x10 fractions followed by one moth break then treated by thee second course of TRT again 3Gy per fraction x10 fractions (5 days per week) if the patients were able to comeback for the second course of TRT. I quoted RTOG trials showing that split course was inferior to continuous TRT for stage III NSCLC in regard to OS and LC. I tried to participate prospective RTOG trials for the limited stage small cell lung cancer and stage III NSCLC.

I worked very closely with Clifton Mountain who was the chairman at that time of thoracic surgery.  He gave me all the specimens of the stage I, stage II non-small cell lung cancer and I started to analyze DNA index, Apoptosis, S phase, EGFR expression and other factors to predict brain and other metastasis.  He was so generous to give me all the specimens for my research. Dr. El-Nagar and Dr. Jae Ro also helped me to review the pathology in details. Then I had post docs from Japan and we analyzed all the specimens to find out the clinical presence of failure, if that is co-related to EGFR expression or what.  Like especially brain metastasis, if that was related to EGFR expression.  So that was a great time for me to be at the MD Anderson. 

When I went to MD Anderson, they were hand blocks and 2D radiation treatment plans.  And I said we really need to start to do more 3D conformal and intensity modified radiation treatment (IMRT).  There were some difficulties, but eventually we started to do more IMRT.  After Lester Peters went back home to Australia.  Jim Cox became the chairman and division head of the radiation oncology.

I asked him to create a proton center to reduce scattering of the low-dose radiation scattering to the children and young adult patients which might cause secondary malignancies later since I witnessed in Hiroshima while I was growing up. There were significantly higher rates of Leukemia, Thyroid cancer, Breast cancer, Stomach, Bladder and Lung cancer as well as multiple myeloma among people who received low dose of radiation. The first thing Jim Cox said that we don’t have enough money.  Then he developed 50 percent from a private foundation and the other 50 % supported by the University of Texas MDACC. We started to treat patients at the Proton Center 2006 and now we have treated more than 7,000 patients.  Proton Center was my dream which came true - that low-dose radiation to the total body for growing up children, which is supposed to reduce second malignancies.  I think that really came from my experience when I grew up in Hiroshima.  I had seen enough of those people who had leukemia and the cancer.  My mother also died of cancer of the stomach.  I’ve lost a couple of cousins from leukemia.  They were young.

But this Proton Center started 2006, and then now we have more than ten years’ experience.  I thought that was really, really kind of my dream - like more confined treatment.  That’s what we are supposed to do being radiation oncologists, target the cancer cells but not scattering or not damage surrounding normal tissue.  I think that’s the most important thing.

The other thing I always thought about working with Jim and also my mentor at the RTOG, like Karen Fu, they really put that biology together.  Not only physics.  And so that’s a very important aspect for the radiation oncologist - to know the biology, cancer biology, to put it with physics together.  We called it improving therapeutic ratio.  That means killing cancer cells, but not killing surrounding normal tissue.  I think that’s what we have to learn.

And we have to learn from the patient by following up.  I think more and more we are kind of pressed the time, and also the insurance does not allow us to use certain high technology or some experimental molecular targeted treatment.  Then we don’t spend much time.  We just have to treat the patient almost like a machine which is very, very sad to me.  You mentioned things.  We can pull out everything from the computer and that we don’t spend much time, and that’s what we have learn from the patient.  We have to listen to the patients, and I feel that there is not much time to do that.

Christopher Rose:  Ritsuko, I was thinking as I looked at your CV and also what you just reported to us that your career in lung cancer starting back with that very first paper with Dan Eisert and Jim going all the way up to now has seen all of the changes in lung cancer as a paradigm for everything else in radiation therapy or radiation oncology.  And particularly at MD Anderson, you are presiding right now at this very moment at learning how to use very large fractions in a conformal way SBRT, and also using protons, and also using radiation therapy for oligometastatic cancer.  All of that is occurring on your watch in the lung cancer group.

I’m wondering.  I mean I read the paper that you just presented on the results of passive scattered protons.  It’s disappointing that it doesn’t seem to be better.  Is it your thinking that now we understand end-of-range biology better as well as with pencil beam that we will finally see the promise of protons or charged particles with lung cancer?  The largest killer, if you will.

Ritsuko Komaki:  Yes.  You know, you pointed out a very, very good point.  Because when I did the residency program with Dan Eisert and Jim Cox and Roger Byhardt, it was just awful.  In lung cancer, the outcome was so bad and we really said, okay, we have to do something.  Like even periodic stage, the five-year survival was really, really bad - 15 percent.  So many people are still smoking.  Even my attendings, they were smoking.  I still remember that.  But I said, okay, let’s try.

So Jim Cox and Dan Eisert, they gave me projects.  Let’s find out where do they fail.  Like adenocarcinoma, they do fail in the brain.  And the small cell lung cancer, they fail in the brain.  So once we know where they fail, maybe we can give some kind of preventive.  And that’s the way we started to do some of this prophylactic cranial irradiation for the small cell lung cancer then.

But what we found out, around that time when I was resident, there was no good equipment.  We had to ask Dr. Fletcher to get high energy equipment at the Medical College of Wisconsin so we can do a better treatment.  But when I came to MD Anderson in 1988, they were still using almost square or rectangular fields and I said we should not use these techniques.  I remember diagnostic a diagnostic radiologist who wrote a book of Radiation Pneumonitis and Fibrosis. He mentioned that how terrible this radiation causes fibrosis in the lungs, which was square or rectangular fields due to 2 dimentional technique.  I said, well, once we do IMRT, you don’t see these square or rectangular fields anymore.  So I decided to show how we can do.  Well, we started the 3D conformal treatment. About two months after radiotherapy, there was no square or rectangular fibrotic changes in the lung and he could not figure out where I gave the treatment. Then he decided to retire although my husband James D Cox invited him to attend RTOG meeting to put his input about Radiation Pneumonitis and Fibrosis.

We do not cause that square or rectangular fibrotic changes nor big elective nodal fields, and then we started to do more and more SBRT and then proton treatment. The margins of the treatment fields beyond the tumor started to be tighter by application of CT and PET imaging studies as well as endoscopic bronchial ultrasound (EBUS) application to define pathological nodal metastasis to avoid elective nodal radiation.  I really think we have to work very hard.  Technically, you know, we improved much more.  It is amazing when we look back, when we started in like 2006, and then now how much we became more sophisticated to arrange the beam and also tumor motion and the margin.  So we have done a lot.  It’s just not coming overnight.  Eventually we can use like IMPT and just scanning neutron contamination, and then I think eventually we will get better without causing much of the toxicity and have more targeted treatment.  Not only just physically targeted, but also we have to learn if anybody who has EGFR mutation that they can start to do a tyrosine-kinase inhibitor and then shrink it down.  And when they develop mega-metastasis or recurrence, we can do a proton treatment.

So it depends on what the biological status or genetic mutation.  We don’t need to just jump in surgery, or radiation treatment, or proton treatment.  We have to be oncologists.  That means we have to know biology, as well as physical aspect.  We are still learning a lot about the proton treatment for lung cancer.  If it doesn’t move much, like in superior surface, it’s much easier so give it.  But in the middle of the lungs and if we have to encompass cardiac area, we will have to make sure we are not radiating a lot of heart.  That’s what we learn from our study, but we had to do a lot of learning by ourselves.  It’s not the radiation pneumonitis, but the cardiac toxicity.  It does cause the problem.  So the death related to like lung cancer or maybe thymic tumor, we have to make sure we are not radiating a lot of heart.  The volume of the heart is very important.

Arjun Sahgal:  What are your thoughts?  You’ve been in the proton business for a long time.  Obviously you’ve been doing the trials.  Chris, I am not sure if we can spend a few minutes but it would be nice to think, you know, what are your thoughts about carbon ions.  I mean that’s really been proposed as something potentially better.  Do you have any thoughts one way or the other? 

Ritsuko Komaki:  Okay.  Every time I go back to Japan, I still speak Japanese and I have so many friends in Japan, they ask me why not carbon.  They really tried to push me to get the carbon ion at MD Anderson.  The problem I face is carbon ions, just like neutrons, the high LET, the good part it does not matter hypoxic area that will overcome.  But we are not sure about the late effect to the normal tissue.  It’s just not clear from the carbon ion.  They have tendencies to separate late effect of the carbon ion.

So by looking back when I was fellow at MD Anderson, I saw the patients who were treated by neutron under NCI grant.  The tumor itself, like a superior surface tumor or parotid gland tumor, that disappears.  But later on, especially like in GYN and prostate cancer, they developed incredible subcutaneous fibrosis like wooden hard skin, that was related to the neutron treatment which made them to use mixed-beam.  But still because of the late effect, they have to stop the neutron beam treatment.

I still have memory of that late effects from neutron beam.  That’s why this carbon ion which has high LET like neutron needs to be very carefully administered for selected patients with soft tissue sarcoma or osteosarcoma or very small peripheral lung cancer. But we really have to watch out for anybody who are using that carbon ion like on breast cancer or even lung cancer with mediastinal nodal metastasis (stage III) which requires concurrent chemoradiotherapy unless they can be treated by molecular targeted treatment. I have big concerns about the late effect from any cancer treatment.  So depending on the type of malignancies and age of the patients.

Christopher Rose:  I remember seeing the children at Hammersmith, and it was the same thing there.  I guess the trick is going to be that they’re going to have to do a lot of work to understand the RBE of the carbon.

Ritsuko Komaki:  That’s correct.

Christopher Rose:  And if it’s going to change along the path of the Bragg peak, it’s going to be really very, very difficult to model.  You know we could talk for two hours more, and maybe we should.  But I would ask you what advice you would give to your young trainees in academic radiation oncology who want to achieve a global impact?

Ritsuko Komaki:  Okay.  We have excellent residents, but they have to learn to listen to patients.  They have to learn from their patient.  They have to respect the patient and then also colleagues.  You know in Asia and Europe, they do respect the experienced physicians.  But United States, they are losing that.  They just depend on computer systems.  They feel like they will learn everything from computer, and that they don’t have much respect.  I want them to learn from their patients.  Also the residents are not to be trained, they are not horses or soldiers.  They need to be taught how to think.  Nothing really stays the same way, and so they really have to be taught how to think.  I think that’s a very important thing.

My role model when I grew up, that was Marie Curie.  She always said that, “Life is not easy for any of us, but we must have perseverance and above all confidence in ourselves.  We must believe that we are gifted for something, and that this thing must be attained.”  That they have to have some confidence in themselves, and they don’t just attack other people.  That among the residents, they have a lot of competition.  That is really pathetic.  But they have to have some confidence.  Then the other thing they learn, this is also from Marie Curie, “Nothing in life is to be feared.  It is only to be understood.”  They have to think about that, and then be curious to the ideas but not to a person.  I really want them to learn that.

Christopher Rose:  So you have been for me not just a wonderful teacher, but of course a wonderful travel agent.  Whenever I go someplace in the world, you’ve invariably been there first and have so much knowledge of what to do.  Can you tell us something about hobbies that you have and things that you do outside of work that are of interest to you?

Ritsuko Komaki:  My hobby, gardens.  I am crazy about gardens and the flower and nature, and that is why I love to travel.  Especially like a Japanese garden.  I can sit there and meditate, and I sip my green tea.  I just love gardens and the flowers.  I cannot live without flowers.  So in marriage, my husband will tell you almost every day I have to get some flower and I do flower arrangement.  Without flower, my life is dead.  Some people, they have to drink some wine or something.  But without flower, the sun is gone.  So I have to get a flower.  My passion is flower arrangement and traveling.

I love to travel because I can discover something different.  And of course traveling, it’s not only nature but also the people who are kind and have passion in their own country, and then the food, and all those things.  I just discovered wherever I go that it’s really touching my soul.  And I love traveling especially in very old cities - Italy, Spain, France, of course Japan.  Someday I would like to live in Japan for a long time.  But, yeah, that’s my passion.

Christopher Rose:  Is there anything that we have forgotten that you would like to memorialize in this discussion that we’ve had today?

Ritsuko Komaki:  As I mentioned, we need to be oncologists.  So that means we have to be cancer biologists, as well as to know physics.  Then I think one thing I really want the people to know, things go around and come around.  That’s our nature.  Human beings, if you did something right or kind things, eventually it will come back.  That’s what I want to remind all my residents and young colleagues.  We are getting so busy every day and we really don’t have enough time to care each other, but I think that’s very important - to be kind to each other and the patient especially.

Christopher Rose:  Arjun, do you have any additional questions for Ritsuko?

Ritsuko Komaki:  One more thing --

Arjun Sahgal:  Your career has been inspiring to all of us, and you really shared your knowledge in a wonderful way.

Ritsuko Komaki:  Thank you so much for interviewing me.  I am honored.
Christopher Rose:  Ritsuko, you were about to say one other thing.  Did you want to add another thing?

Ritsuko Komaki:  One thing, we really have to -- this is not just myself.  Always Jim says the same thing.  Learn from our failure.  I’m passionate to cure the patient.  I will do everything to cure the patient, but also I always learn something. When we fail, we have to learn from that.  I think that’s very important.  That’s why I like a personal failure for how and what we failed, and we learn from that.

Christopher Rose:  This has been terrific.