Kenneth Kraemer and Deborah Tamura

00:03 Hi, my name is Debbie tomorrow. I'm 63 years old today's date is June 5th 2015. This is the National Institutes of Health clinical Center. And

00:20 Dr. Ken Kramer is the principal investigator of our protocol and he is my boss.

00:32 Hi, I'm Ken Kramer. I'm currently 71. This is June 5th, 1915 and we're here at the NIH and I'm a principal investigator in dermatology Branch the National Cancer Institute.

00:58 Teresi me the first message. I thought you supposed to say who I am your relationship to me of various the resources. I feel all the patients and gets but going and keeps me in line.

01:19 Dr. Kramer, I've always been really interested in about why you know, you've been interested next p and I'd also really like to know about the first patient that you ever saw with XP 6p because it's too hard to say xeroderma pigmentosum, which actually means dry a pigmented skin. And this is a very rare genetic disease frequencies of that one in a million and I first came to the National Institutes of Health 1971 and said she was assigned a project to work with dr. J Robbins who was working on the xeroderma pigmentosum patients a few years before that. It has been discovered by James Klever and that this disease XP is caused by a defect in DNA repair and these children with XP have a high frequency of cancer, and they're very sensitive.

02:19 Is the sun white inside being in the Cancer Institute, we figured we'd have any way to get inside sin to why people get skin cancer and how it's related to sun exposure in DNA repair. Then we started seeing the patients in that became a I got hooked on that initially hours of the Public Health Service for 3 years, and I was doing so well, I went down to Florida and did a residency and dermatology and I came back to NIH to continue working with patients with xeroderma pigmentosum.

02:55 So tell me about the the first patient that you ever saw first person mode. So I was actually to hear from Maryland and the she lives out on a farm and she unfortunately had many of skin cancer. She was taking care of before we saw her by doctors at Johns Hopkins University and they removed dozens of skin cancers from her face. She lived on a farm in the family. I didn't realize what she had and they had her Outdoors quite a bit in that was what caused her to get get the skin cancers are we helped her here at the NIH as she was being a tree that she's one of the few patients that was actually being treated here for many of her tumors are most of the patients are just referred and there a come from all over the country. In fact all over the world, but she was treated here and she stayed

03:56 For a long time. She was really very friendly. She was have eye problems that I know of the skin, but the I was involved and she had that tumors under skin tumors ever I-80 was care for a very well 5 a.m. Ophthalmologist here. And I remember amazingly she was very warm and friendly working with the social workers. And whenever there was a special occasion, she would bake her special treat which was red velvet chocolate cake. She'd bring in for everybody had a good time. Unfortunately, she died a number of years ago, but she was in her forties when she died.

04:41 So

04:44 Debbie what how many patients have we seen here at NIH?

04:49 Well

04:50 We seen a little over a hundred patients with with XP and when you consider that it's a pretty rare disease, that's probably a lot of the patients that live here in the United States. We've seen patients from New Jersey that the patient from New Jersey that that we saw was that the first patient you so since I started you you recruited me hear from Hawaii genetic background because this is a genetic disorder and a lot of the issues are related to genetics.

05:45 And I'd actually seen one other XP patient when I was in in graduate school and was struck by the fact that this particular patient had many sunburns and because of December ends that that patient had the the family had been accused of neglect and that always drop stuck in the back of my mind and then when I came here to work with you and I I met my first XP patient on did the young woman from New Jersey and learned that not at all XP patients worse than sensitive and this particular girl all she did was get freckles after being out in the sun and talking with her family. She developed her freckles when she was before age 1 beginner and that's not normal.

06:46 And then quite quickly after that and she developed many skin Cancers and I and I don't I don't think that I really understood the impact of having so many skin cancer so much skin surgery and having to live really shielding yourself in the sun until I was able to sit down and talk with this very wonderful young woman. She she really taught me many things about living with xeroderma and how to live a full acted like she was an occupational therapist. She did a lot of stuff even though she was having all these Skin Surgery sand and sadly she developed a brain tumor.

07:35 And doctors here were very helpful in helping to diagnose and treat her treat her for many years. She had surgery she had radiation. Ultimately she did pass and we went to her funeral in the, New Jersey.

07:52 And hurt her family still to this day every once in a while will contact us and ask about how things were going to help the patients and it helps our research. But also we learn a lot from the patients and how they deal with that and we're one of the few patients in the world actually wear these people can get help. I am at with zero with a sprayer disease with xeroderma pigmentosum many time because it's so rare they were often never seen anyone else with that or know how to deal with what happens when they go to school to me.

08:32 Well in the old days, for example, when these last two patients that we talked about went to school. There was nothing that could be done for the by the school. They would make the kids go outside and play they would not do anything to protect them from the Sun. And now that we have laws. I can help that the families with helping them understand what their rights are for protecting their children. So there they will UV film the windows. They will provide the children with activities so that although they can't go out and play that they have activities that are what we call you these safe inside a step. That's very good in the schools have been remarkably.

09:25 I'm willing to go to help the children and do these things. I have to cover make sure the fluorescent bulbs are covered up and the windows are tinted and patients can get the disability parking so they can get close to don't have to beat the parents don't have to have them an outside and that's moved forward it. What about the organization what's happened with the patients getting together? There are several UTI, or I'm sorry XP support organizations. Now, there's two in the United States the XP family support group in the XP society and they provide written information. They have camps they have educational support meetings for the families. They have Facebook pages, so that what was that one time of

10:25 Are isolating condition now the families get together and share tips and and just support each other when they're when they're kids have to have surgery for exam amazes me when I started this in 1971. There was none of this and all the things I was right articles and text books and show these horrible pictures of the patients and now they were diagnosing them earlier and they're protecting them. They're doing much better. So with our new textbook paper papers Reesha and pictures of successful patients who doing well, but not all the patients have a skin disease. Is that right? That's true. There is any any part of the body that's exposed to ultraviolet radiation, which the primary sources the sun becomes damaged and so many of the

11:24 People who is either been diagnosed late or come from countries where there's not as good Medical Care will develop eye problems. They will become blind style has tumors on the eyes and

11:44 Dr. Kramer on we saw those two young boys from Tanzania.

11:50 Back in 2005. That's right then and there has a bigger challenge. We wanted to be able to tell which ones have that or not and I guess the simplest way we found for doing that was just doing Simple hearing test and we did a study with the Audiology people and with medical students every passing through our lab Miriam to time sheet for instant. We went through we had 40 Years of of test of hearing test on the patients and we show that just doing a simple audiogram would help them to test to predict whether they'll develop their logic disease or not. I think about 25% of the patients to develop a severe Progressive neurologic disease and so XP is also a model not just for skin.

12:50 Disease by pervert aging on premature aging of the nervous system as well as the skin.

12:59 So what about that patient from West Virginia that we start? We were following her in this from the seventies when I first saw her that you've made her when you came she was actually the first XP patient that I met who was an adult with the significant neurologic disease and it was

13:24 Talking with her mother and then eventually with her father that taught me about this neurologic degeneration so that this particular patient when she was born was perfectly fine, but she was also quite Sun sensitive and then over the years. She began to have neurologic declined where she went from being a perfectly normal intelligent little girl to developing learning disabilities and then eventually when I met her she was wheelchair-bound she had lost a great deal of her hearing but even despite that she was happy and she would tell me all the different things that she was doing what book she was looking at in and things like that and and then as her neurodegeneration,

14:24 Graston, she could no longer talk and she could no longer eat and she needed a feeding tube her father began calling me on the phone one month to tell me what was happening with her from the neurologic standpoint and

14:45 This was has been a great Aid because when I talked with other families now I can give them.

14:54 Done anticipatory guidance about things that they might need for their home in the way of disability care and and and things like that and when this patient passed away the family invited me to come down to give the eulogy at a funeral and

15:15 This was an honor and a privilege but it also gave me the opportunity to talk to a bunch of people who maybe you've never heard of that pee and it again educate them about some of the symptoms of the condition and how perhaps they would be able to identify this in their own family are in friends because one of the things that we know is that identifying this early is very helpful. We working closely with many other of the specialist here at NIH the radiologist are very very good at helping you with the neurologist work with with a physical therapist occupational therapist. Who else do we have in the eye doctors in this is a multi-system disease and the NIH is wonderful and having all of these resources and you were able to twist the arm convinced.

16:15 For my patients that might wave be have a game at a depth of knowledge that they wouldn't otherwise have in that helps them and it also helps our research and have the patience one of the study's we did a number of years ago was to see if we could prevent skin cancer in these patient and we use the drug that you can use for acne treatment called Accutane and we found that I could say was very effective in preventing new skin cancers in these patients.

16:51 However, it caused a lot of side effects. So it's not that generally used for everyone, but they do now use Accutane in the general population for prevention of skin cancer disorders.

17:08 Now what about the we were getting patients from all over the world? What about those brothers from Suzanne? Why did they come here?

17:20 That that's

17:23 I I kind of jokingly call them my Sudanese Sons. They were referred to us by us a free clinic here in the DC area. They come to the United States about a year before that from the Sudan by Egypt and they had developed.

17:47 Really significant eye problems. If you think about living in the Sudan or in Egypt with XP and not really being well not well educated about it and they had a lot and I damaged one is the boys had a big tumor on the tip of his tongue and you don't think about the tip of your tongue is being spent exposed. But if you're outside and you lick your lips, you're exposing your tongue to the sun people with XP develop cancers on the tip of their tongue. And so these two boys had severe eye issues and the one boy had a a tongue tumor and they landed at the free clinic here in in the DC area because nobody else really knew what to do with them and they didn't have any health insurance and instead the free clinic.

18:37 Sent me an email with these boys pictures and 22 and the other boy. I was 17 what language do they speak? They only spoke Arabic?

19:00 So when I say I saw the pictures I knew right away that yes, they did have XP and we had luckily I had another some other boys that we had used the services of dr. Jaime Ibrahim from the dental clinic. So I forwarded the email of this young Man's Tongue tumor to dr. Ibrahim who immediately said let me know what I can do to help you and and I knew yes, you know, we will get this going and so I began communicating with the doctor at the free clinic and arrange to have the boys come in to be seen and between dr. Kramer and dr. Digiovanna. And dr. Ibrahim and Khadijah Bronx dermatologist.

20:00 We had the whole NIH sort of rallying to take care of these guys and the ENT doctors were helping us with that and they even local Physicians who we doing of surgery on that volunteer their services came in Emmett eye doctors at Johns Hopkins were working on that as well. So there's this is a very impersonal institution as they say, but in fact we were able to when we've reached out where there were many yet. I doctors who are willing to volunteer their time up here and outside of NIH to help them. And so what happened to them then they were ended up learning English.

20:47 So I asked her after we got their health stabilized because they had other health issues other even than just the tongue tumor in the eye tumor in the skin tumor skin tumors.

21:02 We were able to get them into the International Rescue Mission in Baltimore because they could be considered to be refugees and we got them Refugee status. The Medicaid they started attending on english-language school. They began completing their high school education in Egypt because of the way that they looked they've been essentially kicked out of school. And so those boys were very bright and they pursued their High School diplomas and one boy then went on to Community College and got his associates degree.

21:51 And I'm began working the other the other boy on had much more the older boy had much more sun damage and and did volunteer work with that the International Rescue organization, but

22:09 Because of all the help that we had received from all of our physicians at here at the NIH these boys didn't die that's good. And then that you mention that I we were approached by a college student. I think it was from a there were two boys in Tanzania and she had been on a summer out of humanitarian work actually just out from college and said she was in Tanzania. She was in the school for blind children. And what did she find?

22:50 She was she was she is an amazing young woman and emerald.

23:00 Contacted the XP society when she learned about xeroderma in two of the boys that were at the school for the Blind. And again, if you think about if you have xeroderma pigmentosum in your growing up in 10 Dania, you may not develop skin cancers right away, but you're certainly going to have a lot of damage to your eyes and both of these boys did and they were they were both blind and she contacted the XP Society about bringing these boys to participate in the XP camp and then the XP Society contacted us and that's an Upstate New York. And they and we said, you know of yeah, let's go for it. We'll we'll see if we can work things out to see them.

23:53 What language do they speak Swahili the school for children who went blind and so at Emerald went back and then bake sales and raise a little money and then managed to get get money to bring them to the United States plus a teacher from the school and then we have to go through a lot of Hoops to get them seeing here of they have to have all the patience it at night nature on it protocol in the protocol in fives consent. They have to understand consent the most of all I could send documents were written in English. So we had to find somebody who could understand translate that to Swahili is just that wonderful and then once it was translated to have to go back to the

24:53 Parents who are out in the fields in in Tanzania and get them to sign information and get them to also let the one of the teachers at the school to come here and act as a guardian for the boys. So when they came here, what did you get from Debbie?

25:09 What is it thinks? I always do when kids come this is that give him a little little things and I gave these two boys little plastic cars cuz they were used to run with 7 in the other was 9 and much to my surprise dance with the First toys that these of these little boys I've ever had and one meal a day and they had that tumors on their face on the lip and that when they

25:41 The people there would still try to do surgery. They didn't actually have very good facilities, but that way we're able to do some of the surgery but then if it if the Region's returned they put salt on the wound which was really a very very painful that they have they we managed to get the about the first we have to have the boys evaluated which is why they came for the initial. And then it turned out they actually needed some treatment but with the heavens originally signed for that so they were here for a while we manage. We got the translators from where were the transmission there was one translator who was originally from Kenya. He was there a US citizen and I was in the Army is a lawyer and he was volunteering with our translation service. So he came and translated with the boys for the first week that they were here and he became very close with the boys and their translator are at and they're at their teacher.

26:41 And I'm took them out for dinner and got them things was very nice. And then they went back to the camp for a while is because we needed surgery will have to arrange to get them to come back. And so with that said about the whole second the second round of getting permissions and cutting back to their parents in the tents in the end and then coming back and we had it again happy at your ear nose and throat people for helping to do the surgery and the eye doctors. We had a home there was actually a whole article about this in the NIH record in December 2005 indicating how how it takes a village to to treat them so they came back and they are emeralds brought her College friends and they were off at the Children's in there with all the other patients and the voice of America came. What did they do?

27:41 The second week that the boys were here and she did a whole show on the boys and on the NIH and an XP, so and we know that XP is present in Africa and certainly is not well diagnose to treated. So this was the really one of the first

28:10 Radio shows that addressed this issue in in in Africa

28:18 Answer that that was good till day they managed to get for surgery and then they went back to 10 Cydia and then we heard they had a huge celebration when the boys came very happy to see them again, but Emerald not being wanted to let things go there. She had Lids made a whole list of things that could be done to improve the school it was there and dr. Phil Murphy here in NIH had a relative that made him who had a foundation that was helping set up medical clinics in Miller and helping people with medical problems throughout the world. And so we stand we got him in touch with emerald and with a list of things. She said they needed and he managed to go and get local workers and Tanzania to improve the efficiency.

29:18 These children have xeroderma so they should be protected from the Sun but building they were in had no windows to build put Windows in for the door in and get other for the other.

29:32 Other things said that it would be more like it a regular school with us and protection. So what happened there when I think the other thing that we need to remember is that there are other Sun sensitive conditions and albinism is really quite common in Tanzania. And so albinism is it genetic disease where on people are unable to make the pigment that protects your skin against UV so individuals with albinism will have very light to white colored skin and very light colored hair, but they also have significant Vision issues so that they would be in that school for the blind. So this building that was built was not just helpful for the children with the XP but it was also helpful for the children with albinism also because they they to get skin Cancers and so when that building

30:32 Was finished and the additional on

30:37 Materials for the blind children were brought brought to the school. They had a huge on celebration and Dad me and brought Emerald there for the the building dedication far from Mount Kilimanjaro. And one of my colleagues. Off of Hatfield who works at NIH went out there with a group of college students and he was getting he had previously climbed Mount Kilimanjaro. But this time he was going to let the students do it themselves so we can let him know about these this family at least boys, and he went to the school and Moshe and was able to see it my voice or actually doing very well.

31:32 An N again the boys were we got to the school in touch with the XP family support group which sends them sunscreen by the boatload so that the kids with the XP but also the kids with the with the albinism. Can you send screen for for protection if you think about how how poor these countries are the sunscreen is often just out of the reach for

32:09 For for people who is a very interesting patients, we're continuing our research and we go way back and following the patient's since we saw them almost 40 years ago and the patients are getting protected earlier in life and getting fewer skin Cancers and Debbie started talking about the women growing up now and then what do we find recently that the women with XPS I reach adulthood.

32:39 I started my nursing career in Maternal Child Nursing & Women's Health. And so one of the things that we began working with an OBGYN physician who sells aborted in genetics, dr. Melissa Meredith and we began and she's here to NIH and we began asking, you know women about their pregnancies and about their menstrual periods. And as it turns out these women were beginning to experience menopause very early and in fact the first patient that dr. Kramer had had Matt had actually also develop menopause early in his 20s, but those kinds of issues are way overshadowed by having hundreds of skin Cancers and and I cancer so those kinds of things

33:35 Where I

33:39 Wear something that now that the the patients are much better protected will now become health issues that we need to to look at. So this is helping me women if we know about that we can warn them and let them know that that they if they want to have children. They might want to do that earlier rather than later and there are others of steps I could take is that go into menopause and similarly. We're learning at the same time about the DNA repair in xeroderma naging the hall aging process. Clearly Now is linked to as some DNA damage and so we're helping the patients and we're helping at Learning in general.

34:24 Okay, so I think clearly would see that it takes a village to keep things going. We have so many diseases very challenging and the patient service.

34:38 I have a very severe problems is not just a patient's but the whole family's we learn a lot of scientifically by studying them and then we learn from the patients and learning about the the different aspects of problems with DNA repair and Debbie's very effective is bringing you to Bear all of the resources at NIH and organizing visits. The patients are here for 3 to 5 days. And then I see many yes specialist in that that was able to talk with the specialist and tell them a bath. What specific problems they are. So who do you think has been helping us? Which it which areas are there have been helpful?

35:24 Well to be perfectly honest with you. There isn't really one specific area that spend the most helpful. I think that as as you said, dr. Kramer, it does take a village. We've had everyone from the hearing people to Psychiatry that and I think the thing that has perhaps been the most helpful is the patience in the families themselves. It amazes me the resilience of people living with this rare very severe disease how they're willing to come and spend time with us and how they're willing to share their lives and their stories and themselves with us and help other people that they will never know throughout the world.