 It's a real honor to be here, and I thank you for the very kind invitation. So I'm a hematology doctor or blood specialist working at UCSF, and I wanted to talk to you about a common blood condition, which is called thalassemia. And why this is important is the topic of my talk today. So when we talk about thalassemia, thalassemia is a type of anemia. And there are many different types of anemias, but what exactly is anemia itself? Anemia is having less hemoglobin in the blood. So hemoglobin is what we need to carry oxygen, and that's what gives our powers our bodies. And if the hemoglobin falls below the normal range, can we say that we have anemia? Like this is somebody with a normal amount of blood, and this is less amount of blood. So we can test blood and find out if somebody has anemia or has normal blood. And like this person has a normal red color, but this hand is very pale, so that's because there is less blood there. So when anemia is very mild, it doesn't cause any symptoms. Nobody even knows that they have anemia. But even if it becomes more severe, then lots of problems can happen. So you can have dizziness, lightheadedness, you feel fatigued, tired, can't do your work. And in children, we also see a loss of appetite and poor growth. But like I said, when the anemia is mild, then there are no symptoms at all. What causes anemia? Thalassemia isn't the only cause, actually. The most types of anemias are caused by nutritional deficiencies. And among those, iron is the most important one. And especially in young children and also in adult women and in older people also, we find iron deficiency between the most common cause of anemia. Then there's some other types. But the one that I want to talk about today is a type of familial or inherited anemia. And this type is the type of anemia that gets passed on from one generation to the next. And it is called thalassemia. And it just happens to be the most common type of anemia almost in the world. This is the most common type of anemia, but it affects more the people who have ancestors that come from Asia, from the Indian subcontinent, the Middle East and the Mediterranean region and North Africa. So we think that anemia is a really big problem and people should be routinely tested for it. But who should be the target for testing? Every newborn, when they reach one year of age, they're supposed to be tested by pediatricians at the time of school entry and especially in teenage girls and anybody who has a history of anemia in the family that may be inherited and should be tested. And in women and adults, it's important to test for that, too. Now what is thalassemia? So like I said, thalassemia is a genetic anemia, so it's inherited. So this means there is a problem or a defect in the gene which is needed to make hemoglobin. And when we normally have two copies of the gene to make hemoglobin, but when one gene is missing, that's called thalassemia trait. And that's very mild. It doesn't cause any problems. Most people don't know that they have thalassemia trait. But if a child gets both the defective genes or the thalassemia trait genes from the parents, then he has no gene to make hemoglobin, and that's a very severe problem and that's called thalassemia major. And when a child has thalassemia major, then they can't make blood on their own and they need to be given blood from outside or beyond regular transfusions. So if you look at the world map, and this isn't the whole thing, but just to make the point that the crosses or the red crosses here are representing the regions of the world where thalassemia is more prevalent. And this is a very broad band and I would think it affects a majority of the world population. But the reason I'm here today is also because to raise awareness that it impacts large populations living in the Middle East and North Africa, also in Southeast Asia, Indonesia, India, Pakistan and Bangladesh. So thalassemia trait, like I said, is very important because if both parents have the trait and the child can get the trait from both the parents and that becomes a very serious disease or thalassemia major. And the testing for thalassemia trait is very easy. Anybody who has anemia, they should get tested. If they don't have iron deficiency, then very likely they have thalassemia trait. And this is a simple test and our hospital has been involved in raising awareness that people should know whether or not they have anemia and if they have, then they should get tested for thalassemia. So it's especially important for women to be tested during pregnancy and to provide counseling to parents of prospective children about the risk for thalassemia in the child. Now when both, if a child inherits thalassemia trait from both the parents, then they have the serious type of thalassemia disease, we call it thalassemia major. And now you can't make hemoglobin on your own, so you need to give blood transfusions. And transfusions are needed every three to four weeks throughout life to maintain the health of the patient or the child. And if you start thinking about how many transfusions, it could be 16 to 18 transfusions in a year, maybe over 10-year period, something like 150 to 200 transfusions. And over lifetime, more than 1,000 transfusions, more than 2,000 units are transfused to maintain the health of the patient. So blood transfusion is a very important part of what we actually do. So we serve a large population of patients with thalassemia and we transfuse them at our hospital in Oakland. Now blood is available, but when we talk about blood transfusion, we have to match blood. And we all know that there are blood groups and the blood groups are, there's blood group A, blood group B, O, and then there's RH positive, RH negative. These are major blood groups. And this is sufficient, we only need the testing for these blood groups. If we need once in a while, we need a transfusion such as for surgery or if we have a trauma or bleeding, and we need one-off transfusion. But that's not the case for patients with thalassemia because they need repeated transfusions. So in these cases, many minor blood groups become important. So it's what is different between the patient and the donor that becomes important, the minor blood groups become important. These are small changes in how our red blood cells look like. Because if you keep transfusing cells that don't match with the patient, then this becomes, develop antibodies. And because of the antibodies, they can have a major reaction and they can reject the blood. And that's a life threatening situation. So these minor blood groups are different based on where our ancestors come from. So those who come from Africa versus those come from East Asia versus those who come from Mediterranean or those who come from Northern Europe, they all, we all have small differences between the minor blood groups. And in the Bay Area, in San Francisco Bay Area, we have more donors that come from the European background. But most of our patients are either Asian or they are from the Mediterranean or the Middle East or South Asia. And there is this mismatch. And that's the primary reason why we have reached out. And we want to encourage blood donation by the groups, the ethnic groups that have a higher incidence of allocemia. So we can have easier time matching blood to the patients, to our patients when we transfuse. So blood transfusion is a large part of what we do. We do blood camps in our hospitals so that our employees who work there, they can donate blood. And then we reach out to groups such as the MCC to become professionals. And they can live well into their old life, and they can enjoy life just like everybody else does. So in a sense, in the last minute I want to say, that we are a center that is seeking partnerships throughout the Bay Area. So that we can collectively improve how we manage our patients. It's a common condition to have thalassemia in the Bay Area. We have over 300 patients that we serve in Oakland. It's the largest such program in the Bay Area. In fact, it's the largest program in the country. And we recommend testing for thalassemia trait in all the groups where our ancestors have come from, the places that I talk about. So this is a large part of the world. And this testing should be done in many different places. It should be easily available. And if anybody would like to be tested, they can just contact us and we can arrange for that. We want to increase the amount of knowledge that is in the communities about thalassemia because even when thalassemia is very common, most people somehow don't know about it. And we encourage that the diagnosis be made early so that we can treat our patients in the best possible way so they can flourish and have a good life. Thank you very much. So I did present very briefly on the importance of anemia. So anemia is something that is so common that in many countries in the world, a lot of countries where our ancestors come from. Half of the population, or a third of the population has anemia, just low blood. And that makes us not be able to perform at our full potential, at our optimal level. So we can't think as hard, we can't work as hard, we can't work as long. We can't take care of the things, our kids, our fields, all the other things that we do. Because if the blood is not enough, then it doesn't provide enough energy to the body. It doesn't distribute the oxygen enough. So when we think of anemia or low hemoglobin, we realize that the most common reason for that is because the diet is not good. So a lot of people have low iron in the diet. Or there could be other things that are deficient. That by far is the most common problem, but there is a second type of anemia, which is also common, not as common as the iron deficiency, definitely not as common as that. But which affects maybe 5% to 10% of the population. So it's not rare, it's 5% to 10%. That means millions and millions of people. And that anemia is called thalassemia. Now what is different between this and the first type of anemia is that it's not related to diet. It's not related to what we eat. It is a genetic condition, it's inherited. It is passed on from generation to generation. Why it happened in the first place? Why did man or humans, why did we get thalassemia in our genes? Is because at one time, malaria was so serious that people who had the thalassemia gene could survive better when they had malaria than those who did not have that gene. So the gene for thalassemia became more common. Nowadays, many parts, many of those areas which where malaria used to be very common in the ancient times, no longer has malaria, right? But the gene that we acquired at that time is still persistent because it keeps getting passed on from generation to generation. So thalassemia is the type of genetic or inherited or familial anemia. That's the main message so that if one person in the family has it, it's possible that somebody else might have it too. If a child has it, then the brother or the sister, they may also have it. So if somebody is diagnosed, then we recommend that the family be tested for that. Now the thalassemia, the anemia is not severe. It's mild. So the hemoglobin drops by about two to three grams. So for men, if the normal hemoglobin is 14, 15, 16, right? If you have thalassemia, it drops down to 12, maybe 11, not lower than that. And in women, it can drop to 10 and a half to 11 or close to 10 sometimes. So the anemia is not severe and because it's not severe, so it doesn't cause any symptoms in those people. And if you don't have symptoms, you're not going to get tested. You never know that you have thalassemia. And that's where the things start to become a little more complicated. Because if you don't have your thalassemia and your partner, your wife or your husband also has the thalassemia, then the child can get thalassemia from both parents. And this double type of thalassemia is what we call thalassemia major. And that child cannot make any hemoglobin, cannot make any blood on their own. And that's the serious form and because so many people, millions and millions of people have thalassemia and show that number of children that are born with thalassemia major is also very large. And in most cases, it comes as a complete surprise to the family because the man and the woman both don't know that they have thalassemia, they have not been diagnosed. But when the child is born, everything looks fine in the beginning, but then within a few months, they realize something is wrong. Because the child is getting more pale, he's not thriving, not eating and not gaining weight, looking sick. And when they go to the doctor and the doctor does a blood test, they find that the hemoglobin has dropped all the way down, sometimes even as low as two or three grams, so this becomes life-threatening. So that's the specialty that we deal with is taking care of children that have this life-threatening severe form of thalassemia. In our center, we have over 300 patients that we take care of. And we are the largest such center, not just in the Bay Area, but actually in the entire country. And the reason why we have patients is because we are in the Bay Area. And the Bay Area is a melting pot of all ethnicities, civilizations from all over the world. And many of us have come from countries where thalassemia has been very common for centuries and thousands of years. So the good thing about this is that because we are here in California, in the Bay Area, we can provide very good care because we have the facilities and what's needed to provide safe blood transfusion, we have enough blood. It's all healthy donors who donate blood. And we can, these children can not just survive, but they can thrive. They grow up, they look completely normal, they go to school, they go to college, get a job, they get married, and we have patients throughout their lifespan. So we have patients as young as a few months old. We have patients who are in their 60s. And we can see that it's possible to live a good, healthy life if you have the resources to take care of patients. And one of the most important, I will talk about the advances in treatment and how we can cure thalassemia towards the end. But I first want to make the point about the most important resource to take care of thalassemia is blood. So if you can't make blood, then you have to transfuse blood from outside so that your body can function. But the blood that we transfused lasts only for a few weeks and then it has to be replaced by more blood. And this is a continuous process. So children who have thalassemia major, the serious form of thalassemia, they get transfused every three to four weeks. And this is for their entire lives. And to be able to do that, you need a system that provides safe blood transfusion. And the safety comes from many different reasons. But one of the big ones is that we have the ability to match the donor blood with the patient's blood very closely. So this close matching is the key because our blood has both... There are small differences in red blood cells between the donor and the patient. And if you repeatedly give that blood, then the patient can develop antibodies against the blood. And that's a serious problem because if you have antibodies, now you can get a reaction and you can reject the blood. And then the treatment becomes very difficult. So the question is how are we able to match the blood closely? So the more closely we want to match the blood, the less is the availability of blood. So you start with 100 blood units. Of those, only five may be a match to our patient. But sometimes there are not even five units. I mean, there may be one or two units that are fully matched to our patient. So one of the things that we do and the way we are reaching out to your group is to increase the donation of blood so that the donors are coming from... They have the same background in terms of ethnicity, in terms of where in the world they come from, similar to our patients. So then it's more likely that the blood is going to match. So we expand the donor pool. It doesn't matter whether we expand... If you only expand the donor pool from 100 to 110, but it doesn't seem to matter very much. But those extra 10 units are the ones that are more likely to match with our patients. And that is the key thing. So for us, it's a big thing to be able to encourage donation from non-traditional donors. So traditionally, most donors are Caucasian white donors that have this thing that repeatedly every three, four months they go and donate blood. But we also encourage... So we do blood drives in our own hospital because we have a mix. Our people who work there, they are from all different ethnicities. So they come and donate blood. So that's one thing. We do two or three times a year. We hold a camp in our own hospital. And then we work with the blood centers and we ask them how can we help to hold blood drives in different parts of the Bay Area. It could be in the Asian community. It could be among the Chinese. It could be among African Americans. And now increasingly, because we have had a recent increase in patients that are coming from the Middle East, for example. We're also looking for more or increased donation from that region. So that's a big part of why we are here. And we are lucky to... We are very fortunate really because the organization is built in such a way that blood donation and blood drives is really just a part of what the organization does. And that's really... We are just fortunate to be able to tap into that. And we are very, very grateful for that. So I want to end by just saying that there have been advances in the field so that patients who are born with the disease don't have to live their whole lives like that. So that's what we call cure. And in our hospital and other parts also, if you have a brother or sister who is a fully matched bone marrow donor, you can do a bone marrow transplant. And that cures the disease. But more recently, we have also started doing gene therapy. So all patients, everybody is eligible for gene therapy. And it's hoped that in the coming years, maybe in the next 10 or 15 years, the number of patients who actually continue to need blood is going to go down because more and more patients are going to get cured by gene therapy. That is the hope. Are there any blood susceptibilities to this disease? No, it's... Well, the susceptibility is not due to a blood group, but it's because of our genetic makeup. So there was a map that I had shown earlier that showed where thalassemia is more likely, which... Wait, so it's a very big area. Yeah, it's probably... Yeah, it's about 80% of the world population, I would think. It's a very big area. Yes, I brought Bangladesh. It's just till we told about the thalassemia major and minor group. And these patients are required always the blood transfusion. Which one of the blood transfusions you've got? Either it is full blood transfusion or the plexilboreum. And if we are giving always the plexilboreum, it will develop the polycythemia. Then what will be the result? I think I could clear it a little bit. So you're asking about the difference in transfusing packed cells versus whole blood. Not whole blood or plexilboreum. Which one is better? Which one is better? Because we are always giving the plexilboreum between the blood and the polycythemia. Right. They're another hazard for the patients. And in that case, how many times we can give the whole blood cell because the patient needs whole time to hold a long life and then it's the transfusion of blood. Which kind of blood you should... But what is the best type of blood to give? So when you look at blood, we think of blood as it's red in color. And we think it's a solution. It looks like a red-colored solution. But it's not a solution. If you put blood in a tube and let it sit for half an hour, you will see that the top part becomes watery, right? And all the red cells, the red part sinks to the bottom. Right. So the top part is the plasma. If that doesn't have any hemoglobin in it, all the hemoglobin is in the bottom part. So if you take a unit of blood and take out the plasma or the water part and leave the red cells behind, and then whether you transfuse just the red cell part or the packed cell part, or whether you transfuse the full unit, the increase in hemoglobin will be the same. But the patient doesn't need the plasma, the water. They already have that's normal. What they only need is the red blood, red part. And that's why we prefer the packed cells. Sir, blood volume will be increased. Yeah. That will give the hazard for the patient. Yes, yeah. So volume is increased, but the hemoglobin is not increased. Hemoglobin is the same whether you use packed cell or whether you use whole blood. Yeah, I have a question. So basically, so do you think like when people get married, before marriage, they should do these tests? Yes. So that's the reason why this is not a straightforward question to answer is because every society has to come up for their own answers for that. And there are some, in some countries, I know it is almost a law that you need to know your thalassemia status before you can agree to a marriage or the marriage can be registered. But it's only in some countries that is the case, but in majority of the countries, I don't think the society may not accept that limitation. But it is recommended from the medical field, it's highly recommended that people know what their thalassemia status is. So there is another disease like CF, like cystic fibrosis? Yeah, so like one of my friends, his child has it, and then he said like both parents has. Correct. So thalassemia is just one example of this type of genetic disease. We call these recessive diseases, which means that recessive diseases that if you only have one copy of the gene, like the cystic fibrosis, if you have only one copy of the gene, you're perfectly normal. And you wouldn't know that you have that copy of the gene. But if your partner also has the same copy of the gene, if both husband and wife have the same, then the child can get a double copy, and the child has the disease. So the same thing for thalassemia, it's exactly the same thing as cystic fibrosis. If you saw these thalassemia bed patients, we need to marry with their normal people. Then what will be the spring? The child will only have thalassemia trait, but not the serious form of thalassemia. Yeah, so it's even more important than that time that let's say the man has thalassemia and is getting transfusions, then the woman should be tested. So the best thing is that she doesn't have any thalassemia, then the child cannot develop thalassemia. They're not the major type of thalassemia, not the serious type. We have, I just want to say, we have a lot of patients who have children, and they're healthy children, they're grown up, and we've seen them growing up. It's just wonderful to see all of that. The thalassemia patients are prone to diabetes, thalassemia patients, they are prone to diabetes. So they're prone to diabetes if their disease is not well controlled? Yeah, that is correct. And the control is, I didn't go into that today, that's the iron part, so because blood brings in iron into the body. And if there's a lot of iron, that can cause diabetes. So you have to control the iron along with the blood transfusion. So thalassemia doesn't cause diabetes, but it's the treatment for thalassemia as blood transfusion, and if you don't control iron that comes with the blood, then you get that. So it used to be more common in the past, but nowadays it's not that common. So for the cure, you mentioned about the... Yeah, yes. Right, so gene therapy has only developed in the last decade, really. I think 2014 was the first trial it started, and we've been part of the trials since then. And then two years ago, not even two years, a year and a half ago, it actually got approved as a treatment by the FDA. And then it took many months for things to kind of get together, but four months ago, we did our first patient, we did gene therapy on the first patient. It was not on a clinical trial, but using the medicine now. It's sold as a medicine, the gene therapy. And the patient has done, well, it doesn't need transfusions anymore. Yeah, we did the first gene therapy after the approval in the country, the first patient we did in our hospital. She's done great. And now we have many more patients who are waiting to get gene therapy. So this is like for Thalassemia major? For Thalassemia major, right. So for the bone marrow transplant, the best is if you have a brother or a sister who's fully matched to you, because otherwise the body can reject the bone marrow. So that matching is very important. But most of the times you may not have a brother or sister who's matched because families tend to be small these days. You know, you may have two or three, sometimes four children in the family. And the risk is chance that you'll match to somebody is only one in four. So if you're lucky, then maybe sometimes there are only two children in the family and they're a match. And sometimes there are four or five, but nobody's a match. So it's only about maybe 20 to 30% of cases where a match is possible. For most others, they don't have a match. Right? 100% 13 or? No, it's a one in four chance. Yeah, the probability is random because we have two genes for everything. So two genes for making hemoglobin. One is working and one is not working. And if we can either pass on the working gene or the non-working gene to the child. So it's 50-50 from each parent. And for both parents together, then it's a 25%. One in four, yeah. One is, I have a two question. One is, when you check the DNA testing, what is the accuracy of the testing? And my second question is, if someone is identified, they have problems and they go by gene therapy, what will be the total cost for the treatment? Okay. So the DNA testing is, it's almost 100%. It depends on the test that you choose to do. But now we are going to move to the test that there are almost 100%. We never say anything is absolutely 100%, but it's close enough. Yeah, it's not 60, 70%. It's almost 100% DNA tests that accurate now. The question of the cost is, the cost for every new treatment nowadays is reaching into the millions. And that's the reason why, so for gene therapy for Thalassemia is more than 2 million, maybe even closer to 3 million. Is that annual? No, no, it's just a one-time cost for gene therapy. Yeah, because it's a one-time treatment. Yeah, so you give the gene therapy and then the normal cells will grow and they'll make hemoglobin, so you don't need transfusion. So it's a one-time, but it's a very big cost. And that is a problem because we can do that in America, but it's not something that you can do in other countries. So just gene, why is that expensive? Why is that expensive, yeah. Well, some of it, it's just the cost of making this, so here's the, in brief, here's the process that happens. So what we're trying to do is modify what we call stem cells. So stem cells are cells that live in our bone marrow. They divide and then they make new cells, but they have the capacity to divide infinite types. So these are stem cells. So these are the cells that we want to modify. So we put in a new gene, which is a working gene. So first you have to remove the stem cells from the body, some of them, not all of them. And then that has to be taken into a laboratory where they use a virus. The virus carries the new gene. The virus enters into the stem cells, and then the gene becomes a part of the stem cell. From there, it takes many months of testing to make sure everything is safe before it's ready to be returned back to the patient. And yeah, yeah. So certainly there's a lot of expense, but like everything else, drugs are extremely expensive and part of it is the actual cost of the drug and the part of it is the margin that they have to have because they spend all the money trying to develop the drug, etc. And some of it is just too much anyway. So it's covered by the insurance, yeah. Yes. Exactly, so I think that factors into the calculations of how drug companies calculate how much to sell the drug for, but certainly giving somebody independence from transfusions. It's not just an economic or financial calculation, but it's also how it changes their life that they no longer have to be connected to a hospital. You know, they can be anywhere and do anything that they want. So it's the main thing here. Yeah, yeah. So, yeah, we view blood donation as a kind of a completely selfless process. What we are looking at is just increasing the diversity of blood units that are available in the area. And the patient could be anywhere. It doesn't have to be in our hospital. They could be with Kaiser, they could be in Sacramento, they could be elsewhere. The whole region benefits from it. Because if a blood bank is not able to find a unit, they'll ask the next blood bank if they have that unit. Yeah. So these are not donations that are directed towards a particular patient. They're... But you said you do it in your own center. We just give it to the blood center. So if they have more units that are coming from a diverse group of donors, they're able to find the unit more quickly every time. And it's just a better match. Yeah, we have a different blood supplier. There are two main ones. The red cross is one and the other one is called Vitalant. Vitalant is the other group. But it doesn't matter to us really. Like we said, it has to benefit everybody. It's not just for our hospital. Yeah, blood donation is one, but in general, we are interested in just having the awareness of Thalassemia in all the communities that are... We've done the same thing with many other groups. Especially the many Asian communities, Southeast Asian communities, for example. Sometimes I found like... Because my doctor said, oh, you have iron deficiency. So he started to give me iron. So I started to take it. Then he thought I was something and then sent me to a blood doctor. He said that I had actually like my blood cell was smaller and I did not need iron. So you might have Thalassemia. Yeah, that is what he said, like minor. Minor, exactly. So yeah, so there may be 15 of us sitting here. So if one of us is likely to have it, even if you didn't tell me, I would just guess that one of us has it. So that brings it to five to eight percent. That's just in the general population. So it's that common. Yeah, yeah. I have one in my family, like she has to take regular blood. Oh, okay, okay. Yeah, so that is how I knew. Otherwise, it is very uncommon. I don't think anybody else knew about this. No, the questions that you were asking were very detailed questions and some of them were very difficult. You are a physician, right? I am a physician working in Dhaka. I was recently... We are working on diabetes. Oh, not diabetes. In diabetes. I recently met a very senior hematologist from Dhaka, from Bangubandu Sheikh Mushi Medical University. That's the one of the Sheikh working in Dhaka. Yeah, so I'm going to be in touch with him. I got his card. I met him in a meeting. Okay, thanks. I'm not. I've only gone up to Kolkata. So my friends have been there because we were trying to do some work with seeing if we can help in any way to improve the care because we talk about 100 patients or there are tens of thousands of patients. The numbers are just so many that it's very... So we extend our willingness to help and maybe to train somebody if they want to come here, spend one or two months just learning what is new and how Thalesimha is managed here. Even with limited resources, what is it that we can improve? Yes, so there are two types of gene therapies. So the question is why describe one type of gene therapy in which you add a normal gene into the cell using a virus. But there is a second type of gene therapy which is called the CRISPR gene therapy. And in CRISPR gene therapy, you don't add a new gene, but you change a gene that's already in the cell. And that doesn't need to be done with a virus. They have other methods of getting the CRISPR is the name of a chemical or an enzyme. So once it gets into the cell, it can change the gene inside. So now it can make more hemoglobin. So that is still under investigation. We may see an approved treatment with CRISPR maybe next year for sickle cell. It's always in the news too. It was very big, very big for our field. Okay, thanks everybody. So thank Dr. Ashutosh for his talk.