Turning Blood Red:
The Fight for Life in
Cooley's Anemia

Arthur Bank's Book about the Potentially Fatal Disease and his Life in Science

For more than 40 years, Arthur Bank, M.D., has been a scientist, hematologist, and educator at P&S and NewYork-Presbyterian Hospital. A world-renowned authority on hematology research, he has been a leader in Cooley’s anemia research, has published extensively on human globin gene regulation and human gene therapy, and has received NIH grants throughout his career. Now professor emeritus of medicine and of genetics and development, he headed the division of hematology from 1980 until 2005. A graduate of Columbia College, he received his M.D. from Harvard Medical School.
     A new book by Dr. Bank, “Turning Blood Red: The Fight for Life in Cooley’s Anemia” (World Scientific Books), interweaves narratives of the hardships facing patients and family members with the disease and his own progress as a scientist trying to unravel the cause of this potentially fatal disorder in hemoglobin biology. Cooley’s anemia, a genetic disease that affects millions of people worldwide, arises from a reduction or lack of b globin and an excess of α globin, the two proteins that comprise hemoglobin, the oxygen carrier in red blood cells. Also known as b thalassemia, Cooley’s anemia is most prevalent among people of Greek and Italian ancestry. Patients require blood transfusions for their entire lives and take iron-chelators to counter the iron that builds up from transfusions. Besides describing his research and the present treatment for the condition, Dr. Bank’s book discusses what may be on the horizon for patients: gene therapy, stem cell transplantation, and advances in prenatal diagnosis.
P&S Journal contributing writer Robin Eisner spoke with Dr. Bank about his book.

Why did you write the book?
I have always loved writing, but during my career I had to write grants to funding agencies and papers for peer-reviewed journals and did not have time to explore other kinds of writing. I semi-retired in 2005 and decided to write about my 40 years of being involved with the Cooley’s anemia community and my research on the disease. I wanted to focus on the patients — what it is like for them to live with the disease and their feelings. I also wanted to describe the process and challenges of research during my career and show how new research may help lead to future treatments, such as gene therapy. Currently, I am involved in an ongoing clinical trial for gene therapy in France that places a gene for b globin into red blood cell precursor cells in the bone marrow as a way to potentially cure Cooley’s anemia and sickle cell anemia, also caused by a defect in the hemoglobin gene. [Sponsor of the trial is Genetix Pharmaceuticals Inc., which Dr. Bank co-founded in 1990 with two other scientists from Columbia.] In the book, I wanted to show the passion of a scientist as well as the compassion of a physician.

Who do you think might be interested in reading the book?
Cooley’s anemia has been the poster child for understanding genetic disease, in terms of figuring out the mutations in the genome that cause the condition and why in biological terms the alterations do so. My research spans the revolution in molecular biology and the book shows that as tools developed, we were able to adapt them and use them to gain insights about the disease. The book is written with the hope that patients, lay people, and those with more knowledge about biomedical science will come away with a deeper understanding about the disease and about basic and clinical research. I gave drafts of the more complex passages to friends and family without experience in medicine to help me determine what they couldn’t understand so I could rewrite the passages to provide more accessible explanations.

What message about basic and clinical research are you trying to convey in the book?
Science is hard to do and success is hard to come by. One has to persevere in science. A scientist never knows if he or she will discover something important. You have to love the process of doing the science, not just the result of the research. Working in the lab day to day I didn’t think I was going to cure Cooley’s anemia, because it would be too much of a leap. On the other hand, I am cautiously optimistic about the possibilities of gene therapy and stem cell research to become new therapies some day. Interestingly, though, when talking to patients while researching the book I found that many were conservative in their approach to trying new drugs, such as oral iron- chelating agents. [The iron-chelating drugs used predominantly in the past and currently are taken by subcutaneous injection.] Even though they had been injecting themselves every day, they did not want to switch to something new. They were doing fine on the old medication so felt no need to change.

What do you consider to be your most significant research findings?
My biggest contribution to understanding the pathology of Cooley’s anemia, I believe, is clarifying the role of excess α globin in causing the severity of the anemia. It had been thought before my work way back in the ’60s that the lack of b globin was primarily responsible. But it was both the reduced b globin and the excess α globin that was killing cells in the bone marrow that give rise to the red blood cells. The ability to detect the excess α globin protein in fetal blood led to the first antenatal — or prenatal — diagnostic assay for the disease in the ’60s and ’70s, before the use of DNA analysis for diagnosis became widespread. The test allowed parents who might have had other children with the disease and were therefore at risk to make informed decisions during a new pregnancy.
     The second would be my contribution to globin gene therapy. We started working with the idea of fixing the disease by adding a normal human b globin gene in mouse models 20 years ago and then recently were able to move to human subjects. In our human trials, we use a lentiviral vector that has less potential for side effects than other vectors used in gene therapy before. To date, two patients have received the treatment. The first patient did not receive enough cells with the new gene. The second patient seems to have enough cells with the new gene and is making significant amounts of new hemoglobin. For the last nine months, the second individual has not needed any transfusions. But we don’t know how long it will last and what side effects may emerge.
     Third, I am also proud of my work in trying to understand the regulation of the genetic switch from fetal hemoglobin to adult hemoglobin. In Cooley’s anemia, infants in utero survive using fetal hemoglobin, but soon after birth the fetal genes shut off and the adult hemoglobin genes including the human b globin gene, which is flawed, switch on. We discovered that a protein called Ikaros, a transcription factor, is very active in causing the switch from fetal to adult hemoglobin. Ikaros only works to make adult hemoglobin. If we could find an anti-Ikaros, such a molecule might leave the fetal hemoglobin genes on in patients and could potentially cure the disease.

Why did you become a hematologist?
In college I was the sports editor of the Columbia Spectator. I loved to write, but I knew I needed a day job and decided to go into medicine. I told the interviewer at Harvard that I wanted to help people. He said there were lots of things to do in medicine. I hadn’t done research in college or medical school, but after graduating from Harvard, I worked at the National Institutes of Health in a research laboratory and fell in love with the process of figuring out biological problems. I became interested in hematology because I always liked looking at blood cells under the microscope. Red blood cells and other blood cells are accessible for study, you can easily get samples, and I was intrigued by the idea that one blood stem cell, in the mouse at least, is responsible for making all the different cells of the blood. How does that happen? Why do things go wrong? Looking at blood also allows you to make diagnoses, and, even back then, there were treatments, such as transfusions, for many blood-based diseases.
     I was also very interested in the emerging field of molecular biology. After leaving the NIH, I came to New York to work with Paul Marks’49 at Columbia. He was running the only hematology program in the city working on the molecular biology of hemoglobin production in red blood cells. In the 1960s, I started out using the Clegg column [a column that allowed the separation of α and b globin molecules] to track the excess α globin. With time, I set up my own laboratory and moved on to studying mRNA and then the globin genes themselves, as new technology became available. I was always leapfrogging on the results of other scientists to keep moving forward.

What is next for you?
I officially retire from Columbia at the end of 2009. I am already working on my next book. It will be about my life in medicine as a doctor and a patient.

Arthur Bank, M.D.“Turning Blood Red”: An Excerpt
By Arthur Bank, M.D.
Linda De Pasquale is a survivor by all criteria. She has survived Cooley’s anemia amazingly well for 45 years, one of its longest survivors. Even apart from the burden of having Cooley’s anemia, her life has been one of great emotional turmoil. Yet, as she looks out the window of her condominium near Sandy Hook, New Jersey, and sees the endless Atlantic in its majesty on this sunny day, she is mostly smiling and upbeat. She is grateful for her life so far, and determined most of all to continue to enjoy it on her own terms.
     She has been receiving blood transfusions every two weeks for the past 44 years. And she has been injecting herself for 30 years, since 1977, with Desferal, the iron-chelating drug that has kept her iron levels within reasonable limits and thus kept her alive.
     “I first started getting Desferal intravenously for a week on and then a week off for a month, and then subcutaneously.” She is mindful of all who have since passed away. “Twenty years ago, there were several of us together getting transfused at New York Hospital [now NewYork-Presbyterian]. Today, there are very few older patients left. Why is that? I don’t know.”
     I tell her, “Neither do I.”
     “There must be different forms of Cooley’s anemia and maybe I have a mild one,” she says. I tell her that I don’t think so. “I have no sure answer but anyone who has required as many transfusions as you, and had a sister with the disease, must have the severest form,” I say. And she and I remain dumbfounded as to the why of her longevity, but both of us are happy and smiling that she is alive and well as we look out, from her new apartment, at the blue Atlantic, past the sandbar that is Sandy Hook. We see Long Island off in the distance, almost like a different world far away.

“Turning Blood Red: The Fight for Life in Cooley’s Anemia” by Arthur Bank was published in December 2008 by World Scientific Publishing Co. Excerpt printed with permission of publisher, author, and patient.

 

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