By Anne McLeod, MD
Highlighting an ASH meeting that
featured more than one hundred abstracts on basic and clinical scientific
breakthroughs in the study of red-cell disorders was the presentation of the
first Ernest Beutler Lecture and Prize to two scientific giants of thalassemia
research, Dr. Thomas Maniatis, the Jeremy R. Knowles Professor of Molecular and
Cellular Biology at Harvard University, and Dr. Yuet Wai Kan, the Louis K.
Diamond Professor of Hematology at the University of California – San
Francisco. This award was recently established to honor the late Dr. Ernest
Beutler (1928 - 2008), past ASH president and a physician-scientist active in
the field of red-cell disorders for more than 50 years. The award is a two-part
lectureship that recognizes major translational advances related to a single
topic. It honors two individuals, one who has enabled clinical or translational
advances by basic science work and the other for achievements in clinical
science or translational research. Drs.
Maniatis and Kan
have made ground-breaking contributions to the diagnosis and treatment of
thalassemia through the development of techniques that led to the cloning of
the globin genes in the 1970s,
pioneering molecular genetic studies for the prenatal and postnatal
DNA-based diagnosis of thalassemia.
Both Drs. Maniatis and Kan have been previously
honored by ASH for their work. Dr. Maniatis received the E. Donnall Thomas
Lecture and Prize in 1994, and Dr.
Kan, a past ASH president, was
presented with the Dameshek Prize in 1979 and the Stratton Medal in 1980.
During the Beutler Lecture, Dr. Maniatis discussed his pivotal role in the
development of gene cloning methods and their application to studies of globin
gene organization and expression. His advances in basic science were translated
by Dr. Kan
into advances in the diagnosis of thalassemia. In his lecture, Dr. Kan
addressed the development of prenatal and DNA diagnostic tests for thalassemia,
current and experimental treatments, and the impact of stem cell technology on
future therapy for this disease.
Both Drs. Kan and Maniatis stated
that they were honored and humbled to be the first to receive the Prize. “It
means a great deal to me as I knew Ernie for many years,” Dr. Kan
said. Dr. Beutler was the ASH president in 1979 when Dr. Kan received the
Dameshek Prize, giving this award special meaning for Dr. Kan. Dr. Maniatis was
honored to receive the award because it “is based on work my laboratory carried
out many years ago, which means that work had a lasting impact.”
Although their research has moved
in different directions over the years since they were first honored by ASH,
some aspects are unchanged, Dr. Maniatis shared. “The fundamental mechanistic
approaches I apply to my current research are the same as those I took 15 years
ago, but I have moved from erythroid cells to neurons. During the past few
years, I have directed much of my efforts toward understanding disease
mechanisms in the neurodegenerative disease amyotrophic lateral sclerosis
(ALS).” Dr. Kan has continued to work in the field of
thalassemia, but said, “In the earlier days, we worked on the classification of
hemoglobinopathies and thalassemia. Our more recent work is to investigate the
treatment of these diseases.” Dr. Kan used Dr. Maniatis’ work to achieve some of his early
successes: “We turned to DNA tests [when working toward prenatal diagnosis] of
these conditions, and the cloning of globin genes by Tom Maniatis greatly
facilitated these tests,” Dr.
Kan explained. Today both feel
that keeping up with ever-changing advances in biomedical research and
maintaining focus on important problems are two of the biggest challenges they
continue to face in their careers.
Dr. Kan discovered his passion for hematology,
as many of us do, after treating a patient. “I was first attracted to study
thalassemia when I was asked to see a newborn affected by homozygous
alpha-thalassemia. Eventually, I made thalassemia and sickle cell my main
research focus, which led to my interest in genetics.” Dr. Maniatis became
interested in genetics in graduate school; ironically, a mid-1970s moratorium
on all research involving recombinant DNA led to his joining the lab of James
Watson. There, the birth of his classic book Molecular Cloning: A Laboratory
Manual was born. Few graduate students have made it through a molecular biology
project without referencing this collection of scientific recipes.
The rewards of working in the field
of human genetics have not ceased for either award recipient. For Dr. Kan
the discovery of DNA polymorphisms and the wide application of DNA tests
continue to keep him interested and enthusiastic. For Dr. Maniatis, the rewards
lie in “the excitement of discovery and the impact of these discoveries on
human diseases, and, second, the gratification of mentoring young scientists
who go on to make important independent contributions to research and
teaching.” Dr. Beutler would be proud indeed.
Dr. McLeod indicated no relevant conflicts of
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