His Brother's Keeper: A Story from the Edge of Medicine
http://www.100md.com
《新英格兰医药杂志》
Jonathan Weiner is a talented science writer. He won a Pulitzer Prize for his book on Darwin's finches and a National Book Critics Circle Award for one on the genetics of behavior in drosophila. Here he tells the poignant story of Stephen Heywood, a carpenter whose right hand became weak in 1997; he was 28 years old. The diagnosis of amyotrophic lateral sclerosis (ALS) was confirmed later; only 5 percent of all people with ALS have symptoms before the age of 30. Also known as Lou Gehrig's disease, ALS is incurable and lethal.
Stephen's brother, Jamie, was working as an assistant to Nobel Prize winner Gerald Edelman at the Neurosciences Institute outside San Diego, California. An engineer trained at the Massachusetts Institute of Technology, Jamie Heywood was hired to bring think-tank discoveries to market, and with his commitment to saving his brother's life, he came upon the idea of gene therapy. Weiner heard about the plan from a neuroscientist friend and was himself primed for the project. He had promised to write an article for the New Yorker, and he had a personal interest: his mother had been diagnosed with another nasty neurologic disease, a parkinsonism–behavior–dementia disorder, also incurable. Weiner contacted Jamie Heywood and rapidly became part of the project himself. He was attracted by the pursuit of an idea at "the edge of medicine," a fuzzy line where hope blurs with harsh reality.
Jamie created a foundation to develop the idea. He enlisted the aid of two of the most outstanding ALS investigators: Robert Brown at Harvard, who had confirmed the diagnosis, and Jeffrey Rothstein at Johns Hopkins, who had found that the malfunction of a particular gene in ALS could result in the accumulation of glutamate, a natural neurotransmitter; an excessive amount of glutamate could be toxic to motor neurons. Jamie also found Matthew During, a Philadelphia neurosurgeon, who would insert corrective genes directly into Stephen's spinal cord.
Weiner tells the story as though it were powerful fiction by focusing on the personal aspects of the case but not ignoring the social issues. In the end, gene therapy was halted when a teenage volunteer in a trial at the University of Pennsylvania died. So instead of the gene, Stephen's doctors injected stem cells into his cerebrospinal fluid; this was not harmful but gave no benefit.
Some call it "guerrilla science" when families direct research themselves because they are impatient with the bradykinetic pace of conventional research. It can take years to develop an experimental approach, prepare an application for funding, wait until the application is reviewed and revised, and finally get started on the research. Stephen's family did not know how long he would live. In fact, he is still alive in 2004, but at the time it seemed that he might live only a year or two. They were understandably in a hurry.
Rothstein was involved at two levels. His research findings had provided the idea of gene therapy. By the time that approach was scratched, he had become a leader in stem-cell research. Throughout the book, Rothstein is quoted as a voice of caution; animal experiments should precede human application, he warns, to ensure safety and to provide evidence of efficacy.
In the end, Jamie Heywood raised millions of dollars — a story in itself. His foundation's Web site now lists six doctoral scientists who focus on "high-throughput drug development" and screen thousands of compounds already approved for other uses by the Food and Drug Administration. The trick is to develop an assay that reliably predicts which drugs could be beneficial in treating ALS.
Among the questions raised in the book are whether the company could raise more research money as a for-profit or a nonprofit entity, whether someone with a deadly disease can give truly informed consent to participate in risky human experiments, whether nonscientists can "pick something to do that the researchers in the field didn't pick," and whether conventional science is too timid in moving from laboratory to sick people.
Can we learn from this experience? Stephen's hope rests on the remarkable progress made in the past decade and now accelerating worldwide. Most funding comes from the National Institutes of Health; private donors choose from organizations like the Muscular Dystrophy Association or the ALS Association, family sponsors like the Heywoods or the Estess family's Project ALS, or medical schools. Supporting fundamental ALS research is laudable in all these approaches.
In the meantime, both of the Heywood brothers have married and had children. Readers will appreciate their fascinating story and will certainly join them in the hope that basic research will pay off. All of us who are engaged in patient care and research in ALS devoutly believe it will, but when?
Lewis P. Rowland, M.D.
Columbia University Medical Center
New York, NY 10032
lpr1@columbia.edu(By Jonathan Weiner. 356 p)
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Jamie created a foundation to develop the idea. He enlisted the aid of two of the most outstanding ALS investigators: Robert Brown at Harvard, who had confirmed the diagnosis, and Jeffrey Rothstein at Johns Hopkins, who had found that the malfunction of a particular gene in ALS could result in the accumulation of glutamate, a natural neurotransmitter; an excessive amount of glutamate could be toxic to motor neurons. Jamie also found Matthew During, a Philadelphia neurosurgeon, who would insert corrective genes directly into Stephen's spinal cord.
Weiner tells the story as though it were powerful fiction by focusing on the personal aspects of the case but not ignoring the social issues. In the end, gene therapy was halted when a teenage volunteer in a trial at the University of Pennsylvania died. So instead of the gene, Stephen's doctors injected stem cells into his cerebrospinal fluid; this was not harmful but gave no benefit.
Some call it "guerrilla science" when families direct research themselves because they are impatient with the bradykinetic pace of conventional research. It can take years to develop an experimental approach, prepare an application for funding, wait until the application is reviewed and revised, and finally get started on the research. Stephen's family did not know how long he would live. In fact, he is still alive in 2004, but at the time it seemed that he might live only a year or two. They were understandably in a hurry.
Rothstein was involved at two levels. His research findings had provided the idea of gene therapy. By the time that approach was scratched, he had become a leader in stem-cell research. Throughout the book, Rothstein is quoted as a voice of caution; animal experiments should precede human application, he warns, to ensure safety and to provide evidence of efficacy.
In the end, Jamie Heywood raised millions of dollars — a story in itself. His foundation's Web site now lists six doctoral scientists who focus on "high-throughput drug development" and screen thousands of compounds already approved for other uses by the Food and Drug Administration. The trick is to develop an assay that reliably predicts which drugs could be beneficial in treating ALS.
Among the questions raised in the book are whether the company could raise more research money as a for-profit or a nonprofit entity, whether someone with a deadly disease can give truly informed consent to participate in risky human experiments, whether nonscientists can "pick something to do that the researchers in the field didn't pick," and whether conventional science is too timid in moving from laboratory to sick people.
Can we learn from this experience? Stephen's hope rests on the remarkable progress made in the past decade and now accelerating worldwide. Most funding comes from the National Institutes of Health; private donors choose from organizations like the Muscular Dystrophy Association or the ALS Association, family sponsors like the Heywoods or the Estess family's Project ALS, or medical schools. Supporting fundamental ALS research is laudable in all these approaches.
In the meantime, both of the Heywood brothers have married and had children. Readers will appreciate their fascinating story and will certainly join them in the hope that basic research will pay off. All of us who are engaged in patient care and research in ALS devoutly believe it will, but when?
Lewis P. Rowland, M.D.
Columbia University Medical Center
New York, NY 10032
lpr1@columbia.edu(By Jonathan Weiner. 356 p)
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