Autism:There's Hope on the Horizon
Early in his career, Dr. Wigler developed methods for engineering animal cells with his collaborators at Columbia University, Richard Axel and Saul Silverstein. These methods are the basis for many discoveries in genetics, and the means for producing medicines used to treat heart disease, cancer, and strokes. Dr. Wigler continued his genetic explorations, and in the early 1980s isolated the first human cancer genes. In the mid 80s, Dr. Wigler and his collaborators demonstrated conservation of cellular pathways in humans and yeast, thereby providing deep insights into the function of the cancer genes.
In the early 1990s, Drs. Wigler and Clark Still developed a method for building vast chemically indexed libraries of compounds, an approach that is still in use for drug discovery. During the same period, Wigler’s group developed the concept and applications of representational analysis, RDA, which led to identifying new cancer genes and viruses. He later enhanced this concept through use of microarrays, a method now widely used commercially for genetic typing.
Dr. Wigler’s research is presently focused on the genomics of cancer and genetic disorders. He expects this work will eventually improve the targeting of cancer treatment and lead to early detection tests for cancer. His studies in human genetics led to the discovery of a vast source of genetic variability known as copy number variation (CNV), and to the breakthrough that spontaneous germline mutation is likely to be a contributing factor in autism. His genetic theories and methods suggest to new approaches to understand many other cognitive and physical abnormalities.
For his fundamental contributions to biomedical research, Dr. Wigler is a recipient of numerous awards and honors and is a member of the National Academy of Science and the American Academy of Arts and Sciences.
Question: What will be the impact of your\r\n research on autism\r\ntreatment?\r\n\r\n
Michael Wigler: Yes, well there are two ways\r\n in which our\r\nwork could inform clinical treatment. \r\nIn the area of early diagnosis. \r\nIf there’s a child and it’s developing—it’s giving off \r\ndevelopmental\r\nclues there might be something wrong, if we had a list of the kind of \r\ngenetic\r\nlesions we could screen for, we might be able to determine early on that\r\n this\r\nchild is going to develop a form of autism. And \r\nif it’s correct—most disorders are correctable to the\r\nextent that they are correctable, are more correctable early than late, \r\nwhen we\r\nknow how to correct or treat, we’ll be able to start that sooner. So, early diagnosis is going to be\r\nimportant for any disorder. That’s\r\none way.\r\n\r\n
Another way is children with a particular genetic \r\nabnormality,\r\nthat is, those children who share genetic abnormality, may have one \r\nparticular\r\nway of treating them that’s different than children who have a different\r\nabnormality. We will only learn\r\nabout that once we can separate these children according to their \r\ngenetic\r\nabnormalities. That’s going to\r\ntake many, many years.\r\n\r\n
The third way is that in some cases, we will be \r\nidentifying\r\ngenes, who by their very nature, tell us this is a correctable, \r\ntreatable,\r\nsyndrome. For example, we find a\r\ngene that’s involved in metabolism. \r\nThis child is perhaps got really a storage disorder of some type,\r\n but\r\naltering the diet in those cases might be able to treat the child. But unfortunately, we don’t yet know\r\nthe identities of the autism genes. \r\nWe have regions and there’s a huge effort underway. \r\n I would say, in particular by doing\r\nvery exhaustive sequence comparisons of children to their parents, we \r\nwill\r\nidentify the actual culprit genes. \r\nAnd that will take us two to four years. And\r\n there may be, unfortunately, I’m estimating around 400\r\nsuch genes that each one of which can cause autism. But\r\n when we have those genes, we see what they do; we can\r\nsee what pathways they are interacting with, some of those will suggest\r\nimmediately treatments that can be tested. We \r\nwill be able to make animal models and test drugs in\r\nanimals to correct these things.\r\n\r\n
So, in general, the way to understand a disorder is\r\n to\r\nunderstand its causes and then address those causes. In\r\n the case of autism, most people would agree, I think most\r\nscientists would agree the causes are genetic, and we have a pathway to\r\ndiscover the genes. So it will be\r\neasier to diagnose, classify by diagnosis into behavioral and even drug\r\ntreatments, and discover new drug treatments.
Recorded April 12, 2010
New research on the underlying causes of autism could soon lead to earlier diagnoses and better treatments.
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