I recently read a fascinating book, The Emperor of All Maladies by Siddhartha Mukherjee.  This year’s Pulitzer Prize winner for non-fiction is an extraordinary account starting with a discussion of the history of cancer from ancient times and rapidly moving to a discussion of the history of leukemia dating from the mid-19th century. The tale then moves rapidly to review the work of the “father of chemotherapy”, Sydney Farber, in the early and late 1940s.

This book is amazing because it is a serious science and medical history, yet it is engaging, even thrilling to read. Needless to say as a physician, I’m fascinated with medicine and science and as a former college history major, I love what history can teach us that we can apply today. If you take the time to read this, you’ll learn how a complex human disorder that potentially can affect us all has been understood piece by piece and to an extraordinary extent has been successfully treated, and in some cases, even “cured”.

Cancer is not one condition. It is a conglomerate of many diseases that share a common biology: the potential for any cell type to change and become malignant, to grow at uncontrolled rates and to spread from one location to another in the body. Cancer has many causes. We certainly know that tobacco smoking is a primary cause of lung cancer. Women who have a certain gene for breast cancer susceptibility have much-increased rates of breast and ovarian cancer. Screening and prevention strategies like mammography, pap smears and colonoscopy have reduced the mortality of their respective cancers by huge degrees.

When I started studying medicine, childhood leukemia was universally fatal. Now it is likely to be “cured”! How did the understanding, prevention and treatment of cancer get from where it was in the 1940s to today? In 1971, through the leadership of some powerful political allies, led by Mary Lasker, a New York philanthropist and socialite, the National Cancer Act was passed and signed by President Richard Nixon. Thus began America’s journey in the “War Against Cancer” which continues today. (Humm… Why do we Americans need to have wars to get things done; cancer, poverty, AIDS, terror? – autism??) Now forty years later we have achieved a great deal indeed. The riddle of cancer has not been solved, but we’ve made huge progress in understanding and treating it.

So what does any of this have to do with autism?  

I recently attended the 10th International Meeting for Autism Research (IMFAR). The Autism Blog has had other tidbits from the largest such meeting to date. On the evening prior to the meeting’s start I joined my old friend Dr. Marty Stein, one of the pioneers of Developmental/Behavioral Pediatrics, at a colleague’s house for their monthly journal club. I was asked to tell what I thought was new and significant in autism. During the course of the evening, I asked the question, “How long do you think it will be before we have a “cure” for autism”? Some thought I was joking but I wasn’t. I’m going to ask that same question to you all out there in the blogosphere at the end of this post.

What do I mean by a “cure”?

Diabetes is not cured (not yet). But it is managed, effectively treated and lives are prolonged. HIV/AIDS isn’t prevented or cured yet but when treated correctly people can live long, healthy lives. Certain kinds of childhood leukemia are eradicated in over 80% of children presenting for treatment today. And we can prevent and treat lots of serious diseases such as heart disease, arthritis, asthma, and other chronic conditions.  

Vaccines have prevented and even eradicated many terrible infectious diseases. When I was a medical student I spent a summer doing research on a diarrhea ward in Karachi, Pakistan. I visited a whole ward of people dying of smallpox. Smallpox doesn’t exist anywhere any more. “Cure” may mean many things, from prevention and eradication to management that substantially reduces symptoms so that affected individuals are indistinguishable from those not so affected. Why should this not be the future for autism? 

Two talks I heard at IMFAR have even more strengthened my belief that we will do what we’ve done with cancer with Autism Spectrum Disorders. Dr. Eric Courchesne is a neuroscientist at UC San Diego. He was one of the first to demonstrate that there appears to be more rapid growth in the brains of children with autism during the 6-24 month period than for typically-developing children. He is continuing to try to understand why some children with autism appear to have more brain cells in their frontal and parietal lobes that are then not appropriately pruned and connected the way that typical brain development occurs.

Is this part of the puzzle of why children with autism have such trouble learning communication and social behavior? We suspect that certain genes are responsible for this rapid production of extra neurons. But Dr. Courchesne asked the equally intriguing question, “Perhaps it is not that too many cells are created, but rather that the repair mechanisms, which would limit the number of unconnected cells, is faulty.” (This is a big over simplification of some very complex neuroscience). Perhaps what effective therapy, (including behavioral treatments) does is rid the brain of these poorly connected cells and their pathways.

This is a huge paradigm shift from thinking about “bad” genes causing problems to finding and turning on the genes that fix things in the brain. Here’s the analogy to cancer.  In our DNA, we all have both oncogenes (genes that cause cancerous growth) and tumor suppressor genes (genes that suppress growth). Maybe finding the genes that are analogous to tumor suppressor genes in the brain, mechanisms that correct the overgrowth of under-connected neurons may be part of the answer.

Dr. Ricardo Dolmetsch, a brilliant young neuroscientist from Stanford, gave another astounding talk. Dr. Dolmetsch became interested in autism research when his own son was diagnosed. He is a basic scientist who studies calcium channels, the highly regulated “holes” in cell membranes that allow critical ions such as sodium and calcium to enter and leave each cell. 

He’s been studying a very rare condition, Timothy Syndrome (TS). TS causes heart arrhythmias as well as an autism-like picture among other features. The genes that cause TS are known but how they cause clinical manifestations are not. So Dr. Dolmetsch is able to, in the laboratory, take a tiny plug of skin from a patient, grow the skin fibroblasts and change those skin fibroblasts into stem cells. Then with more biologic magic, he turns those patient’s now transformed stem cells into cardiac cells and neurons. He showed a beautiful movie of normal transformed cardiac cells beating rhythmically 60 times a minute in a cell culture. Then transformed TS patient cardiac cells were shown beating very irregularly. Using such a cell preparation, numerous drugs could be tested in the laboratory to find the best one to correct the arrhythmia in that particular patient. 

Wow! Imagine being able to take a patient’s unique cells and study them in the lab, figure out what doesn’t work right in their neurons and then craft a therapy just for those cells. Sounds like science fiction but so did chemotherapy for cancer just 50-60 years ago. Just as we have made huge progress in the prevention, early detection and treatment of many forms of cancer, I believe that we will do the same thing for Autism Spectrum Disorders. 

The analogies with cancer research are not that far off. Autism is not one condition. There are many “autisms”. But like cancer, the “autisms” share similarities. Both have significant genetic causes, both may have environmental triggers and both require concerted community, political and scientific effort. 

So when will we find cures for these “autisms”? What do you think: 10 years, 25 years, 100 years, never? 

Send us your comments. Let’s have a conversation.