Son Shifts Autism Research’s Focus to Quest for a Drug
自閉症研究重點轉向藥物
By Claudia Dreifus

The biochemist Ricardo E. Dolmetsch has pioneered a major shift in autism research, largely putting aside behavioral questions to focus on cell biology and biochemistry.
生化學家杜梅契是自閉症研究重大轉變的先鋒，拋開行為學問題，專攻細胞生物學與生物化學。

Dr. Dolmetsch, 45, has done most of his work at Stanford University in California, although he has taken a leave to join Novartis Institutes for BioMedical Research in Cambridge, Massachusetts.
45歲的杜梅契多數研究是在加州史丹福大學做的，目前請假加入麻州劍橋的諾華生醫研究院。

“Pharmaceutical companies have financial and organizational resources permitting you to do things you might not be able to do as an academic,” he said. “I really want to find a drug.”
他說：「製藥公司的財務與組織資源讓你能做學者未必能做的研究。」

A condensed version of an interview with Dr. Dolmetsch follows.
以下是他受訪的紀要。

Q. Did you start out your professional life studying the biochemistry of autism?
問：你一開始就研究自閉症的生化原理嗎？

A. No. In graduate school and as a postdoc, I’d done basic research on the ion channels on the membranes of cells.
答：不。在研究所與博士後時期我做的是細胞膜離子通道基礎研究。

Then, around 2006, my son who was then 4 was diagnosed with autism. We had suspected it. He did all sorts of things that were very unusual.
接著，大約2006年，我四歲的兒子確診罹患自閉症。我們早就猜到了。他會做各種很怪的事。

Q. Given the signs, why did you wait that long to seek a diagnosis?
問：症狀出現後為何等那麼久才尋求診斷？

A. I’m from Latin America, and my Latin thing was, “This is the way boys are.” After a while, his teachers said, “You probably ought to have him seen.”
答：我來自拉丁美洲，傳統態度是，「男孩就是這樣」。過了一段時間，老師們說：「你可能應該帶他就診。」

Autism, it turns out, is a whole bunch of diseases, clumped into one big group. After many confusing months, we finally heard “autism.” My response immediately was: “We’re not going to leave any stone unturned to help him.”
自閉症是多種疾病合成的一個大群組。困惑數月後，我們終於聽到「自閉症」一詞。我當下的反應是：「我們將竭盡所能幫助他」。

It turned out, however, that there weren’t many medical things to be done. There are behavioral approaches which can improve things, though none are a cure. Once we understood this, I started really changing the direction of my lab to things more directed towards autism and neurodevelopmental diseases. These include childhood epilepsy, fragile X syndrome and schizophrenia.
然而我們發現醫學上可做的不多。一些行為學方法可改善情況，卻都無法根治。明白之後我開始改變實驗室的研究方向，更著重與自閉症及神經發展疾病有關的東西，包括童年癲癇、X染色體脆折症與精神分裂症。

Q. So fate chose your research topic for you?
問：也就是說，命運決定了你的研究主題？

A. I don’t believe in “fate.” There was motivation. I started reading and realized the one big change that could give autism research some traction was the genetics revolution. Because of it, we can now identify gene mutations associated with the neurodevelopmental diseases – there are about 800 different mutations associated with autism. What’s missing, in most cases, is an understanding of what the mutations do so that we might then alter the molecular biology of the nervous system’s cells to make them function more normally.
答：我不相信「命運」。是有了動機。我開始閱讀，明白可能使自閉症研究有所突破的一大改變是遺傳學革命。如今，它讓我們得以辨識與神經發展疾病有關的基因突變。與自閉症有關的突變約有800種。多數情況下我們欠缺的是對突變作用的理解。這種理解或可幫助我們改變神經系統細胞的分子生物作用，使它運作更正常。

For the best results, you need to study actual human tissue.
要有最好的結果，就得研究真正的人體組織。

That got me thinking about cancer, where there’s been a revolution in treatment. When you get breast cancer – which like autism isn’t one disease – the tumor is molecularly characterized to help oncologists understand what cancer you have and what sort of treatments will work against it. Could we find something similar for the neurodevelopmental diseases?
這使我想到治療上已有革命性進展的癌症。如果妳患了乳癌（與自閉症一樣均非單一疾病），腫瘤的分子特色能讓腫瘤專家確定妳罹患哪種癌，該如何治療。我們能否為神經發展疾病找到類似方法？

Q. There’s no way to obtain brain tissue samples from living children with autism. Is this a stumbling block for your research?
問：我們無法取得自閉症兒童的大腦組織樣本。對你的研究來說是障礙嗎？

A. Yes. But there’s a way around it. Shinya Yamanaka [who won a Nobel Prize in 2012] has been reprogramming human skin cells to become stem cells and thus all kinds of other cells, including the cells of the nervous system. Thanks to him, we can now make nerve cells that look like the neurons of a human embryo. If you could take skin cells from an autistic child and turn them into neurons, we might be able to understand what kind of autism the child has and what chemical fixes might help.
答：是。不過還是有解。日本學者山中伸彌（2012年諾貝爾醫學獎共同得主）已能誘導人類皮膚細胞成為幹細胞與各種細胞，包括神經系統細胞。有了這個研究成果，我們現在已可製造看似人類胚胎神經元的神經細胞。若能取得自閉兒的皮膚細胞，再把它變成神經元，或許就能瞭解他患了何種自閉症，並找出可能有幫助的化學療方。

Q. You do a lot of fieldwork with actual patients. Why do it?
問：你以真實病人為對象做了許多實際研究。為什麼？

A. You get a lot of information when you actually talk to parents. I’m convinced this research is most effective when you start with the patients.
答：與病人的父母交談，會獲得許多訊息。我深信從病人著手，這種研究會產生最大的效果。

Another thing: I find that meeting families is motivating. There is a big difference between working on some sort of associated mutation and actually meeting somebody affected.
另外一點。我發現，與病人家屬見面會產生激勵作用。埋首研究某種相關突變與實際探視受到影響的人，差別可大了。

原文參照：
http://www.nytimes.com/2014/03/25/science/seeking-autisms-biochemical-roots.html

2014-04-08聯合報/G5版/UNITEDDAILYNEWS 陳世欽譯 原文參見紐時週報十版下