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Science and technology
科學(xué)技術(shù)
Arthritis and botulinum toxin
關(guān)節(jié)炎與肉毒桿菌毒素
Something to celebrate
值得慶賀
Botulinum toxin may help relieve chronic pain
肉毒桿菌毒素也許能夠幫助緩解慢性疾病的痛苦
An inflammatory problem
炎癥的痛楚
ARTHRITIS is the bane of millions of lives.
關(guān)節(jié)炎是數(shù)百萬人的噩夢(mèng)。
Though it comes in many forms, their common theme is inflammation of the tissues around a joint in the skeleton.
關(guān)節(jié)炎有多種形式，但它們共同的特征是關(guān)節(jié)處組織的炎癥反應(yīng)。
Treatment is merely palliative: anti-inflammatory drugs, painkillers or both.
對(duì)此的治療手段往往是治標(biāo)不治本：消炎藥，止痛藥，或者兩者同時(shí)用。
But a piece of research published this week in Biochemistry, by Edwin Chapman of the University of Wisconsin and his colleagues, offers arthritis sufferers hope from a strange quarter: botulinum toxin.
但是由威斯康辛大學(xué)埃德文·查普曼博士以及他的同事們?cè)诒局苌锘瘜W(xué)雜志上的發(fā)表的一項(xiàng)研究，為關(guān)節(jié)炎患者提供了希望：肉毒桿菌毒素。
This toxin is one of the most dangerous substances on earth.
這種毒素是地球上最危險(xiǎn)的物質(zhì)之一，
It is made by a bacterium called Clostridium botulinum.
它是由一種叫肉毒桿菌的細(xì)菌合成。
Even a small amount is enough to kill a healthy adult.
僅僅很小的量就足以殺死一個(gè)健康成年人。
The toxin molecules attach themselves to a protein called synaptotagmin, which is found on the surface membranes of nerve cells at their junctions with muscle cells.
這種毒素能結(jié)合到一種叫做synaptotagmin的蛋白上，SYT則位于神經(jīng)肌肉接頭處神經(jīng)細(xì)胞的細(xì)胞膜表面。
Thence they are ingested into the cell, where they disable another protein, SNAP-25, the role of which is to help release a chemical messenger called acetylcholine.
然后這種毒素被吞入細(xì)胞內(nèi)部，進(jìn)而讓另外一個(gè)叫SNAP-25的蛋白失活，SNAP-25的作用是幫助一種叫乙酰膽堿的化學(xué)信使的釋放。
This messenger’s job is to tell muscle cells to contract. Without that signal, muscles stops working. If this happens all over the body, death is rapid.
這種化學(xué)信使的作用則是讓肌肉細(xì)胞進(jìn)行收縮。沒有這種信號(hào)的話，肌肉便停止工作了。如果全身都發(fā)生這樣的情況，死亡便接踵而來。
Inject the toxin locally, though, and you can do some good.
然而局部注射肉毒素還能帶來好處。
It wipes away frown lines and other wrinkles, which are caused by overstimulated muscles,
它能撫平額頭和其他部位的皺紋，這些皺紋恰恰是因?yàn)榧∪獗贿^度刺激引起的。
thus allowing ageing celebs to appear on the covers of gossip magazines without embarrassment.
它使得那些上了年紀(jì)的名流們毫無尷尬的出現(xiàn)在街頭雜志的封面。
More seriously, it is used to treat disorders ranging from headaches to muscle spasms.
它更為嚴(yán)肅的用途是治療各種生理紊亂，包括從頭痛到肌肉痙攣。
It only works, however, in cells that have synaptotagmin on their surfaces.
然而，它僅僅能在那些表面具有SYT蛋白的細(xì)胞中起作用，
Which is where Dr Chapman comes in.
這正是查普曼博士的切入點(diǎn)。
Inflammation is also caused by chemical signalling.
炎癥反應(yīng)同樣是由化學(xué)信號(hào)引起的。
Cells called macrophages summon all sorts of others to an injury, to try to repair it.
巨噬細(xì)胞召集其他免疫細(xì)胞到達(dá)受傷處，并試圖修復(fù)傷害。
If repair cannot be effected, though, the signalling never stops.
但如果修復(fù)不起作用，則這些信號(hào)就不會(huì)停止。
The swelling causes pain, and the patient suffers.
腫痛造成痛苦，而病人只能忍受。
But macrophage signalling also involves SNAP-25, so Dr Chapman thinks he can use botulinum toxin to shut the cells up.
但是巨噬細(xì)胞的信號(hào)通路中也包括SNAP-25，因此查普曼博士想，他能夠用肉毒素來關(guān)閉這些免疫細(xì)胞。
The problem is that macrophages have no synaptotagmin on their surfaces.
問題在于，巨噬細(xì)胞的表面并沒有SYT蛋白，
They do, though, have other proteins, called Fc receptors.
他們表面有的是另外一種被稱為Fc受體的蛋白。
What is needed is a way to get toxin molecules to attach themselves to Fc receptors.
現(xiàn)在只需要找到一個(gè)辦法，讓肉毒素結(jié)合到Fc受體上去，
And this is what Dr Chapman thinks he has managed.
而查普曼博士認(rèn)為，他辦到了這一點(diǎn)。
His trick is to link each molecule to an antibody.
他的絕招是將每個(gè)分子與抗體連接起來。
An antibody is a protein that binds to a hostile invading organism.
抗體是一種能結(jié)合入侵有機(jī)體的分子，
If this does not kill the invader outright, then it acts as a flag for the bug in question to be eaten by a macrophage.
如果抗體不能馬上殺死入侵者，則它將作為入侵者的一個(gè)標(biāo)記，使得它們有可能被巨噬細(xì)胞所吞噬，
That happens when the antibody that is attached to the invader also attaches itself to an Fc-receptor molecule.
這個(gè)過程只有當(dāng)結(jié)合在入侵者上的抗體同時(shí)也能和Fc受體分子結(jié)合時(shí)才會(huì)發(fā)生，
This done, the invader is ingested.
而這個(gè)步驟一完成，則入侵者就被吞噬了。
Dr Chapman’s plan was to use this mechanism to get macrophages to eat toxin molecules.
查普曼博士的計(jì)劃是，利用這個(gè)機(jī)制，讓巨噬細(xì)胞把肉毒素吞進(jìn)去，
Once inside, they would disable SNAP-25 and thus stop the release of signalling molecules in the way they do in nerve cells.
而進(jìn)入細(xì)胞之后，它就能使SNAP-25失去活性，從而像在神經(jīng)細(xì)胞中一樣，阻止信號(hào)分子的釋放。
The result, the theory goes, would be an end to the chronic inflammation that arthritis causes, and thus to the chronic pain.
如果這個(gè)理論可行，那么由關(guān)節(jié)炎所導(dǎo)致的慢性炎癥將被終結(jié)，同時(shí)被終結(jié)的，還有長期以來的痛苦。
The first stage works.
第一步看起來是可行的。
The toxin/antibody complex successfully gloms onto the macrophages.
肉毒素與抗體的復(fù)合物成功地黏附上巨噬細(xì)胞，
The toxin does get inside them.
肉毒素確實(shí)進(jìn)入了巨噬細(xì)胞內(nèi)部，
And the cells do stop signalling.
這些細(xì)胞也的確中止了信號(hào)通路。
It is a long way from there to a treatment,
從這一步到治療仍有很長的路要走，
but Dr Chapman has made the trick work in mice as well as Petri dishes.
但是查普曼博士已經(jīng)用這個(gè)方法在培養(yǎng)皿的細(xì)胞中和在老鼠身上獲得了成功。
Many more animal trials will be needed before it can be tested on people.
在人體上進(jìn)行測(cè)試前，還需要完成更多的動(dòng)物實(shí)驗(yàn)，
But for those who suffer the chronic pain of arthritis, it is a hopeful start.
但是對(duì)于那些正在長期忍受關(guān)節(jié)炎痛苦的人們來說，這是一個(gè)充滿希望的開始。
