【雙語(yǔ)閱讀】疫苗能阻止藥物濫用嗎?.

　　疫苗能阻止藥物濫用嗎?人們也許能通過(guò)疫苗來(lái)阻止成癮藥物的使用。對(duì)藥物濫用者進(jìn)行免疫來(lái)對(duì)抗他們受到的折磨是一個(gè)吸引人的課題。 原理上，這應(yīng)該不會(huì)太難。

　　Science and Technology

　　Combating addiction

　　Can a vaccine stop drug abuse?

　　It may be possible to vaccinate people against addictive drugs

　　THE idea of vaccinating drug addicts against their affliction is an intriguing one. In principle, it should not be too hard. The immune system works, in part, by making antibodies that are specific to particular sorts of hostile molecule. Such antibodies recognise and attach themselves to these molecules, rendering them harmless. Vaccines work by presenting the immune system with novel targets, so that it can learn to react to them if it comes across them again.

　　The problem is that the molecules antibodies recognise and react to are the big ones, such as proteins, that are characteristic of bacteria, viruses and other infectious agents. Small molecules, such as drugs, go unnoticed. But not for much longer, if Kim Janda of the Scripps Research Institute in San Diego has his way. In a paper just published in the Journal of the American Chemical Society, Dr Janda and his colleagues suggest how a vaccine against methamphetamine, a popular street drug, might be made. If their method works, it would open the possibility of vaccinating people against other drugs, too.

　　The idea of a methamphetamine vaccine is not new. The problem is getting the immune system to pay attention to a molecule that is such a small target. The way that has been tried in the past is to build the vaccine from several components.

　　First, there is a large carrier protein that forms a platform for the target. Then there is the target itself, a set of smaller molecules called haptens that are attached to the carrier. These may either be the drug in question or some analogue of it that, for one reason or another, is reckoned to have a better chance of training the immune system. Finally, there is a chemical cocktail called an adjuvant that helps get the immune system to pay attention to the carrier protein and the haptens. Dr Janda noticed that past experiments on methamphetamine vaccines had all revolved around tweaking either the carrier protein or the adjuvant, rather than tinkering with the haptens.

　　He thought he might be able to change that, on the basis of work he had carried out previously, trying to design a vaccine against nicotine. In particular, nicotine is a highly flexible molecule. That makes it hard for the immune system to recognise. To overcome this, his team on the nicotine project had to work out how to fix their haptens to the carrier protein in a way that rendered them less capable of twisting and turning, and thus made them easier for the immune system to identify.

　　In the new study, Dr Janda and his colleagues report that they have performed a similar trick with methamphetamine haptens. They used computer models to visualise the haptens in three dimensions and thus work out how the molecules could be rearranged such that they could not spring, twist or turn when being examined by the immune system. In light of this information they designed six new methamphetamine-like. Once built, they attached the new hapten molecules to carrier proteins, mixed them with adjuvant, injected the results into mice and waited. After several weeks they tested the mice to see if the animals&apos blood contained antibodies to methamphetamine.

　　Of the six new haptens, three successfully provoked the mice to make such antibodies. As a bonus, one of those three also stimulated the production of antibodies against another widely used drug, amphetamine. That is still a long way from providing a working vaccine, but it is an important step forward. And if human immune systems react in the same way to the new vaccines as murine ones do, the day when a drug addict might be offered vaccination rather than opprobrium will have come a little closer.

　　【中文對(duì)照翻譯】

　　科技

　　打擊毒癮

　　疫苗能阻止藥物濫用嗎?

　　人們也許能通過(guò)疫苗來(lái)阻止成癮藥物的使用

　　對(duì)藥物濫用者進(jìn)行免疫來(lái)對(duì)抗他們受到的折磨是一個(gè)吸引人的課題。 原理上，這應(yīng)該不會(huì)太難。 免疫系統(tǒng)可以部分參與產(chǎn)生那些針對(duì)某些有害分子的抗體。 這些抗體可以識(shí)別并與那些有害分子結(jié)合，使他們變成對(duì)身體無(wú)害的物質(zhì)。 疫苗則是通過(guò)向免疫系統(tǒng)提供新的靶物質(zhì)的方法起作用的，因此當(dāng)免疫系統(tǒng)再次遇到這些物質(zhì)時(shí)，它就會(huì)知道該如何作出反應(yīng)。

　　問(wèn)題是抗體能識(shí)別和做出反應(yīng)的分子是大分子，比如蛋白質(zhì)，這是細(xì)菌，病毒和其他致病原的特征。 小分子，如毒品，就不被識(shí)別了。 如果位于圣迭戈斯克里普斯研究所的金-簡(jiǎn)達(dá)有解決辦法的話，這種情況就能結(jié)束了。 在剛出版的一期《美國(guó)化學(xué)會(huì)會(huì)志》中，簡(jiǎn)達(dá)博士在一篇論文中指出了一種對(duì)抗街上常見(jiàn)藥--甲基苯丙胺的疫苗可以被合成的方法。 如果他們的方法湊效的話，那將使給人們注射疫苗來(lái)對(duì)抗其他藥物成癮成為可能。

　　甲基苯丙胺疫苗的想法并非什么新鮮事。 問(wèn)題在于要使免疫系統(tǒng)對(duì)如此小的目標(biāo)做出反應(yīng)。 之前曾嘗試過(guò)的方法是利用幾種物質(zhì)共同構(gòu)建疫苗。

　　首先，要有一個(gè)大的載體蛋白來(lái)構(gòu)成給靶物質(zhì)的平臺(tái)。 然后是與載體結(jié)合的靶物質(zhì)本身，他們是一組叫做半抗原的較小的分子。 這些小分子可以是目標(biāo)藥物或其它一些類(lèi)似物，他們有這樣或那樣的理由被認(rèn)為能夠更好地鍛煉免疫系統(tǒng)。 最后，有一種叫做佐藥的雞尾酒幫助免疫系統(tǒng)對(duì)載體蛋白和半抗原做出反應(yīng)。 簡(jiǎn)達(dá)博士意識(shí)到過(guò)去對(duì)甲基苯丙胺的實(shí)驗(yàn)中，疫苗一直在周旋，使載體蛋白或佐藥發(fā)生扭曲，而非與半抗原互補(bǔ)。

　　他覺(jué)得基于之前所展開(kāi)的工作，他有能力改善那種情況，并嘗試設(shè)計(jì)出一種對(duì)抗尼古丁的疫苗。 尼古丁是一種尤其高活性的分子。 這使得免疫系統(tǒng)難以識(shí)別它。 為了克服這個(gè)問(wèn)題，他的尼古丁項(xiàng)目的團(tuán)隊(duì)必須使他們的半抗原以一種特定方式與載體蛋白結(jié)合，從而使得這些蛋白不易扭曲反轉(zhuǎn)，從而讓免疫系統(tǒng)更容易識(shí)別。

　　在一篇新的研究中，簡(jiǎn)達(dá)博士和他的同事指出他們用類(lèi)似的方法處理甲基苯丙胺半抗原。 他們利用電腦模型來(lái)展現(xiàn)三維半抗原并解決了分子重新排布的問(wèn)題，使他們?cè)诿庖呦到y(tǒng)檢查時(shí)無(wú)法彈出，扭曲，旋轉(zhuǎn)。 在該辦法的啟發(fā)下，他們?cè)O(shè)計(jì)出6種新的甲基苯丙胺樣的半抗原。 一旦構(gòu)建完成，他們把這些新的半抗原分子結(jié)合到載體蛋白上，并與佐藥混合，注射進(jìn)小鼠體內(nèi)，等待結(jié)果。 數(shù)周后他們檢測(cè)小鼠血液內(nèi)是否含有甲基苯丙胺的抗體。

　　在6種新的半抗原中，其中3種成功刺激小鼠產(chǎn)生這些抗體。 另外有一個(gè)意外收獲，在那3種當(dāng)中有一種可刺激產(chǎn)生另一種廣泛使用的藥物--苯丙安的抗體。 雖然距離能夠供應(yīng)疫苗的日子還有很長(zhǎng)一段路要走，但這是前進(jìn)中重要的一步。 如果人類(lèi)免疫系統(tǒng)對(duì)新疫苗的反應(yīng)機(jī)制就像鼠科動(dòng)物那樣的話，藥物成癮的人獲得的是疫苗而非外界辱罵的這一天的來(lái)臨就更近了。

　　疫苗能阻止藥物濫用嗎?人們也許能通過(guò)疫苗來(lái)阻止成癮藥物的使用。對(duì)藥物濫用者進(jìn)行免疫來(lái)對(duì)抗他們受到的折磨是一個(gè)吸引人的課題。 原理上，這應(yīng)該不會(huì)太難。

　　Science and Technology

　　Combating addiction

　　Can a vaccine stop drug abuse?

　　It may be possible to vaccinate people against addictive drugs

　　THE idea of vaccinating drug addicts against their affliction is an intriguing one. In principle, it should not be too hard. The immune system works, in part, by making antibodies that are specific to particular sorts of hostile molecule. Such antibodies recognise and attach themselves to these molecules, rendering them harmless. Vaccines work by presenting the immune system with novel targets, so that it can learn to react to them if it comes across them again.

　　The problem is that the molecules antibodies recognise and react to are the big ones, such as proteins, that are characteristic of bacteria, viruses and other infectious agents. Small molecules, such as drugs, go unnoticed. But not for much longer, if Kim Janda of the Scripps Research Institute in San Diego has his way. In a paper just published in the Journal of the American Chemical Society, Dr Janda and his colleagues suggest how a vaccine against methamphetamine, a popular street drug, might be made. If their method works, it would open the possibility of vaccinating people against other drugs, too.

　　The idea of a methamphetamine vaccine is not new. The problem is getting the immune system to pay attention to a molecule that is such a small target. The way that has been tried in the past is to build the vaccine from several components.

　　First, there is a large carrier protein that forms a platform for the target. Then there is the target itself, a set of smaller molecules called haptens that are attached to the carrier. These may either be the drug in question or some analogue of it that, for one reason or another, is reckoned to have a better chance of training the immune system. Finally, there is a chemical cocktail called an adjuvant that helps get the immune system to pay attention to the carrier protein and the haptens. Dr Janda noticed that past experiments on methamphetamine vaccines had all revolved around tweaking either the carrier protein or the adjuvant, rather than tinkering with the haptens.

　　He thought he might be able to change that, on the basis of work he had carried out previously, trying to design a vaccine against nicotine. In particular, nicotine is a highly flexible molecule. That makes it hard for the immune system to recognise. To overcome this, his team on the nicotine project had to work out how to fix their haptens to the carrier protein in a way that rendered them less capable of twisting and turning, and thus made them easier for the immune system to identify.

　　In the new study, Dr Janda and his colleagues report that they have performed a similar trick with methamphetamine haptens. They used computer models to visualise the haptens in three dimensions and thus work out how the molecules could be rearranged such that they could not spring, twist or turn when being examined by the immune system. In light of this information they designed six new methamphetamine-like. Once built, they attached the new hapten molecules to carrier proteins, mixed them with adjuvant, injected the results into mice and waited. After several weeks they tested the mice to see if the animals&apos blood contained antibodies to methamphetamine.

　　Of the six new haptens, three successfully provoked the mice to make such antibodies. As a bonus, one of those three also stimulated the production of antibodies against another widely used drug, amphetamine. That is still a long way from providing a working vaccine, but it is an important step forward. And if human immune systems react in the same way to the new vaccines as murine ones do, the day when a drug addict might be offered vaccination rather than opprobrium will have come a little closer.

上12下

共2頁(yè)