托福各單項備考是相互聯系的,托福聽力和托福閱讀作為語言學習中偏向于輸入的部分,可以有效積累重要語料素材助力作為輸出部分的托福口語和托福寫作能力提升。在備考托福閱讀的過程中我們可以通過擴展英文文章閱讀去輔助閱讀和其他各單項能力的提高,積累地道英文表達,提升語感和熟練度。下面我們看一篇經濟學人雙語閱讀文章:對抗衰老。
Fighting ageing
Youthful spirits
Blood transfusions from young animals can revitalise old ones. Trials are now running to see if that is true for people, too
對抗衰老
青春血液
輸入年輕動物的血液可助年老動物重現活力。在人類身上是否亦是如此?試驗正在進行中
IT WAS one of the oddest experiments in the history of dentistry. In the early 1950s a researcher called Benjamin Kamrin was looking into the causes of tooth decay. To do so, he turned to that scientific stalwart, the lab rat. Specifically, he cut small patches of skin from pairs of rats and then sutured the animals together at the site of the wound. After about a week of being joined in this way, the animals’ blood vessels began to merge. The result was two rats whose hearts pumped blood around a shared circulatory system. This state of affairs is called parabiosis.這是牙科史上最怪異的試驗之一。20世紀50年代初,一位名叫本杰明·卡姆林(Benjamin Kamrin)的研究人員為研究蛀牙的成因,求助于科學試驗的忠實伙伴——大鼠。具體來說,就是從好幾對大鼠身上分別切下小塊的皮膚組織,然后在切口處把這些大鼠兩兩縫合在一起。如此合體約一周后,它們的血管開始融合。結果是兩只大鼠的心臟會向共享的循環系統供血。這種情況被稱為聯體共生(parabiosis)。
Parabiosis works best on animals that are closely related genetically. By getting his rats to share blood, as well as genes, and then feeding the animals a variety of diets, Kamrin hoped to prove (which he did) that it was sugar in food, and not some inherent deficiency in individuals, that was responsible for rotting their teeth.在基因密切相關的動物身上,聯體共生的效果最佳。卡姆林讓這些大鼠共享血液和基因,然后向它們投喂各種食物,希望以此證明導致齲齒的是食物中的糖分,而非個體的某種先天不足。他最終成功證明了這一點。
Other people, though, have used the technique to find more striking results. For example, mammalian bone density usually drops with age. Three years after Kamrin’s work, however, a gerontologist called Clive McCay showed that linking an old rat to a young one boosted the density of the oldster’s bones. In 1972 another paper reported, even more spectacularly, that elderly rats which shared blood with young ones lived four to five months longer than similarly old rats which did not.其他人則利用該技術獲得了更驚人的發現。例如,哺乳類動物的骨密度通常隨年齡增長而下降。然而,卡姆林的研究過了三年后,老年病學家克萊夫·麥凱(Clive McCay)證明了把老年大鼠和幼年大鼠聯體能提升老年大鼠的骨密度。1972年,另一篇論文更令人咋舌地指出,相比同類老年大鼠,分享了幼年大鼠血液的老年大鼠能多生存四至五個月。
The rats themselves, unsurprisingly, were not always keen on the procedure. Early papers describe the dangers of “parabiotic disease”, in which one animal’s immune system rebels against the foreign blood, and also explain how rats must be socialised carefully before being joined, to stop them biting each other to death.當然,大鼠們本身并不太喜歡這個過程。早期就有論文描述過“共生病”的危害——發病時動物的免疫系統排斥外來血液。論文也解釋了在把這些試驗鼠聯體之前,必須先小心地讓它們熟絡起來,防止互相撕咬致死。
“The technique itself is kind of gross and crude,” admits Michael Conboy, a biologist and parabiosis researcher at the University of California, Berkeley. Perhaps for that reason, research had more or less died out by the late 1970s. These days, though, it is back in the news—for a string of recent discoveries have suggested that previous generations of researchers were on to something. The blood of young animals, it seems, may indeed be able to ameliorate at least some of the effects of ageing. And the technique is promising enough to have spawned human clinical trials.加州大學伯克利分校的生物學家和聯體共生研究員邁克爾·康博伊(Michael Conboy)承認,“這種技術本身有些野蠻和倒人胃口。”也許是這個原因,到了20世紀70年代后期,這方面的研究已差不多銷聲匿跡。不過,最近這種技術又重新回到人們的視線里,因為近期有一連串發現顯示,前幾代研究人員其實已經摸索到了一些重要的東西。看起來,年輕動物的血液好像確實能夠緩解至少一部分的衰老的影響。以該技術的前景,足以催生這方面的人體臨床試驗。
No jokes about vampires, please
拜托,別拿吸血鬼開玩笑
This modern interest in parabiosis dates back to 2005, when Dr Conboy (who was then at Stanford University), his wife Irina, and a group of other Stanford researchers published a paper in Nature. In it they described joining mice aged between two and three months with members of the same strain that were 19-26 months old. That is roughly equivalent to hooking a 20-year-old human up to a septuagenarian. After five weeks, the Conboys and their colleagues deliberately injured the older mice’s muscles. Usually, old animals heal far less effectively from such injuries than young ones do. But these mice healed almost as well as a set of young control animals. The young blood had a similar effect on liver cells, too, doubling or tripling their proliferation rate in older animals.聯體共生的現代研究始自2005年。當時在斯坦福大學工作的康博伊(Conboy)和妻子伊琳娜(Irina)以及斯坦福的其他幾位研究人員在《自然》雜志上發表了一篇論文。文章描述了對兩至三個月大的小鼠和19至26個月大的同種小鼠所做的聯體試驗。這大致相當于把20歲的年輕人與七旬老人聯體。五周后,康博伊夫婦和同事故意損傷了受試老年鼠的肌肉。通常,老年動物受到這類損傷后的恢復速度遠不及年輕動物。但這些老年小鼠的痊愈效果堪比對照組的年輕小鼠。年輕血液對肝細胞也有類似效果,使老年小鼠體內肝細胞的增殖速度提高了一或兩倍。
Since then, a torrent of papers have shown matching improvements elsewhere in the body. No one has yet replicated the finding that young blood makes superannuated mice live longer. But it can help repair damaged spinal cords. It can encourage the formation of new neurons in mouse brains. It can help rejuvenate their pancreases. The walls of mouse hearts get thicker as the animals age; young blood can reverse that process as well.自此,有大量論文顯示動物體內其他方面也存在類似的改善。但至今尚未有研究重復出年輕血液延長老年鼠壽命這一結果。但研究證明年輕血液有助修復受損的脊髓,還可促進小鼠的大腦形成新神經元,幫助它們的胰腺恢復活力。小鼠的心臟壁會隨年齡增長而變厚,年輕的血液還可逆轉這一過程。
The effects work backwards, too. Old blood can impair neuron growth in young brains and decrepify youthful muscles. Intriguingly, the phenomenon even seems to operate across species. In April Tony Wyss-Coray, also at Stanford, showed that infusing old mice with blood from the umbilical cords of infant humans improved their performance on memory tests.其中也存在逆向效果。老年血液會損害年輕大腦中的神經元生長,并使年輕的肌肉衰老。有趣的是,這種現象似乎甚至可以跨物種顯現。今年4月,同為斯坦福大學研究人員的托尼·魏斯-克雷(Tony Wyss-Coray)表示,老年小鼠輸入人類嬰兒的臍帶血后,在記憶測試中的表現有所提升。
There have been enough results, says Janet Lord, who runs the Institute of Inflammation and Ageing at Birmingham University, in Britain, to remove any doubt that something impressive is happening. But finding out exactly what is trickier. The working theory is that chemical signals in young blood are doing something to stem cells in older animals. Stem cells are special cells kept in reserve as means to repair and regrow damaged tissue. Like every other part of the body, they wear out as an animal ages. But something in the youngsters’ blood seems to restore their ability to proliferate and encourages them to repair damage with the same vigour as those belonging to a younger animal would.英國伯明翰大學炎癥和老化研究所(Institute of Inflammation and Ageing)的負責人珍妮特·洛德(Janet Lord)說,現有研究結果足以讓人消除懷疑,確信有一些非同一般的因素在起作用。但要確切說明到底是什么就不那么容易了。初步的理論是,年輕血液中的化學信號對年老動物中的干細胞施加了某種影響。干細胞是儲備在體內的特殊細胞,用于修復和再生受損組織。就像身體其他各部分一樣,干細胞也會隨動物的年齡增長而老化。但年輕血液中的某些成分似乎能令干細胞恢復增殖能力,并促進它們像年輕動物的干細胞那樣有效地修復受損組織。
Nobody yet knows exactly what that something is, but people are looking hard. In all probability, says Dr Lord, it is not one thing at all, but dozens or hundreds of hormones, signalling proteins and the like, working together. Researchers have been comparing the chemical composition of old and young blood, searching for those chemicals that show the biggest changes in level between the two. These include oxytocin (a hormone better known for its role as a transmitter of signals between neurons); two proteins called GDF-11 and TGF beta-1, both of which are already known to affect cell behaviour; and B2M, another protein which, among other things, affects the body’s ability to absorb iron from food.還沒有人確切知道到底是什么在起作用,但人們正在仔細分辨。洛德表示,很有可能不止一種,而是數十或數百種激素、信號蛋白及類似物質在共同作用。研究人員比較了年老及年輕血液的化學成分,尋找兩者間含量水平差異最大的化學物質。這其中包括催產素,這種激素更為人熟知的作用是在神經元之間傳遞信號;還有名為GDF-11和TGF beta-1的兩種蛋白質,已知兩者均會影響細胞的行為;另外還有一種名為B2M的蛋白質,它的作用之一是影響身體從食物中吸收鐵的能力。
Even with a list of targets, working out what is going on is hard, says Richard Lee, a cardiologist at Brigham and Women’s Hospital in Boston, Massachusetts. Blood is complicated stuff, and the tools available to analyse it are far from perfect. Dr Lee’s own work is a good example. In 2014 his group suggested GDF-11 as a possible rejuvenating factor. The following year a team at Novartis, a big pharmaceutical company, said that they were unable to replicate those results. The trouble, said the group from Novartis, was that the test used by Dr Lee’s team was sensitive to proteins besides GDF-11, messing up the results. Dr Lee’s team replied within months that, no, it was in fact the Novartis test that was flawed, because it was itself picking up extra proteins. And there, at the moment, the matter stands.即便有了目標清單,要弄清楚發生作用的過程還是很難,馬薩諸塞州波士頓市布列根和婦女醫院(Brigham and Women’s Hospital)的心臟病專家理查德·李(Richard Lee)說道。血液是很復雜的東西,現有的分析血液的工具也遠非完美。李博士自己的研究便是個好例子。2014年,他的團隊發現GDF-11有可能是一種“返老還童”因子。第二年,大型制藥公司諾華(Novartis)的一個團隊稱無法重復該結果。諾華團隊表示,問題在于李博士團隊的測量方法對GDF-11以外的蛋白質也有敏感性,影響了測量結果。幾個月后,李博士的團隊予以否認,稱有問題的其實是諾華團隊的測試,因為正是該團隊的測試在過程中混入了其他蛋白質。目前此事件尚無進一步發展。
There are further possible explanations for parabiotic rejuvenation besides blood chemistry. One is that older animals may also benefit from having their blood scrubbed by young kidneys and livers, which mere blood transfusion would not offer. A paper published by the Conboys and their team in 2016, which described blood exchanges that were done in short bursts (thus eliminating the possibility of such scrubbing) reported rejuvenating effects, but ones that were not as widespread as those obtained by full-on parabiosis.除了血液化學方面的因素,聯體共生的“返老還童”現象還有其他可能的解釋。其一是,老年動物可能也同時受益于年輕腎臟和肝臟對血液的凈化作用,而這單靠輸血是無法實現的。康博伊及其團隊在2016年發表的一篇論文稱,在短時間內完成的血液交換(因而消除了上述凈化過程的可能性)具有復壯的效果,但不如全面聯體共生后那樣全面。
Another idea is that cells from the young animal, rather than chemicals in its blood, could be doing some of the work. By modifying the genes of a mouse so that its cells glow under ultraviolet light, researchers can track where those cells end up when the mouse in question is linked to another. They have found that only a few cells from a younger mouse take root in an older animal it is linked to. This does not quite rule the theory out, says Irina Conboy, for the number of cells may not reflect their importance. Immune-system cells, for instance, multiply rapidly when needed. And they are precisely the sorts of cells that might help an older animal.另一個想法是,也許是來自年輕動物的細胞發揮了些許作用,而非血液中的化學物質。研究人員改造了一只小鼠的基因,使其細胞能在紫外線下發光,從而在這只小鼠跟其他小鼠聯體時跟蹤這些細胞的去向。他們發現,在與老年鼠聯體時,只有少數幼鼠的細胞轉移到老年鼠體內。但這并不能完全推翻上述理論,伊琳娜·康博伊(Irina Conboy)說,因為細胞數量不一定反映其重要性。舉個例子,免疫系統細胞在必要時可迅速繁殖。它們正是那種可能會對老年動物有所幫助的細胞。
The mechanisms by which parabiosis operates, then, are foggy. But that has not dissuaded some companies from setting up trials to see if young blood can work its magic in people as well as rodents. Persuading patients to have themselves stitched to another person so they can share circulatory systems might be tricky. So instead of full-on parabiosis, these trials are using donated blood plasma.如此說來,聯體共生的作用機制仍是個謎。但這并沒有阻止一些公司展開試驗,探究除了嚙齒類動物之外,年輕血液是否也會在人類身上發揮神奇的效應。說服患者與他人縫合成一體以共享循環系統可能不大容易。因此,這些試驗運用了捐獻血漿,而非采取全面的聯體共生。
Blood simples
輸血蠢行
One such firm, based in California, is called Ambrosia. It has attracted plenty of raised eyebrows for charging its participants, who must be at least 35 years old, $8,000 to join. For that, they get an infusion of blood plasma from a donor under 25. Most clinical trials work by comparing the treatment under investigation either with another, established treatment, or with a placebo. Ambrosia’s trial will not do this. Jesse Karmazin, Ambrosia’s founder, says it would be hard to persuade people to pay if there were a chance they might not get the real thing. Instead, he says, patients will serve as their own controls. This will be done by comparing their blood chemistries before and after the treatment.這類公司中有一家位于美國加州,名為Ambrosia(“長生珍饈”)。該公司要求參與試驗者必須年滿35歲,并收取8000美元的費用——這一價格令不少人感到驚訝。付錢后,參與者被輸入來自25歲以下捐獻者的血漿。大部分臨床試驗要么是將所研究的療法與另一種已經證實的療法作對照,要么是與安慰劑組作比較,Ambrosia的試驗則不然。其創始人杰西·卡馬辛(Jesse Karmazin)表示,如果受試者有可能被分到對照組,那么就很難說服他們付這筆錢來參與試驗。他說,患者將充當自己的對照組,通過比較接受治療前后的血液化學成分來進行臨床試驗。
The unusual trial design, the charge for participation and the sheer amount of hype surrounding anti-ageing research has led some to accuse Dr Karmazin of being more interested in money than science. Not so, he says. Because blood plasma is a natural product, he says, it is not patentable. Without the prospect of a profitable new drug, no drug companies are interested in sponsoring his work. “If I could run this trial for free, I would,” he says. “But the reality is I can’t.” Indeed, Dr Karmazin would not be drawn on how—or if—he plans to turn an eventual profit. But he argues that, with plenty of blood plasma already being collected, both for transfusion and to extract important biochemicals such as clotting factors from it, checking to see if it might have other useful properties is only sensible. Although Ambrosia is not yet ready to publish its results, its initial findings, he says, are encouraging.由于不尋常的試驗設計,加上參與費用和圍繞抗衰老研究的大量炒作,已有一些人指責卡馬辛意在賺錢甚于科研。他否認了這一點。他說,血漿是一種天然產品,因此不能申請專利。如果沒有希望研發出有利可圖的新藥,制藥公司就不會有興趣贊助他的研究。“我要是能免費做這個試驗,我會免費的,”他說道,“但現實是我不能。”的確,卡馬辛不愿意透露他是否或者如何計劃籍此最終獲利。但他認為,已有大量血漿被收集起來,既為輸血之用,也為抽取凝血因子等重要生化物質,測試血漿是否有其他有用特性恰是明智的做法。盡管Ambrosia公司還未準備好發表研究成果,但他說初步結果令人鼓舞。
Another firm, called Alkahest, which was spun out of work done at Stanford, has had less trouble attracting money. It began its life in JLABS, a biotechnology “incubator” run by Johnson & Johnson, a big drug firm, and has secured $50m from Grifols, a Spanish company that processes blood plasma into various products. It has commissioned a trial in which 18 people with Alzheimer’s disease will be given four infusions of plasma taken from young donors, over four weeks. The main goal, says Karoly Nickolich, Alkahest’s boss, is to see if the treatment is safe. That should, he says, be fairly straightforward. Blood transfusions are, after all, routine procedures. The study will also, though, check whether the blood used can reverse some of the effects of Alzheimer’s, as seems to happen in mice in analogous circumstances.另一家名為Alkahest(“萬能溶劑”)的公司源于斯坦福大學的研究項目,在吸引投資上阻力較小。它最初成形于大型制藥公司強生設立的生物科技“孵化器”JLABS,并從生產各類血漿制品的西班牙公司Grifols獲得了5000萬美元的投資。Alkahest已經委托開展一項試驗——在四周內,向18名阿爾茨海默癥患者分四次輸入年輕獻血者的血漿。Alkahest公司的老板卡羅伊·尼克里奇(Karoly Nikolich)表示,試驗的主要目標是了解療法是否安全。他說,結果應該會相當明確,畢竟輸血是常規醫療手段。不過,該研究也將檢驗所用的血液能否逆轉阿爾茨海默氏病的某些影響,這對處于類似情況下的小鼠似乎是有效的。
Alkahest plans to present the results of its study at a conference in November. Because the trial is being run by researchers at Stanford, rather than by the firm itself, Mr Nickolich does not yet know what they are likely to show. But if the treatment is safe, he says, and if it proves effective, then the next step will be to identify and isolate the responsible compounds. Unlike blood plasma, such compounds would be patentable—particularly if they were then made synthetically. And such synthesis would be needed. As Mr Nickolich observes, even if things go well, there is simply not enough donated blood around to treat the world’s 44m Alzheimer’s patients with plasma extracts.Alkahest公司計劃在11月的一次會議上介紹其研究成果。由于試驗是由斯坦福大學的研究人員而非公司自己進行的,尼克里奇還不清楚可能會展示怎樣的內容。不過他說,如果療法是安全的且被證明有效,那么下一步便會是識別及分離發揮效力的化合物。不同于血漿,這類化合物是可以申請專利的,尤其是以后需要人工合成的話。而且也的確需要合成制造。正如尼克里奇認為的那樣,即便試驗一切順利,獻血量也不足以提取血漿物質來治療全球4400萬名阿爾茨海默癥患者。
Some researchers are more wary than Mr Nickolich about the wisdom of such trials. Michael Conboy points out that transfusions are risky. “You can occasionally get immune reactions even with well-matched donors,” he says. “In the worst cases you can get full-on anaphylaxis [an extreme allergic reaction that can be fatal].”對于這類試驗是否明智,一些研究人員比尼克里奇更為謹慎。邁克爾·康博伊指出,輸血是有風險的。“即便血漿來自配對得當的獻血者,也可能出現免疫排斥反應,”他說,“最糟糕的情況是出現全身過敏反應(一種可能致命的極端過敏反應)。”
For his part, Dr Lee worries about the hype that inevitably attaches itself to “anti-ageing” treatments. “I never use terms like ‘anti-ageing’ or ‘rejuvenation’ when I talk about laboratory science,” he says. “It conveys a false sense of hope.” Dr Lord agrees that talk of reversing ageing is premature. But, she says, there are reasons for cautious optimism. Improving the ability of old muscles to repair themselves, for instance, might not be enough to fend off the Reaper for ever. But frailty, and the falls it causes, are a problem for the elderly. Mitigating the damage from Alzheimer’s, even if it cannot be cured, would also be a boon. Rather than lengthening lifespan, says Dr Lord, it is better to think about lengthening “healthspan”. That is not immortality. But it would still be quite something.而李博士則擔心對這類試驗的大肆宣傳難免會使其與“抗衰老”療法掛鉤。“在談論實驗室研究時,我從來不用‘抗衰老’或‘返老還童’這些詞,”他說,“這會產生誤導,讓人空歡喜。”洛德也認同現在談論逆轉衰老還為時尚早。不過她說確有理由持審慎樂觀態度。例如,改善老化肌肉的自我修復能力也許不足以長久對抗死神,但年老體衰以及由此導致的跌跤對老年人來說的確是個問題;即便無法治愈阿爾茨海默癥,能減輕其損害也是一個福音。洛德說,與其追求延年益壽,還不如考慮怎樣延長“健康期”。這不是長生不老,但仍會是件了不得的事。