第十篇

An AIDS Mystery Solved

(1) About 15 years ago, a well-meaning man donated blood to the Red Cross in Sydney, Australia, not knowing he has been exposed to HIV-1, the virus that causes AIDS. Much later, public-health officials learned that some of the people who got transfusions? containing his blood had become infected with the same virus; presumably they were almost sure to die. But as six years stretched to 10, then to 14, the anxiety of health officials gave way to astonishment. Although two of the recipients have died from other causes, not one of the seven people known to have received transfusions of the man’s contaminated blood has come down with AIDS. More telling still, the donor, a sexually active homosexual, is also healthy. In fact his immune system remains as robust as if he had never tangled with HIV at all. What could explain such unexpected good fortune?

(2) A team of Australian scientists has finally solved the mystery. The virus that the donor contracted and then passed on, the team reported last week in the journal Science. contains flaws in its genetic script that appear to have rendered it innocuous?. “Not only have the recipients and the donor not progressed to disease for 15 years,” marvels molecular biologist Nicholas Deacon of Australia’s Macfarlane Burnet Centre for Medical Re-search, “but the prediction is that they never will.” Deacon speculates that this “impotent” HIV may even be a natural inoculant? that protects its carriers against more virulent strains? of the virus, much as infection with cowpox warded off smallpox in 18th-century milkmaids.

(3) If this ______ proves right, it will mark a milestone in the battle to contain the late-20th century’s most ter-rible epidemic. For in addition to explaining why this small group of people infected with HIV has not become sick, the discovery of a viral strain that works like a vaccine would have far-reaching implications. “What these results suggest,” says Dr. Barney Graham of Tennessee’s Vanderbilt University, “is that HIV is vulnerable and that it is possible to stimulate effective immunity against it.”

(4) The strain of HIV that popped up? in Sydney intrigues scientists because it contains striking abnormalities in a gene that is believed to stimulate viral duplication. In fact, the virus is missing so much of this particular gene — known as nef, for negative factor — that it is hard to imagine how the gene could perform any useful function. And sure enough, while the Sydney virus retains the ability to infect T cells — white blood cells that are critical to the immune system’s ability to ward off infection — it makes so few copies of itself that the most powerful molecular tools can barely detect its presence. Some of the infected Australians, for example, were found to carry as few as one or two copies of the virus for every 100000 T cells. People with AIDS, by contrast, are burdened with viral loads thousands of times higher.

(5) At the very least, the nef gene offers an attractive target for drug developers. If its activity can be blocked, suggests Deacon, researchers might be able to hold the progression of disease at bay, even in people who have developed full-blown AIDS. The need for better AIDS-fighting drugs was underscored last week by the actions of a U.S. Food and Drug Administration advisory panel, which recommended speedy approval of two new AIDS drugs, including the first of a new class of compounds called protease? inhibitors?. Although FDA commissioner David Kessler was quick to praise the new drugs, neither medication can prevent or cure AIDS once it has taken hold.

(6) What scientists really want is a vaccine that can prevent infection altogether. And that’s what makes the Sydney virus so promising — and so controversial. Could HIV itself, stripped of nef and adjacent sections of genetic material, provide the basis for such a vaccine, as Deacon and his colleagues cautiously suggest? Ongo-ing work on SIV, the simian? immunodeficiency virus that causes an AIDS-like illness in monkeys, indicates that this might be less far-fetched than it sounds. Ronald Desrosiers at the New England Regional Primate Re-search Center has demonstrated that when the nef gene is removed from SIV, the virus no longer has the power to make monkeys sick. Moreover, monkeys inoculated? with the nef free SIV developed marked resistance to the more virulent strain.

(7) But few scientists are enthusiastic about testing the proposition by injecting HIV — however weakened — into millions of people who have never been infected. After all, they note, HIV is a retrovirus?, a class of infec-tious agents known for their alarming ability to integrate their own genes into the DNA of the cells they infect. Thus once it takes effect, a retrovirus infection — unlike those of viruses that cause measles, smallpox and any number of others diseases — is permanent. While some retroviruses are benign, others can strike without warn-ing. Some remain hidden for years, only to trigger disease late in life when the immune system starts to de-crease.

(8) This makes vaccine development extremely risky. A weakened strain of SIV that protected adult monkeys, for example, looked safe until researchers at the Dana Farber Cancer Institute in Boston showed that newborn monkeys with immature immune systems did not respond as healthy adults do. All the young primates, in fact, developed the very disease the weakened virus was supposed to prevent. For this and a host of other reasons, most AIDS researchers argue that the only prudent strategy is to concoct? a hybrid? vaccine, putting the key features of a disabled AIDS virus into something more benign than a retrovirus. Among the leading candidates: the vaccinia virus that successfully wiped out smallpox.

(9) A handful of researchers, however, argue that the more dangerous retroviral vaccine should not be written off prematurely. Desrosiers, for one, believes the situation in parts of the developing world (where the chance of HIV infection may reach 40% among sexually active adults) has become so desperate that a retroviral vaccine may be worth the ______. A live vaccine made from HIV, he maintains, can be made safer by removing not just the nef gene but several others as well. Desrosiers has found that he can cripple HIV by chemically deleting four of its nine known genes and still get a virus that replicates, at least in chimpanzees.

(10) At present, concerns about safety are so overwhelming that effors to develop a live retroviral vaccine are unlikely to win much support. But that could change as studies of long-term survivors — that small, charmed circle of people who have been infected with the AIDS virus but have remained disease-free — provide new in-sights into the weaknesses of the viral enemy and the untapped strengths of its human targets. “These individu-als,” observes Dr. Warner Greene, director of the Gladstone Institute of Virology and Immunology in San Fran-cisco, “are natural experiments, and they hold a great secret that we are still trying to decipher?.” Indeed, it is entirely possible that the eight Australians who have caused such a stir will be cited by medical texts as the first people on the planet to be successfully, if accidentally, vaccinated against the AIDS virus — a virus that until now has seemed all but invincible.

【參考譯文】: 艾滋之謎揭曉

(1) 大約在15年前，澳大利亞悉尼有一位人士好心向紅十字會(huì)捐血，不知道自己已感染HIV-1型——這是造成艾滋病的病毒。多年以后，公共衛(wèi)生官員發(fā)現(xiàn)，有些接受他血液輸血的人，也受到病毒感染。這些人應(yīng)該是難逃死亡的噩運(yùn)�？墒�6年、10年、14年過(guò)去了，衛(wèi)生官員的焦慮變?yōu)轶@奇。雖然其中有兩個(gè)人因其他原因死亡，可是接受遭污染血液輸血的這7個(gè)人當(dāng)中，沒(méi)有一個(gè)人罹患艾滋病。更引人注目的是，那位捐血人——一個(gè)有性行為的同性戀者——仍然活得好好的。他的免疫系統(tǒng)十分強(qiáng)壯，就像從沒(méi)染上HIV一樣。這種意外的好運(yùn)要如何解釋？

(2) 一批澳大利亞科學(xué)家終于解開(kāi)了謎團(tuán)。他們?cè)谏现艿摹犊茖W(xué)》期刊發(fā)表報(bào)告指出：這位捐血人染上然后傳出去的病毒，基因結(jié)構(gòu)有缺陷，可能因此變成無(wú)害。澳大利亞麥法蘭? 伯奈特醫(yī)學(xué)研究中心的分子生物學(xué)家迪肯嘖嘖稱奇：“捐血人與輸血人不僅15年來(lái)沒(méi)有發(fā)病，而且應(yīng)該永遠(yuǎn)不會(huì)發(fā)病�！钡峡洗竽懠僭O(shè)這種無(wú)能的HIV甚至可能是天然的疫苗，可以保護(hù)帶原者不受更厲害的病毒品種侵襲，就好像18世紀(jì)擠牛奶的女工感染牛痘之后就能抵抗天花一樣。

(3) 如果這個(gè)預(yù)感成真，那么在圍堵20世紀(jì)末最可怕的傳染病的戰(zhàn)斗上，要立下一座里程碑。因?yàn)�，發(fā)現(xiàn)一種具有疫苗功能的病毒品種，不僅能解釋這一小群受到HIV感染的人何以不發(fā)病，還具有更深遠(yuǎn)的涵義。田納西州范德堡大學(xué)的格雷姆博士說(shuō)：“這些結(jié)果暗示HIV也有弱點(diǎn)，也表示有可能刺激免疫系統(tǒng)來(lái)有效地對(duì)抗它。”

(4)在悉尼發(fā)現(xiàn)的這種HIV品種，引起科學(xué)家高度的頭趣，因?yàn)樗�有一個(gè)基因嚴(yán)重異常。一般認(rèn)為這是刺激病毒去復(fù)制自我的基因。這種病毒在這個(gè)叫做“否因”（代表否定因素）的基因中大部分殘缺不全，很難想象這個(gè)基因能產(chǎn)生什么作用。果然，這種悉尼病毒雖然有能力感染T細(xì)胞（免疫系統(tǒng)對(duì)抗感染時(shí)最關(guān)鍵的白血球細(xì)胞），可是復(fù)制的能力極差，連最強(qiáng)大的分子工具也很難偵測(cè)到它的存在。就拿受到感染的這些澳大利亞人來(lái)說(shuō)，其中有些人體內(nèi)每10萬(wàn)個(gè)T細(xì)胞才有一二個(gè)病毒。相反的，艾滋病患者則要承擔(dān)高幾千倍的病毒量。

(5)“否因”基因最低限度對(duì)制藥公司是很大的誘惑。迪肯認(rèn)為，假如能夠阻斷這種基因的活動(dòng)，研究人員就有可能阻止病情的進(jìn)展，就算是已經(jīng)全面發(fā)作的艾滋病病人也一樣有用。對(duì)更好的艾滋藥物需求十分殷切，這由美國(guó)食品藥物管理局（FDA）顧問(wèn)小組上周的一項(xiàng)行動(dòng)可以看出。這個(gè)小組建議盡快批準(zhǔn)兩種艾滋新藥，包括一類全新的化合物，稱為蛋白酶抑制劑。FDA局長(zhǎng)戴維? 凱斯勒迅速贊揚(yáng)這些新藥，可是這兩種藥都無(wú)法預(yù)防艾滋病，在感染艾滋病毒后也無(wú)法治愈。

(6)科學(xué)家真正想要的是能完全預(yù)防感染的疫苗，所以悉尼病毒才被寄以厚望，也才會(huì)引起爭(zhēng)議。HIV病毒除去“否因”與鄰近的一些基因物質(zhì)后，是否真如迪肯和他的同僚審慎暗示的一樣，可以作為艾滋病疫苗的基礎(chǔ)？這個(gè)構(gòu)想聽(tīng)來(lái)很牽強(qiáng)，但是目前對(duì)猿猴免疫不全病毒（SIV，造成猿猴罹患類似艾滋病的病毒）所做的研究顯示并非毫無(wú)根據(jù)。新英格蘭區(qū)靈長(zhǎng)類研究中心的戴斯羅士已經(jīng)證明，從SIV中除去“否因”基因后，病毒就無(wú)法使猿猴發(fā)病。而且，猿猴接種過(guò)已去除“否因”的SIV后，會(huì)發(fā)展出明顯的抵抗力，可以抵抗毒性強(qiáng)的SIV品種。

(7) 但是沒(méi)有幾個(gè)科學(xué)家熱衷于檢驗(yàn)這個(gè)構(gòu)想——在幾百萬(wàn)個(gè)沒(méi)有感染過(guò)艾滋病的人身上注射HIV（不論削弱到什么程度）�？茖W(xué)家指出，畢竟HIV是逆轉(zhuǎn)錄酶病毒。這種傳染媒介原以一種可怕的能力著稱：能把本身的基因合并到受感染細(xì)胞的DNA內(nèi)。所以一旦感染上逆轉(zhuǎn)錄酶病毒，就永遠(yuǎn)擺脫不掉。這和造成麻疹，天花以及其他許多疾病的病毒都不一樣。有些種類的逆轉(zhuǎn)錄酶病毒是良性的，也有一些發(fā)作起來(lái)毫無(wú)征兆。有些則是潛伏多年，直到人進(jìn)入老年，免疫系統(tǒng)功能衰退時(shí)才發(fā)病。

(8)因此，開(kāi)發(fā)疫苗的風(fēng)險(xiǎn)極大。舉例來(lái)說(shuō)，有一種削弱了的SIV病毒可以保護(hù)成年猴子，似乎也很安全�？墒遣ㄊ款D戴納? 法柏癌癥研究所的人員后來(lái)發(fā)現(xiàn)，初生的小猴，免疫系統(tǒng)尚不成熟，反應(yīng)也和健康的成猴不同。這些小猴全部發(fā)生了當(dāng)初用弱性疫苗所要預(yù)防的疾病。因?yàn)檫@個(gè)案例，再加上許多別的原因，艾滋病研究人員大多主張，唯一較謹(jǐn)慎的策略是調(diào)配出混種病毒，也就是把弱化艾滋病毒的主要特征放到比逆轉(zhuǎn)錄酶病毒良性的病毒中。最理想的對(duì)象包括當(dāng)年成功撲滅天花的疫苗病毒。

(9)也有少數(shù)幾位研究人員，主張不能斷然否定掉危險(xiǎn)性較高的逆轉(zhuǎn)錄酶病毒疫苗。戴斯羅士就認(rèn)為，某些發(fā)展中國(guó)家的情況十分危急（有性行為的成年人感染HIV的比例可以達(dá)到40% ），值得冒險(xiǎn)一試逆轉(zhuǎn)錄酶病毒疫苗。他主張可以把HIV病毒中的幾種基因與“否因”一并移除，就能增加活疫苗的安全性。戴斯羅士發(fā)現(xiàn)，可以用化學(xué)方式刪除HIV9種已知基因中的4種，破壞掉HIV的力量，制造出來(lái)的病毒仍然會(huì)復(fù)制——至少在黑猩猩身上可以。

(10)目前對(duì)于安全性的關(guān)注高過(guò)一切，要想培養(yǎng)活的逆轉(zhuǎn)錄酶病毒疫苗，不大可能得到太多人支持�？墒乔闆r也可能改變。對(duì)艾滋病長(zhǎng)期生存者的研究（也就是那一小群感染到艾滋病毒卻一直沒(méi)有發(fā)病的幸運(yùn)者），可以讓我們更深入了解病毒的弱點(diǎn)與人類尚未發(fā)現(xiàn)的力量。舊金山格萊斯頓病毒與免疫研究所所長(zhǎng)格林博士表示：“這幾個(gè)人是大自然的實(shí)驗(yàn)，手中握有一大奧秘，還有待破謎�！贝_實(shí)，這8名引起軒然大波的澳大利亞人，很有可能被醫(yī)學(xué)文獻(xiàn)列為地球上最早成功地（盡管是意外地）接受艾滋病毒免疫注射的人——雖然到目前為止艾滋病毒好像還是所向無(wú)敵。