-
. David
Ho
was
sitting
in
the
audience
during
an
AIDS
meeting
in
2007
when
the
presenter
flashed
a
cartoon
onscreen to make a point. Along with
his colleagues, Ho chuckled at the image of a
blindfolded baseball player swinging
mightily at an incoming pitch. But as
amused as the scientists were, they were sobered
too; they knew that the player in the
cartoon was them. A swing and a miss,
the image was saying, one of many in the long
battle against AIDS.
2007
年世界
艾滋病大会，
何大一博士与同事一道正安静的坐在观众听着嘉宾的讲解，
讲台上的宣讲者在摆弄屏
幕上的一幅卡通漫画，上面画着一个被蒙上双眼的棒球
运动员正准备猛击来球，这个幽默细节让何博士暗自发笑。
科学家们都很搞笑，但他们也
清醒得很，他们知道画面上那个盲目的棒球小子指的就是他们自己。挥棒出去，没打
中，
这场跟艾滋病搏斗的战争已经打了很久，但结果还是如此。
certainly
got
the
message.
For
nearly
a
quarter
of
a
century,
he
and
other
AIDS
scientists
had
been
whiffing
repeatedly,
failing
to
make
contact
as HIV
stymied
them
again
and
again. Powerful
drugs
to
foil HIV
could
do
only
so
much. To corral the epidemic and truly
prevent HIV, only a vaccine would do. The problem
was that no vaccine strategy
had ever
succeeded in blocking the virus from infecting new
hosts, and that wasn't likely to change in the
near future.
struck a special chord
with me,
felt that frustration.
何大一可能读懂了漫画，近
1/4
世纪以来，他和其他的艾
滋病科学家们在同艾滋病的博弈中，一次次被狡猾的
艾滋病毒戏耍，击败。能拿来对付艾
滋病毒的最强药物也仅仅是凑合而已，要限制它的传染，只有靠疫苗了；但问
题是没有一
种疫苗策略能成功的阻止艾滋病毒感染新的宿主，而且这种局面在不远的未来也不见得有所改观。“那
副漫画形容得恰如其分，”何大一说，“我觉得它很准确的描述了我们能成功的机会，我们都感受到 了挫折。
that
meeting,
much
has
changed,
but
the
fundamental
problem
of
developing
an
effective
AIDS
vaccine
remains. On the
positive side, in 2009, scientists announced that
they had developed the first vaccine to show any
effect
against HIV infection
—
although that effect is,
by all measures, modest. The vaccine's ability to
reduce the risk of new
HIV infection
31% is nowhere near the 70% to 90% that public-
health experts normally view as a minimum
threshold for
an infectious-disease
vaccine. Even further behind in development, but
still promising, are two new antibodies identified
by
a group of researchers working at a
number of labs that, at least in a dish, seem to
neutralize the virus and thwart attempts to
infect healthy cells.
从
07
年的艾滋病大会算来，情况已经改观了很多，但要开发一种有效的艾滋
病疫苗依然问题重重。
2009
年情
况
出现了转机，科学家们宣布他们开发出了一种新的疫苗，这种疫苗表现出一定的抗病毒感染效果，虽然这种效果<
/p>
只能算作一般；新疫苗能将艾滋病毒感染风险由原来的
70
％
-90
％降低到
3
1
％，通常公共健康专家只将这个数字看
作感染类疾病疫苗预防
作用的最低门槛。更令人鼓舞的是，通过数个实验室一组研究者的通力合作，已经鉴定出了
两种新的抗体，至少我们有克制病毒并阻止它感染健康细胞的法宝了。
excitement over those advances,
however, has been tempered by the still raw
memories of a humbling retreat in
2007,
after
a highly
anticipated
shot
against
the
virus
was
deemed
a
failure. While
nobody
expected
spectacular
results,
neither did anyone
expect such a stunning defeat, and the scientific
community is still struggling to recover from it.
still a long ways away from having an
effective HIV vaccine that physicians can reach
into the cabinet and pull out in a vial
and inject into a person,
这些进
展让人备受鼓舞，大家还依稀记得
2007
年的时候，原本被寄
以厚望能对付病毒的试验失败，那种被打
击的痛苦记忆让人永生难忘，大家都以为没指望
了，就像没人能料到那场溃败一样。科学界也暗暗鼓劲，要从失败
的阴影中恢复过来，哈
佛医学院的艾滋病专家布鲁斯·沃尔克说：“要获得一种有效的艾滋病疫苗，能让医生们随
拿随用，我们还任重道远。”
may
be
true,
but
Ho,
who
has
been
working
to
develop
an
HIV
vaccine
of
his
own,
now
believes
that
a
traditional shot, one that relies on
snippets of a virus to both awaken and prod the
immune system to churn out antibodies,
may not be the best way to fight HIV.
Rather than expecting the body to do all the work
of first recognizing then mounting
an
attack against the virus, why not just present the
body with a ready-made arsenal of antibodies that
can home in on HIV?
It's the
immunological equivalent of a frozen dinner; the
already cooked antibodies eliminate all the hard
work of prepping
and priming the immune
system to do battle.
布鲁斯的话的确有道理，但何大一独自发
明了一种更像传统疗法的艾滋病疫苗，依靠活化的病毒片段刺激免疫
系统产生抗体，现在
看来，这种方法也许不是对抗艾滋病魔的最好手段。与其指望自身机体完成识别和歼灭病毒，
还不如为机体装配上一套现成的抗体武器，这样就可以在身体内部打赢一场艾滋病毒消灭战，这是在免疫上是 等同
的，且更容易实现。已经准备好的抗体免去了许多复杂的前期工作，它可以动员免疫
系统立刻投入战斗。
's a bold strategy
and one that has never been tried before in the
AIDS field, but Ho is willing to stake his
reputation
and that of his nearly
20-year-old facility, the Aaron Diamond AIDS
Research Center (ADARC) in New York City, on his
hunch. So is the Bill & Melinda Gates
Foundation, which has steered nearly $$7 million
his way to pursue the theory. Ho has
redirected more than half of his lab to
the project, and the results so far have reignited
his passion for discovery; he's now
back at the lab bench overseeing
experiments.
这是一个大胆的想法，在艾滋病领域还没有人这样干过，但
何大一凭借自己在艾伦·戴蒙德艾滋病研究中心
（
ADARC<
/p>
）二十年的研究经验，搭上自己的名誉也要毅然决然的赌上一把，比尔与梅琳达盖茨基金会
也为此赞助
了他
700
万美元。
何大一调动了自己实验室一半多的研究力量投入这项工作，
目前的结果
重新点燃了他战斗的热情，
他又回到实验室监督实验进程。
can't help breaking into a grin
whenever he discusses the new project, and smiles
haven't come easily to him of
late. In
the 1990s, he and ADARC established themselves as
leaders in the AIDS field by pioneering the early
use of the
antiretroviral (ARV)
cocktails that have reduced the death rate from
AIDS (for which Ho was named TIME's Person of the
Year in 1996). But in recent years, the
center has suffered a series of setbacks,
including a scientific paper that required a
partial retraction, and the departure
of key scientists. These challenges have some in
the field wondering whether ADARC
—
and its golden-boy
director
—
are on the verge
of the next big breakthrough in AIDS or are
wandering down yet another
detour in
the long and maddening fight against the disease.
每当何大一谈到这个新项目时，嘴角都不由自主的露出一丝微笑，实际上他肩上的压力大
到难以令他开颜。
90
年代，何大一革命性的率先使用抗逆转录
病毒的鸡尾酒疗法，降低了艾滋病人的死亡率，同时也确立了自己以及
ADARC
在艾滋病研究领域的领导地位（何大一因此获得了
1996
年时代年度人物奖）。但最近几年，
ADARC
却
遭
受了一系列的挫折，论文被撤回，重要科学家离开，这些挑战让一些人对
ADARC
的前途感到担忧：在这场对抗艾
滋病的持
久战役中，
ADARC
和它的金牌带头人已经接近新的重大突破
了，还是依然在徘徊不前？
First
Responder
抗艾第一人
er
successes Ho does or doesn't have ahead of him, he
long ago earned his credentials in the AIDS field.
As a
physician at the University of
California, Los Angeles, in the early 1980s, he
began keeping a diary of patients who were
rushed to the emergency room with a
mysterious amalgam of symptoms such as pneumonia,
cancer and, most important, a
devastating drop in immune function.
After a few months, he noticed a pattern: most of
the patients were gay men. Intrigued,
he became nearly obsessive about
chronicling the growing wave of cases. Within two
years, Ho and the rest of the world
would know that they were seeing the
first cases of AIDS.
不管何大一这次成功与否，
他在艾滋病领域长久以来建立起的权威形象不会受到动摇。
早在二十世纪八十
年代，
作为一名加州大学的医师，何大一开始为那些被推到急诊室的病人做日志，这些病
人都有一些奇怪的并发症状，如
肺炎、癌症等，更重要的是，他们都发生了严重的免疫功
能缺陷，几个月过后，他发现了一个规律：大多数这样的
病人都是男同性恋。随着记录的
病例越来越多，何大一对这种疾病也越来越感兴趣。两年以后，何大一和全世界都
认识到
这些人类首次接触的病例就是后来让人谈之色变的恶魔：艾滋病。
's preoccupation with HIV only grew as
the virus continued to baffle scientists.
Expecting the unexpected was the
best
way to confront HIV, he soon learned, and he
quickly amassed an impressive array of scientific
firsts in the field. As
director of
ADARC, which was founded in 1991 and was one of
the first research centers dedicated solely to the
study of
AIDS,
he
led
a
team
that
pioneered
the
'em
early
and
hit
'em
hard
approach
to
drug
therapy,
now
the
core
of
the
ARV-
cocktail treatment that is keeping millions of
HIV-positive patients alive. His lab showed how
HIV therapies would
be most effective
in the days and weeks immediately after HIV
infected a new host. That understanding came from
their
breakthrough finding that rather
than sitting latent for years after infection, as
many experts believed at the time, HIV was
actively challenging the immune system
from Day One. Soon after that revelation, ADARC
scientists were the first to add
to
existing data on how HIV worked by identifying a
second, key receptor that the virus uses to invade
cells.
当艾滋病还在让其他科学家一头雾水的时候，何大一已经一步一步在这个
领域开始了前瞻性的研究，他很快明
白，期待未知才是对付艾滋病最好的法宝，很快在他
身边聚集起了一批该领域内的科学精英。当时有一批致力于艾
滋病研究的专业研究中心成
立，成立于
1991
年的
ADARC<
/p>
也是其中之一，何大一出任中心主管，不久他领导的团
队前瞻性的
提出了对艾滋病毒“早期打击，从重打击”的药物治疗方案，这就是鸡尾酒疗法的核心概念，这种疗法
救活了成千上万的艾滋病患者。他的实验室让人们看到，在艾滋病毒感染新宿主的头几天或头几周内 ，迅速使用鸡
尾酒疗法会起到极其明显的效果。他们突破性的发现让人们认识到，感染后
坐等着几年的潜伏期太消极了，艾滋病
毒从第一天起就在活跃的攻击免疫系统。之后不久
，
ADARC
的科学家们又第一次向人们展示了艾滋病毒是如何
通
过一个次要的关键受体起作用的，病毒利用这个受体入侵细胞。
Vaccines in
Vain
无效的疫苗
while
AIDS scientists began making inroads in developing
drug therapies, designing a vaccine was proving
nearly
impossible. Despite all that
they have learned about HIV, experts are still
missing one essential ingredient: to this day,
they
do not know exactly what cells or
immune responses could protect the body from HIV
infection. Could an antibody that
binds
to and neutralizes the virus do the trick? Are T
cells, specially formulated to recognize portions
of HIV's surface
proteins, the
solution? Or, as many experts now suspect, is some
elusive combination of those factors the key to
outwitting
HIV?
从新设计疫苗已被证明几乎是不可能的，因此艾滋病科学家们开始在药物疗法上寻找突破。尽管所有的科学家
都了解艾滋病毒，但他们还是会漏掉一个关键细节，时至今日，他们还是不知道到底是哪种细
胞或免疫系统能保护
机体免受艾滋病毒感染；
通过结合病毒的抗
体来消灭病毒能取得成功吗？通过特别改造能识别病毒大部分表面蛋白
的
T
细胞来杀灭艾滋病毒的方法可行吗？更或者，
正如很
多专家怀疑的那样，
将以上因素结合起来就能成功击溃艾
滋病魔
？
t an answer, developing
vaccines is a very halting process.
Nabel,
director
of
the Vaccine
Research
Center
at
the National
Institutes
of
Health
(NIH).
is
constantly
changing
its
genetic makeup through mutations. It's
also a moving target because the proteins of the
virus surface are actually moving
themselves
—
they
are conformationally flexible. The net result is
that the immune system never gets a really good
look at
them.
没有人能回答这些问题，疫苗的开
发也是步履蹒跚，美国国立卫生研究院（
NIH
）疫苗研究中心
主任加里·纳
贝尔说：“艾滋病毒是个活动靶子，因为它不仅通过突变不断改变自己的遗
传结构，而且病毒表面的蛋白质会自己
转移，它们有灵活的空间构象。综上所述，因此免
疫系统无法识得病毒的庐山真面目。”