How this disease changes the shape of your cells - Amber M. Yates

翻译人员: Carol Wang 校对人员: Lipeng Chen

What shape are your cells?

你的细胞是什么形状的？

Squishy cylinders? Jagged zig-zags?

软粘的圆柱体？ 还是锯齿状的之字形？

You probably don’t think much about the bodies of these building blocks,

你可能不太会想这些 基本构体的具体形状，

but at the microscopic level, small changes can have huge consequences.

但在微观层面，微小变化 会产生巨大的后果。

And while some adaptations change these shapes for the better,

虽然一些适应性 改变形状会变得更好，

others can spark a cascade of debilitating complications.

其他适应性改变会引发 一连串的抑制性并发症。

This is the story of sickle-cell disease.

这是镰状细胞病的故事。

Sickle-cell disease affects the red blood cells,

镰状细胞病影响红血球，

which transport oxygen from the lungs to all the tissues in the body.

红血球将氧气从肺部 输送到体内的所有组织。

To perform this vital task,

为了完成这项重要任务，

red blood cells are filled with hemoglobin proteins to carry oxygen molecules.

红血球内充满了 携带氧分子的血红蛋白。

These proteins float independently

这些蛋白质独立漂浮在

inside the red blood cell’s pliable, doughnut-like shape,

红血球柔韧、甜甜圈般的形状内，

keeping the cells flexible enough

让红血球保持足够的灵活性，

to accommodate even the tiniest of blood vessels.

即使是最微小的血管也能通过。

But in sickle cell disease,

但在镰状细胞病中，

a single genetic mutation alters the structure of hemoglobin.

单一的基因突变 改变了血红蛋白的结构。

After releasing oxygen to tissues,

这些突变的蛋白质 向组织释放氧气后，

these mutated proteins lock together into rigid rows.

就锁成整齐的行。

Rods of hemoglobin cause the cell to deform into a long, pointed sickle.

血红蛋白组成的棒状物， 使细胞变形为长而尖的镰刀。

These red blood cells are harder and stickier,

这些红血球变得更硬、更粘，

and no longer flow smoothly through blood vessels.

不再能顺利地流过血管。

Sickled cells snag and pile up–

镰状细胞留在那里 并堆积起来——

sometimes blocking the vessel completely.

有时会堵塞整个血管。

This keeps oxygen from reaching a variety of cells,

造成氧气无法送达各种细胞，

causing the wide range of symptoms

产生镰状细胞病患者

experienced by people with sickle-cell disease.

所经历的多种症状。

Starting when they’re less than a year old,

患者从不到一岁开始，

patients suffer from repeated episodes of stabbing pain in oxygen-starved tissues.

就饱受缺氧组织中 反复发作刺痛感的折磨。

The location of the clogged vessel

血管堵塞的位置，

determines the specific symptoms experienced.

决定了患者所经历的具体症状。

A blockage in the spleen, part of the immune system,

脾脏作为免疫系统的一部分，

puts patients at risk for dangerous infections.

它的堵塞会使患者 面临危险感染的风险。

A pileup in the lungs can produce fevers and difficulty breathing.

肺部的镰状细胞堆积， 会引起发烧和呼吸困难。

A clog near the eye can cause vision problems and retinal detachment.

眼睛附近的堵塞， 会导致视力问题和视网膜脱离。

And if the obstructed vessels supply the brain

如果供应大脑的血管堵塞了，

the patient could even suffer a stroke.

患者甚至会中风发作。

Worse still, sickled red blood cells also don’t survive very long—

更糟的是, 镰状红血球 无法存活很久——

just 10 or 20 days, versus a healthy cell’s 4 months.

只有10或20天， 而健康细胞可以活4个月。

This short lifespan

短暂的寿命意味着，

means that patients live with a constantly depleted supply of red blood cells;

患者的红血球供应不断枯竭；

a condition called sickle-cell anemia.

这就是被称为 镰状细胞性贫血的疾病。

Perhaps what’s most surprising about this malignant mutation

可能这种恶性突变 最令人惊讶的是，

is that it originally evolved as a beneficial adaptation.

它最初进化竟然是良性适应。

Researchers have been able to trace the origins of the sickle cell mutation

研究人员已追踪到镰变起源，

to regions historically ravaged by a tropical disease called malaria.

源于历史上被热带疾病 疟疾破坏的地区。

Spread by a parasite found in local mosquitoes,

经由当地蚊子身上 发现的寄生虫传播，

malaria uses red blood cells as incubators

疟疾用红血球作为孵化器，

to spread quickly and lethally through the bloodstream.

迅速而致命地通过血液传播。

However, the same structural changes that turn red blood cells into roadblocks

然而，将红血球变成路障的 同样的结构变化

also make them more resistant to malaria.

也使他们对疟疾具有 更强的抵抗力。

And if a child inherits a copy of the mutation from only one parent,

如果孩子只从一个家长那里 继承了突变的基因，

there will be just enough abnormal hemoglobin

就会有足够的异常血红蛋白，

to make life difficult for the malaria parasite,

让疟原虫难以生存，

while most of their red blood cells retain their normal shape and function.

而他们的大多数红血球 保持正常的形状和功能。

In regions rife with this parasite,

在这种寄生虫流行的地区，

sickle cell mutation offered a serious evolutionary advantage.

镰变提供了关键的进化优势。

But as the adaptation flourished,

但随着适应性的不断发展，

it became clear that inheriting the mutation from both parents

很明显，从父母双方 继承突变的孩子，

resulted in sickle-cell anemia.

会得镰状细胞性贫血。

Today, most people with sickle-cell disease

如今，多数患有镰状细胞性贫血的人，

can trace their ancestry to a country where malaria is endemic.

其祖先可追溯到 疟疾流行的国家。

And this mutation still plays a key role in Africa,

这种突变在非洲 仍然发挥着关键作用，

where more than 90% of malaria infections occur worldwide.

其中90%以上的疟疾感染 发生在全球范围内。

Fortunately, as this “adaptation” thrives,

幸运的是，随着这种 “适应”的蓬勃发展，

our treatment for sickle cell continues to improve.

对镰状细胞的治疗 也在继续改进中。

For years, hydroxyurea was the only medication available

多年来，羟基脲是唯一可用药，

to reduce the amount of sickling,

它能减少镰变细胞数量、

blunting symptoms and increasing life expectancy.

减缓症状，并延长寿命预期。

Bone marrow transplantations offer a curative measure,

骨髓移植提供了一种治疗措施，

but these procedures are complicated and often inaccessible.

但这些过程很复杂， 往往无法实现。

But promising new medications are intervening in novel ways,

但给人希望的新药物 正以新颖方式干预治疗，

like keeping oxygen bonded to hemoglobin to prevent sickling,

比如把氧气粘合到血红蛋白上， 防止红细胞镰变，

or reducing the stickiness of sickled cells.

或降低镰状细胞的粘性。

And the ability to edit DNA

而且，编辑DNA的能力

has raised the possibility of enabling stem cells to produce normal hemoglobin.

提升了使干细胞产生 正常血红蛋白的可能性。

As these tools become available

随着这些工具的出现，

in the areas most affected by malaria and sickle cell disease,

在受疟疾和镰状细胞病 影响最严重的地区，

we can improve the quality of life

针对这些携带这种 不利的适应性改变的患者，

for more patients with this adverse adaptation.

我们可以提高他们的生活质量。