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

譯者: Lilian Chiu 審譯者: Helen Chang

What shape are your cells?

你的細胞是什麼形狀？

Squishy cylinders? Jagged zig-zags?

濕軟的圓柱狀？鋸齒狀的 Z 字形？

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

對這些組成積木的基本形體， 你可能不太會多想，

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

但從顯微層級來看，小小的改變 可能會造成大大的不同。

And while some adaptations change these shapes for the better,

有些時候，適應作用 會將細胞形狀做更理想的改變，

others can spark a cascade of debilitating complications.

但也有些時候，會造成 一連串讓人虛弱的併發症。

This is the story of sickle-cell disease.

這是個關於鐮形血球貧血症的故事。

Sickle-cell disease affects the red blood cells,

鐮形血球貧血症會影響紅血球，

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

紅血球會將氧氣從肺部 運送至全身各處的組織。

To perform this vital task,

為了進行這項攸關生死的任務， 紅血球充滿了血紅蛋白，

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

用來攜帶氧分子。

These proteins float independently

這些蛋白質各自獨立，漂浮在

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

紅血球的圓滑甜甜圈形狀中，

keeping the cells flexible enough

讓細胞有足夠的彈性，

to accommodate even the tiniest of blood vessels.

可以配合最小的血管。

But in sickle cell disease,

但若得了鐮形血球貧血症，

a single genetic mutation alters the structure of hemoglobin.

一個基因突變 就會改變血紅素的結構。

After releasing oxygen to tissues,

將氧氣釋放到組織中之後，

these mutated proteins lock together into rigid rows.

這些突變的蛋白質 就會堅固地鎖成一列，

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

血紅素形成的長條，造成細胞變形，

成為長形尖頭的鐮刀狀。

These red blood cells are harder and stickier,

這些紅血球比較硬也比較黏，

and no longer flow smoothly through blood vessels.

無法再像原本那樣順暢地流過血管。

Sickled cells snag and pile up–

鐮狀細胞會擱淺然後堆疊起來——

sometimes blocking the vessel completely.

有時會完全阻塞血管。

This keeps oxygen from reaching a variety of cells,

這麼一來，氧氣就無法 被遞送給許多細胞，

causing the wide range of symptoms

因而造成多種症狀

experienced by people with sickle-cell disease.

出現在鐮形血球貧血症患者身上。

Starting when they’re less than a year old,

從還不到一歲的時候，

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

病人因組織亟需氧氣 而一再飽受刺痛的折磨。

The location of the clogged vessel

血管發生栓塞的位置，

determines the specific symptoms experienced.

會決定病人的症狀為何。

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

脾臟是免疫系統的一部分， 如果發生阻塞，

puts patients at risk for dangerous infections.

就會讓病人有受到致命感染的風險。

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

若堆積發生在肺部， 可能會造成發燒和呼吸困難。

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

眼睛附近的栓塞可能會導致 視力問題和視網膜剝離。

And if the obstructed vessels supply the brain

如果供血到大腦的血管被阻塞，

the patient could even suffer a stroke.

病人甚至有可能中風。

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

更糟糕的是，鐮狀紅血球的 存活時間不長——

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

只有十或二十天，相對之下， 健康的紅血球可以存活四個月。

This short lifespan

存活時間這麼短，就表示

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

病人經常會遇到紅血球供應不足；

a condition called sickle-cell anemia.

這種病症叫做鐮狀細胞性貧血。

Perhaps what’s most surprising about this malignant mutation

也許，這種惡性突變 最讓人驚訝的一點是，

is that it originally evolved as a beneficial adaptation.

它原本是種為了利於生存 而做的演化適應。

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

研究者在追蹤鐮狀細胞突變的 源頭上，已經可以追溯到

to regions historically ravaged by a tropical disease called malaria.

史上被瘧疾這種熱帶疾病 所蹂躪的地區。

Spread by a parasite found in local mosquitoes,

瘧疾由寄生在當地 蚊子身上的瘧原蟲傳播，

malaria uses red blood cells as incubators

瘧原蟲會把紅血球當作孵卵器來使用，

to spread quickly and lethally through the bloodstream.

能透過血液來傳播，快速又致命。

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

然而，將紅血球轉變成 路障的這種結構改變，

also make them more resistant to malaria.

也讓它們更能抵抗瘧疾。

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

如果孩子只從雙親之一 遺傳到這種突變，

there will be just enough abnormal hemoglobin

孩子就會有足夠的異常血紅素

to make life difficult for the malaria parasite,

讓瘧原蟲難以生存，

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

同時大部分的紅血球 還保持正常的形狀和功能。

In regions rife with this parasite,

在瘧原蟲充斥的地區，

sickle cell mutation offered a serious evolutionary advantage.

鐮狀細胞突變反而是 演化上的一大優勢。

But as the adaptation flourished,

但，隨著這種適應作用越來越常見，

it became clear that inheriting the mutation from both parents

開始發現，從雙親遺傳到突變

resulted in sickle-cell anemia.

會導致鐮狀細胞性貧血。

Today, most people with sickle-cell disease

現今，大部分的鐮形血球貧血症患者

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

都有祖先來自曾經有瘧疾流行的國家。

And this mutation still plays a key role in Africa,

這種突變仍在非洲扮演關鍵角色，

where more than 90% of malaria infections occur worldwide.

全世界有九成以上的瘧疾 發生在非洲。

Fortunately, as this “adaptation” thrives,

幸運的是，隨著這種 「適應作用」越來越盛，

our treatment for sickle cell continues to improve.

我們針對鐮狀細胞的治療 也持續不斷改善。

For years, hydroxyurea was the only medication available

過去多年來，只有羥基尿素 這種藥物可以用來

to reduce the amount of sickling,

減少鐮狀化的量、

blunting symptoms and increasing life expectancy.

減輕症狀，來延長壽命。

Bone marrow transplantations offer a curative measure,

骨髓移植是一種治療的方式，

but these procedures are complicated and often inaccessible.

但這類手術很複雜， 且通常難以取得。

But promising new medications are intervening in novel ways,

但有些前景看好的新藥物， 能夠以創新的方式干預治療，

like keeping oxygen bonded to hemoglobin to prevent sickling,

比如讓氧氣和血紅素維持結合，

來預防鐮狀化，

or reducing the stickiness of sickled cells.

或是減低鐮狀細胞的黏度。

And the ability to edit DNA

而編輯 DNA 的能力

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

也提升了讓幹細胞產生 正常血紅素的可能性。

As these tools become available

當受瘧疾和鐮狀細胞病 影響最大的區域

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

有了這些選項後，

we can improve the quality of life

我們就能協助這種 不良適應作用的病人

for more patients with this adverse adaptation.

改善生活品質。