Genetic technology
A-Level Biology Topic 19 8:31 English narration · English + 中文 subtitles burned in
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Two cotton plants.
两株棉花。
Same field, same insects, same week.
同一块田，同样的害虫，同一个星期。
The one on the left is barely touched.
左边这株几乎没有被咬。
The one on the right has been eaten to bare stalks.
右边这株被吃得只剩下光秃秃的枝干。
The difference is one gene.
差别只是一个基因。
How do you take a gene out of a soil bacterium and put it into a cotton plant?
怎样把土壤细菌里的一个基因放进棉花里呢？
That is genetic technology.
这就是基因技术。
Today: the tools, the plasmid that carries a gene into a cell, and what it is all for.
今天我们要看：这些工具，把基因带进细胞的质粒，以及这一切究竟用在哪里。
The principles of genetic technology start with two definitions, word for word.
两个定义，要逐字作答。
Recombinant DNA is DNA joined together from two different sources.
重组DNA是把来自两个不同来源的DNA连接起来得到的DNA。
Genetic engineering is changing an organism's DNA on purpose, so a chosen gene is expressed.
基因工程是有目的地改变生物体的DNA，使选定的基因得到表达。
And the gene itself?
那基因本身从哪里来？
There are three sources.
有三个来源。
You can cut it out of a donor's DNA.
可以从供体的DNA里把它剪下来。
You can copy it from messenger RNA, using reverse transcriptase.
可以用逆转录酶，由信使RNA复制得到。
Or you can build it from nucleotides.
也可以用核苷酸把它合成出来。
The first tool is an enzyme called a restriction endonuclease.
第一件工具是一种酶，叫限制性内切酶。
It finds one exact sequence of bases and cuts there.
它会找到一段确定的碱基序列，就在那里切开。
It cuts the two strands in different places, so each end keeps a short single strand.
它把两条链切在不同的位置，所以每个末端都留下一小段单链。
That is a sticky end.
这就是黏性末端。
Cut your gene with the same enzyme and the ends match, so DNA ligase can seal the join.
用同一种酶去切你要的基因，末端正好吻合，DNA连接酶就能把接口封好。
Now you need a way in.
现在需要一条进去的路。
Bacteria carry small extra rings of DNA called plasmids.
细菌体内有一些额外的小DNA环，叫质粒。
Cut one open with the same enzyme, drop the gene in, and let ligase close the ring.
用同一种酶把它切开，把基因放进去，再让连接酶把环封上。
That is a recombinant plasmid — a cloning vector, because it carries the gene into a cell and every bacterium that takes it up makes a clone of the gene.
这就是重组质粒——也叫载体，因为它把基因带进细胞。
The gene alone is not enough.
光有基因还不够。
Two passengers travel with it.
通常还有两位搭档跟着一起进去。
The first is a promoter, the switch that lets the gene be transcribed in its new host.
第一位是启动子， 它是让基因在新宿主里被转录的开关。
Without one, the gene stays silent.
没有它，基因就一直沉默。
The second passenger is a marker gene, often one that makes a fluorescent protein glow.
第二位搭档是标记基因，它常常让细胞产生会发光的蛋白质。
Under ultraviolet light, the cells that glow took the plasmid up.
在紫外光下，会发光的细胞就是吸收了质粒的那些。
Once the promoter switches it on, the host reads the human gene exactly as it reads its own.
启动子一旦把它打开，宿主细胞读这个人类基因，就和读自己的基因一样。
The DNA is copied into messenger RNA, and a ribosome builds the protein, one amino acid at a time.
DNA被转录成信使RNA，核糖体再一个一个氨基酸地把蛋白质造出来。
That is what expressed means.
这就是表达的意思。
Three newer tools finish the kit.
还有三件较新的工具，把工具箱补齐。
Gene editing changes DNA that is already in the genome — inserting, deleting or replacing bases at an exact site.
基因编辑直接改变基因组里已有的DNA—— 在确定的位点插入、删除或替换碱基。
A microarray is a grid of known DNA spots that shows which genes are switched on.
微阵列是一块排着已知DNA探针的方格板，它能显示哪些基因被开启。
And databases store the sequences, so anyone can compare a gene in seconds.
数据库则保存这些序列，让任何人几秒钟就能比对一个基因。
Now, copying.
接下来是复制。
The polymerase chain reaction — PCR — amplifies a tiny sample: it makes millions of copies.
聚合酶链式反应能把极少量的样品复制出上百万份。
It is just three temperatures, repeated.
它其实只是三个温度不断重复。
Denaturation at ninety-five degrees: the hydrogen bonds break and the strands separate.
九十五摄氏度，氢键断开，两条链分离。
Annealing at fifty-five: primers stick to each end of the target.
五十五摄氏度，引物结合到目标片段两端。
Extension at seventy-two: Taq polymerase builds a new strand along each old one.
七十二摄氏度， Taq聚合酶沿着每条旧链合成新链。
Taq is thermostable — it survives the heat, where an ordinary enzyme would not.
Taq能耐高温，普通的酶做不到。
A real exam question.
一道真实的考题。
A sample goes through thirty-five cycles of the polymerase chain reaction, from one molecule of DNA.
一份样品做了三十五轮聚合酶链式反应，起点是一个DNA分子。
How many copies at the end?
最后一共有多少份拷贝？
Pause here and try it yourself.
先暂停，自己算一算。
Ready?
准备好了吗？
Each cycle doubles the number, so you need two multiplied by itself thirty-five times.
每一轮都让数目翻倍，所以就是二自乘三十五次。
Two to the power of thirty-five is about three point four times ten to the tenth — about thirty-four billion copies.
二的三十五次方约等于三点四乘以十的十次方——大约三百四十亿份。
Copying gives you a lot of DNA.
复制让你得到大量DNA。
Sorting it is a different job — gel electrophoresis.
把它们分开是另一件事——凝胶电泳。
The fragments go into wells at the negative end, and the current goes on.
片段被加到负极一端的加样孔里，然后通电。
DNA is negatively charged, so it moves to the positive end.
DNA带负电，所以它向正极移动。
Shorter fragments travel further — they slip through the mesh — while long ones stay near the wells.
短片段容易穿过这张网，跑得最远；长片段留在加样孔附近。
Here is a real gel under ultraviolet light: every glowing band is one length of DNA, read against the ladder on the left.
这是一块真实的凝胶，在紫外光下拍摄：每一条发光的带就是一种长度的DNA， 对照左边的标准梯就能读出来。
Exam questions ask you to explain a gel, not just name it.
考题会要你解释凝胶，而不只是说出名称。
The answer has four moves.
答案有四步。
First, why it moves: phosphate groups make it negatively charged, so it travels to the anode.
第一，它为什么会移动：磷酸基团让它带负电，所以它向阳极移动。
Second, why it separates: the gel is a mesh, so small fragments travel furthest.
第二，为什么会分开：凝胶是一张网，小片段跑得最远。
Third, the conclusion — distance moved depends on fragment length.
第三，结论——移动的距离取决于片段长度。
Fourth, read each band against a ladder of known sizes.
第四，用已知长度的标准梯读出每一条带。
DNA is colourless, so a stain makes the bands visible.
DNA是无色的，要染色才看得见条带。
So what is all this for?
那这一切究竟用来做什么？
Start with medicine.
先看医学。
Take the human insulin gene, put it into a plasmid, give it to bacteria, and grow them in a fermenter.
取出人的胰岛素基因，装进质粒， 交给细菌，再让它们在发酵罐里大量生长。
Purify what they make, and you have human insulin — the exact human protein.
把产物提纯， 你就得到了人胰岛素——与人体完全相同的蛋白质。
This is called a recombinant human protein.
这叫做重组人蛋白。
A human gene in bacteria makes an exact human protein.
细菌里的人类基因，造出与人完全相同的蛋白质。
Insulin for diabetes is the famous one, but not the only one — factor eight for haemophilia, adenosine deaminase for a missing immune system.
治糖尿病的胰岛素最有名，但不只有它——因子八用于血友病， 腺苷脱氨酶用于免疫系统缺失。
Why?
为什么？
It is exactly human, so allergic reactions are rare.
因为它和人的完全一样，过敏反应很少。
It can be made in any amount, so supply never runs out.
因为想造多少就造多少，供应永远不断。
And it comes from no donor and no animal.
而且它不来自任何供体或动物。
These tools also read DNA.
这些工具也能读取DNA。
Genetic screening tests a person's DNA for disease alleles before symptoms appear.
基因筛查在症状出现之前， 检测一个人的DNA里有没有致病等位基因。
The BRCA one and BRCA two alleles raise the risk of breast cancer.
BRCA1和BRCA2等位基因会提高乳腺癌的风险。
Huntington's disease strikes in middle age.
亨廷顿病在中年发作。
Cystic fibrosis is found in a newborn, so treatment starts early.
囊性纤维化在新生儿身上就能查出来，可以尽早治疗。
Gene therapy goes further: it puts a working copy of a gene into the patient's own cells.
基因治疗更进一步：把一个正常的基因拷贝送进病人自己的细胞。
It has been used for a disease in which the immune system never develops, and for some inherited eye diseases.
它已经用于一种免疫系统始终无法发育的疾病，也用于某些遗传性眼病。
Now the farm.
现在看农业。
The same toolkit gives us genetically modified organisms.
同样的工具箱给了我们转基因生物。
GM salmon carry an extra growth hormone gene and reach market size in half the time.
转基因鲑鱼多了一个生长激素基因， 长到上市规格只要一半的时间。
GM soybean carries a bacterial gene that breaks down a herbicide, so the farmer sprays the field and kills only the weeds.
转基因大豆带有一个细菌基因，能分解某种除草剂， 于是农民整片田喷药，却只杀死杂草。
And GM cotton — the plant we started with — makes a protein that kills the insect pests eating it.
而转基因棉花——就是开头那株植物—— 自己就能造出一种蛋白质，杀死啃食它的害虫。
Screening and gene therapy raise hard social and ethical questions.
基因筛查和基因治疗带来一些很难回答的问题。
Who is allowed to see your genetic result?
谁有权看你的基因结果？
Could an insurer use it against you?
保险公司会不会拿它来对你不利？
Is the change safe?
这种改变安全吗？
Who decides for a child?
孩子的事由谁来决定？
GM crops raise their own questions.
转基因作物也有自己的问题。
Are they safe to eat?
吃了安全吗？
Could the genes escape into wild species?
这些基因会不会跑到野生物种里？
Who owns the seed?
种子归谁所有？
In the exam, discuss means both sides: one benefit, one concern, then a judgement.
在考试里，讨论就意味着两面都要写：一个好处，一个担忧，然后给出判断。
Three marks students lose every year.
有三个分，学生年年都丢。
First, name the enzyme.
第一，写出酶的名字。
If a question asks which enzyme cuts DNA, write restriction endonuclease, not the cutting enzyme.
题目问哪种酶切割DNA， 就写限制性内切酶，不要写切割酶。
Second, on a gel, give charge before size: DNA is negative, so it moves to the positive electrode, then the mesh sorts it by length.
第二，凝胶题先说电荷，再说大小： DNA带负电，所以向正极移动，然后凝胶这张网按长度把它们分开。
Third, both sides.
第三，两面都要写。
Discuss means one benefit, one concern, then judge.
讨论就是一个好处、一个担忧，再作判断。
Five leftover facts.
还剩五件事实。
First, reverse transcriptase makes DNA from mRNA, and a gene can also be built chemically from nucleotides.
第一，逆转录酶从信使RNA做出DNA，基因也可以用核苷酸化学合成。
Second, Taq polymerase is thermostable, so it survives the ninety-five degree denaturation step.
第二，Taq 聚合酶是耐热的，所以能挺过九十五度的变性步骤。
Third, DNA is negatively charged because of its phosphate groups, so fragments move towards the anode.
第三，DNA 因磷酸基团带负电，所以片段朝阳极移动。
Fourth, microarrays detect which genes are switched on, and databases store nucleotide and amino-acid sequences so scientists anywhere can compare them.
第四，微阵列检测哪些基因被打开，数据库保存核苷酸和氨基酸序列。
Fifth, recombinant proteins also include factor eight for haemophilia and adenosine deaminase for a faulty immune system.
第五，重组蛋白还包括血友病用的第八因子，以及免疫缺陷用的腺苷脱氨酶。