Imagine you were alive back in the 1980’s and were told
the computers would soon take over everything.
>From shopping to dating and the stock market.
That billions of people would be connected via a kind of web.
That you would own a handheld device
orders of magnitude more powerful than supercomputers.
It would seem absurd but then all of it happened.
Science fiction became our reality that we don’t even think about it
We’re at a similar point today with genetic engineering.
So let’s talk about it.
Where it came from? What we’re doing right now?
And about a recent breakthrough that will change how we live
和对 “正常” 的定义
and what we perceive as “normal” forever.
Humans have been engineering life for thousands of years, through selective breeding.
We strengthened useful traits and plants and animals.
We became very good at this but never truly understood how it works.
直到我们发现了生命的密码： 脱氧核糖核酸 即DNA
Until we discovered the code of life: deoxyribonucleic acid, DNA,
a complex molecule the guide of the growth, development function
and reproduction of everything alive.
Information is encoded in the structure of the molecule.
Four nucleotides are paired and make up a code that carries instructions.
Change the instructions and you change the being carrying it.
As soon as DNA was discovered people try to tinker with it.
In the 1960’s, scientists bombarded plants with radiation
to cause random mutations in the genetic code.
The idea was to get a useful plant variation by pure chance.
Sometimes, it actually worked too.
70年代 科学家向细菌 植物和动物注射DNA片段
In the 70’s, scientists inserted DNA snippets into bacteria, plants and animals
进行改良后以开展研究 或应用在医药和农业领域。 有时也只是好玩而已
to study and modify them for research, medicine, agriculture and for fun.
The earliest genetically modified animal was born in 1974,
making mice a standard tool for research, saving millions of lives.
In the 80’s, we got commercial.
The first patent was given for a microbe engineered to absorb oil.
今天 我们能通过基因工程改造的生命 制造多种化学物质
Today, we produce many chemicals by means of engineered life
比如 挽救生命的凝固因子 生长荷尔蒙以及胰岛素
like life-saving clotting factors, growth hormones and insulin;
all things we had to harvest from the organs of animals before that.
The first food modified in the lab went on sale in 1994: the Flavr Savr tomato,
a tomato given a much longer shelf-life
via an extra gene that suppresses the build-up of a rotting enzyme.
But GM food and the controversy surrounding them deserve a video of their own.
In the 1990’s there was also a brief foray into human engineering.
To treat maternal infertility, babies were made
that carry genetic information from three humans
making them the first humans ever to have three genetic parents.
现在 已经出现了超级肌肉猪 能快速生长的大马哈鱼
Today there are super muscled pigs, fast-growing salmon,
featherless chickens and see-through frogs.
On the fun side, we made things glow in the dark.
Fluorescent zebrafish are available for as little as ten dollars.
All of this is already very impressive but until recently,
基因编译十分昂贵 繁杂 且消耗时间
gene editing was extremely expensive, complicated and took a long time to do.
This has now changed with a revolutionary new technology now entering the stage:
基因编组技术 CRISPR（Clustered regularly interspaced short palindromic repeats)
Overnight, the costs of engineering have shrunk by 99%.
Instead of a year, it takes a few weeks to conduct experiments
and basically everybody with a lab can do it.
It’s hard to get across how big a technical revolution CRISPR is.
It literally has the potential to change humanity forever.
Why did this sudden revolution happen and how does it work?
Bacteria and viruses have been fighting since the dawn of life.
So-called bacteriophages, or phages, hunt bacteria.
In the ocean, phages kill 40% of them every single day.
Phages do this by inserting their own genetic code into the bacteria
and taking them over to use them as factories.
The bacteria try to resist, but fail most of the time
because their protection tools are too weak.
But sometimes, bacteria survive the attack.
Only if they do so can they activate their most effective antivirus system.
They save a part of the virus DNA in
their own genetic code in a DNA archive called CRISPR.
Here it’s stored safely until it’s needed.
When the virus attacks again, the bacterium quickly makes an RNA copy
from the DNA archive and arms a secret weapon, a protein called Cas9.
The protein now scans the bacterium’s inside for signs of the virus invader by
comparing every bit of DNA it finds to the sample from the archive.
When it finds a 100-percent perfect match
it’s activated and cuts out the virus DNA making it useless,
protecting the bacterium against the attack.
需要特别指出的是 Cas9非常精准 可称得上是DNA外科医生
What’s special is that Cas9 is very precise, almost like a DNA surgeon.
The revolution began when scientists figured out that the CRISPR system is programmable.
You can just give it a copy of DNA you want to modify
and put the system into a living cell.
If the old techniques of genetic manipulation were like a map,
CRISPR is like a GPS system.
Aside from being precise cheap and easy,
CRISPR offers the ability to edit live cells, to switch genes on and off
and target and study particular DNA sequences.
它适用于所有细胞：微生物 植物 动物或者人类
It also works for every type of cell: microorganisms, plants, animals or humans.
But despite the revolution CRISPR is for science,
it’s still just a first generation tool.
More precise tools are already being created and used as we speak.
2015年 科学家们在实验室运用CRISPR 切除病人体内的活体细胞病毒
In 2015, scientists use CRISPR to cut the HIV virus out of living cells
from patients in the lab, proving that it was possible.
Only about a year later they carried out a larger scale project
with rats that had the HIV virus in basically all of their body cells.
By simply injecting CRISPR into the rats tails,
they were able to remove more than 50% of the virus from cells all over the body.
In a few decades, a CRISPR therapy might cure HIV and other retroviruses.
Viruses that hide inside human DNA like herpes could be eradicated this way.
CRISPR could also defeat one of our worst enemies: cancer.
Cancer occurs when cells refused to die and keep multiplying
while concealing themselves from the immune system.
CRISPR gives us the means to edit your immune cells
and make them better cancer hunters.
Getting rid of cancer might eventually mean getting just a couple of injections
of a few thousand of your own cells that have been engineered in the lab
to heal you for good.
The first clinical trial for a CRISPR cancer treatment on human patients was
approved in early 2016 in the US.
Not even a month later, Chinese scientists announced that
they would treat lung cancer patients with immune cells
modified by CRISPR in August 2016.
Things are picking up pace quickly.
And then there are genetic diseases. There are thousands of them and they range
from merely annoying to deadly or entail decades of suffering.
With a powerful tool like CRISPR, we may be able to end this.
Over 3,000 genetic diseases are caused by a single incorrect letter in your DNA.
We are already building a modified version of Cas9 that is made to
change just a single letter, fixing the disease in the cell.
In a decade or two we could possibly cure thousands of diseases forever.
But all of these medical applications have one thing in common:
they are limited to the individual and die with them,
except if you use them on reproductive cells or very early embryos.
But CRISPR can and probably will be used for much more:
改良人类 定制婴儿 并可能逐渐但不可逆地
the creation of modified humans, designer babies and will mean gradual but
irreversible changes to the human gene pool.
The means to edit the genome of a human embryo already exists,
though the technology is still in its early stages.
But it has already been attempted twice: in 2015 and 2016, Chinese scientists
experimented with human embryos and were partially successful on their second attempt.
They showed the enormous challenges we still face in gene editing embryos
but also that scientists are working on solving them.
This is like the computer in the 70’s: there will be better computers.
Regardless of your personal take on genetic engineering, it will affect you.
Modified humans could alter the genome of our entire species because their
engineered traits will be passed on to that children and could spread over
generations slowly modifying the whole gene pool of humanity.
It will start slowly: the first designer babies will not be overly designed,
it’s most likely that they will be created to
eliminate a deadly genetic disease running in a family.
As the technology progresses and gets more refined, more and more people may argue
that not using genetic modification is unethical, because it condemns children
to preventable suffering and death and denies them to cure.
But as soon as the first engineered kid is born, a door is opened
that can’t be closed anymore.
早期 人们不会对虚荣特征有太多的关注 但随着基因改良
Early on, vanity traits will mostly be left alone, but as genetic modification
becomes more accepted and our knowledge of our genetic code enhances,
the temptation will grow.
If you make your offspring immune to Alzheimer,
why not also give them an enhanced metabolism?
Why not throw in perfect eyesight? How about height or muscular structure?
Full hair? How about giving your child the gift of extraordinary intelligence?
Huge changes are made as a result of the personal decisions
of millions of individuals that accumulate.
这就是滑坡谬误（译注：一种逻辑谬论，即不合理地使用连串的因果关系，将“可能性”转化为“必然性”，以达到某种意欲之结论。 引自知乎用户 王阿蛮）
This is a slippery slope.
Modified humans could become the new standard,
but as engineering becomes more normal and our knowledge improves,
we could solve the single biggest mortality risk factor: aging.
Two-thirds of the 150,000 people who die today will die of age-related causes.
Currently we think aging is caused by the accumulation of damage to ourselves,
like DNA breaks and the system’s responsible for fixing those wearing off over time.
But there are also genes that directly affect aging. A combination of genetic
engineering and other therapy could stop or slow down aging, maybe even reverse it.
We know from nature that there are animals immune to aging.
Maybe we could even borrow a few genes for ourselves.
Some scientists even think biological aging
could be something that eventually just stops being a thing.
We would still die at some point,
but instead of doing so in hospitals at age 90,
we might be able to spend a few thousand years with our loved ones.
Research into this is in its infancy,
and many scientists are rightly skeptical about the end of aging.
The challenges are enormous, and maybe it is unachievable.
But it is conceivable that people alive today might be the first
to profit from effective anti aging therapy.
All we might need is for someone to convince a smart billionaire
to make it their next problem to solve.
On a bigger scale we certainly could solve many problems
by having a modified population.
Engineered humans might be better equipped to cope with high-energy food,
eliminating many diseases of civilization like obesity.
In possession of a modified immune system with a library of potential threat,
we might become immune to most diseases that haunt us today.
Even further into the future we could engineer humans to be equipped for
extended space travel and cope with different conditions on other planets,
which would be extremely helpful in keeping us alive in our hostile universe.
Still a few major challenges await us. Some technological, some ethical.
Many of you watching will feel uncomfortable and fear that we will create a world
in which we will reject non-perfect humans and preselect features and qualities
based on our idea of what’s healthy.
The thing is we are already living in this world.
Tests for dozens of genetic diseases or complications
have become standard for pregnant women in much of the world.
通常来说 仅仅怀疑胎儿有基因缺陷 就会导致妊娠中止
Often, the mere suspicion of a genetic defect can lead to the end of pregnancy.
Take Down Syndrome for example: one of the most common genetic defects.
在欧洲 如检测到此症状 近92%的妊娠都被中止（译吐槽：生物课本上的那位兄弟 谢天谢地你父母不是欧洲人）
In Europe, about 92% of all pregnancies where it’s detected are terminated.
The decision to terminate pregnancy is incredibly personal, but
it’s important to acknowledge the reality that we are preselecting humans
based on medical conditions.
There is also no use in pretending this will change,
因此 我们在推进该技术进步的时候 必须小心审慎
so we have to act carefully and respectfully as we advance the technology
and can make more and more selections.
But none of this will happen soon:
as powerful as CRISPR is, and it is, it’s not infallible yet.
Wrong edit still happen as well as unknown errors
that could occur anywhere in the DNA and might go unnoticed.
The gene edit might achieve the desired result
disabling a disease, but also might accidentally trigger unwanted changes.
We just don’t know enough yet about the complex interplay of our genes
to avoid unpredictable consequences.
Working on accuracy and monitoring methods is a major concern
as the first human trials begin.
And since we’ve discussed a possible positive future,
there are darker visions too.
Imagine what a state like North Korea could do if they embraced genetic engineering.
Could a state cement its rule forever by forcing gene editing on their subjects?
What would stop a totalitarian regime
from engineering an army of modified super soldiers?
It is doable in theory.
Scenarios like this one are far far off into the future,
if they ever become possible at all.
But the basic proof of concept for genetic engineering like this already exists today.
The technology really is that powerful.
While this might be a tempting reason
to ban genetic editing and related research,
that would certainly be a mistake.
Banning human genetic engineering would only lead to the science wandering off
to a place with jurisdiction and rules that we are uncomfortable with.
Only by participating can we make sure that further research is guided by caution,
在谨慎 理性 合规 透明等理念指导下进行
reason, oversight and transparency.
Do you feel uncomfortable now?
Most of us have something wrong with them.
In the future that lies ahead of us, would we have been allowed to exist?
The technology is certainly a bit scary,
but we have a lot to gain and genetic engineering might
just be a step in the natural evolution of intelligent species in the universe.
We might end disease,
we could extend our life expectancy by centuries and travel to the stars.
There’s no need to think small when it comes to this topic.
Whatever your opinion on genetic engineering, the future is approaching no matter what.
What has been insane science fiction is about to become our new reality,
a reality full of opportunities and challenges.
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