Kathryn A. Whitehead: The tiny balls of fat that could revolutionize medicine | TED

90,028 views ใƒป 2021-08-11

TED


ืื ื ืœื—ืฅ ืคืขืžื™ื™ื ืขืœ ื”ื›ืชื•ื‘ื™ื•ืช ื‘ืื ื’ืœื™ืช ืœืžื˜ื” ื›ื“ื™ ืœื”ืคืขื™ืœ ืืช ื”ืกืจื˜ื•ืŸ.

ืชืจื’ื•ื: zeeva livshitz ืขืจื™ื›ื”: Ido Dekkers
00:13
What if I told you that the pandemic will save the lives of millions of people?
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ืžื” ืื ื”ื™ื™ืชื™ ืื•ืžืจืช ืœื›ื ืฉื”ืžื’ื™ืคื” ืชืฆื™ืœ ืืช ื—ื™ื™ื”ื ืฉืœ ืžื™ืœื™ื•ื ื™ ืื ืฉื™ื?
00:21
It's a difficult thing to consider,
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ื–ื” ื“ื‘ืจ ืฉืงืฉื” ืœื—ืฉื•ื‘ ืขืœื™ื•,
00:23
given how many loved ones we've already lost.
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ื‘ื”ืชื—ืฉื‘ ื‘ืžืกืคืจ ื”ืื ืฉื™ื ื”ืื”ื•ื‘ื™ื ืฉื›ื‘ืจ ืื™ื‘ื“ื ื•.
00:27
But throughout the course of human history,
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ืื‘ืœ ืœืื•ืจืš ืžื”ืœื›ื” ืฉืœ ื”ื”ื™ืกื˜ื•ืจื™ื” ื”ืื ื•ืฉื™ืช,
00:30
massive public health crises
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ืžืฉื‘ืจื™ ื‘ืจื™ืื•ืช ืฆื™ื‘ื•ืจ ืขืฆื•ืžื™ื
00:32
have resulted in innovation in health care and technology.
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ื”ื‘ื™ืื• ืœื—ื“ืฉื ื•ืช ื‘ืชื—ื•ื ื”ืจืคื•ืื” ื•ื”ื˜ื›ื ื•ืœื•ื’ื™ื”.
00:37
For example, the Black Death gave rise to the Gutenberg press
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ืœืžืฉืœ, ื”ืžื’ื™ืคื” ื”ืฉื—ื•ืจื” ื”ื•ืœื™ื“ื” ืืช ื“ืคื•ืก ื’ื•ื˜ื ื‘ืจื’
00:43
and the 1918 flu pandemic led to modern vaccine technology.
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ื•ืžื’ื™ืคืช ื”ืฉืคืขืช ื‘1918 ื”ื•ื‘ื™ืœื” ืœื˜ื›ื ื•ืœื•ื’ื™ื™ืช ื”ื—ื™ืกื•ื ื™ื ื”ืžื•ื“ืจื ื™ืช.
00:49
The COVID-19 pandemic has and will be no different.
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ืžื’ื™ืคืช ื”ืงื•ืจื•ื ื” ืื™ื ื”, ื•ืœื ืชื”ื™ื” ืฉื•ื ื”.
00:54
Just look at our vaccines --
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ืจืง ื”ืกืชื›ืœื• ืขืœ ื”ื—ื™ืกื•ื ื™ื ืฉืœื ื• -
00:55
normally developed over many years,
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ืฉื‘ื“ืจืš ื›ืœืœ ืžืคื•ืชื—ื™ื ืœืื•ืจืš ืฉื ื™ื ืจื‘ื•ืช,
00:58
and the mRNA vaccines were deployed in a mind-blowing 11 months.
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ื•ื—ื™ืกื•ื ื™ ื”- mRNA ื ืคืจืกื• ืชื•ืš 11 ื—ื•ื“ืฉื™ื ืžื˜ืจื™ืคื™ื.
01:06
How is that even possible?
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ืื™ืš ื–ื” ื‘ื›ืœืœ ืืคืฉืจื™?
01:09
It was possible because scientists have been working for many years
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ื–ื” ื”ื™ื” ืืคืฉืจื™ ื›ื™ ืžื“ืขื ื™ื ืขื•ื‘ื“ื™ื ืžื–ื” ืฉื ื™ื ืจื‘ื•ืช
01:13
to get us to the point where we could use mRNA quickly
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ื›ื“ื™ ืœื”ื‘ื™ื ืื•ืชื ื• ืœื ืงื•ื“ื” ืฉื‘ื” ื ื•ื›ืœ ืœื”ืฉืชืžืฉ ื‘- mRNA ื‘ืžื”ื™ืจื•ืช
01:17
in an emergency situation.
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ื‘ืžืฆื‘ ื—ื™ืจื•ื.
01:20
Specifically,
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ื‘ืื•ืคืŸ ืžืžื•ืงื“,
01:21
we've been working on how to help mRNA with its biggest problem,
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ืขื‘ื“ื ื• ืื™ืš ืœืขื–ื•ืจ ืœ-mRNA ืขื ื”ื‘ืขื™ื” ื”ื’ื“ื•ืœื” ื‘ื™ื•ืชืจ ืฉืœื•,
01:26
which is that it doesn't normally go to the right places inside of our bodies.
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ืฉื”ื™ื, ืฉื‘ื“ืจืš ื›ืœืœ ื”ื•ื ืœื ื”ื•ืœืš ืœืžืงื•ืžื•ืช ื”ื ื›ื•ื ื™ื ื‘ืชื•ืš ื’ื•ืคื ื•.
01:32
Fortunately, we got around that problem just in time,
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ืœืžืจื‘ื” ื”ืžื–ืœ, ื”ืกืชื“ืจื ื• ืขื ื”ื‘ืขื™ื” ื”ื–ืืช ื‘ื“ื™ื•ืง ื‘ื–ืžืŸ
01:36
and I'd like to tell you about the technology that we use to do it.
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ื•ืื ื™ ืจื•ืฆื” ืœืกืคืจ ืœื›ื ืขืœ ื”ื˜ื›ื ื•ืœื•ื’ื™ื” ื‘ื” ืื ื• ืžืฉืชืžืฉื™ื ืœืฉื ื›ืš.
01:40
When mRNA is administered,
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ื›ืืฉืจ mRNA ืžืกื•ืคืง,
01:42
it's injected into our muscles or our bloodstream,
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ื”ื•ื ืžื•ื–ืจืง ืœืฉืจื™ืจื™ื, ืื• ืœื–ืจื ื”ื“ื ืฉืœื ื•,
01:45
but we actually need it to go inside of our cells.
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ืื‘ืœ ืœืžืขืฉื” ืื ื—ื ื• ืจื•ืฆื™ื ืฉื”ื•ื ื™ื™ื›ื ืก ืคื ื™ืžื” ืœืชืื™ื ืฉืœื ื•.
01:49
Unfortunately, mRNA is fragile,
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ืœืจื•ืข ื”ืžื–ืœ, mRNA ื”ื•ื ืฉื‘ื™ืจ,
01:51
and our bodies will destroy it before it goes very far.
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ื•ื”ื’ื•ืฃ ืฉืœื ื• ื™ื”ืจื•ืก ืื•ืชื• ืœืคื ื™ ืฉื”ื•ื ื™ื’ื™ืข ืจื—ื•ืง ืžืื•ื“.
01:55
You can think of mRNA like a glass vase that you'd like to send in the mail
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ืชื•ื›ืœื• ืœื—ืฉื•ื‘ ืขืœ mRNA ื›ืขืœ ืื’ืจื˜ืœ ื–ื›ื•ื›ื™ืช ืฉืชืจืฆื• ืœืฉืœื•ื— ื‘ื“ื•ืืจ
01:59
without a box and bubble wrap.
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ืœืœื ืงื•ืคืกื” ื•ืขื˜ื™ืคืช ื‘ื•ืขื•ืช.
02:01
It'll break long before it's been delivered.
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ื”ื•ื ื™ื™ืฉื‘ืจ ื”ืจื‘ื” ืœืคื ื™ ืฉื”ื•ื ื™ื™ืžืกืจ ืœื ืžืขืŸ.
02:05
And without an address on the box,
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ื•ื‘ืœื™ ื›ืชื•ื‘ืช ืขืœ ื”ืงื•ืคืกื”,
02:08
your postal delivery service will have no idea where to take it.
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ืœืฉื™ืจื•ืช ืžืฉืœื•ื—ื™ ื”ื“ื•ืืจ ืœื ื™ื”ื™ื” ืฉื•ื ืžื•ืฉื’ ืœืืŸ ืœืงื—ืช ืืช ื–ื”.
02:13
And so if we're going to use mRNA as a therapeutic,
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ื•ืœื›ืŸ ืื ืจื•ืฆื™ื ืœื”ืฉืชืžืฉ ื‘- mRNA ื›ื˜ื™ืคื•ืœ,
02:17
it needs our help.
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ื”ื•ื ื–ืงื•ืง ืœืขื–ืจืชื ื•.
02:19
It needs protection, and it needs to be told where to go.
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ื”ื•ื ื ื–ืงืง ืœื”ื’ื ื”, ื•ืฆืจื™ืš ืœื•ืžืจ ืœื• ืœืืŸ ืœืœื›ืช.
02:23
And that's where I come in.
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ื•ื›ืืŸ ืื ื™ ื ื›ื ืกืช ืœืชืžื•ื ื”.
02:26
For over five decades, scientists and engineers like myself
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ื‘ืžืฉืš ืœืžืขืœื” ืžื—ืžื™ืฉื” ืขืฉื•ืจื™ื, ืžื“ืขื ื™ื ื•ืžื”ื ื“ืกื™ื ื›ืžื•ื ื™
02:30
have been creating the shipping materials for nucleic acid drugs,
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ื™ื™ืฆืจื• ืืช ื—ื•ืžืจื™ ื”ืžืฉืœื•ื— ืœืชืจื•ืคื•ืช ื—ื•ืžืฆืช ื’ืจืขื™ืŸ,
02:34
like DNA and RNA.
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ื›ืžื• DNA ื•- RNA.
02:38
Through trial and error, we've created packages
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ื‘ืืžืฆืขื•ืช ื ื™ืกื•ื™ ื•ื˜ืขื™ื™ื”, ื™ืฆืจื ื• ื—ื‘ื™ืœื•ืช
02:41
that deliver intact vases to the wrong address;
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ืฉืฉื•ืœื—ื•ืช ืื’ืจื˜ืœื™ื ืฉืœืžื™ื ืœื›ืชื•ื‘ืช ื”ืœื ื ื›ื•ื ื”;
02:46
that delivered to the right address but with a broken vase;
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ืฉื ืžืกืจื• ืœื›ืชื•ื‘ืช ื”ื ื›ื•ื ื” ืื‘ืœ ืขื ืื’ืจื˜ืœ ืฉื‘ื•ืจ;
02:51
packages that get ripped apart by attacking dogs;
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ื—ื‘ื™ืœื•ืช ืฉื ืงืจืขื•ืช ื‘ื™ื“ื™ ื›ืœื‘ื™ื ืžืชืงื™ืคื™ื;
02:55
and packages that throw out the mail carrier's back.
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ื•ื—ื‘ื™ืœื•ืช ืฉืžืฉืœื™ื›ื•ืช ืืช ื”ื“ื•ื•ืจ ืื—ื•ืจื”.
02:59
It's taken many years to get the science right.
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ืขื‘ื“ื ื• ื”ืจื‘ื” ืฉื ื™ื ื›ื“ื™ ืœืงื‘ืœ ืชื•ืฆืื” ืžื“ืขื™ืช ื ื›ื•ื ื”.
03:03
Let me show you the result,
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ื”ืจืฉื• ืœื™ ืœื”ืจืื•ืช ืœื›ื ืืช ื”ืชื•ืฆืื”,
03:05
these tiny balls of fat that we call lipid nanoparticles.
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ื›ื“ื•ืจื™ ื”ืฉื•ืžืŸ ื”ืงื˜ื ื˜ื ื™ื ื”ืืœื” ืฉืื ื• ืžื›ื ื™ื ื ื ื•-ื—ืœืงื™ืงื™ื ืœื™ืคื™ื“ื™ื™ื.
03:09
Let me tell you what they are and how they work.
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ื”ืจืฉื• ืœื™ ืœืกืคืจ ืœื›ื ืžื” ื”ื ื•ื›ื™ืฆื“ ื”ื ืขื•ื‘ื“ื™ื.
03:14
So first of all, "nano" just means really, really small.
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ืื– ืงื•ื“ื ื›ืœ, โ€œื ื ื•โ€ ืคื™ืจื•ืฉื• ืคืฉื•ื˜ ืžืžืฉ ืžืžืฉ ืงื˜ืŸ.
03:19
Think of how small a person is compared to the diameter of the earth.
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ื—ื™ืฉื‘ื• ื›ืžื” ืื“ื ื”ื•ื ืงื˜ืŸ ื‘ื”ืฉื•ื•ืื” ืœืงื•ื˜ืจ ื›ื“ื•ืจ ื”ืืจืฅ.
03:24
That's how small a nanoparticle is compared to the person.
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ืขื“ ื›ื“ื™ ื›ืš ื ื ื•-ื—ืœืงื™ืง ืงื˜ืŸ ื‘ื”ืฉื•ื•ืื” ืœืื“ื.
03:29
These nanoparticles are made up of several fatty molecules called lipids.
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ื—ืœืงื™ืงื™ื ืืœื” ืžื•ืจื›ื‘ื™ื ืžืžืกืคืจ ืžื•ืœืงื•ืœื•ืช ืฉื•ืžืŸ ื”ื ืงืจืื•ืช ืœื™ืคื™ื“ื™ื.
03:34
Fat is an awesome packing material --
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ืฉื•ืžืŸ ื”ื•ื ื—ื•ืžืจ ืืจื™ื–ื” ืžื“ื”ื™ื --
03:38
nice and bouncy.
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ื™ืคื” ื•ืงื•ืคืฆื ื™.
03:41
Interestingly, our cells are also surrounded by fat
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ืžืขื ื™ื™ืŸ ืฉื”ืชืื™ื ืฉืœื ื• ื’ื ื›ืŸ ืžื•ืงืคื™ื ื‘ืฉื•ืžืŸ
03:45
to keep them flexible and protected.
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ื›ื“ื™ ืœืฉืžื•ืจ ืื•ืชื ื’ืžื™ืฉื™ื ื•ืžื•ื’ื ื™ื.
03:49
Years ago, scientists had the idea to create lipid nanoparticles
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ืœืคื ื™ ืฉื ื™ื ืœืžื“ืขื ื™ื ื”ื™ื” ืจืขื™ื•ืŸ ืœื™ืฆื•ืจ ื ื ื•-ื—ืœืงื™ืงื™ื ืœื™ืคื™ื“ื™ื™ื
03:54
that would act like a Trojan horse.
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ืฉื™ืคืขืœื• ื›ืžื• ืกื•ืก ื˜ืจื•ื™ืื ื™.
03:57
Because the lipids in the nanoparticle look similar
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ื‘ื’ืœืœ ืฉื”ืœื™ืคื™ื“ื™ื ื‘ื ื ื•-ื—ืœืงื™ืงื™ื ื ืจืื™ื ื“ื•ืžื™ื
04:00
to the membranes that surround our cells,
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ืœืžืžื‘ืจื ื•ืช ื”ืžืงื™ืคื•ืช ืืช ื”ืชืื™ื ืฉืœื ื•,
04:03
the cells are willing to bring the nanoparticle inside,
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ื”ืชืื™ื ืžื•ื›ื ื™ื ืœื”ื›ื ื™ืก ืืช ื”ื ื ื•-ื—ืœืงื™ืงื™ื ืคื ื™ืžื”,
04:07
and that's when the mRNA is released into the cell.
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ื•ืื– ื”- mRNA ืžืฉืชื—ืจืจ ืœืชื.
04:10
So what, exactly, are the lipids in these nanoparticles?
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ืื– ืžื”ื ื‘ื“ื™ื•ืง ื”ืœื™ืคื™ื“ื™ื ื‘ื ื ื•-ื—ืœืงื™ืงื™ื ื”ืืœื”?
04:15
There are four ingredients in addition to the mRNA,
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ื™ืฉื ื ืืจื‘ืขื” ืžืจื›ื™ื‘ื™ื ื‘ื ื•ืกืฃ ืœ- mRNA,
04:18
and I'll tell you about each one.
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ื•ืื ื™ ืืกืคืจ ืœื›ื ืขืœ ื›ืœ ืื—ื“ ืžื”ื.
04:20
First, there's a lipid called a phospholipid.
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ืจืืฉื™ืช, ื™ืฉื ื• ืœื™ืคื™ื“ ืฉื ืงืจื ืคื•ืกืคื•ืœื™ืคื™ื“.
04:23
This is the primary ingredient in our cell membranes,
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ืฉื”ื•ื ื”ืžืจื›ื™ื‘ ื”ืขื™ืงืจื™ ื‘ืงืจื•ื ื”ืชื ืฉืœื ื•,
04:27
which are the walls of fat that separate the insides of our cells
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ืฉืืœื” ื”ื ืงื™ืจื•ืช ื”ืฉื•ืžืŸ ื”ืžืคืจื™ื“ื™ื ื‘ื™ืŸ ื”ื—ืœืง ื”ืคื ื™ืžื™ ืฉืœ ื”ืชืื™ื ืฉืœื ื•
04:31
from everything that surrounds them.
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ืžื›ืœ ืžื” ืฉืžืงื™ืฃ ืื•ืชื.
04:33
Phospholipids have a head that likes water
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ืœืคื•ืกืคื•ืœื™ืคื™ื“ื™ื ื™ืฉ ืจืืฉ ืฉืื•ื”ื‘ ืžื™ื
04:38
and a tail that likes other fatty things.
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ื•ื–ื ื‘ ืฉืื•ื”ื‘ ื“ื‘ืจื™ื ืฉื•ืžื ื™ื™ื ืื—ืจื™ื.
04:41
So when you throw a bunch of phospholipids together in water,
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ืื– ื›ืฉื–ื•ืจืงื™ื ืงื‘ื•ืฆื” ืฉืœ ืคื•ืกืคื•ืœื™ืคื™ื“ื™ื ื™ื—ื“ ืœืžื™ื,
04:45
they form this beautiful structure called a lipid bilayer.
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ื”ื ื™ื•ืฆืจื™ื ืืช ื”ืžื‘ื ื” ื”ื™ืคื” ื”ื–ื” ืฉื ืงืจื ื“ื• ืฉื›ื‘ื” ืœื™ืคื™ื“ื™ืช.
04:49
Here, the heads face the inside and the outside of the cell,
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ื›ืืŸ, ื”ืจืืฉื™ื ืคื•ื ื™ื ื›ืœืคื™ ืคื ื™ื ื•ื”ื—ืœืง ื”ื—ื™ืฆื•ื ื™ ืฉืœ ื”ืชื,
04:53
which is water,
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ืฉื”ื•ื ืžื™ื,
04:54
and the fat-loving parts of the molecule hang out together in the middle.
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ื•ื”ื—ืœืงื™ื ืื•ื”ื‘ื™ ื”ืฉื•ืžืŸ ืฉืœ ื”ืžื•ืœืงื•ืœื” ืžืกืชื•ื‘ื‘ื™ื ื™ื—ื“ ื‘ืืžืฆืข.
04:59
In lipid nanoparticles,
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ื‘ื ื ื•-ื—ืœืงื™ืงื™ื ืœื™ืคื™ื“ื™ื™ื,
05:00
phospholipids have a similar role
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ืœืคื•ืกืคื•ืœื™ืคื™ื“ื™ื ื™ืฉ ืชืคืงื™ื“ ื“ื•ืžื”
05:02
of keeping all of the other ingredients organized.
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ืฉืœ ืฉืžื™ืจื” ืขืœ ื›ืœ ื”ืžืจื›ื™ื‘ื™ื ื”ืื—ืจื™ื ืžืื•ืจื’ื ื™ื.
05:06
Second, there's a lipid called cholesterol.
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ืฉื ื™ืช, ื™ืฉ ืœื™ืคื™ื“ ืฉื ืงืจื ื›ื•ืœืกื˜ืจื•ืœ.
05:10
Why, if cholesterol has a bad reputation,
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ืžื“ื•ืข, ืื ืœื›ื•ืœืกื˜ืจื•ืœ ื™ืฉ ืžื•ื ื™ื˜ื™ืŸ ืจืข,
05:14
would we want to use it in a therapeutic nanoparticle?
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ื”ื™ื™ื ื• ืจื•ืฆื™ื ืœื”ืฉืชืžืฉ ื‘ื• ื‘ืชื•ืš ื ื ื•-ื—ืœืงื™ืง ื˜ื™ืคื•ืœื™?
05:18
It turns out that while cholesterol can be bad when it's in our bloodstream,
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ืžืกืชื‘ืจ ืฉื‘ืขื•ื“ ื”ื›ื•ืœืกื˜ืจื•ืœ ื™ื›ื•ืœ ืœื”ื™ื•ืช ืจืข ื›ืฉื”ื•ื ื ืžืฆื ื‘ืžื—ื–ื•ืจ ื”ื“ื ืฉืœื ื•,
05:23
it's actually a really good thing for our cell membranes.
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ื”ื•ื ื‘ืขืฆื ื“ื‘ืจ ืžืžืฉ ื˜ื•ื‘ ืขื‘ื•ืจ ืžืžื‘ืจื ื•ืช ื”ืชื ืฉืœื ื•
05:27
And that's because those phospholipids I just told you about,
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ื•ื–ื” ื‘ื’ืœืœ ืฉื”ืคื•ืกืคื•ืœื™ืคื™ื“ื™ื ื”ืืœื” ืฉื‘ื“ื™ื•ืง ืกื™ืคืจืชื™ ืœื›ื ืขืœื™ื”ื,
05:30
they are entirely too free with themselves,
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ื”ื ืœื’ืžืจื™ ื—ื•ืคืฉื™ื™ื ืžื“ื™ ืขื ืขืฆืžื,
05:34
and they are prone to falling apart.
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ื•ื”ื ืžื•ืขื“ื™ื ืœื”ืชืคืจืง.
05:37
Cholesterol is a stiff molecule
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ื”ื›ื•ืœืกื˜ืจื•ืœ ื”ื•ื ืžื•ืœืงื•ืœื” ื ื•ืงืฉื”
05:39
that wedges itself in between the other lipids
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ืฉื ื•ืขืฆืช ืืช ืขืฆืžื” ื‘ื™ืŸ ื”ืœื™ืคื™ื“ื™ื ื”ืื—ืจื™ื
05:43
to fill in the gaps and hold them all together.
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ื›ื“ื™ ืœืžืœื ืืช ื”ืžืจื•ื•ื—ื™ื ื•ืœื”ื—ื–ื™ืง ืืช ื›ื•ืœื ื‘ื™ื—ื“.
05:47
It plays a similar role in our lipid nanoparticles.
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ื”ื•ื ืžืžืœื ืชืคืงื™ื“ ื“ื•ืžื” ื‘ื ื ื•-ื—ืœืงื™ืงื™ื ื”ืœื™ืคื™ื“ื™ื™ื ืฉืœื ื•
05:50
It provides structural support so the nanoparticles don't fall apart
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ื”ื•ื ืžืกืคืง ืชืžื™ื›ื” ืžื‘ื ื™ืช ื›ื“ื™ ืฉื”ื ื ื•-ื—ืœืงื™ืงื™ื ืœื ื™ืชืคืจืงื•
05:55
in between the injection and when they get into our cells.
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ื‘ื™ืŸ ื”ื”ื–ืจืงื” ื•ื”ื›ื ื™ืกื” ืœืชืื™ื ืฉืœื ื•.
06:00
Third, there's a lipid called an ionizable lipid.
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ืฉืœื™ืฉื™ืช, ืงื™ื™ื ืœื™ืคื™ื“ ืฉื ืงืจื ืœื™ืคื™ื“ ืžื™ื•ื ืŸ
06:04
Here, "ionizable" means that when these particles are in the bloodstream,
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ื›ืืŸ, โ€œืžื™ื•ื ืŸโ€ ืคื™ืจื•ืฉื• ืฉื›ืืฉืจ ื—ืœืงื™ืงื™ื ืืœื” ื ืžืฆืื™ื ื‘ื–ืจื ื”ื“ื,
06:08
they're neutrally charged, which helps with their safety.
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ื”ื ื‘ืขืœื™ ืžื˜ืขืŸ ื ื™ื™ื˜ืจืœื™, ืžื” ืฉืขื•ื–ืจ ืœื‘ื˜ื™ื—ื•ืชื.
06:13
Then they switch to a positive charge inside of our cells,
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ื•ืื– ื”ื ืขื•ื‘ืจื™ื ืœื‘ืขืœื™ ืžื˜ืขืŸ ื—ื™ื•ื‘ื™ ื‘ืชื•ืš ื”ืชืื™ื ืฉืœื ื•,
06:17
which helps them release the mRNA.
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ืฉืขื•ื–ืจ ืœื”ื ืœืฉื—ืจืจ ืืช ื”- mRNA.
06:21
Ionizable lipids are special because they have to be made in the lab,
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ืœื™ืคื™ื“ื™ื ืžื™ื•ื ื ื™ื ื”ื ืžื™ื•ื—ื“ื™ื ืžื›ื™ื•ื•ืŸ ืฉื—ื™ื™ื‘ื™ื ืœื™ื™ืฆืจื ื‘ืžืขื‘ื“ื”,
06:26
and scientists around the world
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ื•ืžื“ืขื ื™ื ื‘ืจื—ื‘ื™ ื”ืขื•ืœื
06:28
have tested tens of thousands of these materials
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ื‘ื“ืงื• ืขืฉืจื•ืช ืืœืคื™ื ืžื”ื—ื•ืžืจื™ื ื”ืืœื”
06:32
to find ones that are good at delivering mRNA safely.
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ืœืžืฆื•ื ื›ืืœื” ืฉื”ื ื˜ื•ื‘ื™ื ื‘ื”ืขื‘ืจืช mRNA ื‘ืื•ืคืŸ ื‘ื˜ื•ื—.
06:37
And because they're made in the lab,
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ื•ืžื›ื™ื•ื•ืŸ ืฉื”ื ืžื™ื•ืฆืจื™ื ื‘ืžืขื‘ื“ื”,
06:39
they tend to be proprietary to the company that invented them.
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ื”ื ื ื•ื˜ื™ื ืœื”ื™ื•ืช ื‘ื‘ืขืœื•ืช ื”ื—ื‘ืจื” ืฉื”ืžืฆื™ืื” ืื•ืชื.
06:43
So, for example, Moderna and BioNTech, the company that partnered with Pfizer,
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ื›ืš ืœืžืฉืœ, ืžื•ื“ืจื ื” ื•ื‘ื™ื•ื ื˜ืง ืฉืฉื™ืชืคื” ืคืขื•ืœื” ืขื ืคื™ื™ื–ืจ,
06:51
they discovered different ionizable lipids,
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ื’ื™ืœื• ืœื™ืคื™ื“ื™ื ืžื™ื•ื ื ื™ื ืฉื•ื ื™ื,
06:54
and that is the only important ingredient in their COVID-19 vaccines that differ.
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ื•ื–ื” ื”ืžืจื›ื™ื‘ ื”ื—ืฉื•ื‘ ื”ื™ื—ื™ื“ ืฉืฉื•ื ื” ื‘ื—ื™ืกื•ื ื™ COVID-19 ืฉืœื”ื.
07:01
And even then, their ionizable lipids aren't even that different,
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ื•ื’ื ืื–, ื”ืœื™ืคื™ื“ื™ื ื”ืžื™ื•ื ื ื™ื ืฉืœื”ื ืื™ื ื ื›ื” ืฉื•ื ื™ื
07:06
which is reassuring, because when independent groups of scientists
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ืฉื–ื” ืžืขื•ื“ื“, ื›ื™ ื›ืืฉืจ ืงื‘ื•ืฆื•ืช ืขืฆืžืื™ื•ืช ืฉืœ ืžื“ืขื ื™ื
07:10
converge on similar solutions,
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ืžื’ื™ืขื™ื ืœืคืชืจื•ื ื•ืช ื“ื•ืžื™ื
07:13
it's easier to trust the result.
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ืงืœ ื™ื•ืชืจ ืœืกืžื•ืš ืขืœ ื”ืชื•ืฆืื”.
07:15
Finally, one more ingredient.
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ืœื‘ืกื•ืฃ, ืขื•ื“ ืžืจื›ื™ื‘ ื ื•ืกืฃ.
07:18
This one is a polymer called polyethylene glycol.
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ื–ื” ืคื•ืœื™ืžืจ ืฉื ืงืจื ืคื•ืœื™ืืชื™ืœืŸ ื’ืœื™ืงื•ืœ.
07:22
So let's call it PEG. That's much easier.
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ืื– ื‘ื•ืื• ื ืงืจื ืœื–ื” PEG. ื–ื” ื”ืจื‘ื” ื™ื•ืชืจ ืงืœ.
07:25
PEG is a water-loving molecule.
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PEG ื”ื•ื ืžื•ืœืงื•ืœื” ืื•ื”ื‘ืช ืžื™ื.
07:28
So it surrounds the lipid nanoparticle and it holds it all together.
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ืื– ื”ื•ื ืžืงื™ืฃ ืืช ื”ื ื ื•-ื—ืœืงื™ืง ื”ืœื™ืคื™ื“ื™ ื•ืžื—ื–ื™ืง ืืช ื”ื›ืœ ื™ื—ื“.
07:32
You can think of the other three lipids as the box and the bubble wrap
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ื ื™ืชืŸ ืœื—ืฉื•ื‘ ืขืœ ืฉืœื•ืฉืช ื”ืœื™ืคื™ื“ื™ื ื”ืื—ืจื™ื ื›ืขืœ ืงื•ืคืกื” ื•ืขื˜ื™ืคืช ื‘ื•ืขื•ืช
07:37
for the mRNA,
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ืขื‘ื•ืจ ื”- mRNA,
07:38
and the PEG as the packing tape.
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ื•ืขืœ ื”- PEG ื›ืขืœ ืกืจื˜ ื”ืืจื™ื–ื”.
07:41
You may have heard in the news about a tiny fraction of people
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ืื•ืœื™ ืฉืžืขืชื ื‘ื—ื“ืฉื•ืช ืขืœ ืžืกืคืจ ื–ืขื™ืจ ืฉืœ ืื ืฉื™ื
07:45
that have allergic responses to the vaccine.
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ืฉื™ืฉ ืœื”ื ืชื’ื•ื‘ื•ืช ืืœืจื’ื™ื•ืช ืœื—ื™ืกื•ืŸ
07:49
There is some evidence that PEG could be contributing to these allergic reactions.
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ื™ืฉื ืŸ ืขื“ื•ื™ื•ืช ืœื›ืš ืฉ- PEG ื™ื›ื•ืœ ืœื”ื™ื•ืช ื’ื•ืจื ืœืชื’ื•ื‘ื•ืช ืืœืจื’ื™ื•ืช ืืœื”.
07:55
And that's because people are routinely exposed to PEG
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ื•ื–ื” ื‘ื’ืœืœ ืฉืื ืฉื™ื ื ื—ืฉืคื™ื ื‘ืื•ืคืŸ ืฉื’ืจืชื™ ืœ- PEG
08:00
in cosmetic and household products,
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ื‘ืžื•ืฆืจื™ ืงื•ืกืžื˜ื™ืงื” ื•ืžืฉืง ื‘ื™ืช,
08:03
and some people have already developed antibodies against PEG.
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ื•ื›ืžื” ืื ืฉื™ื ื›ื‘ืจ ืคื™ืชื—ื• ื ื•ื’ื“ื ื™ื ื ื’ื“ PEG.
08:08
But why would this happen to some people and not to others?
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ืื‘ืœ ืœืžื” ืฉื–ื” ื™ืงืจื” ืœื—ืœืง ืžื”ืื ืฉื™ื ื•ืœื ืœืื—ืจื™ื?
08:13
It turns out that every person's immune system is different,
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ืžืกืชื‘ืจ ืฉืžืขืจื›ืช ื”ื—ื™ืกื•ืŸ ืฉื•ื ื” ืืฆืœ ื›ืœ ืื“ื,
08:16
and just the same way that some people are allergic to latex,
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ื•ื‘ื“ื™ื•ืง ื‘ืื•ืชื” ืฆื•ืจื” ืฉื—ืœืง ืžื”ืื ืฉื™ื ืืœืจื’ื™ื™ื ืœืœื˜ืงืก,
08:20
other people are allergic to PEG.
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ืื ืฉื™ื ืื—ืจื™ื ืืœืจื’ื™ื™ื ืœ- PEG
08:24
It's important to keep in mind, however,
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ืขื ื–ืืช, ื—ืฉื•ื‘ ืœื–ื›ื•ืจ,
08:27
that PEG has had a long history of safe use
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ืฉ ืœ- PEG ื™ืฉ ื”ื™ืกื˜ื•ืจื™ื” ืืจื•ื›ื” ืฉืœ ืฉื™ืžื•ืฉ ื‘ื˜ื•ื—
08:30
as part of FDA-approved drug formulations,
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ื›ื—ืœืง ืžืชื›ืฉื™ืจื™ ืชืจื•ืคื•ืช ืฉืื•ืฉืจื• ืขืœ ื™ื“ื™ ื”- FDA,
08:34
and these vaccine allergies could be caused by things other than PEG.
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ื•ื”ืืœืจื’ื™ื•ืช ืœื—ื™ืกื•ืŸ ืขืฉื•ื™ื•ืช ืœื”ื™ื’ืจื ืžื“ื‘ืจื™ื ืื—ืจื™ื ืž PEG
08:40
More research is needed to get to the bottom of these side effects.
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ื“ืจื•ืฉ ืžื—ืงืจ ื ื•ืกืฃ ื›ื“ื™ ืœื”ื’ื™ืข ืœืขื•ืžืง ืชื•ืคืขื•ืช ื”ืœื•ื•ืื™ ื”ืœืœื•.
08:45
All right, so let's take a step back and look at our whole nanoparticle.
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ื‘ืกื“ืจ, ืื– ื‘ื•ืื• ื ื™ืงื— ืฆืขื“ ืื—ื•ืจื” ื•ื ืกืชื›ืœ ืขืœ ื”ื ื ื•-ื—ืœืงื™ืง ืฉืœื ื• ื›ื•ืœื•.
08:50
Beautiful, right?
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ื™ืคื”, ื ื›ื•ืŸ?
08:52
When these ingredients all fit together nicely,
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ื›ืืฉืจ ื›ืœ ื”ืžืจื›ื™ื‘ื™ื ื”ืœืœื• ืžืฉืชืœื‘ื™ื ื™ืคื”,
08:55
the result is a deliverywoman's dream.
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ื”ืชื•ืฆืื” ื”ื™ื ืžืขืœ ื•ืžืขื‘ืจ ืœืžืฆื•ืคื”.
08:58
In the case of the vaccines,
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ื‘ืžืงืจื” ืฉืœ ื”ื—ื™ืกื•ื ื™ื,
09:00
after these nanoparticles get injected into our muscle,
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ืื—ืจื™ ืฉื”ื ื ื•-ื—ืœืงื™ืงื™ื ืืœื” ืžื•ื–ืจืงื™ื ืœืฉืจื™ืจ ืฉืœื ื•,
09:03
they take the mRNA into our cells.
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ื”ื ืœื•ืงื—ื™ื ืืช ื”- mRNA ืœืชืื™ื ืฉืœื ื•.
09:06
There, the mRNA acts like an instruction manual
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ืฉื, ื”- mRNA ืžืชื ื”ื’ ื›ืžื• ืžื“ืจื™ืš ื”ื•ืจืื•ืช ื”ืคืขืœื”
09:10
that tells our cells to make a foreign protein,
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ืฉืื•ืžืจ ืœืชืื™ื ืฉืœื ื• ืœื™ื™ืฆืจ ื—ืœื‘ื•ืŸ ื–ืจ,
09:14
in this case, the coronavirus spike protein.
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ื‘ืžืงืจื” ื–ื”, ื—ืœื‘ื•ืŸ ืกืคื™ื™ืง ื‘ื ื’ื™ืฃ ื”ืงื•ืจื•ื ื”.
09:17
When our immune cells see the spike protein,
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ื›ืืฉืจ ืชืื™ ื”ื—ื™ืกื•ืŸ ืฉืœื ื• ืจื•ืื™ื ืืช ื—ืœื‘ื•ืŸ ื”ืกืคื™ื™ืง,
09:21
they rush to protect us from it,
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ื”ื ืžืžื”ืจื™ื ืœื”ื’ืŸ ืขืœื™ื ื• ืžืคื ื™ื•,
09:23
and they teach themselves to remember it,
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ื•ื”ื ืžืœืžื“ื™ื ืืช ืขืฆืžื ืœื–ื›ื•ืจ ืื•ืชื•,
09:25
so that they can kill it if it ever returns.
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ื›ื“ื™ ืฉื™ื•ื›ืœื• ืœื”ืฉืžื™ื“ ืื•ืชื• ืื ื™ื—ื–ื•ืจ ืื™ ืคืขื.
09:29
As we speak,
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ื‘ื–ืžืŸ ืฉืื ื—ื ื• ืžื“ื‘ืจื™ื,
09:30
the mRNA vaccines are out there saving lives from the coronavirus.
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ื—ื™ืกื•ื ื™ ื”-mRNA ื ืžืฆืื™ื ืฉื ื•ืžืฆื™ืœื™ื ื—ื™ื™ื ืžื ื’ื™ืฃ ื”ืงื•ืจื•ื ื”.
09:36
They were our first and best tool to combat this nightmare,
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ื”ื ื”ื™ื• ื”ื›ืœื™ ื”ืจืืฉื•ืŸ ื•ื”ื˜ื•ื‘ ื‘ื™ื•ืชืจ ืฉืœื ื• ืœื”ื™ืœื—ื ื‘ืกื™ื•ื˜ ื”ื–ื”,
09:41
and they are our best hope of responding swiftly to viral variance
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ื•ื”ื ื”ืชืงื•ื•ื” ื”ื˜ื•ื‘ื” ื‘ื™ื•ืชืจ ืฉืœื ื• ืœืชื’ื•ื‘ื” ืžื”ื™ืจื” ืœืฉื•ื ื•ืช ื•ื™ืจืืœื™ืช
09:46
because we can keep our lipid nanoparticle packaging the same,
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ื›ื™ ืื ื—ื ื• ื™ื›ื•ืœื™ื ืœืฉืžื•ืจ ืืช ืืจื™ื–ื•ืช ื”ื ื ื• -ื—ืœืงื™ืงื™ื ื”ืœื™ืคื™ื“ื™ื™ื ื–ื”ื•ืช,
09:50
and all we have to do is swap out the mRNA that's inside.
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ื•ื›ืœ ืžื” ืฉืขืœื™ื ื• ืœืขืฉื•ืช ื”ื•ื ืœื”ื—ืœื™ืฃ ืืช ื”- mRNA ืฉื ืžืฆื ื‘ืคื ื™ื.
09:55
But here's the best part:
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ืื‘ืœ ื”ื ื” ื”ื—ืœืง ื”ื˜ื•ื‘ ื‘ื™ื•ืชืจ:
09:57
for mRNA therapeutics,
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ืœื˜ื™ืคื•ืœื™ mRNA,
09:59
these vaccines are only the beginning.
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ื—ื™ืกื•ื ื™ื ืืœื” ื”ื ืจืง ื”ื”ืชื—ืœื”.
10:03
mRNA can be used to treat or cure many diseases.
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ื ื™ืชืŸ ืœื”ืฉืชืžืฉ ื‘- mRNA ืœื˜ื™ืคื•ืœ ืื• ืœืจืคื•ื™ ืžื—ืœื•ืช ืจื‘ื•ืช.
10:08
So in the future, we will likely have treatments for many terrible diseases,
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ืื– ื‘ืขืชื™ื“ ืกื‘ื™ืจ ืฉื™ื”ื™ื• ืœื ื• ื˜ื™ืคื•ืœื™ื ืœืžื—ืœื•ืช ื ื•ืจืื™ื•ืช ืจื‘ื•ืช,
10:13
including cystic fibrosis,
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ื›ื•ืœืœ ืกื™ืกื˜ื™ืง ืคื™ื‘ืจื•ื–ื™ืก,
10:16
muscular dystrophy
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ื ื™ื•ื•ืŸ ืฉืจื™ืจื™ื
10:17
and sickle cell anemia.
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ื•ืื ืžื™ื” ื—ืจืžืฉื™ืช.
10:19
These diseases are caused by mutated proteins,
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ืžื—ืœื•ืช ืืœื• ื ื’ืจืžื•ืช ืขืœ ื™ื“ื™ ื—ืœื‘ื•ื ื™ื ืฉืขื‘ืจื• ืžื•ื˜ืฆื™ื”,
10:23
and we can use mRNA to ask our cells
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ื•ืื ื• ื™ื›ื•ืœื™ื ืœื”ืฉืชืžืฉ ื‘- mRNA ื›ื“ื™ ืœื‘ืงืฉ ืžื”ืชืื™ื ืฉืœื ื•
10:26
to make the correct version of these proteins.
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ืœื™ืฆื•ืจ ืืช ื”ื’ื™ืจืกื” ื”ื ื›ื•ื ื” ืฉืœ ื”ื—ืœื‘ื•ื ื™ื ื”ืืœื”.
10:30
We'll have treatments for cancer -- breast, blood, lungs -- you name it.
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ื™ื”ื™ื• ืœื ื• ื˜ื™ืคื•ืœื™ื ื‘ืกืจื˜ืŸ - ืฉื“, ื“ื, ืจื™ืื•ืช - ื›ืœ ืžื” ืฉืชืจืฆื•.
10:35
Here, we'll use mRNA to teach our immune cells
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ื›ืืŸ, ื ืฉืชืžืฉ ื‘- mRNA ื›ื“ื™ ืœืœืžื“ ืืช ืชืื™ ื”ื—ื™ืกื•ืŸ ืฉืœื ื•
10:40
how to find and kill cancer cells.
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ื›ื™ืฆื“ ืœืžืฆื•ื ื•ืœื”ืฉืžื™ื“ ืชืื™ื ืกืจื˜ื ื™ื™ื.
10:44
And then, if we're lucky, we'll have vaccines
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ื•ืื–, ืื ื™ื”ื™ื” ืœื ื• ืžื–ืœ, ื™ื”ื™ื• ืœื ื• ื—ื™ืกื•ื ื™ื
10:48
against some of the most deadly and feared pathogens across the globe,
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ื ื’ื“ ื›ืžื” ืžื”ืคืชื•ื’ื ื™ื ื”ืงื˜ืœื ื™ื™ื ื•ื”ืžืคื—ื™ื“ื™ื ื‘ื™ื•ืชืจ ื‘ืจื—ื‘ื™ ื”ืขื•ืœื,
10:53
including malaria, Ebola and HIV.
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ื›ื•ืœืœ ืžืœืจื™ื”, ืื‘ื•ืœื” ื•- HIV.
10:59
Some of these products are already in clinical trials,
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ื—ืœืง ืžื”ืžื•ืฆืจื™ื ื”ืืœื” ื ืžืฆืื™ื ื›ื‘ืจ ื‘ื ื™ืกื•ื™ื™ื ืงืœื™ื ื™ื™ื,
11:02
and the success of the COVID-19 vaccines will pave the way
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ื•ื”ืฆืœื—ืช ื”ื—ื™ืกื•ื ื™ื ื ื’ื“ ื ื’ื™ืฃ ื”ืงื•ืจื•ื ื” ืชืกืœื•ืœ ืืช ื”ื“ืจืš
11:07
for future generations of these therapies.
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ืœื“ื•ืจื•ืช ื”ื‘ืื™ื ืฉืœ ื˜ื™ืคื•ืœื™ื ืืœื”.
11:11
This is how the pandemic will save the lives of millions.
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ื›ืš ืชืฆื™ืœ ื”ืžื’ืคื” ืืช ื—ื™ื™ื”ื ืฉืœ ืžื™ืœื™ื•ื ื™ื.
11:17
It catalyzed the most rapid vaccine development in history
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ื”ื™ื ื–ืจื–ื” ืืช ืคื™ืชื•ื— ื”ื—ื™ืกื•ื ื™ื ื”ืžื”ื™ืจ ื‘ื™ื•ืชืจ ื‘ื”ื™ืกื˜ื•ืจื™ื”
11:21
and brought to life a niche, previously unapproved form of technology.
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ื•ื”ืคื™ื—ื” ืจื•ื— ื—ื™ื™ื ื‘ื˜ื›ื ื•ืœื•ื’ื™ื” ื ื™ืฉืชื™ืช, ืฉื‘ืขื‘ืจ ืขื“ื™ื™ืŸ ืœื ืื•ืฉืจื”.
11:27
And in our desperation, we gave that technology a chance.
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ื•ื‘ื™ื™ืื•ืฉื ื•, ื ืชื ื• ืœื˜ื›ื ื•ืœื•ื’ื™ื” ื”ื–ื• ื”ื–ื“ืžื ื•ืช.
11:32
Now we're collecting long-term safety and efficacy data
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ืขื›ืฉื™ื• ืื ื—ื ื• ืื•ืกืคื™ื ื ืชื•ื ื™ ื‘ื˜ื™ื—ื•ืช ื•ื™ืขื™ืœื•ืช ืœื˜ื•ื•ื— ืืจื•ืš
11:36
from hundreds of millions of people.
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ืžืžืื•ืช ืžื™ืœื™ื•ื ื™ ืื ืฉื™ื.
11:40
And with these data, interest in the technology,
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ื•ืขื ื”ื ืชื•ื ื™ื ื”ืืœื”, ืขื ื™ื™ืŸ ื‘ื˜ื›ื ื•ืœื•ื’ื™ื”,
11:44
funding for the technology
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ืžื™ืžื•ืŸ ื”ื˜ื›ื ื•ืœื•ื’ื™ื”
11:47
and trust in the technology
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ื•ืืžื•ืŸ ื‘ื˜ื›ื ื•ืœื•ื’ื™ื”
11:50
will continue to grow.
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ื™ืžืฉื™ื›ื• ืœื’ื“ื•ืœ.
11:53
Looking ahead,
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ื‘ืžื‘ื˜ ืœืขืชื™ื“
11:55
the packaging and delivery of mRNA to the right organs and tissues
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ื”ืืจื™ื–ื” ื•ื”ืžืฉืœื•ื— ืฉืœ ื”-mRNA ืœืื™ื‘ืจื™ื ื•ืœืจืงืžื•ืช ื”ื ื›ื•ื ื™ื
12:00
will continue to be one of the most significant challenges
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ื™ืžืฉื™ื›ื• ืœื”ื™ื•ืช ืื—ื“ ื”ืืชื’ืจื™ื ื”ืžืฉืžืขื•ืชื™ื™ื ื‘ื™ื•ืชืจ
12:03
to implementing this technology.
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ืœื™ื™ืฉื•ื ื˜ื›ื ื•ืœื•ื’ื™ื” ื–ื•.
12:06
And so my colleagues and I are going to be busy for a very long time.
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ื•ื›ืš ืขืžื™ืชื™ื™ ื•ืื ื™ ื”ื•ืœื›ื™ื ืœื”ื™ื•ืช ืขืกื•ืงื™ื ื”ืจื‘ื” ืžืื•ื“ ื–ืžืŸ.
12:11
Ultimately, I'm here with a message of hope.
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ื‘ืกื•ืคื• ืฉืœ ื“ื‘ืจ, ืื ื™ ื›ืืŸ ืขื ืžืกืจ ืฉืœ ืชืงื•ื•ื”.
12:15
We are on the cusp of a revolution.
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ืื ื• ื ืžืฆืื™ื ื‘ืคืชื—ื” ืฉืœ ืžื”ืคื›ื”.
12:20
mRNA is about to change the world forever,
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mRNA ืขื•ืžื“ ืœืฉื ื•ืช ืืช ื”ืขื•ืœื ืœื ืฆื—,
12:24
and it's all thanks to these fatty little balls
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ื•ื”ื›ืœ ื”ื•ื“ื•ืช ืœื›ื“ื•ืจื™ื ื”ืงื˜ื ื™ื ื•ื”ืฉื•ืžื ื™ื™ื ื”ืืœื”
ืฉืœื•ืงื—ื™ื ืืช ืชืจื•ืคืช ื”ืคืœื ื”ื–ื• ื‘ื“ื™ื•ืง ืœืžืงื•ื ื‘ื• ื”ื™ื ื ื—ื•ืฆื”.
12:27
that take this miracle medicine to exactly where it's needed.
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12:31
Thank you.
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ืชื•ื“ื”.
12:32
(Applause)
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(ืชึฐืฉืื•ึผืื•ึนืช)
ืขืœ ืืชืจ ื–ื”

ืืชืจ ื–ื” ื™ืฆื™ื’ ื‘ืคื ื™ื›ื ืกืจื˜ื•ื ื™ YouTube ื”ืžื•ืขื™ืœื™ื ืœืœื™ืžื•ื“ ืื ื’ืœื™ืช. ืชื•ื›ืœื• ืœืจืื•ืช ืฉื™ืขื•ืจื™ ืื ื’ืœื™ืช ื”ืžื•ืขื‘ืจื™ื ืขืœ ื™ื“ื™ ืžื•ืจื™ื ืžื”ืฉื•ืจื” ื”ืจืืฉื•ื ื” ืžืจื—ื‘ื™ ื”ืขื•ืœื. ืœื—ืฅ ืคืขืžื™ื™ื ืขืœ ื”ื›ืชื•ื‘ื™ื•ืช ื‘ืื ื’ืœื™ืช ื”ืžื•ืฆื’ื•ืช ื‘ื›ืœ ื“ืฃ ื•ื™ื“ืื• ื›ื“ื™ ืœื”ืคืขื™ืœ ืืช ื”ืกืจื˜ื•ืŸ ืžืฉื. ื”ื›ืชื•ื‘ื™ื•ืช ื’ื•ืœืœื•ืช ื‘ืกื ื›ืจื•ืŸ ืขื ื”ืคืขืœืช ื”ื•ื•ื™ื“ืื•. ืื ื™ืฉ ืœืš ื”ืขืจื•ืช ืื• ื‘ืงืฉื•ืช, ืื ื ืฆื•ืจ ืื™ืชื ื• ืงืฉืจ ื‘ืืžืฆืขื•ืช ื˜ื•ืคืก ื™ืฆื™ืจืช ืงืฉืจ ื–ื”.

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