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PROFESSOR: Welcome back.
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So, lecture two.
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We're going to now dive into our triangle.
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As I told you about in the last lecture, the entire course is
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organized around our coat of arms, the coat of arms function being
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understood two ways.
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Biochemistry, genetics.
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Fundamentally studying the most interesting and richest molecules,
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proteins, but we'll talk about other kinds of molecules.
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Genes, the object of study of geneticists, and the
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connection of the two.
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But today we're going to start with understanding this picture by
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beginning several lectures on biochemistry.
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All right.
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Biochemistry.
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Again, you have to put yourself back in the mindset.
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To understand how science is done you have to think about what discoveries
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meant to the people who were discovering them and what was so
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surprising.
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So put yourself back in the mindset of somebody just before the turn of the
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20th century.
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They knew about phenomena.
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I'll tell you about a phenomenon that they knew about, that you've
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probably heard of.
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Fermentation.
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A popular subject, for example.
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I'll name this section in a moment.
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If you take a glass filled with sugar water or fruit juice, and you just
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leave it sitting out just at room temperature, over the course of some
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days, you'll begin to see bubbles develop.
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Sugar water, fruit juice, bubbles develop and come out and you will also
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find that if you try to drink it, you've made alcohol.
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This is, of course, the basis of beer, wine.
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That bit of bubbles is also the basis of bread.
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So this is an observation as old as the hills, that if you take sugar
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water or fruit juice and you leave it sitting out, you develop bubbles.
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The bubbles were known to be carbon dioxide and alcohol came out of it.
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And this carbon dioxide drives the production of bread.
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That's where you can have bread rise.
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And the alcohol.
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You get beer, you get wine.
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You also had one other very strange thing, another product.
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In addition to the production of carbon dioxide and the production of
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alcohol, people noticed that the thing got cloudy.
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And this is cloudy stuff that also seemed to be produced from this sugar
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water was yeast.
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For a long time people thought the yeast was a product of fermentation.
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They didn't know that yeast was a living organism.
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They didn't know it was a cell.
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They thought it was a product of fermentation.
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And it took some pretty clever science to show that the yeast was not a
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result of fermentation, it was the cause of the fermentation.
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Because there was a little bit of yeast there, it produces fermentation
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and it grows and divides and makes more and more yeast cells, and the
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yeast is the cause.
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So Pasteur was involved in showing that you needed living organisms there
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in order to produce the fermentation.
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Fermentation, ferment, from the Latin [LATIN]
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to boil.
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The bubbles coming off there.
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Really cool stuff.
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The problem was they got into their heads so solidly that you needed this
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living organism yeast to do the fermentation that people began to ask,
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was this something only living matter could do?
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Now the chemists at the time, in the 1700s and the
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1800s, were really curious.
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This looked like chemistry.
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You were taking sugar, you were producing carbon dioxide and alcohols.
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How could this be made to work?
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Did you need a living organism to do it?
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People worked really hard to try to somehow extract from the living
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organism something capable of doing fermentation
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without a living organism.
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And they failed miserably.
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Miserably.
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They tried sodium hydroxide treatment of this yeast and see if they could
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extract things.
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They tried boiling it at high temperatures to extract things.
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They tried letting it sit for days and then whatever they did the resulting
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goop that they got could not do fermentation.
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You might now guess that the reason they couldn't do fermentation is they
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had managed, with their harsh treatment of high temperatures and
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sodium hydroxide and other things like that, to have destroyed that which
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might carry out fermentation.
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But that was not the conclusion in the late 1800s.
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The conclusion was that fermentation, this miraculous transformation that
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life could carry out, was inherently only possible because of a living
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organism being present.
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It was inherently necessary to have living protoplasm to do this.
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It was not chemistry, it was beyond chemistry.
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It was some vitalism.
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And it was referred to as vital forces, vitalism, the idea that in
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addition to the laws of physics and the laws of chemistry there were these
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other properties that life had that couldn't be understood as chemistry.
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And that was pretty much the view up until the 1890s.
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As late as the 1890s this idea that there was some magic living things
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could do was still holding sway.
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That was called vitalism, this concept.
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And what I want to start talking about is the death of vitalism.
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It turns out that vitalism came because nobody could manage to get
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something that could do this fermentation.
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If you could somehow show that you could extract the thing that could
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ferment without the need of the organism, that would be a big deal.
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A guy called Eduard Buchner came along and, for a variety of reasons I won't
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go into, but in the mid-1890s said, you know, maybe we should try to be a
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little more gentle with this yeast thing.
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And, as so often happens in science, it was technology that drove it.
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He invented powerful new technology.
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He invented this powerful technology right here.
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The powerful technology that he invented was first this thing here.
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A long mortar hanging and a little pestle here in which he could put the
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yeast, add some sand, some quartz, little particles of sand, and swing
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this thing around very gently.
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And the little sand would crack open the yeast and the yeast would become
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kind of a doughy, gray, mushy mixture.
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And he only did that for a couple of minutes, just going around and around
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and around.
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Then what he did was he scooped it off and he put it in a piece of canvas.
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And he covered canvas up into a little package and he stuffed
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it into this press.
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And he turns to press and squeezes out yeast juice.
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And remarkably, the yeast juice was able to carry out fermentation.
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Now he had to convince people that it wasn't that a whole lot of cells had
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somehow gotten in the yeast juice.
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So he had to convince people that there weren't cells there.
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And he showed there really weren't cells there, or not very many cells.
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And even a few cells getting in wouldn't be a problem,
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because it was so active.
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It was doing so much fermentation it couldn't be accounted for by a couple
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little strays cells.
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So he had to be very scientific about it.
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But he eventually publishes in 1897 that this yeast juice can carry out
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fermentation.
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The stuff that carried out fermentation was referred to as, you
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know, something from yeast.
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The Latin name here referring to yeast is zyme.
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The thing that was in yeast was called an enzyme.
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There were enzymes.
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Something in yeast.
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They didn't quite know what it was.
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And these enzyme or enzymes could carry out this miraculous
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transformation.
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Well, Buchner like knocked everybody's socks off with this.
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And, amongst other things, Buchner wins the Nobel prize
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for this for chemistry.
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Nobel prize in chemistry for the year in 1907.
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One of the first Nobel prizes, the seventh Nobel prize given in chemistry
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goes to Buchner for this landmark thing.
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Now, I got to say, this whole notion is so remarkable that I went back and
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pulled out Buchner's Nobel lecture 1907 in which when he gets invited to
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Sweden on December 10 for Alfred Nobel's birthday and gives a
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talk and all that.
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It's still so cool.
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And we have on the web in the resource box associated with the course
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Buchner's lecture.
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I'm just going to read you a little bit from the end of Buchner's lecture.
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Because on the one hand he's so excited that they understand this, and
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on the other hand he realizes, boy, we hardly know anything.
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Like, I can't tell you what these enzymes are at all.
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We've managed to show that yeast juice can do this.
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We don't need a living organism.
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Vitalism isn't right.
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But boy, I have no clue what's going on.
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And so honest here.
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It's wonderful.
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"Distinguished audience," he says in his closing remarks, "as you'll see,
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we are still far from an understanding of the processes involved in alcohol
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fermentation of sugar, as well as from a more detailed description of the
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nature of the zymes" which he also was using for enzyme.
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"Quite the contrary, every step we take the present leads to fresh
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complications.
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We must be thankful, however, if the increasingly narrow and steep paths do
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not end in an unclimbable cliff." He had no idea that they'd ever be able
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to understand what these enzymes were about.
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He goes on for a little bit, and he says, "Nevertheless, there is no cause
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for discouragement.
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The progress made in the field of fermentation processes is clearly
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revealed when you compare our present knowledge with that of just a few
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decades ago.
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The differences between the vitalistic view and the enzyme theory have been
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reconciled.
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The fermentation process becomes comprehensible to us now that it is
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possible to separate it from the rest of the processes of life.
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Just as the first step toward the explanation of the phenomenon of
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combustion rested on the fact that it was possible to separate the
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generation of light and heat from the processes of oxidation." He's thinking
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about this in a very broad sense.
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And he says, "We are seeing the cells of plants and animals more and more
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clearly as chemical factories where the various products are manufactured
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in separate workshops." A very industrial revolution
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kind if view here.
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"The enzymes act as the overseers." What a factory view of
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the late 1800s here.
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"Our acquaintance with these most important agents of living things is
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constantly increasing.
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Even though we may still be a long way from our goal, we are approaching it
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step by step.
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Everything is justifying our hopes.
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We must never therefore let ourselves fall into the way of thinking
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ignorabimus, we shall never know.
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But we must have every confidence that the day will dawn with even those
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processes of life, which are still a puzzle today, will cease to be
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inaccessible to us natural scientists."
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That's one hell of a way to end a Nobel lecture.
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And it's a statement about what is amazing about science was that it all
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seemed unimaginable that we were ever going to understand what those enzymes
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were about at essentially the turn of the 20th century.
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And of course you know perfectly well we do know, and we're going to cover
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in the next couple of lectures what all of that is about.
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And all the things we don't understand today, you can just apply Buchner to
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that as well.
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So all right, that's where we are.
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Buchner the death of vitalism, and now we've got actually dive in and
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understand how all that stuff works.
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What are those enzymes?
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Can we understand these amazing properties of life?
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Properties of being able to carry out chemical transformations, properties
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of being able to, oh, I don't know, even more simple things.
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Having cells in the first place.
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Membranes around cells.
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How in the world you do that?
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Like, what makes a membrane the divides a cell's
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inside from its outside?
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How you do other sorts of things?
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Can we understand all of those things in terms of fundamental chemistry?
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That's what biochemistry's asking us here.
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So before we go on to the next segment, test
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yourself with this problem.
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