biochemist's view of biology::
Understand... is a word that means different things to different people.
Understanding something in
science means verifiable prediction.
among the sciences, one builds upon the other
One of the main things we are going to do this semester is to explain how living things function at the level of chemistry. We will cover biochemistry, genetics, molecular biology (kind of a combination of biochemistry and genetics) and evolution. We will bring in other topics such as cell biology, but this and other basic areas of biology will be mainly left to the next semester.
Having put all this emphasis on biochemistry, let me pull back a bit and reassure you that we will not be going deeply into chemical mechanisms. This is not a course in chemistry, and although there is a prerequisite of one year of college chemistry, actually a strong high school course would also be OK. But we will be using the language of chemistry, discussing biological material as chemical structures, not just English words. We will deal extensively with organic chemicals, but organic chemistry is not necessary. Most of the special chemistry you need to know will be described as we go along.
::Characteristics of living
things:: Complex structure In this course we will emphasize a common denominator approach; we will
focus on unifying principles rather than on characteristics that distinguish
one living thing from another. The latter is often used to good effect
in for example,
ecology ... evolution (Darwin examined finches -
he looked for the differences that set each species apart). It turns out
that the common denominator approach works very well because, amazingly,
we living things all do these three things (maintain a complex structure,
chemically interact with the environment, and reproduce),
, the same way. Although in theory it
needn't necessarily have come out that way (elephants do it one way, dandelions
do another way) life, on earth at least, has evolved using one basic biochemical
strategy. As this unity became apparent,
biologists began gravitating to simpler and simpler living systems to
use as models for basic processes. So let's consider, what is the
simplest living system?
In this course we will emphasize a common denominator approach; we will focus on unifying principles rather than on characteristics that distinguish one living thing from another. The latter is often used to good effect in for example, ecology ... evolution (Darwin examined finches - he looked for the differences that set each species apart). It turns out that the common denominator approach works very well because, amazingly, we living things all do these three things (maintain a complex structure, chemically interact with the environment, and reproduce), basically, chemically , the same way. Although in theory it needn't necessarily have come out that way (elephants do it one way, dandelions do another way) life, on earth at least, has evolved using one basic biochemical strategy.
As this unity became apparent, biologists began gravitating to simpler and simpler living systems to use as models for basic processes. So let's consider, what is the simplest living system?
We can do a similar experiment with a complex living thing, say, a person, and ask for the smallest unit that exhibits the characteristics of living things in our short list:
Take a piece of skin of a person, put it in culture (i.e., bathed in a nutrient solution simulating "blood"). It .... grows (reproduces) has a complex structure (if looked at under a microscope), and interacts with the culture medium chemically (nutrients are consumed, substances are excreted from the skin fragment).
The person is alive, the person's arm is alive, and even the arm skin piece is alive by the 3 criteria above.
Shake the skin piece in a salt solution for a few hours; this frees up spheres (seen easily with a microscope), or cells, that make up the skin tissue. These cells also are alive: they retain the 3 characteristics we have defined, and most dramatically, they reproduce: one cell becomes many.
Now put them in a powerful blender, break them into sub-cellular pieces: Some structure still is present (but much less) and some metabolism can be measured (but much less), but there's no reproduction. These subcellualr fragments and molecuels are not living; they're dead, killed actually.
things are made up of cells, the basic building
block in biology.
"All living things are made up of cells (or their by-products), and all cells come from other cells by growth and development."
And since a cell is alive, it represents a simple object for study, suitable for learning the most fundamental processes that characterize living things.
Let's take a quick look at this skin cell:
Click here for a better picture of a typical animal eukaryotic cell.
[See Ch. 4 of Becker and/or Ch. 4 of Purves to read more about cell structure if you want. Most intro bio courses include this material at this point]
The size of this skin cell is about 10 µm in diameter. (µm = µ = micron = one millionth of a meter)
[As an aside, consider some units of size here: 1 millimeter (mm) = 1/25 inch (easily visualized, pinhead size); 1 micron ("micrometer", µm = 1/1000 mm, approximate the limit of a light microscope; the human eye can resolve 100 µm (0.1 mm)]
Typical animal cells = ~10 µm in diameter
The smallest cells are ~ 1 µm (~ at the limit of the light microscope, [~ the wavelength of visible light])
[ Aside : pushing to smaller length units, a nanometer = nm = 1/1,000,000 of a mm, = the size (diameter) of small molecules:
e.g., water (~0.5 nm), the alcohol ethanol (~1 nm), the sugar glucose (~1.5 nm)
[a term less used but that you may run into: the Ångstrom (A or Å)= 1/10 nm = distance between two atoms in a molecule (e.g., 2 A)]
The smallest cells are ~ 1 um. What about these smallest cells, the 1 micron cells? Smaller should be simpler yet, no? There'd be less room for much stuff. This is true. The smallest cells are those of bacteria:
They are 1-2 µm in cross-section, so they are about 1/1000 the size of our 10 µm skin cell (comparing a cube of 1 um dimensions vs. a cube of 10 um dimensions).
They have a more complicated surface (there is a hard cell wall outside the plasma membrane, to protect them).
But there is no true nucleus, and much less complicated machinery inside, no big organelles. Indeed, bacteria are about the size of many animal or plant cell organelles (e.g., a mitochondrion). Click here for a better picture of a prokaryotic cell.
A second big simplification (besides size): the skin cell was one of billions that made up the organism. For most bacteria, the number of cells in the organism is: ..... one.
That is, most bacteria are unicellular organisms.
Before we go any further considering bacteria, the simplest of all living things, let's see how they fit into a classification of all other living things according to these 2 criteria so far raised: simplicity and unicellularity.
Click here for a view of an evolutionary classification of all living things
The simplest cell is a bacterial
Study of the basic characteristics of life in
simple bacterial cells has facilitated understanding in biology.
E. coli grow by binary fission. First the cell grows larger, and then when it has attained a size about double that at its smallest size, it divides into 2 cells.
Their doubling time in a simple growth medium is about 1 hour.
::What are cells made of?::
Notice there is only one organic (= carbon (C)-containing) compound in this medium (glucose). The remaining substances are inorganic salts, providing the elements potassium, phosphorous, magnesium, sulfur, nitrogen, hydrogen and oxygen. There are also a few more metal elements needed in very small amounts.
E. coli can be made from
We will be considering how E. coli, and some other kinds of cells, do exactly this (that is, reproduce), over the next 2 months.
I found myself explaining some of this to my father-in-law once; he had seen a diagram of the glucose molecule on my computer screen and asked what it was. I explained that it was glucose, and, with this lecture in mind, that glucose was just about all you needed to make an E. coli cell. Figuring me for a biotechnologist, and expecting ever-greater things from biology from his reading of the Tuesday Times, he said, "Are you serious? You mean you can synthesize a living E. coli cell in the laboratory from glucose? How do you do it?" When I explained: "Well, you need to start with one E. coli cell to get the second one ", his face dropped. "Oh. Okay, but that's cheating," was his reaction.
He was taking life, cell growth, for granted, because it was so familiar: children get taller and taller, the grass has to be mowed twice a week, mold the size of a quarter appears on an old peach overnight. No, we can't put together a brand new E. coli cell in a test tube; that would be a truly amazing feat. But is it really any less amazing that E. coli can do it, without a test tube? In one hour, take 10 million glucose molecules and transform them into 5000 different things, all organized to fit together in a cell that can do it all over again, in one more hour. How? How do these little cells know what to do, know how to do it, and how do they actually carry it out? If, like my father-in-law, you're not really curious about the answer, then you're probably in the wrong course.
We can break the problem down into several parts, which will give you a preview of where we're headed:
To understand the question,
we first must know just what molecules a cell is made of .
2. How do we get those chemicals?
3. Where does the energy for this process
4. Where does E. coli get the information for doing all this?
Before we get down to business with question #1 (the chemical definition of the cell), let's consider some mathematical consequences of this reproduction by binary fission, or bacterial cell growth.
fission leads to exponential growth.
1 cell --> 2 cells in 60 min., or 1 generation; 60 min. = Doubling time = tD
How can we calculate the time it will take to get a billion cells, so we know when to come back to the lab to collect these cells for analysis?
Let g = number of generations. From the binary fission mechanism: after 2 gens. --> 4 cells, after 3 gens. --> 8 cells, etc.
If we started with one million cells, then N = 106 x 2g
More generally, starting with No cells: N = No x 2g
Since we want to know what time to come back, it is more convenient to express generations in terms of time. If we let tD = the generation time, or doubling time, then the number of generations that have passed during the time interval t is just t/tD. So generations, g = t/tD.
So now N = No x 2t/tD, an equation that expresses exponential growth (with respect to time)
Or, more generally and simpler to write: N = No x 2kt , where k=1/tD, a constant for a given cell type under a defined condition (i.e., growth medium and temperature).
N = No ekt, where k = ke = ln2/tD, and, writing it another way: ln(N/No) = ket
and: N = No10kt, where k = k10 = log2/tD, and: log(N/No) = k10t
Note here that the growth constant k is being defined differently for the different bases used to express the exponential nature of the growth.
The derivation of these forms is described in the exponential growth handout.
Below in italics was not in the live lecture by intention, since it is more easily followed at your leisure here. Now to return to the problem we set for ourselves, of how long it would take for one E. coli cell to grow into 1 billion cells. We could solve this equation for t, since we know we want N to be 1 billion, No is 1, and tD is 1 hr. Taking the logarithm base 2 of both sides of the base 2 equation N/No=2t/tD:
we get log2 (N/No) = t/tD, then, solving for t, we get t = tD[log2(N/No)].
And plugging in the numbers we have: t = log2 (1,000,000,000/1) = log2(109) hours (since the doubling time was in hour units)
log2 of any number X = lneX/lne2 = lneX/0.69 = more simply: lnX/0.69 (since "ln" with no other indicator means log base e)
or, log2X = log10X/log102 = logX/0.3 (since "log" with no other indicator means log base 10)
Applying this last one (base 10) to our problem, and since you now know that the log2 = 0.3 from the line above:
t = log2(109) = log(109) /0.3 = 9/0.3 = 30. So it would take 30 hours for one cell to become one billion.
Related exponential transformations are: 2x = 10xlog2 and 2x = exln2,
And useful numbers are: log(2) = 0.30, ln(2) = 0.69
log2(N/No) = t/tD
So log2(N/No) = log(N/No)/log2 = t/tD
log(N/No) = (log2/tD)t = Kt, where K = log2/tD = 0.3/tD
or, converting back to the exponential form:
N = No10Kt, where K=0.3/tD as mentioned before.
Since most scientific calculators have natural log functions, similarly, we can write
N = NoeKt, where this K = ln2/tD = 0.69/tD , which is the usual form of the exponential growth equation
We could also have approached this question of rates of change of N with time more directly and naturally using calculus. If you have a million cells, then after one generation time you will have gained 1 million. If you had 200, then you would have gained 200. In general, the rate of increase of N with time is just proportional to the number of cells you have at any moment in time, or:
dN/dt = kN
Separating variables: dN/N = kdt
Integrating between time zero when N = No and time t, when N = N, we get:
lnN - ln No = kt - 0, or ln(N/No) = kt, or
N = Noekt, which is exactly what we derived above.
We can now calculate this constant k by considering the time interval over which No has doubled; in that case N/No = 2 and t = tD, so 2 = ektD. Taking the natural logarithm of both sides:
ln2=ktD, or k=ln2/tD, so the constant comes out exactly as before as well.
You will need mostly arithmetic, some algebra, and an ability to work with exponential notation and an occasional logarithm.
There are several problems of this type in the problem book, solving for N, for t, for No, etc.; be sure to do them.
Note the 3 phases: a lag (while the cells are getting geared up), log (logarithmic) phase or exponential phase (linear on a semi-log plot such as this), and finally stationary phase (after the nutrients have been exhausted and/or toxic excreted products have built up as the culture becomes dense).So we can treat cell reproduction quantitatively, and that's what growth looks like mathematically. We now start on the problem of how the bacterium E. coli reproduces, how it grows; how we get two E. coli cells from one. First we need to know what are the chemicals that need to be made if we are to create one net E. coli cell. We need to turn to the nature of the chemicals that make up an E. coli cell, so we know what it is that we need to make in an hour.
We will start with the most abundant and most important molecule in the cell, not an organic molecule, but water, H2O. We will use our discussion of the water molecule as a springboard for introducing different types of chemical bonds that are important in biology. Lecture 2 will start with the structure of the water molecule and how that structure determines its properties.(C) Copyright 2001 Lawrence Chasin and Deborah Mowshowitz Department of Biological Sciences Columbia University New York, NY
Clickable pictures are from Purves, et. al., Life, 5th Edition, Sinauer-Freeman's Images of Life 5.0.
A production of the Columbia Center for New Media Teaching and Learning