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Welcome to this course on personalized medicine.
Personalized medicine is getting a lot of press, and people are very interested in
the idea that their medicine should be personalized.
But in fact the idea that
we take care of patients in a very highly individualized way is not something new.
Hippocrates, the father of modern and ancient medicine,
said it is more important to know what sort of
person has a disease than to know what sort of a disease a person has.
That's another way of saying that it's important to understand the patient and
then you'll understand the disease.
More recently, Sir William Osler, the father of modern medicine, a Canadian who
went to Johns Hopkins to found the famous department of medicine there and
ended at his career at Oxford, is widely quoted.
I'll just read you the bottom quote.
You can read the top one to yourself.
The good physician treats the disease.
The great physician treats the patient who has the disease.
That's another way of saying that the great physician understands
what it is about their patient that's special,
that's individual, that's unique, and tries to tailor the therapy for them.
So those ideas have been around for a long time.
So the question is what is so special about this vogue for
personalized medicine.
So we've known forever that occasional patients seem different from
the average somehow.
How long they live, how susceptible or resistant they are to disease,
how well they'll respond to drugs or how badly they'll respond to certain drugs.
The excitement in personalized medicine is that we now have new tools
with which to understand this variability and to exploit it.
So one of the new tools is an understanding of the DNA molecule, and
we'll talk about that in the next few modules.
But it's important to understand that without the advent of modern
computer technology, we would not be able to analyze the DNA sequences that we have,
and understand how it is that those should be applied to individual patients.
So, I think that the revolution in personalized medicine
Is taking advantage of these two developments.
One in the science of DNA, and
the other in the science of managing large data sets.
So large data sets are not just DNA, but other kinds of data sets.
What you surf at Google, what your X-rays look like, what your Shopping habits
are like it, and taken together, that is defining the new science of big data.
And big data is another way of looking at very, very large data sets and
trying to understand what it is about an individual person, a patient or
a shopper that makes them different.
We're all familiar with that from surfing the web, and you can imagine that you
could surf your DNA web and do the same kind of individualization.
Okay, so the promise of this personalized medicine,
big data intersection is that we will learn more about disease susceptibility or
response to drugs by looking at DNA patterns,
by looking at patterns in electronic medical records,
by looking at patterns of proteins that we can measure in blood samples,
by looking at other kinds of large data sets to understand what it is that makes
an individual special, and one of the things that we're going to use that for
is to engage patients in their own care and their individualization.
Now the problem there is that patients vary and
their level of excitement around the concepts of personalized medicine.
So people vary for many, many reasons that have very little to do with their
health, their biological health, but have everything to do with their environment,
the way they were brought up, their educational levels.
People vary in their religious beliefs, some people really believe very,
very deeply that certain forms of treatment should never be applied.
Other people are willing to apply other forms of therapy.
So the way you're brought up makes a difference in your attitude toward this
new science of personalized medicine.
The level of education makes a big difference.
I show here a picture of a food label.
Some people can look at that food label and grasp
immediately the important information that they need for their own care.
Other people can't read, so those food labels are not very useful to them.
Many patients take more than one medicine.
Here's a picture of a patient with many, many, many pill bottles.
So some patients can handle taking 20 medicines.
Other patients just don't have the intellectual or financial capacity
to take 20 different medicines, all of them on different schedules,
all of them with the potential of interacting with each other.
So we have to individualize at the level of understanding these kinds of factors.
And of course, the other factor that is making a huge difference
is the level at which people have access to electronic media.
Increasingly, we're seeing patients communicating with their doctors
through the computer.
We're seeing patients communicating, downloading information from the web,
whether it's good or bad, and some patients have access to that information.
Other patients don't.
So that creates another opportunity for
individualizing care based on what a patient can and wants to do.
And so those are important pieces of the individualization or
personalization puzzle.
So my basic philosophy in designing this course has been to
illustrate the potential of personalized medicine using a case based approach.
We'll talk about individual clinical cases and how personalizing
through genetics or other mechanisms can result potentially in improved care.
The first few modules are going to deal with some principles in genetics and
principles in drug therapy.
Some of that will be elementary for
those of you who have been to medical school, and I ask your indulgence.
The goal is to get everyone up to speed so we can use common terminology and
common concepts when it comes time to approach the cases.
And after the cases we'll have a couple of modules on
exactly how personalized medicine is being rolled out in healthcare systems.
Thinking about the ethical issues a little bit, thinking about the issues around
extensive, large, personalized databases, extensive, large electronic
medical records, and some of the obstacles that people are encountering,
when they're implementing those systems, and some of the potential solutions.
So I thought I would start a little bit in this module with some very,
very basic principles in genetics and mostly history.
So we've known for a long time, actually since the middle of the 1700s
that individuals vary in their fingerprints.
Everybody has a unique fingerprint.
That was actually discovered by a Czech physiologist named Purkinje,
whose picture is shown here.
And he came from this small central European republic
which is now the Czech Republic.
He came from near Prague.
And that'll become important in a second.
Now this picture shows two young men.
They are, in fact, not the same person, but they look very much the same,
and this illustrates the idea that genetic information, or information on how you
look and how you respond to your environment is transmitted across
generations and how is it that we transmit information from a parent to a child.
The one in the straight pajamas is the son, the one in the blue and
red sweater is the father.
So this is why the Czech Republic is important,
because in the nineteenth century a monk working in the Czech Republic in Moravia
named Gregor Mendel developed the rules around which we
understand genetic information is passed from one generation to another.
Mendel's basic experiment was to breed peas together.
So he would take peas and the pea,
he would look at the characteristics of the peas.
Now the word we use to describe the characteristics is the phenotype.
So the phenotype that he was looking at was whether the peas are smooth or
wrinkly, and he would mate smooth peas and wrinkly peas,
and in the next generation, he would look, and all the peas were smooth.
And then he would mate the smooth peas with each other.
And out of every four pea plants, three of them would generate smooth peas and
one of them would generate crinkly peas.
He did this experiment over and over and over again, hundreds of times in fact,
thousands of times, and developed rules that we now use to understand the way in
which genetic information is transmitted from one generation to another, and
we'll go over those in a subsequent module.
So the next great advance in our understanding of the way information is
transmitted from one generation to the next
occurred in the early 1950s when these two young scientists, Crick and
Watson, described the structure of a molecule they were studying.
The name of the molecule is DNA.
They published their article describing the structure of DNA
in a single page in the Journal of Nature, and arguably won the Nobel Prize for
that single publication.
Here's a picture of that particular publication and
what's interesting is that the cartoon drawing
of the structure of DNA was actually drawn by Francis Crick's wife.
There are two quotes that I think are really interesting in this article.
One of the quotes is the very first sentence.
The very first sentence says, we wish to suggest a structure for the salt of DNA.
The structure has novel features which are of considerable biological interest.
So these guys are structural biologists and they're studying this large molecule,
and they know that it has something to do with heredity.
But they actually, the way in which heredity works, the way in which
information is transmitted from generation to generation is not known.
And they saw the structure of DNA, and
they look at the structure and they say " wait a second.
Now we understand how information might get transmitted from one generation to
the next." So from structure they infer function, and
from function they infer mechanisms for heredity.
The other sentence that is fabulous in this article is the last
sentence of the science.
And the last sentence is a real example of understatement,
since it is not escaped or noticed that the specific pairing we have postulated
immediately suggests a possibly copying mechanism for the genetic material.
So the problem is, how does anything transmit from one generation to the next.
If it does that,
there has to be a mechanism for the molecules to copy themselves.
So here's the idea, this is the DNA molecule that we're all familiar with.
Everybody likes to focus on the sides of the double helix, the double helices.
But what's really interesting and what's the workhorse in this molecule is actually
the little rungs of the ladder that are connecting those two double helices.
And the way it works is that there are four components to those
rungs of the ladder.
We abbreviate them A, C, T, and G.
C and G always talk to each other, and A and T always talk to each other.
So when there's a T on one strand, there will be an A on the other strand.
That's called base pairing, and the things that hold those two base pairs together
are indicated in this cartoon by dots.
Those dots indicate a chemical bond, but it's not a very strong chemical bond.
So what Crick and Watson recognized is that it's not a strong chemical bond, and
that means it could fall apart.
If it falls apart, the molecules starts to unwind, and
then each side becomes a template for creating daughter strands so
they look at this structure and they say " isn't that interesting." If this happens
then each daughter strand can copy it's self and we have a mechanism by which
Information might be transmitted from one generation to the next.
We'll talk more about that in subsequent modules.
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