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Female Speaker: We were unable to actually isolate a gene.
Male Speaker: What is responsible for turning these on or
turning these off?
Male Speaker: But the cancer virus itself had RNA as its
genetic material.
Male Speaker: Well let's take a look at this.
Is this really dangerous?
Male Speaker: Once you had centrifuged the DNA molecules,
it was extremely laborious and difficult.
Female Speaker: The pressing guidelines, which prohibit --
Female Speaker: When I was finally was called upon to testify,
by this time it was 1:00 in the morning.
Male Speaker: And this was the starting of the biotechnology
revolution.
Male Speaker: The underlying problem in biology after discovering
the genetic code and the mechanisms of protein synthesis were answering the question, how
to turn a gene off and on.
How do you control DNA?
Male Speaker: Jacob and Monod approached this problem with
a combination of genetics and physiology and a little bit of biochemistry, but mostly genetics
and physiology, to try to understand a very simple system in bacteria, the system that
bacteria had for using the sugar lactose as a source of their carbon and energy.
Male Speaker: But back in 19 -- middle '60s, we didn't know
what any of these genes did.
And we didn't know in the case of the oppressor whether the gene made an RNA molecule or a
protein molecule or what.
Male Speaker: We wanted to get more into the details.
Some of us doing genetics, people like Wally Gilbert doing biochemistry.
How do you study a gene biochemically?
You need to have at least partially purified that gene.
Male Speaker: John Beckwith came to work with me first.
And he actually worked on genetics oppressors.
He was a great performer in that area.
And so what he decided at one stage was to say, "Well I'll purify the Lac gene [spelled
phonetically]."
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Male Speaker: The basis of our being able to isolate the
Lac gene comes from the structure of DNA itself.
And what we had done was to isolate two viruses.
If we took apart the DNA strands, the two DNA strands, of each of these viruses and
slapped them together, the Lac genes would form very nice pairs because they were identical
to each other.
They were complementary to each other and would form these tight bonds.
So what you ended up with was a structure in which you had Lac genes forming a nice
double helix, but these two other strands of the virus sticking out and not forming
the tight bonds.
And we were actually able to visualize that on a microscope and first of all, they were
beautiful pictures because they were exactly what we had predicted, which was very nice.
And this is the first time that gene have been taken out of a chromosome and purified
in a test tube.
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We called a press conference on the day that the paper was published and announced our
discovery.
But at the same time, at this press conference, we also talked about some of our ethical concerns
about genetic manipulation and so the media reports, which were worldwide on our finding,
were a mix of reporting genetic advances and suggesting how close we might be coming to
curing genetic diseases, et cetera, which was a bit of a stretch.
But I mean, down the road, it's related to that certainly.
Male Speaker: John Beckwith's electrifying feat demonstrated
that you could obtain a single gene from bacteria; however, his approach was not useful for obtaining
genes from higher organisms, including human beings.
But then in 1970, Howard Temin and David Baltimore came along and independently discovered an
enzyme called reverse transcriptase that enabled the genetic information in an RNA tumor virus
to be integrated into the DNA of a cell.
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Male Speaker: The day I did the first experiment and I got
this little blip, my wife actually was working in the lab there and so I turned to her and
showed it to her.
And she said, "No," she said, "that's just background noise."
And I said, "Well, you know, maybe it is, maybe it isn't.
We'll have a look."
And concentrated the virus and then, you know, that was the whole story because now we were
ten-fold over the background.
There was no question that it was real.
And I just more or less told everybody in sight about it because it was really very
exciting.
However, this was just a day before Nixon bombed Cambodia and sent me and everybody
else out into the streets.
So I went on strike for a week after having discovered the reverse transcriptase as actually
the first thing that I did.
And the experiments weren't complete yet.
They were, I froze away the experiment in progress, came back after a week and then
finished that experiment and a few others to nail it.
Male Speaker: So once Baltimore had reverse transcriptase,
he realized that you could use it to transform the messenger RNA back into, say, the DNA
of any gene, including a mammalian gene.
Male Speaker: So we had captured genes, mammalian genes,
for absolutely the first time in history.
And this was, in some ways, the starting of the biotechnology revolution because now companies
could do that, insulin, whatever you wish.
And the reverse transcription to this day is the way to capture a messenger RNA.
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Male Speaker: So once you could isolate genes, scientists
wanted to manipulate them, play with them, try to figure out what they do.
Two of the scientists who had the same ambition were Herbert Boyer and Stanley Cohen.
They were at a scientific conference in Waikiki, Hawaii in November 1972 and they found themselves
together munching corned beef sandwiches in a deli late one night.
They got to talking about this problem and they decided they might have a way to accomplish
this purpose.
This involved using things called restriction enzymes that cut DNA at a specific place,
so once they could cut it, then they could insert the DNA of interest in a plasmid and
put the plasmid into a bacterium, and watch what the DNA does.
Male Speaker: It was a natural collaboration and as we talked
about this, we realized that this would be a very exciting scientific opportunity.
So we decided at that time to collaborate in trying to reconstruct plasmids.
Male Speaker: The experiment went as follows.
Stanly would send us DNA.
We'd cut it up, put it back together again.
We'd send that DNA to Stanley.
He would transform it into the bacterium.
He would send those bacteria back to us.
We'd take out the plasmid DNA, cut it up, and look at it in the gel.
That was sort of the division of labor.
And so Bob Heeling [spelled phonetically] and I, when we did the first analysis of what
we thought was a recombinant DNA molecule, we stained the gel.
And it was late afternoon, and went to the dark room and turned on the black light and
there was this picture, and it was very evident that we had resorted the fragments of DNA,
successfully recombined them, and we had recombinant DNA molecules.
Male Speaker: Now these results, exciting as they were,
didn't necessarily mean that we could use this to clone pieces of totally foreign DNA.
Male Speaker: We immediately thought, well the next thing
we need to do to really prove that this is going to have some impact beyond microorganisms,
that we needed to put a piece of what we call eukaryotic DNA, that is DNA that comes from
an organism other than a microorganism, like an elephant, human, or what eventually turned
out to be our first demonstration was with frog DNA.
Male Speaker: It was clear when we did that experiment that
it was now possible to transplant genes from virtually any source into bacteria.
And that was a very exciting potential because it was apparent to Herb and to me that this
meant that one could study genes from complex organisms.
One could eventually clone all of the genes of the human genome or from any organism and
study them individually.
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Female Speaker: In the summer of 1973, Herb Boyer gave a talk
at a garden conference and it was clear then that you could take DNA from anywhere, you
know, from a human cell, from a banana, from a fish, you name it, and put it into a little
bacterial plasmid and grow the bacteria up and you would have enough molecules to be
able to do chemistry on these things.
But as soon as that was apparent, the same day that he gave a talk, several of the younger
people there immediately raised the question as to whether you could in that way make things
that might be dangerous.
Male Speaker: The questions led to a moratorium unprecedented
in the history of science.
It also led to a meeting, an international meeting to which scientists came from all
over the world, in Asilomar, California in 1975, to discuss this problem.
The people who were there were frankly conflicted.
On the one hand, they wanted to avoid the moral taint that had befallen the scientists
who participated in the atomic bomb project, but on the other hand they wanted to get on
with recombinant research.
Their exercise in social responsibility led them to include the press and there was considerable
open debate.
Female Speaker: I remember feeling as though I never knew
what was going to happen.
I didn't know what the right way to proceed was and here I was a member of the organizing
committee.
It was just a tremendous amount of science to get your arms around.
It was a huge public issues for which we had no background or training.
Male Speaker: We talked all this through and came out saying,
in this case, we don't know enough.
We can't be absolutely certain that this is all so safe.
And that was a wrenching thing for people to say because what we were really saying
to ourselves was we're not going to do certain kinds of experiments until we've gone through
a whole process of convincing ourselves that we don't have a -- we're not letting some
genie out of the box here.
Female Speaker: At the end of Sylmar, the great significance
was we felt that experiments could forward, and could go forward with some sense of assurance
that we weren't going to be doing really nasty stuff.
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Male Speaker: If we hadn't invited the press to Sylmar then
the stories would have been less good than they were.
The information would have been less precise than it was.
We would have been in worse shape than we were.
Male Speaker: Well, the National Institutes of Health, which
was the principal federal agency that would sponsor recombinant research, took the Sylmar
guidelines to account when it began drawing up its own rules for the conduct of recombinant
research.
The NIH issued its rules in June 1976 and they were designed to protect the public health
and safety.
However, a number of people, scientists, laymen, and government officials around the United
States were suspicious of these guidelines.
Their main reason for suspicion was that the guidelines had been drawn up by the same people
who were going to be doing the research.
This apprehension expressed itself quite forcefully in Cambridge, Massachusetts.
Male Speaker: The city council held hearings on recombinant
DNA and they then set up a committee to evaluate the potential dangers of this research.
And the committee was made up of citizens across the spectrum of the city and included
scientists and experts, but also ordinary citizens, you know, working housewives, et
cetera.
Male Speaker: At the time of the great Cambridge crisis
of post-Sylmar and the mayor of Cambridge, egged on by some of my friends was trying
to, you know, ban recombinant DNA in Cambridge.
Female Speaker: I must say that I've been surprised recently
to find myself being put among those who are not concerned.
I have been concerned and I continue to be concerned.
I feel --
Female Speaker: When I finally was called upon to testify,
by this time it was 1:00 in the morning and it was a circus.
There was music, there were flags, there were demonstrations and there were, you know, several
different Nobel prize winners arguing different sides of the issue to the Cambridge City Council.
Male Speaker: There were only two libraries of clones in
Cambridge.
One was our yeast library and the other one was Tom Maniatis', you know, cDNA, what we
would now call cDNA libraries.
And we were both basically chased out of town for a while.
In the end, MIT defended me and that was great, but Tom had to move to Cold Spring Harbor
to continue his work for a while.
Male Speaker: There is an inevitability to the fact that
if a community of scientists say there might be danger here that the general public is
going to hear, there is danger here, and we saw it all in the chambers of City Hall in
Cambridge, in Congress, and in the press.
We saw every bit of it and you have to go through it.
I don't see any way we could have avoided that.
Secrecy is not the answer to getting public acceptance.
You've just got to go through a messy process.
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