n
this interview, Special Topics correspondent Gary Taubes talks
with Dr. Sandra McElligott about her highly cited paper,
"Transformation of microbes, plants and animals by
particle bombardment," (T.M. Klein, R. Arentzen, P.A.
Lewis, S. Fitzpatrick-McElligott, Bio-Technology 10[3]:
286-291, March 1992). This paper ranks at #3 in our analysis
of the 25 most-cited papers on genetically modified crops in
the past decade, with 81 citations to date. Dr. McElligott
runs a firm called Bio.enterprise, which works with start-up
companies developing new technologies in the biological
sciences.
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What
prompted your study of gene transformation by particle bombardment?
It was pretty straightforward. I was working for DuPont in their
Medical Products Department, but most of my work was in molecular
biology, looking at gene transfer and gene expression, and
developing new products for them. I was doing research and was
simply asked to work on this project involving the gene gun.
Can
you describe for us what a gene gun is and how it works?
The gene gun was a technique developed at Cornell University by
John Sanford, Ted Klein, and Ed Wolfe. It's a weird technology. You
coat DNA onto particles and shoot them into
plant cells with a BB gun. That's the form of the technology that
scientists were studying at that time. DuPont licensed it from
Cornell to see if it had applications to their genetically modified
plants program. I was invited to join because there was some idea
that maybe the technology could be used with in vitro animal
cells as well. When I heard that idea it became very obvious, at
least to me—in sort of a "eureka" experience—that you
could use this on live animals. It offered the possibility of
actually using it on skin cells to modify certain cells, which is
eventually what happened. Our US patent was issued in February 2001
for the use of the technology for DNA vaccines, and it’s referred
to as genetic immunization .
What
was the message in your highly cited 1992 Bio-Technology paper?
The paper was written very early in the development of the
technology. Literally, what we did was look at genetic
transformation using this technique, in microbes, plants, and
animals. The message is the broad application of the technology to
gene transfer.
What
do you think gave the paper such impact?
I have a hard time answering that question, because it was so
unexpected. I didn't even plan on writing the paper. I was giving a
talk in Copenhagen, and one of the editors asked me if I would write
an article based on the work I was doing. I decided I would bring in
a few of my colleagues and we could write on the whole field as
opposed to just one aspect of the technology. Part of it may be—and
I'm just guessing at this point—that it is highly cited because it
talked about using the technique for specific plants, in particular,
in the transformation of corn and soybean, which are fairly
high-value crops. And, as you know, genetically modified crops are
considered controversial because of the question of what they might
be doing to the environment. So that plays a part. How would they
influence other plants out there? Would they cause problems in terms
of transfer of DNA to other organisms, for example? So there is a
fear of the unknown that plays into this.
How
has this field evolved since you wrote your paper?
The field has gone off in very different directions. Some
research has led to improvement of the technique and the use of
different types of genes. And now that they're doing a lot more
sequencing, it becomes possible to put particular gene sequences
into various kinds of plants. But I am not a real plant expert; my
novel concept was simply using the technology in live animals for
genetic immunization, gene transfer, and gene therapy.
Have
you followed that work closely since you wrote the paper?
Not closely. I have changed fields since then and this work is no
longer my focus. But the work has been continuing, although it still
has a long way to go to make it useful.
What
was the greatest obstacle to pursuing this research?
There were many obstacles. Mostly, though, it was the fear of
going forward with the work because it was considered so
controversial. DuPont is a very conservative company, and I remember
that the idea of transforming cells, particularly in live animals,
was considered too much potential liability to get involved. As a
result, they licensed the technology out as soon as another company
came along that wanted to license it. That's why I really got out of
the research so early. In a nutshell, it was just so new that it was
very difficult to get acceptance, even inside the company.
Were
there any particularly trying or difficult moments that stick in your
memory?
Yes, many. Although I remember one in particular. One of the vice
presidents had talked to some of the molecular biologists within
DuPont, and they had stated that the technique wouldn't work. We
would not be able to get transformation of cells within animal skin,
because of all the possible things that could go wrong. Fortunately,
we had already proved that we could transform live animal skin cells
by that time, but we still had to listen to all these reasons why it
wouldn't work.
What
do you see in the future for the kind of genetic immunization
technology that you discussed in this paper?
If it does work, the major use that I see is in being able to
immunize with the conserved region of, say, the AIDS virus. As you
know, the virus mutates rapidly and so if you could use the
conserved region of one of its proteins, you could immunize with
this technology and reduce the risk of getting the disease from the
virus itself. However, there are still major limits at this point as
to the length of DNA you can use.
And
what are you doing now that you're well out of this business?
I have started a new company called Bio.enterprise. It's involved
in helping start-up companies and new technologies develop in
various areas of biotechnology and life sciences. Our services
include: funding strategies, technology development, technology
assessment, product development, marketing research, and patent
strategies. We have worked with companies in nutraceuticals,
non-invasive drug delivery and sensor devices, drug discovery,
vaccines, and plants genetically modified to produce drugs. What I’m
doing now is working with life science incubators to start new
businesses from technologies developed within universities and as
spin-offs from large companies.
Sandra McElligott, Ph.D.
Bio.enterprise LLC
Port-of-Technology/University City Science Center
Philadelphia, PA, USA
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ESI Special Topics,
September 2002
Citing URL - http://www.esi-topics.com/gmc/interviews/SandraMcElligott.html
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