Sense and Antisense in Biotech: The First Antisense DNA Company

ployer-employee axis, as I have detailed elsewhere in
some amusing vignettes (1). His lab and mine even
collaborated and published together on one occasion,
which was both fun and yet a bit contentious when we
were writing the paper. Our different writing/presentation
styles aside, this project and publication turned
out to have been a good idea (7).
Well before the 1986 paper (6), it had become clear
to both Zamecnik and me that his antisense DNA work,
especially the HIV axis, might warrant a start-up company.
I was worried about the lack of an issued patent,
thinking that Zamecnik’s 1986 paper might be deemed
obvious in light of his (unpatented) 1978 disclosure of
the core idea and art of enablement. Yet, I also felt that
the HIV paper had use “written all over it”, and in at
least U.S. law, this feature can often reign in patent
claim allowances.
The Worcester Foundation did not have a formal
patent income-allocation policy at the time, nor did
we even have a policy that required our scientists to
assign their rights to the institution (although I soon
introduced both). Zamecnik was consistently attentive
to the ways the Worcester Foundation might
benefit if his idea became the basis of licensed
intellectual property. I believe this reflected his prior
association with the Worcester Foundation as a
trustee, as well as his gratitude to Hoagland for
having taken him in. I had also directed some
discretionary funds to his lab after becoming president
and was very much behind his program in all
ways, including with our trustees and donors, and I
think he was grateful for that.
START-UP, OR NOT
Zamecnik’s son is a banker, and they were both connected
to their respective A-lists of Boston Brahmin
grandees, plus his son had some international connections.
Zamecnik also had numerous contacts in pharma
who had been medical students, fellows, or house
officers at Mass General, and he began conversations
with many of them. By 1987–88, we were both aware
that antisense DNA was on the start-up landscape, but
as we later realized, we were not as well connected to
big pharma or the blue-ribbon venture community as
he thought or as I innocently had assumed that we
might be based on his contacts. But R&D representatives
from Merck, Bristol-Myers Squibb, and other large
companies were willing to come and visit us at the
Worcester Foundation, and Zamecnik and I also went
to New York to visit a number of banks and venture
groups, among which I recall Rothschild Ventures as
being the most engaged. We also had a visit from
Hambrecht & Quist, and my recollection is that Zamecnik
didn’t think they understood the science. However,
neither Zamecnik nor I had developed a full-scale
business plan (one of our key mistakes), so all of these
companies, banks, and venture groups saw us as amateurs—a
charming and brilliant scientist with some
SENSE AND ANTISENSE IN BIOTECH
provocative lab results and the cheerful head of his
institution tagging along. Also, the Worcester Foundation
had no analogues of Stanford’s Niels Reimer or
MIT’s John Preston sitting in and advising us. In
retrospect, how I wish we had had such minds at the
table at the time. In October 1988, when Zamecnik and
the Worcester Foundation had reached a zenith in
their dyspepsia over how to commercialize antisense
DNA, I sought a meeting with MIT’s John Preston, who
was good enough to meet with me and offer advice.
This led me into a longstanding relationship with
Preston’s successor, Lita Nelsen, who, like Preston,
shared valuable time with me, even though I was not at
MIT nor was this MIT intellectual property. Nelsen’s
generous willingness to help me think through the
start-up situation and later, licensing issues is something
for which I shall be forever grateful to her.
ALMOST THE FIRST ANTISENSE DNA
COMPANY
The Worcester Foundation, of course, had filed a
patent application prior to Zamecnik’s HIV publication,
and by mid-1988, we had gotten an Allowance of
Claims, leading us to start a different conversation with
potential investors, given that some degree of patent
protection was now a realistic possibility. Thus armed,
Zamecnik and I, together or in other cases on our own,
embarked on another round of discussions with
pharma and banks but still with the same headaches
after every meeting. But then, Zamecnik came upon a
Harvard Medical School-launched venture fund. It was
initially called Ion Corp., but by the time Zamecnik
contacted the company, it was known as Medical Science
Partners. Harvard Medical School’s idea was to have
this entity provide, or help provide, access to seed capital
to nucleate start-ups based on the institution’s inventors
and licensable technology. Zamecnik’s courtship of Medical
Science Partners was technically off-base, as he was no
longer at Harvard, nor did it hold any rights to his
inventions. However, Zamecnik was still an emeritus professor
at Harvard Medical School, and this got him access
(conversationally, at least) to Medical Science Partners.
We had several meetings with its partners, André Lamotte
and Joseph Lovett, and Zamecnik and I both felt
that this was looking like a productive axis of conversation.
Yet, Zamecnik had been bitterly disappointed by
the reaction of pharma, as well as the negativity of the
banks that we had visited in Manhattan. As is often as
the case with an inventor and visionary, he saw his
concept as a perfect Aristotelian-Cartesian reality, but I
viewed it, from my own nucleic acid expertise, as a very
high mountain, not as lab science but in the clinic.
However, I had to put aside my concerns about antisense
as medicine, because as president of the Worcester
Foundation, I had the responsibility to do everything
that I could to turn his work into both an entity to
hopefully, in some possible way, improve the human
condition and also, to potentially return some money to
3597