Sense and Antisense in Biotech: The First Antisense DNA Company

Paul Zamecnik at the time he moved from the Worcester
Foundation back to Mass General (1997), where he continued
to push forward on antisense DNA therapeutics and
publish actively until just weeks before his death in 2009. His
last publication appeared 1 year before he died, and there
were others in the works. His first publication had been 63
years earlier (1). Reproduced with permission of the University
of Massachusetts Medical School Archives, Lamar Sutter
Library, University of Massachusetts Medical School, Worcester,
MA, USA.
visionary scientist of genetic mechanisms and the other
one of America’s vanguard research-based medical
institutions—had now come back together once again,
a reannealed RNA double helix” (1).
In this article, I have, up to now, referred to Riordan’s
start-up only as “the company”. As biotechnologyoriented
readers recognized early in this article, the
company is of course Gilead (formally Gilead Science).
The biblical line from Jeremiah (8:22), “Is there no
balm in Gilead?” was the posed question to which the
African-American spiritual responded in an affirmative
reply, “There is a balm in Gilead”.
Paul Zamecnik was a pioneer of molecular biology,
and Michael Riordan (now retired) was a pioneer of
bridging molecular biology and business. We should
applaud both phenotypes. This story also teaches that
commercialization of even an idea embodied in foun-
dational and so unassailably correct molecular biology
as antisense DNA was, may nonetheless run into steep
challenges and even cause a company to change direction
and still make contributions to human well being.
So, things do not turn out as the first business plan
asserts, circumstances are almost always more complicated
than first assumed, and “There are more things in
Heaven and Earth ” (as Shakespeare had his character
Hamlet say).
I am grateful to Robert Langer (M.I.T) for encouraging me
to write up this story after an initial conversation, and to John
Goodchild, formerly of the Worcester Foundation and Hybridon,
for confirming certain details and triggering other
important recollections.
The author’s work is supported by National Science Foundation
Grant MCB-1051398 and the Vitold Arnett Professorship
at the University of Massachusetts Medical School.
Note added in proof: While this article was in press the author
learned that there is yet another closure of Paul Zamecnik’s
journey. In 2011 the Massachusetts General Hospital received
a gift to create the Paul Zamecnik Chair in Cancer Research.
The first incumbent will be invested in 2012.
REFERENCES
1 Pederson, T. (2011) Paul C. Zamecnik 1912–2009. Biographical
Memoirs, Washington, DC, National Academy of Sciences
2. Stephenson, M. L., and Zamecnik, P. C. (1978) Inhibition of
Rous sarcoma viral RNA translation by a specific oligodeoxynucleotide.
Proc. Natl. Acad. Sci. USA 75, 285–288
3. Zamecnik, P. C., and Stephenson, M. L. (1978) Inhibition of
Rous sarcoma virus replication and cell transformation by a
specific oligodeoxynucleotide. Proc. Natl. Acad. Sci. USA 75,
280–284
4. Calvet, J. P., and Pederson, T. (1979) Heterogeneous nuclear
RNA double-stranded regions probed in living HeLa cells by
crosslinking with the psoralen derivative aminomethyltrioxsalen.
Proc. Natl. Acad. Sci. USA 76, 755–759
5 Folkman, J. (1990) The fine line between persistence and obstinancy
in research. In Vision and Values for Pharmaceutical Innovation.
ALZA Conference Series, vol. 3, 20th Anniversary Symposium
(Mitchell, ed.), C. Palo Alto, CA, USA, ALZA Corp., 141–149
6. Goodchild, J., Taguchi, Y., Sarin, P., and Zamecnik, P. C. (1986)
Inhibition of replication and expression of T-cell lymphotropic
virus type III in cultured cells by exogenous synthetic oligonucleotides
complementary to viral RNA. Proc. Natl. Acad. Sci. USA 83,
4143–4146
7. Agrawal, S., Mayrand, S. H., Zamecnik, P. C., and Pederson, T.
(1990) Site-specific excision from RNA by RNase H and mixedphosphate-backbone
oligodeoxynucleotides. Proc. Natl. Acad. Sci.
USA 87, 1401–1405
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SENSE AND ANTISENSE IN BIOTECH
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