A CHANCE discovery that a stringy little invertebrate is not always what it
seems will help in the development of a promising new anticancer drug.
Researchers in California have found out why some populations of Bugula
neritina, a marine fouling organism, produce the drug but others don鈥檛. The
organism comes in two genetically distinct types.
One form of B. neritina makes a chemical called bryostatin-1. This
is one of the few drugs extracted from marine animals that shows real promise as
an anticancer drug, and could eventually form the basis of a market worth
$1 billion a year. Now in advanced trials as a treatment for leukaemia,
and at an earlier stage of testing against melanoma, it also shows potential for
stimulating the immune systems of breast cancer patients.
鈥淏ryostatin-1 has a unique mode of action against cancer cells, so it would
be a useful addition to the armoury,鈥� says Margo Haygood of the Scripps
Institution of Oceanography in La Jolla, California. The compound has been
licensed to the pharmaceuticals company Bristol-Myers Squibb. CalBioMarine, a
small company in California, is perfecting methods of culturing Bugula
on coastal 鈥渞anches鈥�
(鈥淗ostages of the deep鈥�, 快猫短视频, 14 September 1996, p 38).
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If ranchers are to produce a steady supply of bryostatin, they need to breed
their stock from animals they know make the drug. 鈥淔or production purposes it鈥檚
important to know that not all Bugula neritina is the same,鈥� says
Haygood. But next month, at the Oceans 98 meeting in San Diego, she and her
colleague Seana Davidson will explain the difference. Their discovery should
help to identify populations of Bugula suitable for aquaculture.
By chance, Haygood and Davidson discovered that there are two 鈥渃hemotypes鈥� of
Bugula. They were more interested in a bacterium called Endobugula
sertula which lives inside the bryozoan, and which they suspect plays a key
role in the manufacture of bryostatin-1.
It was only when they sequenced a ribosomal gene from bacteria taken from 10
populations of Bugula, from different parts of the US, that they found
that there are two distinct types of E. sertula. 鈥淭he two groups differ
by four nucleotides, but the difference is very striking,鈥� says Haygood. One
type occurred in bryozoans that produced bryostatin-1; the other was found only
in nonproducers.
Interestingly, when the researchers checked where each population of
Bugula had been collected, they found that all those that produced
bryostatin-1 came from water deeper than 10 metres. None of those from shallower
water made bryostatin-1.
With such a clear ecological difference, Haygood and Davidson wondered if
their hosts were genetically different too. Davidson sequenced a stretch of DNA
from Bugula and again found two types. 鈥淭he difference is not trivial,鈥�
says Haygood. 鈥淭hey may be two different subspecies or even two different
species entirely.鈥� This doesn鈥檛 solve the issue of whether the bacterium makes
the chemical, but it gives drug prospectors a better idea where to get the right
sort of Bugula.