The magic-bullet drugs of the past century are beginning to tarnish. Today's bugs are smarter and tougher. Indiscriminate use has contributed to the demise of many drugs. The challenge we face is to recharge our bug-busting capability. But where do we look?
Porifera, more commonly known as sponges, are primitive marine organisms that inhabit the world's sea floors. Lacking both the ability to run away from would-be attackers and the physical defences of fangs or claws employed by others, these sponges are masters of chemical warfare.
One defence a sponge might deploy is a chemical agent that inhibits fast-growing larval cells while not impeding the growth of its own cells - a biological response that we might use as a drug to combat rapidly dividing cancer cells or parasites while not targeting healthy host cells.
Another approach a sponge might employ is to inhibit cell adhesion, preventing larval cells from getting a foothold - the anti-fouling defence. Knowledge of natural anti-fouling agents could teach us how to dispense with toxic alkyl tin additives in marine paints, as well as how to coat medical implants with non-toxic non-stick materials for longer and more efficient operating lives.
Furthermore, the ability to selectively inhibit cellular communication could reveal new strategies to combat disease. Viral infection, for example, relies on the virus engaging with and exploiting the replication potential of host cells. Taking our lead from sponge defence strategies, it may not be necessary to kill these uninvited guests, rather just send them to Coventry.
Sponges are also seen as tasty targets to would-be predators. Toxins and foul-tasting feeding deterrents could see off such marine diners, while built in anti-bacterial and anti-fungal agents attend to any wound infection.
Given the many thousands of sponge species evolving over aeons in varied marine ecosystems, each with their own predator/ prey interplay, this evolutionary scenario has been played out countless times, yielding an extraordinary array of molecular solutions. It is this molecular diversity that is a valuable resource.
The marine natural products research group at the University of Melbourne is expert at unravelling the defensive chemistry of marine sponges. Students from the group regularly travel to remote and not-so remote regions of the southern Australian coast to dive, snorkel, trawl or simply explore tide pools. Never knowing which specimen could contain the winning "molecular" ticket is part of the appeal, and like any lottery it is a numbers game that is incredibly addictive.
Over the past decade, the group has pioneered the bio-prospecting of southern Australian waters, discovering hundreds of novel molecules, some with potent biological properties. Several thousand sponge extracts have been subjected to high-throughput biological screening aimed at targeting substances effective against commercial livestock parasites, as well as anti-bacterial and anti-fungal agents with potential application in human and animal health, and crop protection.
Solvent extracts of marine sponges that exhibit interesting biological profiles are subjected to sophisticated bioassay directed fractionation and spectroscopic analysis to isolate and identify active agents. These substances, along with semi-synthetic and synthetic analogues, are then subjected to in vitro and in vivo evaluation in the hope of discovering just a few new magic bullets with which to reload and survive - until next time.
Robert J. Capon leads the marine natural products research group at the University of Melbourne, Australia.