Tuesday, March 14, 2006

Cancer-treating coral compound and bioprospecting

Compound from Coral Could Combat Cancer. Good alliteration.... This article in Scientific American (via 3 Quarks Daily) suggests a new source of cancer treatment via the bioprospecting of a type of Pacific coral called Isis hippuris. Good. But I want to say a few words about bioprospecting here. First, some selections from the article.
Natural compounds have proven to be a treasure trove of medicinal properties. For example, the bark of the Pacific yew tree yielded a compound that has helped battle some forms of cancer. Such finds have led to a new industry--bioprospecting--and such prospectors have fanned out across the globe in search of nature's remedies. Now a compound isolated from coral collected off the coast of Okinawa has shown the ability to slow down and possibly prevent virus replication and it may hold promise as a cancer treatment...

In vitro and in vivo, the steroid [dubbed "hippuristanol"] blocked a critical step in the process that allows a virus to thrive...

The only problem will be ensuring a steady supply of the promising compound without denuding the western Pacific's reefs.
Bioprospecting has been, since the late 1980's, viewed as the savior of threatened ecosystems. There's nothing new to the practice of bioprospecting (although the term itself is only a couple of decades old). Human beings have always used plants, insects, and other organisms for medicinal and other purposes. Where the practice becomes a savior, however, is in pharmaceutical and biotech firms bioprospecting in threatened areas, doing genetic sampling, and then running tests on the samples in the lab. As a conservation mechanism, bioprospecting grew out of scientists’ concerns for conservation of biologically diverse areas and was proposed as an economic answer to the destruction of biodiverse habitats through activities such as logging. The answer was to “do right” through bolstering “both economic and conservation goals while underpinning the medical and agricultural advances needed to combat disease and sustain growing human numbers” (WRI 1993).

A relatively small chorus of economists argues, however, that biodiversity has negligible marginal value for companies and is unlikely to produce significant economic benefits for biodiverse countries (Simpson 1997, 2000; Simpson, Sedjo and Reid 1999; Southgate 1997; Costello and Ward 2004). Douglas Southgate maintains that “the best available evidence… suggests that there is no strong reason for pharmaceutical companies to pay a great deal to maintain supplies of genetic inputs from tropical forests” (1997). According to David Simpson, “losses in biological diversity may have little bearing on whether the next miracle drug is found” (1997, 12).

While the history of drug discovery research shows several examples of leads that have culminated in profitable marketed products - an estimated one-fourth of all medicines are derived from natural products (Landell-Mills and Porras 2002) - there are fundamental limitations to this assumption. One is that the process from collecting, taxonomic labeling, extraction and bioassays, patenting, pre-clinical and clinical trials, to product is costly. The process of developing a prescription drug cost an estimated $800 million in 2001 (Tufts University for the Study of Drug Development 2001). A recent estimate by Bain and Co. puts the cost at $1.7 billion, 55% higher than during the 1995-2000 period (Mullin 2003). The process is also time-consuming – typically, 10-15 years.

Some firms maintain that natural products discovery through genetic prospecting remains an important form of research into the indefinite future. Others at the forefront of the industry, however, suggest that genetic prospecting or natural products research is much less important than previously thought (Service 1999). Virtually all drug development proceeds by “rational drug design,” involving computer visualizations, laboratory production, and high-throughput screening. Genomics and combinatorial chemistry have radically altered the drug research landscape. Instead of designing drugs through testing and altering natural chemical samples from organisms, drugs can be developed from an understanding of how genes and proteins behave. Some researchers have contended for some time that combinatorial chemistry could render genetic prospecting redundant (see interviews in Macilwain 1998; Service 1999). Some university-based drug development chemists contend that such technologies render prospecting for samples from natural products at least less significant; at best, promotion of these technologies and methodologies is cyclical, built largely around cost-effectiveness, institutional inertia, and the potential value of natural products research versus the shorter time horizon of developing drugs through rational drug design (private interviews, 2005; see also Olsen, Swanson and Luxmoore 1997). Olsen, Swanson and Luxmoore maintain that “perceptions of the difficulties associated with [natural products research] appeared to lag behind technological advances which would significantly reduce those difficulties” (1997). One wonders, however, why perceptions do not seem to have changed much over more than a decade. Others suggest that the best approach is a balanced combination of rational drug design, combinatorial chemistry, and natural products research (Lahana 1999). Finally, even if genetic prospecting does remain an important element in drug development, research on extremophiles (organisms inhabiting severe environments such as marine thermal vents) and microbes in environments such as toxic waste dumps indicates that there is no guarantee that genetic prospecting and its benefits are ineluctably tied to biodiverse areas.

Biodiversity's marginal value may indeed be negligible, while new drug development technologies indicate decreasing industrial dependence on genetic prospecting. If so, and if drug development firms are increasingly turning to rational drug design and other methods of drug development, then the basic premise of the United Nations Convention on Biological Diversity (CBD) - that conserving biodiversity is a function of developing genetic resources for pharmaceutical and biotechnological application - rests on tenuous grounds, not to mention the entire discourse on bioprospecting as a sustainability mechanism. If there are few future monetary benefits from biodiversity, if indeed its marginal value is close to zero, then expressed conservation objectives could further succumb to short-term, economically beneficial but environmentally destructive agricultural and timber harvesting practices, as well as development projects that damage or destroy coral reefs.

When potential disease-treatments such as the hippuristanol steroid are discovered, there's call for guarded optimism. The problem comes at the level of prospecting, extraction/sampling, testing, and product development. The economics, dependent on incentive structures for companies to do natural products research, doesn't seem to play out. Keep an eye on this one. My bet is that it eventually drops off the map, as many celebrated bioprospecting ventures have done.


Anonymous said...

The argument of bioprospecting as support for biodiversity has long seemed weak to me.

Let's say that a new and effective drug is found in this way, as taxol was. Your quote gets at one of the big problems:

The only problem will be ensuring a steady supply of the promising compound without denuding the western Pacific's reefs.

Highly active compounds of the type that can make effective drugs are found in tiny, tiny quantities in whatever organism. That means you have to have a lot of that organism in order to make the drugs available.

There are several solutions to this: farming the organism (corals and yew trees take too much time to come to maturity and you'd need lots of space); developing a genetically modified laboratory organism to produce the drug (lots of time again, and no assurance of results); or developing a laboratory synthesis of the drug.

It's the last that eventually made taxol usable. It also takes time, but organic chemists can usually come up with a synthesis. That also puts them in a position to synthesize related but different drugs that may be more effective.

So biodiversity is useful only for the exploration phase, which, as you note, is marginal economically, particularly to the countries hosting the biodiversity.

There's a more basic objection that I have. Not being a philosopher, I'm not quite able to enunciate it.

It seems to me that biodiversity and, more specifically, the life in the oceans and tropics, should be valued for itself, not for its potential economic contributions. The economic value argument seems tailored toward the free-marketeers, more for persuasion than as an argument of inherent value.

The argument for exploration is basically that those countries with great biodiversity should maintain themselves as card catalogs for the more developed countries, just in case we need some new drugs. Not too different from the "maintain your vistas for ecotourism" argument.

None of this respects any of the life in those countries, including the human.


MT said...

"The problem comes at the level of prospecting, extraction/sampling, testing, and product development. "

I would expect tech transfer and partnering between industry and academia to matter hugely, because going in search of glory with the scuba gear is the kind of high risk venture only a grad student will do, but they may not get the peanuts needed to pay them if Novartis or whoever isn't guaranteed the rights to whatever they find. BTW I think this is a little like peak oil, and also a little not like peak oil. Like PO the resource is definitely there in biodiversity, and the issue is cost to extract vs. alternatives. Unlike PO we don't need new drugs like we need energy, at least absent a national medical emergency or a sense of responsibility we have not yet witnessed in government. So if the drug companies are culturally or otherwise afraid of the water, they never have to go there, and society will have to settle for whatever trickle of innovation they can generate straight from the lab. Also BTW I think rational design is a lot of hype and not so much is really going on. It's largely panning as usual, but thanks to sequencing there's lots yet to pan from just a few organisms without heading out to the ocean.

MT said...

Do I sound like I know what I'm talking about? Very well, then, I sound like I know what I am talking about. (I am large—I contain multitudes.).

helmut said...

I think that in many cases quantity of an since the genetic sampling and then replication is what is of most use.

The tech transfer business has become crucial mainly because biodiverse countries have long gotten zip from the sampling of plants and other organisms that may be endogenous. Tech transfer works as a kind of leverage point. Not so much in regard to the process of extraction, but in the politics between firms wishing to bioprospect and biodiverse countries. This is a change since the beginning of the CBD (1993), part of access and benefit-sharing schemes.