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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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April 26, 2006

Jungle Rot

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Posted by Derek

There are all sorts of excellent reasons not to cut down the rainforests of Borneo. Biological diversity, erosion, local climate, sheer aesthetics. . .no one should have to scratch their head for very long. But this isn't one of them, at least not the way it's being sold:

"Plants thought to help treat or cure cancer, AIDS and malaria have been found in the rainforests of Borneo, a report from the Swiss-based global conservation group WWF said on Thursday. . . A promising anti-cancer substance has been found in a Borneo shrub by researchers for an Australian pharmaceutical firm, while a chemical found in latex produced by a tree appears to be effective against the replication of HIV, the report said.

In the bark of another species of tree, the researchers discovered a previously unknown substance which in laboratory tests appeared to kill the human malaria parasite, it added."

Going to the source of the story, one finds more details:

"According to the report, Cerylid Biosciences – an Australian pharmaceutical company – has identified a promising anti-cancer substance in a shrub found in Sarawak. A compound present in the plant Aglaia leptantha has been found to effectively kill 20 kinds of human cancer cells in laboratory tests, including those that cause brain and breast cancer, and melanoma.

“The fact that the compound is very effective against a number of tumour cells, presents a very good argument for preserving the plant's habitat in Borneo,” said Dr Murray Tait, Vice President of Drug Discovery at Cerylid Biosciences."

No, it doesn't. The reason I say this is that we have oh, so many compounds already that will kill off twenty different kinds of human cancer cells in the lab. I mean that - tens of thousands of the damn things. Killing cancer cells in a dish is not as hard as it sounds, unfortunately. Now, killing any of them off effectively in a mouse model, that's another story. We probably only have hundreds and hundreds of those around, maybe a few thousand. And getting these things to work in humans? Well, you already know how many of those we have. It's a rather stiff attrition rate, y'know. I note without comment that Cerylid itself doesn't seem to be doing all that well right now.

Keeping Borneo from being clear-cut is a proposition that can be sold on its real merits. It doesn't need this kind of whoop-whoop. All these arguments do, in the long run, is make the people advancing them look like fools or con artists (Rain forest medicine! Jungle cures! Real soon now!). And it makes people think that discovering cancer drugs is actually not all that hard - just look in the right plant, and there it is. We already have enough people who don't realize how long the road is between some neat result in a culture dish and a real drug, thanks very much.

Comments (16) + TrackBacks (0) | Category: Cancer | Press Coverage


COMMENTS

1. Epigenetics News on April 26, 2006 11:19 PM writes...

I think it's well understood that the majority of the general public doesn't know a lot about the difference between accomplishing something in a culture dish and accomplishing the same feat in an animal or human.

But I find it hilarious when I come across Ph.D researchers -- attempting to talk up their recent in vitro discovery -- that conveniently forget about this major issue.

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2. schinderhannes on April 27, 2006 2:12 AM writes...

Let´s assume for a sec there would be a cancer drug ready to use in this plant, what would this mean for the rain forrest? Should we send thousands of forrest workers in there to harvest it in the wild, and dammage the forrest?
Certainly not! One would try to grow plantations , hopefully not after erroding forrest to make space for them, or even better grow the plant cells in cell culture or find the gene and transplant it into a high yielding other plat or or or.

But the drug (or at least the drug lead) already found in natures biodiversity is not a good argument to keep some untouched nature. If this reasoning has to be used at all to preserve nature, it is the hope to someday find new ones!

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3. Process Chemist on April 27, 2006 7:54 AM writes...

This story brings back some memories: Medicine Man, 1992, Sean Connery and Lorraine Brocco.

In the middle of the Brazilian jungle, Sean Connery injects a sample of the all-types-of-cancer-curing juice in his GC. 15 minutes later, the computer screeen spits out the complete structure of the compound (Does HP sell these? I sure as hell would like one!!!)

Lorraine Brocco asks: Can it be synthesized?
Connery responds: NO!
I jump on my seat: Doh!

Ok, it helps the plot of the movie, save the jungle to cure cancer. But it makes any scientist retch in their seats.

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4. Daveh on April 27, 2006 8:09 AM writes...

The Aussies should forget about the Aglaia leptantha farming and move on to the important business of wallaby ranching.

http://www.smh.com.au/news/National/New-penicillin-found-in-wallaby-milk/2006/04/23/1145730796727.html

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5. Palo on April 27, 2006 9:37 AM writes...

But it is a good argument to preserve biodiversity, is it not? Regardless of Cerylid Biosciences spin...

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6. Paul Dietz on April 27, 2006 10:16 AM writes...

I've heard the following argument: interesting compounds from the rainforests are either so common that we don't need to preserve diversity (a small sample of the rain forest will still contain enough to make prospecting worthwhile), or so uncommon that it's impractical to find them (how are you going to find that 1 needle in a haystack of 100 million species?) And there's no middle ground -- for intermediate cases, the compounds are both sufficiently abundant that loss of diversity is unimportant, but sufficiently rare that finding them isn't worthwhile.

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7. Palo on April 27, 2006 1:34 PM writes...

interesting compounds from the rainforests are either so common that we don't need to preserve diversity...

if indeed less than 1% of rainforest plants have been analysed or tested... or even if it was 10x that number... how would anyone know enough to make that claim?

... or so uncommon that it's impractical to find them (how are you going to find that 1 needle in a haystack of 100 million species?)

so... there's million of them... why bother testing... hundreds of thousands? (finding the needle in the haystack is precisely what we do with high throughput techniques)

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8. Paul Dietz on April 27, 2006 1:55 PM writes...

if indeed less than 1% of rainforest plants have been analysed or tested... or even if it was 10x that number... how would anyone know enough to make that claim?

By applying elementary statistics, silly. You don't need to sample anywhere near the number of points you are thinking of in order to obtain useful upper bounds on the probability that a randomly sampled species will yield a 'hit'.

so... there's million of them... why bother testing... hundreds of thousands?

Were you trying to make a coherent point there?

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9. Palo on April 27, 2006 2:31 PM writes...

How can you do samll sampling in samples whose homogeneity you have no clue about? Elementary statistics indeed.

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10. Palo on April 27, 2006 2:40 PM writes...

Paul, I'm sorry if you didn't understand my previouos sarcasm on your second point.

You said: "...how are you going to find that 1 needle in a haystack of 100 million species? ... [they are] sufficiently rare that finding them isn't worthwhile.
You are claiming two things: 1) difficult to find 2) not worthwhile

To 1), I said, not completely true with today's techniques (and in fact, there's many pharma and biotech projects screening plants and microorganisms under sea, among other biodiverse habitats). Now, if 1) is not true, 2) is meaningless.

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11. John Thacker on April 27, 2006 3:14 PM writes...

Of course, this happens with non-natural products as well:

See here.
I give credit to those quoted in the story who tried to tone down the hype, but the reporter still wanted to hype the "Alzheimer's cure in 10 years" as much as possible.

While the protein discovery holds much promise for an effective treatment, St George-Hyslop cautioned that it has yet to be tested in animals and that a drug to mimic its antitoxin effects is likely at least five years away.

"Obviously we now need to find a small molecule or a drug that looks like this protein and that does the same thing as this protein," he said.

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12. bmorse on April 27, 2006 8:00 PM writes...

To be fair, I think the Cerylid website mentions that the compound also shows in vivo efficacy. Even so, I don't think this set of activities alone is a good argument in favor of biodiversity. In my opinion, the more compelling reason is that natural products seem to cover more chemical space than our synthetic libraries. (If indeed this is true. This is hardly my area of expertise, so I could be wrong).

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13. Doc Bushwell on April 28, 2006 9:22 AM writes...

This story brings back some memories: Medicine Man, 1992, Sean Connery and Lorraine Brocco.

In the middle of the Brazilian jungle, Sean Connery injects a sample of the all-types-of-cancer-curing juice in his GC. 15 minutes later, the computer screeen spits out the complete structure of the compound (Does HP sell these? I sure as hell would like one!!!)

Way back in the Jurrasic Era of my youth, I was interested in pharmacognosy and entertained fantastic notions of becoming a female version of Richard Evans Schultes. Medicine Man in spite of suspending belief in its, er, "science," had a goofy, over-the-top appeal. Thus, it wound up in my Netflix queue. My 18 year old son and I watched Sean Connery chewing up the verdant scenery in this flick and likewise, we howled at the immediate analysis of the structure.

Plant and marine natural products chemistry is pretty darned interesting. However, from a pragmatic pharmaceutical point of view, the idea of scaling up synthesis of a compound with, oh, say, 20 chiral centers seems daunting.

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14. Ed Vawter on April 28, 2006 9:47 PM writes...

I've spent about 14 years now in pharmaceutical development and one of the compounds that I always seem to be involved with is Taxol ® aka paclitaxel as well as docetaxel and other taxanes. This is a compound that came out of the NIH hunting through the forests back in the late 60's in this case in the Pacific Northwest. Taxol has 11 chiral centers and while not made by total synthesis at large scale, it is an example of a marketed drug that came of such endeavours.

Permalink to Comment

15. Groko on May 7, 2006 12:06 PM writes...

Good point Ed. There are other promising tubulin binders on its way. Combretastatin is my favourite for market approval. Happens to be very complementary with paclitaxel and carboplatin btw..

http://www.chm.bris.ac.uk/motm/combretastatin/combv.htm

Permalink to Comment

16. Marea on November 20, 2008 5:06 AM writes...

It is always good to preserve biodiversity.
Save the forest, save the world.

So and therefore, please stop any form of wars.
Stop supporting any government plunging into any kind of wars.
BECAUSE
the outcome of wars back-fire and there goes the trees.

Put it this way, you kill the ability of people to grow food in one place (that what wars do), other places will have to compensate the deficiency - grow food for them. That means opening up of forest and more forest than necessary.

You can help stop the destruction of forest.


With love from Borneo.

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