Terra Sigillata

A couple of days ago I recommended a short information table that compared conventional small molecule drugs to biologics (antibody therapies and other peptides/proteins). It was quick and I recommended it for the average Terra Sig reader.

However, I was quick in writing the post, and should have been more critical of the information I was recommending. Quick and concise means nothing if the information isn’t accurate. To be honest, I haven’t gone back to look at the table since – that is, until my colleague Ian Musgrave (I hope he’s not ashamed that I called him “my colleague”) pointed out the error of my ways:

I’m going to respectfully disagree with you here Abel, there is nothing nice about it and it displays an astounding degree of ignorance.

Chemical drugs are essentially made up of elements from the periodic table.

Essentially! essentially! They are composed of elements of the periodic table, as are biologicals. The article makes it sound as if all small molecule drugs are built from raw atoms, and biologicals come from some ethereal plane, where organisms make things constructed from matter not of this world (is the carbon in insulin not from the periodic table, after all).

Few small molecule drugs would be constructed de-novo from raw elements, more often they are made simpler building blocks that are multi-atom compounds to begin with, or modifications of naturally occurring products. Most of the statins are modifications of bacterial fermentation products (their example, Lipitor, atorvastatin, is made synthetically, with
staring products that include the amino-acid valine, derived from fermentation).

What’s wrong with saying that “pharmaceuticals” are small non-protein molecules, and that biologics are proteins or peptides (they may have to explain that, but it would be better than what they have got currently).

Automatic molecule screening systems are used in both small molecule drugs and biologics.

Because they’re not as targeted as biologic drugs, chemical medicines can come with more side effects.

What!!!! The whole point of modern pharmacology is to develop highly targeted drugs (with recent exceptions of multi-target anti-cancer drugs). HMG-CoA reductase inhibitors (for example) are just as targeted as biologicals and have few side effects (most of those due to its effect on the target). Vioxx, which was withdrawn because of side effects, had those
side effects because it was a highly targeted drug. The biological erythropoeitin has a wide range of side effects, with some really nasty ones.

All in all, although it has a few good points, the severe misrepresentation of the small molecule and biological drugs it produces outweighs the benefits.

The rant endeth here.

Uggh, I can’t disagree with a single one of his points and even expanded upon some in my comments back to him. I won’t even try to make excuses. And that’s why I’ve written this retraction. While I’m embarrassed that I recommended such a misleading information source, I’m equally surprised that the attribution for this table was:

Sources: PhRMA, Tufts Center for the Study of Drug Development, WSJ research

Prof Musgrave often uses this blog as a source for his pharmacology students – perhaps he can use this table as an example of how not to communicate information about small molecule drugs vs. biologics.

I should really be recommending it as a source for misinformation and as an exercise in how not to communicate drug information.

Comments

  1. #1 Orac
    December 14, 2007

    Don’t worry about it. I’ve been snookered on occasion on the old blog, too. It’s embarrassing, but all you can do is to retract, brush yourself off, and keep going.

  2. #2 Ian Musgrave
    December 15, 2007

    Abel, I am very proud to be called your colleague. Keep the posts coming, and don’t fret too much about the occasional miscall.

    I’m very interested in the science literacy issue, and I think a critical reading the WSJ article will be a fine tutorial project for my 2nd year students (rubs hands an chuckles to self).

    I’ve been asked to write a short article about my research interests for the local paper, let’s see if I can do better than the WSJ (my beloved partner would probably role her eyes and say “Don’t bet on it”).

  3. #3 AnnR
    December 16, 2007

    You know that by calling attention to this that you’ve confused some of us who read the WSJ for economic news! Rates, tranches, earnings per share I can deal with.

    So “pharmaceuticals” are “small-molecule” and “biologics” are “proteins or peptides” ? They are all made up of chemicals and they are all drugs?

    The reason this catches my interest is I have a vague idea about rituxban – a “biologic” drug that attaches to some protein and “fixes” it so lymphoma diminishes.

  4. #4 Ian Musgrave
    December 16, 2007

    AnnR wrote:

    So “pharmaceuticals” are “small-molecule” and “biologics” are “proteins or peptides” ? They are all made up of chemicals and they are all drugs?

    Well, “Pharmaceuticals” and “drugs” are the same thing[1]. Strictly speaking we should be speaking of “small-molecule drugs” and “large molecule drugs”. Small molecule drugs such as aspirin, the lipid lowering Lipitor and the blood pressure lowering metoprolol are all small molecules.

    Currently, all so-called “biologics” are peptides or proteins, however, therapies based on RNA, or chemical modifications of RNA, may soon be hitting the clinics. The term “biologics” is a bit of a misnomer, and many current small molecule drugs are either directly derived form biological sources or chemical modification of chemicals from biological sources.

    The anticancer drug paclitaxel was originally extracted from the bark of the Pacific Yew tree, now it is made semi-synthetically from simpler molecules derived from biological sources. The lipid lowering drugs were either derived directly from biological sources or semi synthetically manufactured from simpler compounds extracted from biological sources.

    The reason this catches my interest is I have a vague idea about rituxban – a “biologic” drug that attaches to some protein and “fixes” it so lymphoma diminishes.

    I think you mean Rituxan� (Rituximab). Rituximab is an antibody that binds to a particular protein (CD20, which regulates how calcium, a vital regulator of cell function, enters the cells) on a subset of lymphocytes. Antibody binding doesn’t “fix” the lymphocytes, it either kills or disables them (though a variety of mechanisms). Being an antibody, is is a large protein that fits the “biologics” category.

    Rituximab is very useful in lymphoma, and apparently works better in conjunction with other anti-cancer therapies. It is also used in Rheumatoid arthritis, where CD20 bearing lymphocytes are the cause of a lot of the inflammation.

    [1] A drug is any substance that, when injected into a rat, produces and academic publication. That’s pharmacology humour that is.

  5. #5 metabopharm
    December 30, 2007

    I agree with my colleague Ian that it’s a silly table. What the WSJ was attempting to do was separate drugs by manufacturing method –bacterial fermentation production of gene products versus traditional organic synthesis and chemical manufacture. Very different sorts of factories are required. WSJ was taking an industrial strength approach, quite appropriate for its readership. They erred in using the term “discovery” –they meant “manufacture”.

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