Book review

Recombinant protein drugsEditor: P. Buckel

Published by Birkhauser

ISBN 376459048, Price 105 Euros

What has been the real contribution of molecular biology,

i.e. recombinant DNA technology to human therapeutics?

Like Brazil it will always have a great future!

This book of essays on the first generation of protein

drugs made by recombinant protein synthesis is a fas-

cinating melange of gossip, science, history and opinion,

covering the 20 or so years since human insulin was first

introduced. Since then, 1982, we have had haemophiliac

globulins, growth hormone, erythropoietin, colony stimu-

lating factors, interferon and clot busters, all natural

proteins or ‘first generation’ recombinant products. We

can see how the sector has matured now that generic

producers are setting up and much work has taken place to

develop ‘improved’ synthetic versions of natural products.

Now we look to a second generation of artificial or

hybrid proteins such as immunocytokines or engineered

thrombolytics.

The essays on these subjects are all by distinguished

participants in the various discovery/exploitation pro-

cesses. This is recent history, sometimes told starchily,

sometimes well. History always makes for a good read

especially for those keen on repeating it.

As usual, the path to new therapies is not a simple one.

It started with technical difficulties and suffered the usual

unexpected failures and compensatory successes.

Who would have predicted that human insulin would

be less well tolerated than pig insulin? Who would have

seen recombinant erythropoietin as a ‘drug of abuse’ in

the Tour de France? On the postitive side, the introduc-

tion of colony stimulating factors has improved the

practice of oncology, enabling neutropenia induced by

cytotoxic agents to be treated, allowing more effective

chemotherapy. Likewise tissue-type plasminogen activator

has been a significant improvement over streptokinase

in the therapy of myocardial infarction although, not

surprisingly, it is just as difficult to use successfully in

stroke as streptokinase. Plasminogen activators have now

been tinkered with to improve their performance in the

same way as classical medicinal products for treatments

in the conventional pharmaceutical arena.

The next step in recombinant protein therapeutics is

to construct hybrid therapeutic functions. This concept

has not been a great success in medicinal chemistry with

a/bxadrenoceptor blockers but hope springs eternal and

the chapter on immunocytokines makes an interesting

read. There is also a chapter on improving protein

pharmacokinetics, a universal problem.

Finally to generation 3, gene therapy. Here the review

by Friedman exhorts us that ‘definitive control of human

disease is now in our grasp – loosely but without too much

doubt.’ A ringing endorsement?

So have the last 20 years seen recombinant technology

revolutionize therapeutics? There have been big successes,

both medical and financial.

Standing back from the hype it seems, nonetheless, that

a rather slight collection of therapies have, as yet, been

brought forth. Certainly all the recombinant proteins

combined would not equal the therapeutic worth of

vaccines or antibiotics. The more major contribution of

recombinant DNA technology to therapeutics must surely

be its role in the discovery process for conventional

chemical drugs. The chemical plant seems pretty likely

to survive a long while yet.

Peter Lewis

GR Micro Ltd, 7-9 William Road, London NW1 3ER

f 2002 Blackwell Science Ltd Br J Clin Pharmacol, 53, 411 411