Recombinant protein drugs

Abstract

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 fascinating 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 stimulating 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 processes. 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 introduction 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 α/β−adrenoceptor 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.