How Medicines are Born

The following sections are included:

• Foreword — Improving the Culture of Medicine
• About the Authors
• Precautions and Wanings before Using this Book
• Contents

The road to new drugs can follow very diverse directions. It can be straight and quick like a motorway, but more often it is arduous and tortuous, accompanied by mirages, unexpected deviations and scattered obstacles along the way, tormenting pharmacologists today as they did yesterday.

The most up-to-date and elegant method to deliver a new medicine starts, as we have seen, with the knowledge of the mechanisms of the disease to be targeted. Such knowledge helps to design — literally at the writing desk — a drug capable of interfering with the molecules or the biological circuits which are dysfunctional or out of control.

The human body is amazing. We think that we know all of its nooks and crannies, and then a new ligament crops up. In 2013, a group of Belgian scientists actually discovered one close to the knee. You can imagine the reaction: “How is it possible that a ligament has remained undetected by generations of orthopaedic surgeons, anatomists, pathologists, physiotherapists and sport physicians?” Are we not, after all, in the era of magnetic resonance and of the transparent body? These are legitimate points as long as one avoids looking into a human body, a wet and dark mass which is very difficult to reconcile with the neat and clean images presented in anatomy atlases.

In the middle of the 18th century, the British Empire was at the height of its power. Hundreds of ships of His Majesty’s Navy sailed proudly across the oceans of the whole world. The ability to conquer new territories and to stash away large amounts of merchandise and precious objects in George II’s treasure chests depended crucially on the voyages of these vessels. But not everything goes always to plan.

A drug administered at an identical dose to different individuals can be recovered from the blood of these individuals at concentrations which can vary 10- to 20-fold.

In 2013, a large American pharmaceutical company submitted an application for approval of a new sleeping pill to the Food and Drug Administration (FDA), the US authority which clears the path to the use and commercialisation of new drugs. The application, submitted in electronic format, took as much as 41 gigabytes digital storage space. For comparison, all Wikipedia entries in 2013 together took up 9.2 gigabytes. The dossier for the new sleeping pill was not exceptional. The documentation describing the efficacy and safety of every new drug seeking approval needs to be more than encyclopaedic.

In 1988, Daniel Simmons, a professor of chemistry at Brigham Young University in Utah, discovered an enzyme which he named cyclooxygenase-2 (COX-2), because it is related to the previously known COX-1, an enzyme which is inhibited by aspirin.

Can we predict how we will treat diseases within the forthcoming decades? “To make predictions is difficult, particularly when they are for the future ” is a saying, the attribution of which is uncertain. It might be an old Danish proverb, or it might have been coined by the physicist Niels Bohr, the film producer Samuel Goldwyn or the baseball player Yogi Berra.

We are almost at the end of our journey across the world of the imperfect science of drug development, taking you from the original idea all the way to the packaged vial. We have seen that the original idea for a new drug arises from an unmet medical need. From this idea emerges ultimately a compound, the potential new drug. It may be an agent which exists already in nature and can be manipulated in a chemical laboratory to improve its stability or tolerability, or to enable an easy chemical production method. Alternatively the compound is newly synthesised in the chemical laboratory. Or it may be the product of the synthetic capacity of a cell, perhaps a genetically modified one, which constitutes a most proficient chemical laboratory, capable of generating innovative drug molecules such as the monoclonal antibodies and other biologicals in use today.

The following sections are included:

• If You Want to Know More …
• Myths to be Dispelled
• Did You Know That …
• Index