There are many challenges ahead for humanity, such as ensuring a continued supply of essential medicines. Synthetic organic chemists have unlocked many mysteries of naturally occurring medicines and invented plenty of their own. Dr Alice Williamson synthesises the facts.
At the beginning of the 19th Century, German chemist Friedrich Wöhler synthesised urea - a human and animal waste product - in his laboratory. Today, the synthesis of this small and simple organic molecule seems unremarkable, but in 1828 it was big news.
Wöhler had achieved (by accident) what many thought to be impossible – the transformation of inorganic starting materials into an organic molecule. At the time, the commonly held belief was that organic materials, such as urea possessed a ‘vital force’ and could therefore only be obtained by extraction from living things.
Wöhler’s serendipitous discovery heralded a new age of synthetic organic chemistry: the ability of scientists to put together molecules bit by bit in (almost) any way we want. In the decades that followed, chemists synthesised hundreds of naturally occurring compounds and just as importantly, they also realised that they could modify their syntheses to make unnatural versions of those compounds.
Both synthetic and natural compounds have an important role to play in the treatment of disease
Nature is really good at making molecules and many of them have medicinal properties. Since ancient times, plants have been used for the treatment of disease. Today, around one third of the world’s biggest selling drugs are based on naturally occurring molecules made by animals, plants or microbes.
Synthetic organic chemists can synthesise many of these natural products in the laboratory and importantly, the same skills and knowledge required to make copies of nature’s molecules can also be used to make brand new compounds, with unknown properties.
Many of the drugs we rely on have no natural origin. They have been designed and synthesised for the first time in the laboratory. Two common occupants of home medicine cabinets, paracetamol and ibuprofen, were both discovered by chemists. Both drugs have simple structures, can be synthesised cheaply and are listed by the World Health Organisation as essential medicines.
Both synthetic and natural compounds have an important role to play in the treatment of disease. Some synthetic medicines have completely new structures, others are designed to mimic naturally occurring molecules and sometimes chemists even need to synthesise supplies of a natural compound to meet demands.
Importantly, there is no difference between a natural compound that’s isolated from its source and a version of it that is synthesised in the lab. Indeed, chemists compare their lab made version of a molecule with an authentic sample to prove that they are chemically indistinguishable and will therefore have identical medicinal properties.
While in some cases it is possible to isolate sufficient quantities of a medicine from its natural source, this certainly isn’t guaranteed.
Extraction from a natural source is not always practical or possible. For example, some molecules occur in such small concentrations that thousands of kilograms of plant or animal matter would have to be collected in order to obtain enough material to treat one person. And some molecules are found in endangered plants or animal species meaning that it’s more ethical to reproduce them in the laboratory than risk further depletion.
For some medicines, particularly those with complicated structures, it is sometimes possible to extract or culture large quantities of a molecule that is structurally similar to the desired drug and then hand it over to chemists to finish off in the laboratory.
Take Taxol for instance. Taxol is a potent anticancer agent first collected from the bark of the Pacific Yew tree in the early 1960s. Today, Taxol is the most widely used breast cancer drug, and the global supply relies on something called semisynthesis, where Mother Nature and lab chemists work together in a relay to provide the finished product.
The natural supply of Taxol isn’t sustainable because bark from about six 100 year-old trees is required to provide just one course of treatment.[i] And although chemists have designed ways to make Taxol in the lab - which is impressive because the molecule has an incredibly complex structure - the process is too costly for it to be commercially viable. Instead it’s possible to harvest large quantities of a compound with a similar structure (Baccatin III) from the needles of the tree (a renewable resource), and then hand it over to chemists to work their magic on the last part of the synthesis in the laboratory.
So, we have some medicines that are naturally occurring and can either be extracted or made, others that are made in collaboration and some that can only be made in the laboratory.
What is clear is that chemists are central to the supply of medicines. Without chemists, the structure of natural products would remain a mystery and much needed synthetic medicines would be unobtainable. In the future we’ll need to combat diseases we don’t even know about yet, as well as tackle existing threats such as cancer, obesity and antimicrobial resistance.
Wöhler may have disproven the theory of vitalism, but his early works demonstrated that synthetic chemistry is vital.