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First steps to chemotherapy

Exploring the industry's most important dates, we recall December 1942: First trial involving chemotherapy
calendar 1942

More than probably any other disease, cancer has a certain emotional resonance that makes sure it is a constant in people's thoughts and in media headlines.

It is an effect due in part to its potentially devastating consequences, as well as the great prevalence it has around the globe.

According to the report 'Global Cancer Statistics' published in the March/April edition of CA: A Cancer Journal for Clinicians, there were about 12.7 million cases of cancer and 7.6 million cancer deaths  estimated to have occurred in 2008.

It is an increasing burden, too, as populations age and grow across the world, and unhealthy 'westernised' lifestyle choices such as smoking, alcohol and inactivity become more common in developing nations.

Cancer also features as a high priority in the efforts of pharmaceutical companies, although it was not until the middle of the 20th century that the first real developments in treatment began. And, like a lot of medical miracles (such as penicillin, Viagra and lithium's effect on bipolar disorder), the discovery was something of a chance accident.

Dr Paul Ehrlich, the German researcher, had already paved the way for research into cancer treatments – indeed, even coining the term 'chemotherapy' in 1907 – and mustard gas, the World War I chemical weapon, had already been found to have the property of suppressing blood production, or haematopoiesis. But it was World War II that saw the first breakthroughs emerge in what such an effect could have on people's health.

Following a German air raid in Italy, autopsies of the victims discovered that the mustard gas used in the attack had caused suppression of white blood cells.

Dr Louis S Goodman and Dr Alfred Gilman, who had been hired by the United States Department of Defense to investigate the potential therapeutic uses of chemicals used in warfare, took this information to mean that nitrogen mustards could have an effect on white blood cells affected by tumours as seen in patients with lymphomas.

Experiments were done in mice that backed Goodman and Gilman's rationale, and it was in December 1942 that the first conscious efforts were made to tackle cancer in this cell-destroying effort, when 67 patients with advanced lymphomas were injected intravenously with the compounds rather than in the previous method of inhaling gas.

The research team, including Goodman and Gilman, discovered that patients taking the nitrogen mustard experienced a dramatic, if short-lived, improvement in health, establishing the first steps into the treatment of one of the world's most common and feared diseases.

Due to the secrecy of wartime research activities, though, it was not until 1946 that the US government allowed the research of Goodman and Gilman to be published and further research then began.

This included further investigation into 'alkylating agents', a family of compounds such as nitrogen mustard that physically modifies the DNA in a human cell.

The bulk of such research was done in the 1950s, leading to drugs that are still used to treat lymphoma and leukaemia, such as chlorambucil, melphalan and busulphan.

Other types of chemotherapy began to emerge to help treat cancers other than those that affect blood cells.

These included 'antimetabolites', which were developed to resemble naturally occurring chemicals in the body to block the real chemical from being incorporated into a person's DNA. This interferes with DNA production and the normal development and division process of cells, inhibiting the growth of tumours that have a higher cell division rate than other cells.

Antimetabolites are now often commonly used as part of combination therapy.

Platinum derivatives were then discovered in 1965 by Dr Barnett Rosenberg during experiments into cell growth of bacteria, with Bristol-Myers Squibb launching the first such product in the late 1970s with Platinol (cisplatin).

Although described as 'rather like taking a sledgehammer to crack a hazelnut' by Cancer Research, chemotherapy has gone on to become a multibillion-pound industry with pharma companies, governments and the not-for-profit sector constantly funding research into various products and product combinations to help treat a disease of increasing prevalence.

And it is research that, despite the often serious side effects and the lack of an ultimate 'cure', has had real benefits, with recent research from Macmillan Cancer Support suggesting that people now live six times longer after their cancer diagnosis than they did 40 years ago.

With incidents on the increase, though, it is clear more needs to be done, not just with chemotherapies themselves but in how people choose to educate and live their lives to keep cancer rates down. Nevertheless, the discoveries of Goodman and Gilman have an importance that still resonates and one that will lead to an even better arsenal in the fight against 'the emperor of all maladies'.

Tom Meek
The Author
Tom Meek
, web editor at PMLiVE

16th December 2011


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