Your letters on talc risk, gummy bears and antibody binding
Talc carcinogen risk
The toxicity of talc has been a contentious subject for a number of years. The risks encountered by miners and those exposed to surgical dusting powders are well documented. The carcinogenicity of talc is an unresolved issue and the heavy compensation claims levied by the US courts on Johnson & Johnson are bound to cause widespread public concern.
The toxicity of talc has been a contentious subject for a number of years. The risks encountered by miners and those exposed to surgical dusting powders are well documented. The carcinogenicity of talc is an unresolved issue and the heavy compensation claims levied by the US courts on Johnson & Johnson are bound to cause widespread public concern (see p20).
Talcum powder is used by millions of women worldwide for hygiene purposes and up until the mid-1970s was generally recognised as safe. The potential carcinogenic risk of talc was first suspected largely on account of its chemical similarity to a serpentine form of asbestos, which has been linked to ovarian cancer in occupational settings and is a recognised cause of mesotheliomas through inhalation1.
Talc is a hydrated magnesium silicate mined in many parts of the world; natural deposits being commonly associated with asbestos and other minerals. The literature shows that before 1976, talcum powder was often contaminated with asbestos, but following identification of asbestos as a human carcinogen, guidelines were introduced that ‘only talc with no detectable levels of asbestos should be used in cosmetic products’.
Ovarian cancer is the sixth-most common cancer in UK and many inherited and clinical causes documented. However, as far as I am aware, talc exposure is not listed as a cause.2 In the US, however, numerous studies have implicated use of talc in talcum powder and related products applied to genital areas as a cause of ovarian or endometrial cancers. For the most part, the observations have been conflicting or negative but the World Health Organization and International Agency for Research on Cancer have taken a cautionary approach and classified talc as being ‘possibly carcinogenic in humans’ pending more definitive information.
Having studied the literature in detail, I must emphasise that no conclusive evidence has been provided so far, that talc per se is a human carcinogen. For the most part, clinical studies purporting to show that it causes or predisposes to ovarian cancer are based upon questionnaires and interviews with women who estimated the time, frequency and pattern of contact with the talc-containing products over several years. None of the reports provide reliable details of the quality of the products used, their source or the approximate concentrations of asbestos contamination. Talc is not genotoxic, and mechanistic pathology and experimental investigations provide no evidence collectively that talc is a cause of human ovarian cancer. However, where consumer products are contaminated with asbestos fibres – knowingly or otherwise – the risk of cancer is real.
Alan Lansdown FRCPath, FRSC
Imperial College London, UK
1 D M Gertiget et al., J. Natl. Canc. Inst.,2000, 92, 249 (DOI: 10.1093/jnci/92.3.249)
2 A B G Lansdown, The Carcinogenicity of Metals. Cambridge: RSC 2014
Tracking our failures
Failed investigations are equally important to successes for industrial research, as Jennifer Newton notes (Chemistry World, July 2018, p30). Internal knowledge management is crucial to prevent wasting resources on things that have been shown before not to work, including avenues of research first explored perhaps decades before.
It can be a costly mistake to only record projects on their successful completion, and let pressure on finances and resources do away with writing monthly or quarterly research reports. Getting somebody to write up their work at the end of a totally failed project is nigh impossible, as it creates extreme behavioural dissonance for both the manager and research scientist involved. However, regular interim reports can track the work being done and will record the things that didn’t work.
P H Gamlen FRSC
I agree with Colin Cook (Chemistry World, July 2018, p4) that the piece on solvent interactions (Chemistry World. June 2018, p5) was a good article. Regarding his query about ‘gummy bears’, I think I can venture to throw some light on that. As an occasional viewer of The Simpsons, ‘gummy bears’ and ‘gummy worms’ feature as the favourite sweets of Bart Simpson and his best friend Milhouse Van Houten. For the ‘gummy bears’ analogy referred to in the article, think of jellybeans with arms and legs!
Graham Howarth CChem MRSC
Philip Ball describes the use of DNA linkers to bring proteins together into a functional relationship (Chemistry World, July 2018, p29). This is a topic familiar to me in respect of cooperative binding. The homopolyvalent advantage in antibody binding is well known; heteropolyvalency less so. Nucleic acid chains are long enough, stiff enough and yet flexible enough for simultaneous binding of linked proteins to distinct sites on a single target molecule, without excessive entropic losses. The structure of these sites may be the same or different; in the latter case, it is heteropolyvalent binding where we expect not only greater affinity but greater discrimination. This has obvious applications in analytical work and possibly also in therapeutics.
Other advantages of nucleic acid linkers may appear obvious too. Oligonucleotides are singularly easy to make nowadays and offer near-perfect selectivity between themselves. If appropriate protein-DNA adducts have been prepared in advance, the actual hybrids can be made in a matter of seconds in any desired combination of specificities; and this final step might happen even within a patient’s body, the adducts being administered individually.
Bispecific antibody constructs are used, for example in histopathology practice, without enhancement of binding affinity – rather, properties of a second antibody are used to identify where the first has bound. In contrast, in sandwich immunoassay analytical specificity is improved by using antibodies to two distinct sites of a target molecule; here heteropolyvalent advantage is being recognised and exploited in a different way.
Hybrids of the kind outlined here have not come into use and there is much yet to do. In the future, cancer treatment may come to depend as much on such heteropolyvalent hybrids as immunology.
Tom Boyde FRCPath MRSC