Naturally blonde, brunette...

Designer ’therapies’ could one day be helping to restore our hair to its former colour and texture, say Bob Hefford and Keith Brown 

Every year we spend millions of pounds on cosmetic surgery, skin creams and cosmetics to ward off the inevitable signs of ageing. Our hair is frequently one of the first casualties of the ageing process. Hair restoratives and colorants can do a good job, but sometimes lack that ’natural’ look that many people crave. But continuing progress in genetics, and in understanding the molecular basis of hair coloration and loss, promise unexpected benefits. Designer gene or drug ’therapies’ that restore our former crowning glories remain speculative, though there is reason to think that they may work. 

Tests of Novartis’s new drug Glivec, for example, revealed a surprising side-effect. 1 Of 133 patients treated with Glivec, a drug designed to combat chronic myeloid leukaemia, nine had progressive darkening of the hair that began about five months after the start of therapy (Chem. Br., October 2002, p10). So far it is not known how Glivec, a tyrosine kinase inhibitor, initiates hair repigmentation or why it affected only a small percentage of patients in this way. Glivec itself will never be used to restore hair colour, but it may give clues to a repigmentation mechanism, and to developing more useful treatments. 

In San Diego, CA, meanwhile, biotech company AntiCancer is exploring an efficient technique to facilitate gene transfer into hair. Initial studies have used a well known gene from a jellyfish that produces a green fluorescent protein, as a marker, and in the longer term a number of other applications may be feasible. AntiCancer researchers have been able to transfer the gene into the hair follicle and shaft by using an adenovirus as the gene carrier or vector. They were able to improve the efficiency of this transfer by using a collagenase enzyme to soften the skin. Hair growing from the follicles glowed green for some time when illuminated by blue light. 

The goal of AntiCancer’s work is of course biomedical, but such results also pose another interesting idea. Might people, already worried about eating GM foods, apply GM procedures for the sake of their appearance? The answer is almost certainly yes. Whatever the motivation, it is clear that people have coloured their hair, and much of the rest of themselves, for many thousands of years. Early hair and skin colouring techniques centred on the use of plants and their extracts, which we would probably describe these days as ’animal byproduct free, naturally derived vegetable based materials from renewable resources’. 

Of the many plants claimed to colour hair, the most historically notable is a privet-like shrub of the Lawsonia genus, from which we obtain henna. Other valuable species include Indigofera, from which we derive indigo and Juglans, which includes the walnut tree whose leaves and nutshells provided yet another early hair colorant. 

Colour effects
These substances often give unpredictable colours and produce colouring effects that fade over different timescales. In addition, being natural does not necessarily mean that the active materials are nowadays judged ’safe for use’. One of the active colouring ingredients from walnut is pyrogallol (1,2,3-trihydroxybenzene), which has been banned for use as a cosmetic in the EU since 1992. The active ingredient in henna is lawsone (2-hydroxy-1,4-naphthoquinone). This material has recently received an unfavourable opinion from the EU’s expert SCCNFP (Scientific Committee of Cosmetic and Non-Food Products) committee, which evaluates the safety of non-food ingredients and products for consumer use.

It remains to be seen what legislation, in particular for henna which is often poorly defined chemically, may or may not follow from this opinion. Indeed, the question of composition is an increasing problem for ’naturals’, because their analysis is not straightforward and their composition often varies. 

Another group of materials coming under increasing scrutiny as hair colorants are lead salts. The Romans were among the first to dye their hair in this way, by dipping lead combs in vinegar - a technology probably borrowed from the Greeks (something that the Romans were quite good at) and which became popular in the 19th century. Lead salts are allowed in hair colouring products by the EU Cosmetics Directive, but will be banned following the implementation of the 7th amendment to the EU Cosmetics Directive in the next few years. Lead salts fall under the category of a class 1 or 2, carcinogen, mutagen or reproductive toxin (CMR), and all such substances will be banned for use in the EU. This is the first time that materials have been banned on the basis of hazard rather than risk. 

Colouring power 
The development of organic chemistry, and in particular the discovery of the colouring power of phenylene diamines and the effects of hydrogen peroxide, markedly changed the techniques available for colouring hair in the 19th century. Modern hair colorants, which emerged from these discoveries, are mainly of two types - albeit in many different brands. The first type relies on pre-formed dyestuffs that colour the hair directly but give relatively short-term effects and can often be washed out in a few weeks.

These molecules, known as direct dyes, may lie on the outer surface of the hair or may penetrate fully into the cuticle and some way into the cortex as determined by their size and charge. Other properties of the hair, such as the degree of damage and porosity, will also affect dye penetration. A high pH (usually about 10) causes the hair to swell and aids penetration, giving longer-lasting or ’permanent’ colouring effects that are more resistant to washing. 

The second and most popular type of hair dye relies on chemical reactions between dye precursors and an oxidant, which must therefore be physically separated in two containers until use. Upon mixing, a reaction occurs that creates dimers, trimers and larger molecular species. When this happens inside hair, the larger coloured molecules are trapped within its cortex. In this type of system ammonia is often used as an alkali to initiate the reaction and swell the hair shaft. Ammonia has the other useful ability of helping to lighten the natural hair colour in the presence of hydrogen peroxide. 

The dye precursors are usually of two types. Most important are the para- and ortho-aromatic diamines, which are readily oxidised and are necessary for the dark shades and depth of colour. Materials known as couplers, which do not form any depth of colour on their own, are necessary to give different colours from the oxidised diamines. These are often hydroxy-substituted aromatic species. 

From this relatively simple technology a plethora of brand positions have been developed so that we now have (to name but a few):

• Temporary
• Wash-in wash-out
• Semi-permanent
• Demi-permanent
• Tone on tone
• Longer lasting semi-permanent
• Shampoo-in
• Permanent
• Highlights, streaks, lowlights and underlights.      

These products are designed individually to last anything from one wash or until the hair ’grows out’ (ie when new growth is sufficiently evident that recolouring is required). However, as the market grows and competition becomes fiercer it is harder to find real differences between the various brands. 

The popularity of hair dyes and high visibility of their effects mean that safety is a major issue. Phenylene diamines used during the 19th century were among the first products to cause concern. Now recognised as allergens, phenylene diamines were originally developed for colouring furs. This unrestricted use of these ’coal tar dyes’, which where originally probably quite impure, led to problems both in Europe and the US. Nowadays the use of phenylene diamines as the para- and meta-isomers is allowed with restrictions in the EU, and a warning must be displayed on the packaging of all hair colouring products that contain them. 

Hair colouring products have been accused of causing just about every form of cancer at one time or another. These accusations sometimes arise from epidemiology studies - which can be of variable quality. One of the latest studies causing concern links the use of hair dyes to bladder cancer and was the subject of an SCCNFP opinion in 2001.  However, the findings are at odds with earlier large-scale studies and reviews which concluded that ’the overall evidence excluded any appreciable and measurable risk of bladder cancer from the personal use of hair dyes’. The hair colouring industry believes ’that taken together the information suggests very clearly that even if hair dyes are a contributory factor in the development of bladder cancer, they are not the prime cause of the disease’.

So where does all this leave us? It is important to remember the distinction between the hazard of a material (an intrinsic property) and the risk (what might happen if it is used in a certain way). It is also important to consider the level of acceptable risk as most activity comes with some risk attached. This idea was recently introduced into the Preliminary report on scientific quality of life criteria in risk benefit assessment from the SCCNFP.  So will consumers be willing in the future to alter their genetic material for a good head of coloured hair? We would not bet against it. 

Source: Chemistry in Britain

Acknowledgements

Bob Hefford and Keith Brown