By David N. Leff
For centuries, going back to Roman times, the bandage for a dog bite incorporated a few hairs from the canine that did the biting. This rationale eventually got transferred to the cure for a hangover ¿ a tipple of the same alcoholic beverage that had caused the morning withdrawal symptoms. Practitioners called this like-cures-like therapy ¿a hair of the dog that bit you.¿
Now, there¿s a high-tech diagnostic strategy that could be termed ¿a hair of the gene that hit you.¿
In fact, a brief report in today¿s Nature, dated March 4, 1999, carries the title: ¿Using hair to screen for breast cancer.¿ Its senior author is biophysicist Veronica James, at the Australian National University Research School of Chemistry, in Canberra, and Sydney University.
She analyzed, by high-energy X-ray beam, the molecular structure of scalp hair from women with breast cancer, compared to samples from healthy women. Her initial tests were inconclusive, it turned out, because the hair donors had had their tresses permanently waved, which disrupted their complex keratin structure. ¿At the beginning we got permed hair samples,¿ James recalled. ¿So, they had to be thrown into the trash bin, after hours and hours of my time on the X-ray beam machine.¿ In subsequent trials, James shifted to pubic hair, which was not subject to this cosmetic deformation.
¿One hundred percent of 23 hair samples from breast-cancer patients,¿ she told BioWorld Today, ¿showed the characteristic rings of intensity in their X-ray scattering patterns.¿ Of hair from 48 women not suspected of the malignancy, 86 percent had patterns that were normal.
¿When I got these strange rings,¿ James recalled, ¿I sent back to ask, What did these people do to their hair? Did they go to the same hairdresser, or use the same shampoo?¿ And I got back the information that they were breast-cancer per se. I was able to pick out the people who had breast cancer that was familial, and those that were sporadic. Eventually, every one I picked out had some reason to be there. There was one person who had had cancer 15 years ago, whom the doctors firmly assured that her cancer was cured. That lady was not on my list of X-ray-imaged molecular hair changes; she was clear.¿
In subsequent trials, which were randomized and blinded, all healthy individuals diagnosed as carrying the BRCA1 breast-cancer gene displayed the telltale ring patterns.
James compared those X-ray patterns to the waves of the sea. ¿The water comes in in waves,¿ she explained. ¿As it hits one of the edges of the land, you will see the waves change direction. If you put them between two rocks, you¿ll see circles emerging on the other sides. The end result appears to be bending off a point, to get those circles.
¿All I do,¿ she continued, ¿is take a wave of X-rays and bounce them off atoms. I go between atoms, and I go through molecules, and I¿ve got all these things arranged in a very powerful parallel way. With a bit of experience we can say, Aha, that pattern is from hair; this one is from tendon, that¿s from something else.¿¿
She said the structure of keratin from hair ¿is very, very different from the structure of collagen from tendon.¿ The molecular pathway from malignancy to hair shaft, she observed, is ¿something which, as yet, I haven¿t proven. What I think is that it lodges in the outside hair membrane, the one between the cortex and the cuticle.¿
James suspects that the cancer message reaches ¿back in the follicle, where hair¿s produced. Once it leaves the follicle, it has no more contact with its roots; it is dead. Nothing can be got out of it or put into it. Blood reaches the follicle, and provides the kinds of nutrients and things that are going to the hair membrane.¿
Physicist David Cookson, at the U.S. National Argonne Laboratories, in Chicago, is a co-author of the Nature paper. ¿The hair is not a crystal structure, of course,¿ said Cookson, who is involved in James¿ use and interpretation of the Argonne¿s high-intensity synchrotron.
¿When you put a single human hair in the way of a very intense X-ray beam, the sort you get from a synchrotron as opposed to one in a clinical lab,¿ Cookson told BioWorld Today, ¿you see a pattern of scattering coming off. This pattern shows a certain amount of structure to the hair. [James] suspected that this structure changes with what appears to be the onset of breast cancer. As a result, she tested with a double-blind study, using hair samples obtained from various sources. Every woman who had been diagnosed with breast cancer showed a change in X-ray diffraction pattern.
¿There were in fact a number of samples that showed the change from patients who had not been diagnosed with breast cancer,¿ he said. ¿However, in that sub-group ¿ which we might call provisional false positives ¿ there were a large number who tested positive for the BRCA1 gene.
¿Now, you have to ask yourself, Is a false positive in fact false, or is it showing something up that is not yet shown in other diagnostic techniques?¿¿ he continued. ¿Such questions can only be answered with a lot more patient hair samples. A sample size of 50 to 60 is not enough to give the answers. But we believe it is more than enough to suggest that further work on this program is very desirable. Our aim here is to assure that groups worldwide will embark on much more extensive studies to build up some decent statistics on it.¿
Potential Payoffs: Cancer Screening, Drug Design
Cookson pointed out that ¿only high-energy synchrotrons are suitable for this kind of work and, of them, the very best, the third-generation, world-class synchrotrons, there are at present only three in the world ¿ in the U.S., France and Japan.¿
Besides their medical uses, Cookson said, such synchrotrons ¿are becoming very important in finding the structure of proteins. Right now, protein diffraction is an area very useful for drug design, for which small X-ray machines are being used. But, as the proteins we solve get bigger and bigger, the crystals therefore get smaller and smaller. And, because the more complicated the protein, the harder it is to get a crystal ¿ which is one of Murphy¿s laws¿ ¿ you need to illuminate it with ever more intense X-rays.
¿As soon as this work reported in Nature is made public, there will be a lot of competition, both from people who are seeking to disprove it, and those who think there may be something in it,¿ he predicted. ¿Potentially, if you take it to the most logical extreme you can think of, this could be a very efficient high-volume screening method for detecting breast cancer. So, the potential payback, in kudos and possibly in money, if the industry takes an interest, could be quite enormous.¿ n