The Hole Story:
Human Studies of Skin Cancer ctd.
Problems with Human Studies
Bill McCarthy says the biggest problem he finds with research involving humans is the accuracy of what people tell him. For instance, he can never be sure exactly how much the answers to the questionnaires reflect what the children are actually doing. This is because he can't monitor it all himself. If the mother says she is regularly putting sunscreen on the child, what does that mean? Does it mean she does it only when she thinks about it, or does she do it every morning? There is always an element of secondhandedness about research of this nature. It is not like taking some blood and examining it under a microscope. When you are relying on people to answer questions there is always an element of uncertainty.
A second problem is that statistics about human populations can be interpreted in a variety of ways and causes for trends are sometimes mysterious, whereas with animal studies a number of factors can be varied in a controlled situation in the laboratory to see which is the one that is significant. For example a project which the Unit worked on with the NSW Cancer Registry on melanoma in NSW found some unexplained results. The Melanoma Foundation and the Australian Cancer Society gave some money to the NSW Cancer Registry to specifically make sure their registration of melanoma was up to date. The Cancer Registry worked very hard over the couple of years up to the end of 1989 to get their melanomas more up to date.
Some very interesting patterns emerged. The pattern most intriguing is that at the moment there seems to be an arbitrary line going through Gosford where the reported incidence of melanoma increases dramatically. Places North of Gosford such as the Hunter Valley and the North Coast have almost twice the registration of melanoma as do places south of Gosford, such as the city of Sydney and the Illawarra area around Wollongong.
The researchers don't know yet why this is so. It could turn out to be just that there is better reporting North of Gosford but at the moment that doesn't appear to be the case. Another possible reason is that people further North live different lifestyles and are exposed to more sunlight. For example, a smaller proportion of the population are migrants in the Newcastle area than in either the Sydney or the Illawarra areas. Or it could be due to factors other than a cancer producing agency, which is causing the apparent increase.
The researchers would desperately like to know the answer to these questions. Is there actually something real happening there or is this phenomenon an error based on the fact that you are dealing with uncertain data? This frustration in not being able to see the reason for that which can be readily observed is one of the major difficulties of research of this type. The outcome is sometimes unexpected and can't always be explained for quite a while. So it may take many years to know the answer as to why there is a much higher incidence of melanoma amongst people living to the north of Gosford than amongst those living immediately to the south.
A third problem is the time it takes to get results using human studies. The Unit is currently doing a study on some people with melanoma using a vaccine to try to prevent the disease. They expect it will take them perhaps 3 or 4 years to get enough patients onto a National Health and Medical Research Council (NH&MRC) trial in order to statistically evaluate it properly. After that it will probably take another 3 to 5 years of following up on those groups to say whether the vaccine actually does make a difference. Even if they believe they have a good vaccine now, it will take a minimum of 6 to 8 years of proving before they can say to people it is worthwhile to use this particular vaccine. It takes all that time to get a worthwhile answer. If the answer is negative then six years work will have been spent just to get a negative answer. That is very frustrating because after all that work the researchers would much prefer the answer to be positive. But unless the research and proving are done meticulously and followed through to the end it is impossible to know whether something actually works.
That is one of the big frustrations of all research. The researchers come up with what looks like a good idea and then it takes years to find out if it really works. If it doesn't they often wish they had never started because if they hadn't they could have been working on something else that might have been a better idea. The other frustrating possibility is that they may take on something like vaccine research, get half way through a particular programme, and then someone else comes up with what looks like a better vaccine. The question they must then confront is; do they abandon the study they are doing without getting an answer and move over to the new vaccine to test it? Or do they carry their own project through to completion and take the chance that they are only working on the second best alternative while someone else is working up a better one that does a better job?
There is always a great deal of frustration in this kind of human research. But in the long run, to McCarthy, it is far more rewarding doing human research than animal research, although it is much more difficult to get a clearly defined answer.
"You can put UV light on the skin of a mouse at regular times of the day for any number of days and assess the results," he says. "With humans, unless you put them in a cage and sit them out on the lawn each day, you simply don't know. They may turn around, for instance, and get a different exposure or they may move 20 yards away, walk under a tree and get an altogether different exposure."
So working on humans is much more difficult. That is why such a lot of basic research is not done on humans. But in the long run humans have to be used to confirm the outcome. Mice experiments are great but in the end you can't be sure whether the results of mice experiments are translatable to humans. Similar things have to be finally done to humans as were done to the mice before you can be certain that the predictions made about mice actually happen to humans too. So it is a much more difficult, time consuming, costly and frustrating thing to work, as they do at the Melanoma Unit, almost exclusively on humans.