Laboratory findings and people

2.6.1What a dish can and cannot tell you

In cell culture, fibroblasts sit in a controlled medium at a controlled temperature, without the blood supply, immune system, mechanical loading, hormonal environment or neighbouring cell populations that they would have in living skin. A substance can be applied at a chosen concentration, held there for a chosen period, and the cells' response measured directly.

This is enormously useful for establishing that an effect is possible and for working out the pathway by which it might occur. It is close to useless for predicting what will happen when the same substance is injected into a face, because almost none of the variables that determine the clinical outcome are present in the dish. Concentration at the cell surface in living tissue is unknown and changing. Duration of exposure is governed by degradation and clearance. The cells are already in an environment that is regulating their behaviour.

2.6.2What an animal study adds, and what it does not

Animal work restores the missing systems: circulation, immunity, clearance, hormonal context. It is a real advance on cell culture and it is where the safety of most interventions is first examined seriously.

It also introduces its own problems. Rodent skin differs from human skin in structure, thickness, healing behaviour and the presence of a muscle layer that humans lack in the same form. Wound healing in rodents proceeds differently. Doses are often far higher relative to body size than anything used clinically. And the models used are usually models of damage, because damage is measurable, whereas cosmetic treatment is applied to tissue that is not damaged in that sense.

That last point deserves emphasis, because it recurs throughout this literature. Demonstrating that a substance accelerates the repair of a wound does not demonstrate that it improves the appearance of intact skin. The biology of repair is a specific programme that is running in the first case and is not running in the second.

2.6.3The attrition rate, which is the point

Across medicine, the proportion of interventions that look promising in the laboratory and go on to demonstrate clinical benefit in people is low. This is not a scandal and it does not indicate incompetence. It reflects the fact that living systems are complicated and that a mechanism which can be shown to operate in isolation frequently turns out to be swamped, compensated for, or irrelevant in context.

Anyone who has followed drug development knows this pattern. Compounds with beautiful preclinical data fail in phase three trials routinely. The response of the research community has been to build an entire apparatus for testing clinical claims properly: randomisation, blinding, prespecified outcomes, registration, independent analysis and systematic review. That apparatus exists precisely because laboratory plausibility is known to be a poor predictor.

A cosmetic device sold on the strength of laboratory plausibility is skipping the part of the process that was built because plausibility is not enough.

2.6.4The fair reading

Laboratory work in this field is not fraudulent and it is not worthless. It has done what preclinical work is supposed to do: identified a plausible mechanism and given a reason to test it in people. The failure is not in the laboratory. It is in the marketing, which presents the completion of the first stage as though it were the completion of the last.

If you are in a consultation and are shown laboratory findings, the useful response is not to dismiss them. It is to ask what happened when this was tested in people, and to notice whether the answer is a study or a change of subject.

2.6.5Language that signals laboratory origin

You can often tell, without checking a citation, that a claim originated in a dish, because the language carries traces of it.

• Upregulates, downregulates, stimulates expression: these describe measurements made on cells, not appearances observed on faces.
• Increases collagen synthesis: a measurement of production, which is not the same as a measurement of the amount of collagen present, which in turn is not the same as a visible change.
• Reduces inflammatory markers: markers are proxies, and a change in a proxy is a step towards a claim rather than the claim itself.
• Promotes cell proliferation: cells in a dish proliferate readily, and proliferation is not automatically a good thing in tissue.

None of those phrases is untrue. Each is an accurate description of a laboratory result. What is misleading is their placement next to a photograph of a face, with no acknowledgement that a great deal has to be true in between.

2.6.6A closing distinction

There is a difference between a treatment that has failed and a treatment that has not yet been tested properly. Polynucleotide cosmetic treatment is in the second category, and it is worth being precise about that, because the second category contains both things that will eventually be shown to work and things that will not.

What a reader can reasonably conclude from the laboratory evidence alone is that the idea is not silly. That is genuinely something. It is not what is being sold.