Rats, Mice, Dishes And The Missing Humans

The ladder of evidence

Not all research tells you the same thing. Scientists often think of evidence as a ladder.

At the bottom are cell studies, done in dishes. They are fast, cheap and precise, and very good for working out how something works. But a dish is not a body.

Above that are animal studies. A living animal has organs, blood flow, an immune system and a brain. That makes the results more relevant, but animals still differ from people in important ways.

Higher still are studies in people, starting with small safety studies and moving up to large controlled trials. Only these can tell you what a compound actually does in humans.

All four studies in this collection sit on the lower rungs.

None of them involve people.

What cell studies are good at

The two cell studies are excellent at one thing: mechanism.

The Wisconsin study is a good example. By filming individual cells every two minutes, it could answer a question no animal study could: does SS-31 block BAX once the death process starts? The answer was a clear no.

The muscle study showed which protective proteins switch on in muscle cells after loss of oxygen, with and without SS-31.

What cell studies cannot do is tell you whether those effects matter in a whole body. A cell in a dish has no blood supply, no immune system, no neighbouring tissues. It also does not have to absorb, transport or clear a compound.

What animal studies add

The brain and liver studies add the realism a dish lacks.

In the brain study, the rats had a real bleed, real swelling and a real blood-brain barrier. SS-31 had to get from an injection in the abdomen all the way to the brain. And the team could measure something cells cannot show: whether the animals behaved better.

In the liver study, the mice had real, long-standing diabetes, built up over months. SS-31 had to work in a body where high sugar was constantly causing damage.

That is a big step up from a dish.

Why animals are still not people

But there are important gaps, and these studies illustrate several of them.

Speed of treatment. In the brain study, SS-31 was given 30 minutes after the bleed. Real patients rarely reach treatment that fast.

Drug handling. Rodents process drugs very differently from people. A dose that works in a mouse does not translate simply into a human dose, as Part 5 explained.

One sex. The brain study used only male rats. The liver study used only male mice for its main experiments, because female mice of that strain did not develop diabetes. We do not know if the results hold in females.

Controlled lives. Lab animals live in identical cages, eat identical food and have no other illnesses. People take other medicines, have other conditions and vary hugely in diet and activity.

Short time frames. The brain study measured effects at 24 hours. The liver study treated for four weeks. Neither tells us about long-term effects, good or bad.

What these studies do not measure at all

Because none of these studies were designed to test safety in people, several important questions are not addressed:

• Side effects
• Long-term safety
• Interactions with other medicines
• Effects in older people, pregnant women or people with other illnesses
• Whether the measured improvements translate into people feeling or functioning better

Those questions can only be answered by careful studies in humans.

Why the gap matters

The history of medicine is full of compounds that looked excellent in cells and animals and then did not work, or caused problems, in people. That is not a criticism of animal research. It is simply why the later rungs of the ladder exist.

Animal and cell studies tell you whether something is worth testing in people. They do not tell you whether it works in people.

Reading these four studies fairly

So what is the fair summary of these four studies together?

They show that, across several tissues and types of stress, SS-31 consistently supports mitochondria in rodents and in cells. It reduces oxidative damage, strengthens the cell's own defences and helps mitochondrial structure. One careful study suggests it does not directly block the cell's self-destruct machinery once that has started.

That is a solid body of early research and a good reason for further study. It is not evidence about what SS-31 does in a person, at any dose, for any condition.

Next, who funded this research and who carried it out, and why that is worth knowing.

This series discusses four laboratory studies in animals and cultured cells. None tested SS-31 in people. Nothing here is medical advice, and SS-31 is discussed for research purposes only.