We define our lives, it seems, not by how much of it we remember, but by how much we forget. Bit by bit, scientists are uncovering the mysteries of memory loss – teasing apart the neurological differences between how the brain naturally forgets, and how disease and trauma change the process.
Much of this research is being done in Melbourne, at the Florey Institute of Neuroscience and Mental Health in Parkville.
In findings published last month, for instance, Florey researchers uncovered the precise hourly rate at which Alzheimer's disease develops – opening the door for a potentially game-changing treatment.
In another investigation, scientists are finding parallels between why babies forget misfortune and why crash victims can't remember the accident. A third study is uncovering the mechanism that prevents many teenagers from forgetting – causing adolescent anxiety, depression and addiction – and its similarities to post-traumatic stress syndrome (PTSD).
And across the breadth of the research, spanning infancy to old age, a brutal irony emerges. In the normal course of events the act of forgetting is not only natural, it is in many ways essential. The brain diseases of late adulthood – Alzheimer's and other dementias – cruelly hijack that process and use it to destroy the person that memory and memory loss, at least in part, created.
"I think forgetting is very useful," said Dr Jee Hyun Kim, a behavioural neuroscientist at the Florey who specialises in infant and childhood memory loss.
"My personal theory is that amnesia is very adaptive. If we remember everything but remember it in a very emotional context, then it might be hard for us to have flexible thoughts about how people or life can be different."
Kim studies the well-known phenomenon of infants quickly forgetting the pain and stress of, for instance, falling over. The memory loss might serve a protective function. In a similar way, the retrograde amnesia experienced by trauma victims might also be helpful, by sparing them the nightmare of reliving bad experiences over and over.
"As much as babies are fragile and we have to be very good raising children, in a way they are born already quite robust," Kim explained.
"So it may be the case that the reason we are so good at forgetting early in life is because, you know, when parents first have children we don't know what to do. There may be a lot of mistakes people make.
"But that's OK. If you make a mistake, you haven't ruined your children."
It's been suggested that infants don't remember minor injuries because their brains simply haven't developed enough to record the events. But this isn't true; research shows that memories are laid down early in life.
In an overview of 40 years of work in the field, published last year, Kim and co-author Heather Madsen reported that although adults have problems remembering anything that happened to them before they were about seven years old, 10-year-old kids can often recall events from their first year, even their first months.
One indication that infant forgetting – as distinct from the failure to form the memory in the first place – has a protective function arises from what happens when a child is subjected to sustained ill treatment.
"Research suggests that if the trauma is repeated, you are more likely not to forget," said Kim.
And remembering bad stuff so early in life can have long-term and devastating consequences, in part because the infant brain is simply not well enough wired to place trauma into a constraining context.
Kim used the example of a father who became angry when he was very tired. At a certain age-dependent level of brain development, a child will recognise dad turns into a monster only when he's exhausted.
"But that's a very high order of cognition, understanding that at different times and in different environments people can change," she said.
"A baby will think only 'my dad gets angry', or 'my dad hates me'. So in a way it's protective that we forget so easily before we form these very fixed ideas about life."
Whether retrograde amnesia arising from accident or assault has a similar protective function is a question still being investigated. A 2017 overview by scientists from the University of Bielefeld in Germany concluded that "research on retrograde amnesia is still in its infancy".
One interesting avenue of study arising from the field, however, centres on the use of certain drugs to artificially induce amnesia. It is an avenue being explored as a possible treatment for post-traumatic stress disorder, in which sufferers are condemned to relive horrific memories over and over.
However, the benefits of such approaches are far from agreed.
"Novel combinations of behavioural and pharmacological interventions with the potential to precisely target and modify memories have generated considerable debate," wrote Dr James Elsey of the University of Amsterdam in December 2016 study called Manipulating Human Memory Through Reconsolidation.
The approach, he reports, might remove bad memories that trigger serious psychiatric illness, but "our memories also form the foundation of our identities".
This raises the critical question of whether changing a person's memories in effect creates a different person altogether.It's a question confronted, often painfully, by those close to people who suffer from neurological conditions that affect the memory, from traumatic brain injury to PTSD to dementia: at what stage, if ever, is the original person replaced by a stranger?
In one significant sense, in relation to Alzheimer's disease, the question is now closer to being answered, thanks to research just published by a team led by the Florey Institute's Dr Blaine Roberts.
Roberts' team succeeded not only in quantifying the exact amount of a particular substance that must accumulate in a human brain to produce the full suite of Alzheimer's memory loss symptoms, it also discovered the rate at which it is lodged.
And in doing so, Roberts and his colleagues have opened up a whole new potential treatment strategy. We don't have to cure Alzheimer's, he says. We just have to slow it down.
The disease, which affects over 400,000 Australians, has long been linked with a build up in the brain of clusters of amino acids called amyloid-beta. It is not an alien substance. It is present in every brain, but Alzheimer's sufferers have more of it.
For the first time ever, Roberts' team succeeded in measuring exactly how much more. The figure turned out to be just five milligrams.
Think about that for a second. Tangles of amino acids that collectively weigh less than a grain of rice can make you lose your mind.
"The experiments clearly show that amyloid has a central role in producing neurodegeneration, which results in the inability to remember," said Roberts.
"It definitely has a central role. Is it the only cause? We just don't know."
Certainly, though, it is a reasonable strategy to suggest that because amyloid-beta deposits increase in line with Alzheimer's severity, any method of slowing that increase is worth investigating.
All brains create amyloid-beta all the time. Its precise function in a healthy brain remains unknown – cholesterol transport, antimicrobial activities and activating enzymes have all been suggested. Every day, however, it is flushed away by a waste disposal structure called the glymphatic system. In Alzheimer's patients that purging is incomplete, leaving some of it behind where it collects inside brain cells.
Roberts and his team have discovered that the portion left behind amounts to only two to five per cent of total production. Such a small amount, he said, can be regarded as a "hard target", a deposit small enough to boost hopes of an effective treatment.
More startlingly, the research revealed for the first time the rate at which it accumulates when the glymphatic system fails to its job properly. It is a finding illuminating and chilling in equal measure.
In those destined to develop the disease, amyloid-beta is deposited at a rate of 28-nanograms an hour – every hour, day and night – for 19.2 years before unambiguous dementia symptoms appear.
To compare: a poppy seed weighs ten thousand times more than an hour's amyloid retention. That's 16 poppy seeds, less than one a year, between the start and the point of no return.
"Now we know that number, we can actually make hard estimates," said Roberts.
"If we can detect somebody who is halfway there – say they've accumulated two milligrams of their five – if we can slow down the rate at which they're accumulating this toxic protein by 50 per cent, we know that will extend the onset of the disease by five to 10 years.
"That's the goal. We may never actually prevent Alzheimer's disease. We don't have to completely block it. We just have to slow it down enough to prevent them from developing the disease."
There is a certain balance, perhaps, in the fact that while in one lab at the Florey Institute Blaine Roberts is searching for ways to stop older people forgetting, in another Dr Despina Ganella is looking for ways to help teenagers start.
"Adolescence is the time when the brain is undergoing the most dynamic changes it will go through in the whole of life," she said.
"This is especially so in the part of the brain called the prefrontal cortex, which is really important for executive function and decision-making, and learning."
The prefrontal cortex isn't, in fact, fully wired up until around the age of 28. In the interim, it temporarily loses the ability it enjoyed in infancy: to forget stuff.
As adolescent counsellors readily attest, teenage brains are particularly stubborn things to deal with.
The standard treatment for trauma-related problems is called exposure therapy. Essentially, the patient is exposed to the thing that induces anxiety – spiders, for instance, or air travel, or crowds – in small, repeated doses until the brain no longer associates it with fear.
In a significant proportion of adolescents, however, the therapy doesn't work. In effect, their brains forget how to forget. This not only makes them especially prone to anxiety and depression, but also to drug addiction.
"Although the structure's there, it's not being utilised efficiently, so it's not doing what we see it doing in adults," said Ganella.
In both rat-based models and human studies there is plenty of evidence to indicate that adolescents, as a cohort, have a range of responses to anxiety. While most have some degree of difficulty managing to forget, a few have no problem at all.
And although neurological networks are programmed by nature, nurture has an important role to play, too.
Teenagers growing up in robust and supportive families may well find themselves protected from the weaknesses of their own prefrontal cortexes, Ganella said. On the other hand, kids growing up with adults who are themselves anxious, depressed, addicted or otherwise mentally ill may have a much tougher time of it.
Because if the parents can't forget, what hope do the kids have?
"A lot of mental health issues enlist very early in life and that's very sad, because it's associated with the inability to forget," said Jee Hyun Kim (who is, incidentally, the head of the lab in which Ganella works).
"With anxiety and addiction it's very clear why forgetting is an issue, because with anxiety you are not forgetting about the things you worry about, and not accepting that they're not going to happen again. You can't forget. You expect them to happen.
"With addiction, your body has a persistent memory of becoming high in the presence of your friends. Your body has the inability to forget, so you relapse when you see so those kids again."
Around the world, neuroscientists like Kim, Ganella and Roberts continue to probe the mysteries of forgetting, and how its functions and causes change throughout life.
In one sense, perhaps a poetic one, it offers a sharp distinction between human beginnings and endings.
Babies, it seems, are only too willing to forget what happened yesterday. Teenagers would love to be able to do so. And the 244 Australians who are each day diagnosed with dementia are desperate to not.