Last
10th of April the prestigious journal Nature published a novel imaging
technique that allows the visualization of intact brain tissue in 3D. By
getting rid of the lipids and using a polymer to fix the rest, the structure -with
all its proteins and nucleic acids intact- can be preserved, while the whole
tissue becomes transparent.
The
paper had considerable media impact, and the following day the invisible brain
was taking the online front page of many of the most popular newspapers
worldwide. The opening of the article at the abc science site stated: “The era
of slicing and dicing for neuro-researchers is over with the arrival of a
see-through brain”. Incredible!
I
immediately sent an email with the news to the whole institute, and then I headed
towards the INI kitchen…. Although my skeptic self was trying to push this idea
away, I feared for a moment to find Rita, John and Simone moaning in agony
while looking with nostalgia old EM pictures at the screens of the zamel
computer. Fortunately, I did not encounter this scenario, but I saw Nuno, who
was preparing his morning coffee with his usual calmness, something that
surprised me a little.
-So
Nuno, did you hear about the news??? - I asked anxiously.
-What
news? - He replied, with his eyes reflecting puzzlement behind his rounded
glasses.
-About
this new method, CLARITY! –I exclaimed- is it such a breakthrough??? Is the tedious
EM going to be replaced forever???
-Oh…
that …– Now his eyes had a sparkle of understanding, the same one that
grandfathers have when children ask them too many why’s in a row- No no, it is
not going to replace EM. It is an important new technique of course, as it
offers some advantages, but we will still need the old methods to properly
assess connectivity.
-B-b-but
the news… - I bubbled. The sparkle at his eyes got stronger, but this time I
could also see on it a trace of resignation.
-I
know… -he said, and he accompanied that gleam with a half smile.
That
day I found myself carrying the sparkle all over the INI. I was all the time
being stopped by other excited master students, who had read the news and
wanted to know more about this new and promising technique. We decided then to continue
the discussion at our student’s monthly Apero, and to invite Nuno to talk about
the real implications of the method.
Because
of the transcendence of the discussion almost all of us were present -although
I suspect that Asim and Dennis cooking abilities had also something to do-. After
an hour of objective analysis, these are the main points that we extracted:
-The
technique allows for deep light penetration imaging, as the processed tissue is
transparent. This seems very promising
because 3D reconstructions can be made without slicing. One limitation however,
is in the optics. Lenses that have a high numerical aperture -which will give
you the resolution to image boutons- and large working distance for deep
imaging are needed. As the authors themselves state in the paper: special adaptive
optics for CLARITY need to be developed.
-The
biggest limitation however comes from light microscopy itself. You cannot have
as much resolution as EM, because a physical limit imposed by the light
wavelength exists. EM would still be needed to image at the synapse level. The
authors, aware of such limitation, manage to combine CLARITY with EM. Yet
another problem arises here, as the lack of lipids makes the characterization
of the synapses difficult.
- One
of the main advantages of the technique is that it allows for molecular
phenotyping while preserving the tissue intact for imaging. Furthermore, as it
is very permeable-because of the lack of lipids- the proteins are more
accessible, making the process way more efficient. The stability of the rest of
the elements in the polymer also allows phenotyping for several rounds.
-
Assuming that the adaptive optics problem is solved, it will be very useful to
track long-range projections. The brain doesn’t need to be sliced, something
that will make the reconstruction faster. However, if you additionally want to
have information at the synaptic resolution, you need to use EM on smaller
volumes.
From
the points above, we see that this new technique presents some clear
advantages. It may help us characterize brain circuits faster, but the key
question here is, in Nuno’s words: how much faster is it going to make us? CLARITY is great, but it is obviously not the
goose that laid the golden eggs…
A couple
of weeks after that event I received an email from my mum. She was asking me about an article she had
read at the newspaper that claimed: “Spanish researchers open a new path to
prevent and mitigate epilepsy”. As you
may imagine, the sparkle came back to my eyes… In order to confirm my
suspicion, I decided to check the original article. On it, the authors
demonstrated that the transcription factor ATF5 is implicated in neural
stress-induced apoptosis. By increasing ATF5 levels neuronal death was
prevented, and as a model, they were using status epilepticus-induced neuronal
death. I would define the correlation that the journalist made between this piece
of research and its implications for epilepsy as “brilliant”. I proceeded then
to write back to my mum, stating all the set of reasons that would turn the
golden eggs goose into a humble fowl. More that an email it looked like a
dissertation, so I don’t know if my mum actually ever read it...
The
following week, however, she was sending me a pile of articles -you have to
imagine me sighting now…- hoping, I guess, that I would approve at least one of
them. I didn’t. This time they were related to Parkinson or maybe Alzheimer, apparently
it doesn’t seem to make much of a difference. In all the cases, an excellent research
gets conveniently filtered and embellished when fallen into the media circus. This
is passively observed by the authors, who I assume find themselves “trapped”
into the middle of the situation. Quite convenient I would say…
Nonetheless, you may ask, isn’t media impact something positive for
research? Doesn’t it bring social awareness and gives importance to our work?
Of course! And that should be promoted. The difference is in how we do it. And
the key question in here is the following: Do we want to be more the herald or
the storyteller? Are we willing to
sacrifice our personal glory in favor of the future of science? This is something
we all- the present and the future scientists- should keep in mind if one day a
journalist knocks at our door. Otherwise
we take the risk to become, inevitably, the boy in our own tale, and it will no
matter how long we keep crying.
- S. Soldado Magraner
