(mysterious music)
Currently, scientists around the world
are working on unraveling the last secrets
of our human body.
To do this, they need expertise, super computers,
and a large dose of good ideas.
The proteome comprises the basic building blocks of life.
Worldwide, researchers are uncovering its secrets.
Almost every new therapy and diagnostic, for that matter,
that we're inventing in my laboratory,
ultimately deals with a proteome.
So we have a gained a lot of progress
in genomic research.
But in the end it's still protein.
So if you can measure protein,
you understand what protein does,
then you can understand disease.
Protein is the next generation
because it's not just what could happen,
it's what is happening.
And throughout medicine we've always looked at disease
after it happened.
We didn't ever get to see that process,
and the ability now of looking at the human proteome,
which is new, is giving us a new window, a new dimension
on each of us that really is moving science forward
at an amazing clip.
Can I decode the proteome?
Can it be done?
Yes.
Imagine a car or any machine
with the same complexity as a car.
Is it possible to take a motor apart
in order to understand how it worked?
I believe we'll be able to do that
with the proteome.
But I can't say how long it might take.
In conference calls and crisis units,
medical doctors and scientists
discuss the current ways to best utilize the information
that has already been gleaned.
What has changed since researchers worldwide
began to focus on proteins in the human body?
Above all, this.
Scientists in large clinics throughout the world
like the Charite in Berlin
are increasingly gaining detailed insight
into what happens in the body
between genes and illnesses.
In terms of protein analysis,
researchers have been making enormous progress
in recent years.
The more progress they make,
the more targeted and effective they will be
in diagnosing the major illnesses like Alzheimer's
and cancer.
The Department of Pediatrics at the Charite.
The case of the three year old, Joanna.
Early on she had been diagnosed
with leukemia by the doctors.
Grueling chemotherapy followed
until the family, on the advice of their doctor,
decided to try a new therapy
based on molecular analysis.
It's no longer a trip into the unknown.
In the early days no one knew
where the journey would take us.
But all that is now rather different.
For us, it's simply that now there is an end in sight.
A year ago we had no idea
what we would be faced with.
The therapy was bringing no progress
and last spring things just wen downhill
until we were able to change the therapy
and things started to improve.
Within the shortest time she had made real progress.
Her blood levels were suddenly so good
and the metabolic equivalence
showed that at last things were looking up.
The targeted treatment carried out
on the basis of molecular analysis
can bring decisive progress,
says the director of the department of pediatrics.
The traditional concept of chemotherapy
is in effect misleading.
Chemotherapy works everywhere
where rapid cell division takes place,
but it can't differentiate
between healthy and cancerous cells.
That means there are many side effects
and we aren't able to target every aggressive cancer cell
and kill it off.
Where children are concerned,
there's often regression and illness.
And in children's cancer treatment,
we have healing rates of 80%.
That's gratifying but 20% dying from their illness
is still 20% too much.
And that is our aim.
To reduce this figure and if possible,
achieve a cure rate of 100%.
The developments are based on a groundbreaking
new understanding of the makeup of the human organism,
to which the research team on under Bernhard Kuster
has made an essential contribution.
He was able to catalog more that 18,000 proteins
in the human body, out of which around 20,000
of the genes are built.
The active agents in the living system
are the proteins, because they provide
the controlling elements.
They also provide the structural elements
of the cells and organs,
as well as, in effect, regulating and controlling
all the vital processes.
In so far as the genome is the static structure,
like an archive in which one can relocate information,
the proteins are the active agents.
At the Max Planck Institute of Biochemistry,
Matthias Mann is one of the most influential scientists
working in the field of protein research.
We believe that proteins are more exciting
because they're the ones that make things happen
in the body.
The genomic aspect is so to speak
the blueprint that stores information,
but everything that takes place in the body
is carried out by proteins.
They digest the food.
They keep the structures in place
and carry out all reactions in the body.
In other words, everything that happens actively
does so by means of proteins.
While most genes do nothing
other than reproduce proteins,
their production, protein synthesis,
is an essential function of life.
They ensure that the genome code of the DNA,
our genetic information,
becomes in the end flesh and blood.
For a considerable time
it was thought that one gene produced only one protein.
But today we know that a gene can be the template
for several different proteins.
This diversity can come about
during translation from the DNA,
or through changes in the proteins themselves.
The protein inventory of a cell
is thus much larger than its genome.
It is estimated that there are one million protein variants.
They are life's kitchen,
determining its structure,
how its put together,
which in turn, makes us what we are,
and determines our state of health.
It's the proteins that, for example,
turn normal cells into tumorous ones,
and as a result, determine the approach to be taken
as far as therapies and medicines are concerned.
The campus of the Technical University of Munich.
In the faculty of bioinformatics,
they're looking for a way through the protein labyrinth
to help develop new tools
for the use in the fight against diseases like cancer.
In computer generated models,
the team under professor Rost
is attempting to find ways
of predicting behavior of the structure of proteins.
The first thing the people carrying out research
into medicine wish to develop
is an image of the protein they wish to target.
What it looks like in its three dimensional form.
That is then the first step.
That can take a long, long time,
in some cases up to 10 years.
In the shortest case, it can take three months.
But in the meantime, there are many that can be
relatively quickly established within months.
Back to the Charite.
Joanna is being treated with a new therapy,
a specific medicine that targets and attacks
the cancer cells without resorting to chemotherapy at all.
For the family, this is uncharted territory
with many unknowns.
Just as it is for the doctor
administering the treatment.
That's always the fundamental question
with every patient undergoing this targeted therapy.
A combination therapy would normally be more effective
from an oncological perspective.
So do you feel confident in saying
in this case we're going for a monotherapy,
we're stopping the chemotherapy,
and we'll continue using only the targeted medicine.
To be able to say this you need good arguments,
and I've collected these arguments
for the tumor conference as well.
These are case histories.
In the meantime, there is somewhat more literature
on these patients,
and when you have arguments to say, good,
we see patients who are responding,
then we can have confidence with Joanna too.
You have to have the courage right from the beginning.
For every therapy you use,
from that moment on,
when a doctor says, your child has a tumor,
you need a lot of courage, strength, and stamina.
And during the last year,
taking the decision on that specific medicine
was one that was not too difficult to take
because we had tried various chemotherapy protocols
for almost two years
and none of them were working.
For us, it was always clear that we wanted to avoid
extreme chemotherapy treatments as much as possible.
And that was the case with this new medicine,
and we haven't regretted that decision.
But it's not only Joanna
who's benefiting from the new treatment.
For research into molecular therapy as a whole,
the experience gained with child tumors
is of enormous significance.
Child cancer cases do indeed provide advantages
as models for such molecular targeted therapies
because they're genetically
not so complex in their structure.
That can also be explained by the fact that
with children, environmental factors
have not yet had a long-term impact.
In other words, we have genetic changes
that have been there in the tissue of the tumor
right from the start,
and which have not been further complicated
by environmental factors.
That's why child tumors lend themselves much better
to the study of such concepts,
and to the creation of molecular profiles.
At the same time,
the protein composition of the cells
is of great significance
and it changes continuously.
In contrast to the static genome,
the proteome is dynamic and varies
depending on the age, state of health,
and on environmental factors throughout one's life.
Thus the caterpillar and the butterfly
that develops from it have the same genome.
The difference in appearance is due entirely
to the different proteome.
The same applies to human beings.
If we know the protein composition of the cells
and the current changes,
then that's the key to fighting the affected cells
with targeted medicines,
with new or simpler and smarter already licensed ones
that contain a suitable combination of active agents.
Meanwhile, cancer, neurological diseases, and diabetes,
are no longer viewed as completely distinct illnesses.
It's going more and more in the direction
of no longer regarding illnesses in terms of problems
with the affected organs,
but rather as an irregularity of molecular processes.
And whether we're talking about the heart, the lungs,
or perhaps the bowels or brain,
the symptoms are, irrespective of where they occur,
an expression of the mechanisms behind them.
At least with cancer illnesses they're often the same,
and when we know that, we can develop a therapy end
to treating patients individually for their specific tumors.
Los Angeles.
David Agus has his institute
at the University of Southern California.
He's one of the most renowned cancer specialists
in the USA.
Often enough, he has had to convey devastating diagnosis.
For him and his colleagues,
this molecular analysis, the exploration of proteins,
offers a completely new approach
and the opportunity for a medical revolution.
It's nothing more and nothing less
than a new orientation of our understanding
of illness and health.
A trial happened in breast cancer a decade ago,
which is very emblematic,
is they took women, premenopausal breast cancer,
and normally we treat them and then we stop
and we wait for them to recur,
and we treat again.
Well in this case, after treatment,
half of the women were given a drug
that builds bone, a drug that was meant for osteoporosis.
And half were given placebo.
And they reduced recurrence of the cancer by 40%.
Why?
Because breast cancer goes to bone.
So if you change the soil,
the seed doesn't grow.
That's such a powerful statement,
that my job as a cancer doctor for example,
isn't to target the cancer cell,
it's to change the body.
To me, cancer is a verb and not a noun.
You're cancering.
You don't get cancer, it's something the body does.
And so that's a radically different way of thinking about
disease and health.
Birmingham, Alabama.
This is where Professor Austad and his team
carry out their research on extremely long-living animals,
like mussels, in order to identify targets
for new medicines.
He is convinced that the key to delaying the aging process
and with it, the avoidance of illness,
lies in the protection of the proteins in our cells.
It's the biology of the cell.
If you just thought of this room
with a bunch of folded paper figures
that had a certain function
and they were bashing into one another all the time
you could see how they could slightly start to get out.
Well if that happens to a protein,
it doesn't function anymore.
Not only does it not function,
sometimes it actually becomes toxic, it becomes poisonous
just because it's taking up room
and it may actually cause things to happen
that it shouldn't.
From Alabama, back to Berlin into the Charite.
This is the story of Sabina Grossman.
Six years ago she was diagnosed with cancer.
It was the beginning of a long and difficult journey.
Because for most cancer patients
the dangers of dying lie not in the initial illness,
but from the cancer cells and protein combinations
that elude the initial therapy and return.
That was what happened to Sabina Grossman.
And then came a diagnosis of uterine cancer,
which I had had, or the precondition for it.
And then, yes, I lived in hope that after a small operation
everything would be okay.
But ultimately since then,
nothing has been okay.
Time and again she had to undergo operations
and was given chemotherapy.
She spent months in hospital.
But the recidivous tumors returned.
Since then, her life has been determined by her illness.
And that was very difficult at the beginning.
I really suffered and struggled
and wanted to return to my previous state of fitness.
And then at some stage you come to terms with it.
At least I learnt that at some stage
I would have to live with it,
and that that is the way it is
and that I can somehow manage.
It is now part of my daily life
and I plan my day accordingly
so that I can manage it.
The Benjamin Franklin University Clinic
is part of the Charite in Berlin.
This is where Sabina Grossman
has been treated over the years.
In agreement with the director of the cancer center,
her doctor presented her difficult case
to the tumor conference.
I've certainly spent a lot of time here
and sometimes I feel much too much at home here.
I know my way around too well.
Sometimes I wish it weren't that way.
That's basically the protein we're facing
with your tumor cells.
Quite a high mutation rate
that's affecting various signal pathways.
What that now means
is that we once again see different pathways represented
in which the genetic changes in your ovarian carcinomas
have played a role.
We're able to draw conclusions from that
and recommend certain targeted therapies.
In principle, that would be chemo with tablets
or what exactly?
Well it's not really a real chemo.
These are targeted therapies,
which attack your tumor cells
along these specifically changed pathways.
What's special with these new therapy options
is that we can basically attack the points of weakness
in the tumor cells
and intervene there where these genetic changes
lead to the pathways being highly regulated.
And if we can manage to switch them off again,
we can slow the growth of the tumor.
With the new analytical possibilities
we can now, for the first time characterize
these tumors biologically in a much better way.
And we can also see what, in all likelihood,
lies behind them, which genetic changes determine
the characteristics of the tumor,
and how we can then attempt to target
the weak points of the tumor.
It was in fact my hope from the beginning
that the research would progress rapidly
and deliver results.
Because it was quite clear that we were stumbling
around in the dark,
and that we were trying out therapies
in the hope that they would hit the target.
And the only things that we knew would hit home
were the operations and everything else,
namely what Miss Letsch has already explained,
had been tried out on other cancers.
And all the time I lived in hope
that by some chance, the research would find something
and that there would be new options
because otherwise it becomes pretty clear
where it will lead.
Targeted therapy fights tumor cells
at the molecular level.
Proteins are responsible for the growth of tumor cells
by sending out too many growth signals to the cells.
This is where many of the newly developed medicines start.
They stop the growth signals,
which encourages the tumor to regress.
Almost all tumor medicines are aimed at the cell proteins.
On the way to the Comprehensive Cancer Center
at the Charite.
This is where experts from the various disciplines
come together to discuss a combined strategy.
It is the clinical and molecular tumor conference,
a kind of task force in the battle against cancer.
Doctors, biologists, and computer scientists
make up a team.
Together they discuss new therapy models
in the case of complicated illnesses.
Models based on continuously changing protein systems.
Not only do we have to understand
how complex it is, but also what makes
the tumor cells metastasize and grow.
That's what we have to try and prevent.
While the old domain was to eradicate the tumor cell,
we know that in many cases that doesn't work,
so it's a question of hindering the tumor cells
from growing, reproducing and metastasizing.
It could be that many of us carry tumor cells
within us without becoming ill.
And our aim is to recreate that situation.
It is in fact the case
that a tumor cell is intelligent,
in so far as it can learn very quickly
how to repel whatever we use to attack it.
We learned that already in the 60's
when in the beginning, we only had one single simple therapy
to treat cancers, and this very soon resulted in relapses,
simply because the tumor cells find mechanisms.
For instance, they can activate pumps in their cells
which are able to filter out the chemotherapy medicines,
and in this way, ensure they're no longer vulnerable
to these chemotherapies.
And there are numerous such mechanisms.
We have to understand what the proteins
in the tumor cells do on the working level,
and look specifically at what sort of intervention
we can initiate that won't damage the body,
but at the same time will neutralize this program
of the tumor cells which allows them to grow unhindered
and metastasize.
I can see clearly here that this is normal mucosal tissue.
And here a tumor nodule is growing inside
the healthy tissue.
And then you see that the cell nuclei
look very different.
That tells us that the cells are not healthy.
While here in the normal tissue
they appear to be uniform and have specific characteristics,
and these areas of tissue,
we analyze them at the protein
and molecular biological levels.
I can only put it that way
but a pathologist will understand it.
The basis for that is,
as it has always been, a classic tissue analysis.
On our way to the Charite's Pathological Institute,
this is where they are attempting to identify
and understand cancer cells.
In Professor Klauschen's laboratories,
they're examining and preparing patient tissue samples.
The aim of the scientists and laboratory assistants
is to be able to recognize the cancer cells
and make an assessment of them.
It's absolutely essential that the colleague
who takes the tissue sample of the lung
recognizes clearly which area contains the tumor
or the pathologically relevant lesion
so that he can cut out a sample precisely there
to undergo further procedures.
In the Charite's pathological department,
the tissue samples are prepared.
They are finely sliced and died
so that a morphological assessment of the tumor
can be made.
That is, in terms of their form and structure.
Here we can see the cells that look, we can say,
very pleomorphic.
That means that the nuclei all look very different
in terms of their form and size.
Here we have tumor cells
and they're surrounded by lymphatic tissue.
That means we have here a lymph node metastasis
of a carcinoma.
The classic laboratory analysis is,
as it has always been,
the basis and reference point
for the new molecular analysis.
The samples are processed further
so they can be evaluated
during the histopathological examination.
Are the tumors malignant or benign?
This is the last stop in terms of classical tissue analysis
as it has traditionally been done.
The new part comes next.
The cancer cells are examined
in molecular analysis as to their specific characteristics.
Where has the DNA undergone change?
And which proteins produce the cancer cells?
Each patient's specific tumor
is given a molecular profile.
This tumor profile is what has to be counted.
The starting point of our work
is the questioning by the clinician
who has a patient with a suspected lung carcinoma
for which there is possibly a good
and tailor made therapy available.
That's why they send the patient's tissue sample
to the pathology department.
We can then sequence the tumor's DNA
and check it for relevant modifications
that are known to us from scientific and clinical studies.
After that, our work is tailor made to the case at hand.
With exactitude, the extent and depth
of this analysis, our knowledge of detailed life
within the tumor increases.
As a result, we receive a mass of data.
When you examine these tumorous cells in depth,
every patient is different.
Each tumor in each patient is different,
and with that many patients, each metastasis is different
and we can't work with that.
We need big data, that is we need to note
all these changes.
In some tumors there are thousands of mutations
at the genetic and protein level.
We have to feed all that into the computer
in order to discover underlying principles,
and then again recognize commonalities
and be able to create computer simulations.
What happens if we neutralize a protein?
What happens in this network?
That's really advanced mathematics
that requires much bigger and faster computers
and people who understand them and can program them.
Berkhard Rost is a pioneer
in the field of bioinformatics.
Without specialists in computing,
developments in research in medicine would be impossible.
If researchers attempted to discover possible
protein-binding partners by experimenting,
they would be fully occupied for decades.
That's why it's essential to develop
an automated procedure.
During the last 10 years
biology has been transformed.
Biology was a science in which the experimenter
would have a particular hypothesis,
and then they deliberated as to how best
they could set up an experiment
in order to established whether it was true or not.
All energy was channeled into that
to try and prove whether the answer was yes or no
to a particular question.
During the last 10 years
that method is being increasingly replaced
by these high through put experiments.
There are experiments that provide me
with a mass of data, but none of these items of data
enables me to say yes or no.
All in all, they may give me something of an idea
how it could be, and that is a context
in which it would be impossible without bioinformatics,
because none of these experiments gives a clear answer.
Without enormous computing
and storage capacity it would be impossible.
And the flood of data is expanding continuously
and exponentially worldwide.
An incredible amount that has to be converted
into useful information if we wish to develop
suitable therapies and medicines.
But the data alone will tell us nothing.
It immediately goes back to bioinformatics.
To the question of what the data means.
What is its significance?
How can I link the data that already exists,
turn it round a little so that it becomes relevant
to my experiment?
In the Swiss Institute of Bioinformatics
in Geneva, they are attempting to master the data.
It is one of the most renowned institutes
in the world working on bioinformatic issues.
Here, for the first time, computers have been used
that are normally employed by Echelon,
the global US spy network,
that has scanned enormous amounts of information
in the search for suspicious words.
Immense quantity of data is too big
to look at it just like people used to do in experiment.
Look at the results with their eyes
and extract conclusion from it.
When you do any type of, for example,
of proteomic studies, you generate a massive amount of data
and you need computers to analyze this data,
to get from this massive data,
what are the important points
for the scientists to look at?
And that requires bioinformatics.
You go from a mass of data, it's like a pyramid,
and at the top of the pyramid you've got knowledge.
And getting from data to knowledge
means computing, extracting things,
throwing out things which are not interesting,
and getting to the gold nuggets,
which are the important knowledge items.
For the research, the Swiss Prot Group
is of existential significance
and forms the UniProt centerpiece,
the largest bioinformatic data bank
for the proteins of all livings organisms.
150 biologists and computer experts
are working continuously on the maintenance
of this unique protein data bank.
It encompasses not only information on the composition
of specific proteins, but also what is known
about their biological function.
If I want to know which protein does what
in a disease, you will actually come to UniProt.
You can come to this database
to understand how it works.
Because it's a reference, it becomes like
an encyclopedia, as I said before,
which sets pretty much the ground.
Now if you have certain type of mutation
that you might see for a genetic disease,
you might actually relate that
to the information that we capture.
So basically in the big data field
you need to have reference sets.
And those reference sets is what we provide in UniProt.
Berlin.
Hans Lehrach carries out his research here
at the Max Planck Institute for Molecular Genetics.
It is one of the leaders in the area
of personalized medicine
because the logical next step
leads to the situation of new therapy models
on the basis of this data and new insights.
The battle against tumors is a very difficult problem.
But one of the tools that we are now trying to create
is the use of exact molecular characterization
of each tumor and of the patient
so that we can try out every treatment.
Every treatment option on a computer model.
Whereas we can only try out very few medicines
on the actual patient,
on a computer model of the patient of course,
we can try out 10,000 different medicines,
and medicine combinations
without damaging the patient in any way.
And at the same time avoid incurring huge costs.
On our way to Alacris Theranostics,
Hans Lehrach's firm analyzes the genes and proteins
of patients.
From each one, computer models of the cancer cells
are created, including all individual molecular changes
and peculiarities.
Here in the laboratory the DNA samples arrive
and we isolate the genetic material.
Then the next technical step is that in practice
we split this DNA into small fragments.
Once the DNA has been prepared we load it into
the sequencing apparatus
so that we can decipher the changes
or the changes in the sequence.
In order to build the models
we have to have the data
that's then incorporated into the model.
And the data is obtained from a rough analysis
of the sequences.
We can then transplant this
into the network model and look for functional consequences
or test out medicines, which, in this model,
could have a potential effect or not.
Or combinations of medicines that either have
or don't have the desired impact.
The perspective is to create
the whole personal avatar on a molecular level.
In the near future, we could have a simulated
model like this of every individual.
The challenge that faces us,
especially in the field of oncology,
is the fact that with cancers, every tumor is different,
every individual is different,
has a different genetic background.
The changes in the tumor vary considerably.
When we look at a lung cancer or a brain cancer,
the variations between patients are so wide
that each patient in essence needs their own
specific treatment.
With the computer model we depict the biochemistry
that takes place in the cell
and basically depict each single step of a reaction,
how a particular gene is synthesized
into a particular protein,
and how this protein later, together with other proteins,
is able to interact and construct the cell signal network.
The model we have at the moment is a cellular model,
but we can already visualize complex
multi-cellular systems as in a cancer.
We can do this because we have several parallel models.
We can envisage that we'll have a physiological model,
or a whole body model of a patient.
However, to reach that point it'll be a long road
and an enormous amount of work.
It'll be the result of a cumulative effort
by many working groups and many firms.
One of the pioneers involved
in the tracing of proteins was Professor Matthias Mann.
His team works at the Max Planck Institute
of Biochemistry in Munich.
His methods have revolutionized protein research.
Without his fundamental research, proteomics wouldn't be
where it is today.
Above all, it was the developments he initiated
in the field of mass spectrometry
that made the mass measurements of proteins at all possible.
The methods he devised are used worldwide today
as standard procedures in Los Angeles as well as in Beijing.
The big problem for proteomics was that
it was very slow and not very sensitive.
We couldn't detect the existence of many proteins.
With these developments it became possible
to detect lots of proteins,
and this in turn provides us
with the biological information, the medical information.
If we only had 10 proteins,
then we wouldn't learn a great deal from that.
But today we can determine 10,000 proteins.
Matt gives us a global overview
about the exact condition of the cell or patient.
Bernhard Kuster's team,
with the identification of more than 18,000
genetically coded proteins,
has achieved another significantly important step.
Investigation has shown that around
10,000 different proteins are to be found
in cells and organs, which control and represent
all vital functions, and are therefore like life's kitchen.
In the meantime, we are now able to identify
the central proteome of various types of cancer.
We know more or less exactly how many proteins there are.
But at the same time, we don't know what thousands
of them do exactly.
That's why we are in the first instance
interested in compiling a map
in order to see which proteins there are all together,
where they're found in the organism,
and how many of them there are.
And ideally that would lead us to an understanding
of what needs to be done.
Some of these proteins have already been well-researched.
Thousands of them not at all.
Time is of the essence.
Precisely in emerging societies like China,
the synthesis between fundamental research,
big data, and the experimental testing
of active agents and active agent combinations
is essential if we are not to lose control
over the so-called diseases of civilization.
China's population is, with 1.3 billion people,
60 times bigger than that of Germany's.
If there are annually around 500,000 new cancer patients
in Germany, then in China, by comparison,
it would be 30 million.
For that reason also, 2.3 billion dollars
have been invested in a new scientific complex.
We have this five year plan.
So now is the 13th five years plan.
So you will notice the first floor
are the mass spectrometers on the first floor.
The second floor, the third floor
are all for wet biology, cell biology,
molecular biology, those type.
And the fourth floor is the bioinformatics.
So our super computer is in the fourth floor.
At the Beijing Protein Research Center,
they're concentrating on resources,
personnel as well as technical.
And today we are globally networked
because the problems are too big to be solved
at a national level.
One of the particular project I work on
is gastric cancer.
Gastric cancer is the number one,
or number two killer in China.
It's a big problem in East Asia.
Proteomics in combination with big data
has become a new standard worldwide
in the researching of all major diseases.
In this way, scientists are coming
to completely new insights,
even concerning the most complex human organ, the brain.
Edinburgh in Seth Grant's Institute.
He's looking at the proteins that are responsible
for some of the more common and devastating illnesses
of the brain.
Here is on the post-synaptic side of the synapse.
And inside there, I would have these molecular machines
situated inside and there is
actually hundreds of those molecular machines
inside this post-synaptic side of the synapse.
So we have a hierarchy from genes to the RNA,
which then makes the protein, which then makes the complexes
and the super complexes, and those are then packed inside
the synapses, and it's those molecular machines
that are controlling innate behaviors,
learned behaviors, and they go wrong in different diseases.
And it's quite simple to explain how they go wrong
in different diseases because many diseases
cause a mutation in a gene,
which causes this protein to malfunction
or not be built properly,
which means that complex now malfunctions,
and that super complex now malfunctions,
and now the synapse malfunctions.
And that's why people with those mutations
end up with psychiatric and neurological disorders.
The understanding that the synapse
has a large number of proteins
and that there is organized into molecular machines
has caused a transformation in the way
we think about brain diseases.
Now, we know all of the proteins in the synapses.
And in the year 2011,
when we characterized all the proteins in the human synapses
we found to our great surprise
that there were gene mutations
that are responsible for more than
130 different brain diseases
that encode these synapse proteins
and these molecular machines.
And when those mutations interfere
with the function of the gene,
it interferes with the function of the proteins
in the molecular machines and causes these 130 diseases.
No longer isolated observations,
only a comprehensive approach promises success.
We have to imagine the human organism
as a very complex processing system.
You can tinker with a single gene
and increase their longevity by as much as 50, 60%.
We understand some of that
but one of the things we're realizing
is that what goes on inside of a cell
is a complicated network.
It really needs to be addressed as a system
because like any intricate system,
like inside of a radio or a computer,
if you remove one thing, you have many, many effects.
Or if you add something else you have many, many effects.
So what we really need,
we really need what they call a systems approach.
An approach to understanding
the entire molecular network inside the cell.
There is one thing of paramount importance.
Proteins are exactly like humans.
They are not isolated beings.
They work, they live in networks,
function within networks,
and if I wish to understand a protein,
then I have to understand how the protein cooperates,
with whom, how the networks are formed.
And networks are something that I can look at experimentally
and on the computer.
But the experimental methods provide uncertain testimony,
so that I have to combine this with computer models.
Boston.
The location of the famous Harvard University.
This is where George Church works,
one of the most famous of today's geneticists.
He is renowned for his research in the field
of synthetic biology,
a biology that combines in new ways
the building bricks of life,
or constructs them artificially.
The human being as a protein construction kit
and the researcher and doctor as the necessary engineer.
We're now composing an atlas
of all the different kinds of cells in the body
and where they are, how they're connected.
Essentially producing not just a road map
but a recipe book that tells us how to make
any cell in any organ on demand.
We can make proteins in a laboratory and then deliver them
to people, or we can make them in the person,
essentially make the manufacturing of the proteins
occur within the person typically through gene therapy.
But do we want all this?
The manufacture of exchangeable parts
on demand for man, the machine.
The Medical Institute at the University of Vienna
where Professor Markus Hengstschlager
works and teaches as a geneticist.
He is a member of the Elite Scientific Advisory Group
appointed by the pope and is today
a member of the Austrian Ethical Commission.
I foresee a situation in which nano technology
will lead to micro machines coursing through our veins
and arteries that can provide us daily, by the minute,
with a picture of our complete physiological condition.
What's our cholesterol level?
What's the general situation
as far as our fat metabolism is concerned?
How is our liver working, etc.
That's the first step.
And then it'll be possible to look at our watch
to register when a heart attack is about to take place.
And this watch will simultaneously pre-book
a bed in the hospital and call the ambulance.
As the next step, I foresee perhaps a few decades later
that these machines will also carry out
the appropriate therapy
if the therapy can be concentrated to the point
of being transportable.
Then we can entertain the idea,
and now I'm being a visionary,
I'm imagining the future,
that this watch will be able to tell you
that you'll possibly have a headache in the next 10 minutes,
but we'll add that if you allow it to dispense
a certain medicine at a particular location,
then it can make sure you won't have a heart attack at all.
There'll be many things I can think of
that will be technologically possible, I'm sure of that.
The question is whether we as human beings
will benefit from this,
or whether, and this is again an ethical question,
there are good reasons for saying we don't want that.
It'll only create more problems rather than benefits.
Will we be able to come to a consensus
about what we wish to have
and what we will not allow?
(curious piano music)
One thing is clear.
As a result of worldwide exploration, research,
and medicine have virtually in real time
achieved insight into the complex system of the body.
How complex is revealed by looking at the protein profile
of a drop of blood.
Proteins are conversation or words.
So this is the conversation in the body
and for the first time ever,
we can visualize this data, the system,
or the conversation in the body.
Through the collection of increasingly
more exact knowledge, we will be able to intervene
more rapidly and effectively when any irregularity,
a disease, threatens the body.
So before, we were looking at DNA.
DNA was the root of everything.
It's the only thing in science we ever got right.
Protein is the next generation
because it's not just what could happen,
it's what is happening.
It is absolutely necessary
in the interest of the survival of society
to develop more intelligent and more secure
model-driven medical and preventative policies.
I can predict that a disposition exists
that can lead to a certain disease like for example cancer.
Then I can perhaps predict
where I could intervene in this protein circulation,
in the protein network,
to regulate it and avoid the disease happening.
And I do believe this.
It would be a positive outcome.
Today we have a large scale global map.
We see the rough picture, the countries and the continents.
Where we want to go is to create a very detailed map
in which every house, every tree, every road
is clearly recognizable,
and that should definitely be achievable
within the next 10 years.
(curious piano music)
I do believe that we'll make quicker progress,
and I would say cautiously
that every five years we'll have control
over a higher percentage of these tumors.
We can see that it's engaging
and that we are having increasing success,
and then the following will happen.
We will start to see the mechanisms
in other patients, and that will lead
to the introduction of completely new impulses
into classical medicine.
In the project to decode the proteome,
scientists worldwide have taken the road together
and worked to better comprehend
the complex building blocks
that make up the human being.
And through the necessary symbiosis of protein research
and big data we will perhaps
be better prepared for diseases.
With model therapies, new medicines,
perhaps to the point of even achieving
a deceleration of aging itself.
Discovery that maintaining the proteome
is a key component of aging,
is the most exciting work that's going on
in my lab right now.
At the same time there are diseases like Alzheimer's
where we're making critical understandings of.
So we're gonna be able to prevent
and reverse those diseases.
So whether dementia be from vascular
or whether it be from Alzheimer's,
we're gonna be able to make an enormous impact
in the relatively near future.
So it's a new era in medicine
and I truly believe we're all lucky to live now.
(mystical music)