Francisco M. Mojica is a microbiologist from Alicante, Spain, where he did his PhD and where he still teaches. He was the first to publish the workings of the CRIPSR-Cas system which has in recent years taken biomedicine by storm due to its many potential applications. Mojica, who recently received the Jaime I award for basic research, came to the PRBB to explain the history of CRISPR and what it means.
How did you discover CRISPR?
It was 1993, during my PhD. I was studying how halophilic archae survive the high salinities of their habitats. Analysing their DNA, I found some sequences that seemed to be repeated up to 600 times in a row, with spaces in between, which was very weird. After publishing this, we saw someone else had found them in a completely unrelated microorganism, E. coli, a bacteria species that lives in our bodies, and we thought these repeats had to be important. So, after my PhD I set to study them more in-depth. After 10 years, I found out the ‘spaces’ between the repeats where actually sequences from different virus that infected the bacteria, and that bacteria with a specific ‘spacer X’ were immune to ‘virus X’, while those without that spacer could be attacked by the virus.
It was August, I was on holidays next to the Salinas de Santa Pota in Alicante – just where the archaea I studied 10 years earlier had been first isolated from! I’m not a fan of too much sun and decided to go to the lab with the aircon and do the DNA analyses. It was then, alone in the lab, that I realised this had to be the bacteria ‘immunity system’. I immediately went to my wife: she’s not a scientists but said “looking at your face I know this must be important!”. I told her one day, this would get a Nobel Prize. But the publishers weren’t so excited. The article was rejected from Nature and four other journals. But we knew better. In the cover letter we said this finding “could have tremendous applications in biotechnology, biology and clinical sciences”. Although I never imagined what was to come…
Where is CRISPR present, and how does it work?
It’s pretty much in all unicellular organisms: archaea, bacteria, but also in plants and even viruses! To understand how it works, let’s say it’s like if bacteria, for example, took pictures of the viruses that attacked them and kept a photoalbum of them. Then when they are attacked by a virus, if they have a picture of this virus, they will be resistant to it. The actual way it works is that when the bacteria is infected by virus X, the ‘spacer X’ (the photo) is activated, binds to the genome of virus X and calls the Cas (CRISPR associated) proteins, which then cut the genome of the virus X at the specific site where the spacer X is bound.
And why has it become suddenly so important?
That specificity and ability to cut make it a brilliant tool for genome editing! It didn’t occur to me at the time, because I was thinking only of bacteria, but once Jennifer Doudna and Emmanuelle Charpentier showed the system was able to function in vitro, and the Feng Zhang’s lab made it work in mammalian cells, applications kept on coming and the publications about CRISPR have grown exponentially!
Can you give us a couple of examples of these applications?
The most talked-about is genome editing. You see, in viruses, if their genome is targeted by a spacer and cut, they die. But in eukaryotic cells, for example in humans, there are systems to repair a cut DNA. So one could create a ‘spacer’ that contains a change you want to introduce in a gene – for example, to correct a mutation – and then you introduce it, together with the CRISPR-Cas system, into the cell to be corrected. The spacer will find its complementary sequence and call the Cas protein, which will make a cut. And then the cell repair system will mend that cut, and copy again the missing DNA sequence – only that, when copying, it will introduce the change you have sent in the spacer. This could be used to correct mutations that cause diseases, or to excise an HIV sequence from a cell, as a recent paper showed!
But there are many other potential applications; using it to study the function of genes, or making bacteria that are resistant to several viruses, which can be good for some biotechnology applications.
How has the CRISPR revolution affected you?
Lots of people with genetic problems now call me to ask how I can help them! I’m not a doctor, so I can’t really tell them much, except that this will take years… but truth is things are going so fast! The 1st clinical trial of CRISPR in humans has already started. They will modify T cells from patients to make them able to attack cancer cells. It’s really amazing. It makes me feel so proud of having been part of this.
Have you changed your focus of research to concentrate on potential applications of CRISPR?
No – I’m a microbiologist. I’m still interested in understanding how this system works. The part that is used as a tool is perfectly characterised, but we still don’t not known how bacteria acquire this immunity, and how they distinguish between the virus DNA and their own DNA. I would like to find out, to know for the pleasure of knowing. If there are practical applications, great. But it’s not my aim.
The CRISPR story is a good example of how basic research can lead to unexpected advances in practical terms…
Yes! And sometimes open, non-directed basic research may have more amazing outcomes than that targeted for a specific aim. For example, the CRISPR-Cas is a whole immune system, with the ability to adapt, to ‘take pictures’ of new viruses. Imagine we could transplant it to a person and that it worked for them like it does in bacteria. It would be immunisation à la carte for any living system! But for this to happen, we would first need to understand how it works in bacteria, why they don’t attack themselves… That’s my job.
Rebecca Lawrence has worked in scientific publishing for over 15 years and is currently involved in several international associations and working groups on data publishing and peer review. Rebecca was responsible for the launch of F1000Research in January 2013, a novel open science publishing platform that “uses immediate publication, transparent peer review, and publishes all source data”. She came to the PRBB to talk about the future of scientific publishing.
What are the current challenges in scientific publishing?
One is the delay between the moment you’re ready to share the science and when it actually gets out there and others benefit from it – it can take from 6 months to a year, or even as long as five! In the digital era this makes no sense. Another is the bias in the peer review, which is inherent to the process because those who review your work must be experts in your field and are therefore likely to be competitors.
Lack of data sharing is a huge issue. In a paper we usually don’t see the raw data that backs up the conclusions, we just take it on trust that the analysis has been done in the best way. Really, the core of the paper should be the data. And finally, a vast amount of results, particularly negative ones, are not being published – we are building the next generation of science on facts that are wrong or at least incomplete!
What can be done to resolve these issues?
We need transparency, and that’s what Open Science advocates, trying to make everything – the article, the data, the software and the review process – as transparent as possible. We now have the tools and it is cheap enough to share all the findings and data, although obviously we need to ensure that this is done in a useful way!
What are Open Science’s potential challenges?
Many researchers are nervous about sharing their data, because they don’t want to give a potential advantage to competitors, but actually you can get priority on the data if you openly share it. And it can be time consuming to sort your data out in a way that is understandable and usable by others. But if you don’t sort it out properly, in five years’ time even you won’t be able to do anything with it!
What can be done to entice authors to share data?
We need to give credit for the data. When people are better recognised for creating the data they will be happier to share it. And this is happening: many journals have started citing datasets properly in the references and we have launched a project with several international standards organisations to help develop dataset-level metrics.
How does F1000Research fit in with all this?
We are using a completely new publishing process that is fully transparent. We offer immediate publication, following a set of basic checks, and then it goes out to invited expert referees. The names and reports of the reviewers are published alongside the article and we also make our reviewers’ reports citable, to provide our referees with additional credit for their work. Finally, we strongly encourage publication of negative and null results, replication studies, all kinds of studies.
Joan Steitz, professor of molecular biophysics and biochemistry at Yale University and the Howard Hughes Medical Institute, came to Barcelona in January 2015 to participate in the CRG faculty retreat. Considered one of the founders in the field of RNA biology and world-renowned for her many seminal contributions, she is also a prominent activist, promoting scientific careers for women. Mother to a son who followed in her footsteps and wife to a Nobel Prize winner, during her stay at the PRBB she gave a talk about her research into non-coding RNAs and participated in a round table about women in science.
Is science a particularly sexist field?
Not really. I would say it’s comparable to law, finances… all high-pressure and competitive professions seem to have the same problem! Actually, a recent issue of Science shows that the most sexist fields seem to be those which people think you need to be a genius to work in – like physics, and even philosophy! Within science, the biosciences are typically viewed as the most gender-balanced.
When you started, there were virtually no female role models in research… how did that affect you?
Well, as student and even a postdoc, it didn’t even enter my mind that I would become a group leader! I was shocked when I had a job offer. Molecular biology was a new field and there were hardly any US universities that had molecular biologists, so that helped. But I didn’t feel prepared for it at all! However, I always like to rise to challenges and I thought if someone can do it, why not me? But it was scary. There were only a couple of other women at Yale at the time.
Have you ever experienced discrimination due to your gender?
I have seen terrible things happen to others but I have only experienced minor issues. Probably like a lot of women in my generation, I feel I’ve been very lucky and escaped major discrimination.
How has the situation improved over the last 20 years?
Things haven’t changed enough, but they have changed incredibly! There used to be very overt discriminatory comments. Now everyone is more sensitised and these things are not said overtly – that doesn’t mean they are not said in private, at dinner tables, for example. And women still get paid less than men for the same job. So we’re still not there.
What can be done and who should do it?
All we have to do is increase the number of women in science, because being in the minority is definitely not helpful; it’s part of the problem! I don’t know how to do that, though. But changes should come from the top. I’ve seen things improving with a new director, only to go backwards again with another. Also, funding agencies and governments should collect information about the percentages of women applying for and getting grants, make it public, give it to people who are taking the decisions, use it to compare over time and see how things are changing. We need to keep an eye on this.
Some countries are better than others…
A good example is the “120% support grant” in Switzerland. A female researcher who has a small child can choose to work part-time and have a 20% reduction in her salary. She then receives 40% of her salary from the government, which she can use for hiring someone to help in her research, or for child care.
There are implicit bias tests which have uncovered really impressive things. You don’t realise how biased you yourself are and how subject to stereotypes until you do the tests. So, I would suggest all researchers do them and reflect on their own attitudes! Maybe part of the change can come from within.
“Cancer prevention requires the vision, courage, and political leadership to make long term decisions”
Christopher Wild has been the Director of the International Agency for Research on Cancer (IARC), the cancer agency of the World Health Organization (WHO), since 2009. Married to a neuroscientist and father of three, this epidemiologist and Man United fan came to the PRBB in March to give the 3rd Global Health session co-organised by ISGlobal, CRESIB, and CREAL.
How has the burden of cancer changed over recent years?
The incidence of cancer globally has increased: there were 14 million new cases in 2012 and it is expected we will reach 24 million new cases by 2035. Also, about 70% of the world’s cancer deaths occur in low- and middle-income countries. This is due to the rise in population sizes and average life expectancy in general, particularly in these countries, but also because they are shifting towards ‘industrialised’ lifestyle habits such as increased smoking, alcohol consumption, unhealthy diets, obesity and lack of physical exercise, which we know are linked to cancer.
Who should ensure decisive action is taken against these known risks?
First the researchers need to provide reliable scientific evidence on which to base decisions. Once the scientific evidence is available it is down to national authorities to make informed regulatory decisions. However, scientists can probably explain the interpretation of their findings more clearly when presenting them to decision-makers.
Why is prevention so hard?
There are different elements involved. First, intervention may require co-ordination across different parts of government and society. Second, there are often infrastructural, economic or cultural barriers. For example, in some developing countries, vaccinating against human papilloma virus to prevent cervical cancer might be interpreted as a signal of sexual promiscuity. This is why I think much more research has to be conducted on the factors which affect the implementation of prevention in routine healthcare settings. This is an often neglected area.
Finally, sometimes the case is not made politically and there is a failure to translate scientific evidence into guidelines. One of IARC’s important jobs is to evaluate prevention strategies, to find out what works. This research must be independent of vested interests, and here the position of the Agency within the UN has a major advantage. It also gives us the opportunity to improve the translation of knowledge into action at the level of individual countries.
Where do we need to invest more in the fight against cancer?
Prevention is central to reducing the rising trend of cancer, and we know that more than 50% of cases could be prevented if what is currently known were to be implemented efficiently; if governments took strong action, such as enforcing anti-tobacco controls, ensuring vaccination against HBV and HPV, promoting healthier lifestyles and improving access to health care including the early detection of breast, cervical, and colorectal cancers. But investment in prevention requires the vision, courage, and political leadership to make decisions and financial commitments that will bear fruit, often many years in the future.
You can read a related post here.
Kim Nasmyth, 63, is a renowned researcher who co-discovered cohesin, a protein complex crucial for faithful chromosome segregation during cell division. Amongst other prizes and distinctions he is a member of the European Molecular Biology Organisation (EMBO), a fellow of the Royal Society and a Foreign Honorary Member of the American Academy of Arts and Sciences (AAAS). The British scientist has been director of the Institute of Molecular Pathology (IMP) in Vienna for seven years and is currently the Head of the Biochemistry Department in Oxford. This chemist with a passion for climbing visited the PRBB last November.
Many of your students have become very successful scientists… what are you like as a mentor?
I have to admit I am not very sympathetic, I don’t go around holding hands with my students. But I help them think clearly, to set their sights high, expect a lot; but also to distinguish between what is achievable and what is not. I try to teach them to strive to give an explanation, not only to produce data.
What is science for you?
I believe the driving force behind science is realising there is a problem: it is what I call the “Apollo 13” symptom. On the other hand, the most dangerous thing in science is to believe you have learned everything, that you can explain it all. In science, the more you learn, the more questions appear. A little bit of knowledge generates a great deal of ignorance. And I think that is what defines real science: that each question you ask, when answered, raises all sorts of other equally, if not more, interesting questions.
You share the motto of the Royal Society: Nullius in verba, take nobody’s word for it. Do you think science can help create an evidence-based society?
I think the scientific way of doing things and a scientific mindset should play a major role in this. But at the moment I believe science is in crisis, as pointed out by a recent article in The Economist. The career we have set up for scientists is encouraging a type of researcher interested only in pleasing their peers, and not in pursuing the truth. We have lost our moral compass, because we have lost our belief in God. We can’t forget that many great scientists of our time were religious, and that helped them to keep to the truth; the fear of burning in hell if they did not do this. We have lost that fear, and now we need to recover that morality without God.
Perhaps scientists have lost their morals, but isn’t there a control system for published research?
Yes, we have control by peer-review but this is such an amorphous global concept. We’ve lost control by the closer community, the people who know you, who know how you work. This is the real way of controlling someone. You would never publish something that the people around you, those that you care about, don’t think is worth it.
How can this control system be improved?
We would need to change the reward scheme, and the whole peer review system. And we would have to be ruthless, shut down the things that don’t work.
On April 29, the III CiSAL (Occupational Health Research Centre) and Park Salut Mar Health Service meeting took place in the PRBB Auditorium, a meeting that filled the room from wall to wall. These annual meetings consist of an open conference, a round table, and a poster session for students. Fernando Benavides, coordinator of the Public Health and Education in Health Sciences programme at the CEXS-UPF and organiser of the meeting, tells us about it.
What was the topic of the meeting?
The meeting centred around seeing work as a source of health, physical, psychological and social welfare. The job has traditionally been seen as a source of accidents and disease, but it should not be seen as a ‘punishment’: it is a source of wellbeing. Not only because it provides income, but because it gives you identity, civic responsibility and personal satisfaction.
If work is health, we’re going wrong …
A society like ours, with 27% unemployment, is a sick society. In Spain today there are 2 million households with no income. And unemployment affects health – there are studies that show that the unemployed have a 15-20% higher risk of premature death, especially because of cardiovascular and mental problems. Therefore it is important to help the sick so that, as soon as possible, they can get back to work.
And this is what was presented at the conference by the speaker.
Ewan B. Macdonald, professor of occupational medicine at Glasgow University, has a programme to improve the physical and mental health of unemployed and increase their odds of finding a job. Because, for example, if you go to a job interview and you are sick you are less likely to succeed.
Tell us about the model this programme is based on.
The biopsychosocial model says that, in addition to biological and biomedical aspects, psychological and social issues are also important in health and disease. They can influence depression, but also cancer and other non-mental illnesses, not only etiology, but also prognosis. Today, for cancer, treatment followed by return to work has a better prognosis than being treated and not going back to work!
Give us an example of what can be done from the workplace.
The Hospital del Mar is becoming a reference model in the healthcare environment with regard to occupational health. Among other challenges, it has managed to reduce sick leave from 6 to 4%. How? By offering individual treatment of cases, introducing flexible hours, flexible types of job, and so on, to encourage the staff to keep working whilst caring for their health. They are also working on prevention, making ergonomic design changes to prevent musculoskeletal problems, the primary cause of absence from work, and which greatly affect quality of life.
How has the perception of occupational health changed over recent years and what do you think the future is?
Companies have become more interested, partly due to ‘obligation’, as there are European regulations to comply with, but also because they see the benefits and have realised that their workers are more efficient and productive. We have to reinvent occupational health, not only to prevent the negative aspects of work, but to enhance the positive aspects, creating healthy environments. The participation of workers is a key element in achieving this goal.
Carles Miquel Colell, coordinator of the Research and Innovation programme for the Generalitat’s Department of Health, is Chairman of the CMRB Ethics Committee (CEIC). Doctor of internal medicine by profession, he started off in the world of healthcare, proceeded to healthcare management, teaching, and currently, research coordination. Dr. Miquel explains the whys and wherefores of the CEIC of the CMRB.
How long has the committee existed?
In Spain in 2006, a unique approval mechanism was created to establish certain safeguards in the use of pre-embryos left over from in vitro fertilization for stem cell research. In particular, it is necessary to ensure that permission be received from the progenitors, that there exists no other research model that would yield the same results and that the research team is fully prepared and has sufficient resources to carry out the project, amongst other things. For this reason the “Commission of safeguards for the donation and use of human tissues and cells” was established in Madrid. And in Catalonia the CMRB CEIC (Clinical Research Ethical Committee) was created to be the sole organisation accredited to authorise these projects before going to the Commission in Madrid.
Who is it made up of?
There are currently 13 people, from different disciplines: a biologist, three pharmacists, a clinical pharmacologist, two nurses, a customer services representative, a gynaecologist, two lawyers, an expert in bioethics and a technician, which is me, and I am the link between the Committee and the Department of Health. We try to make sure there are no CMRB researchers in the committee in order to avoid potential conflicts of interest.
What kind of projects do you evaluate?
Any study that uses stem cells in Catalonia, both embryonic and the newer induced pluripotent cells (iPS). These are obtained from the dedifferentiation of adult cells. But in many countries these types of stem cells are not covered by CEIC specifics, as they are derived from adult, not embryonic or foetal tissue.
What procedure must be followed for a stem cell project? How long does it take?
The researchers have to prepare a series of documents that must first go through the centre’s own ethics committee, if there is one, and later, in Catalonia, through the CMRB CEIC. We assess and improve the project as far as possible before sending it to the Safeguards Committee in Madrid – to which I also belong – who prepare a mandatory report. This can take between 3 and 5 months, depending on whether clarification or further information is requested.
Why is stem cell research important?
The original idea was that of regenerative medicine: to be able to create organs and tissues to substitute damaged or old ones, and researchers are working on that. But even if this promise wasn’t totally fulfilled, these types of cells are still extremely important to the furthering of our scientific knowledge. And in the case of iPSs, they are fantastic models. We can take pluripotent cells from a Parkinson’s sufferer, for example, and use them to study the disease and test potential therapies.
Ian Mattaj, came to the PRBB last October for the celebration of the 10th anniversary of the CRG. This Scottish researcher is the director of the European Molecular Biology Laboratory (EMBL) in Heidelberg, the largest molecular biology institution in Europe. He is also president of the CRG’s scientific advisory board, and he gave us his view on science at the CRG, in Catalonia, Spain and Europe.
How would you sum up the CRG´s first 10 years?
The CRG is remarkably successful for such a young institution. They have been recruiting foreign researchers, not so common in Spain, and they have set up some excellent programmes. It usually takes about 10 to 15 years for a research centre to really develop high quality, but the CRG has done so from the beginning. They have put in place mechanisms, some of them copied from the EMBL, which help ensure the quality of the research.
How has being part of the PRBB helped?
The CRG has no critical mass in every area, so having colleagues close by has definitely helped. We have just done the evaluations of the groups and I have heard about research clubs for neuroscience and computational biology, where researchers from the various centres at the PRBB, and even from other groups in Barcelona, meet and discuss their work every two weeks. This type of environment is really advantageous; it helps foster good research.
What do you think of current research in Catalonia and Spain?
Spain has produced many brilliant scientists, so the education system is obviously working, but the organisation of the public research system and researchers needs to change, along the lines we see in some institutes such as the CRG. Also continuous strong support from the political area is needed. The message of the Catalan government has been to support research that is excellent at international standard, and this is obviously the right way to improve all scientific productivity and even help the country.
How is the economic crisis affecting the R&D system in Europe?
Different countries have different degrees of economic problems, and some like Sweden or Germany have actually increased their budget for science, because they believe it is a good weapon to help fight possible future crises. In other countries I understand that cuts might be needed, but there are different ways to make them. In my opinion, if necessary, only non-high quality research should be cut.
What are the biggest challenges in molecular biology for the coming years?
There are different sorts of challenges. There are aspects of biology about which we know so little that we cannot even imagine understanding them, such as how the brain works to produce consciousness, the sense of self etc., that it is a big long-term challenge.
In the shorter term, I think an important issue will be how we can apply the recent technological developments in biomedicine, such as next generation sequencing, to improve our health. The possibilities are endless, but so far they are only possibilities.
An interview published in Ellipse, the monthly magazine of the PRBB.
Vivek Malhotra was born in India 50 years ago and received his formal education in England. After graduating from Oxford, he went to the US as a postdoc at Stanford. He was a professor at the University of California in San Diego where he has spent most of his life. Married to a Basque biologist, in 2008 he came to the PRBB where he coordinates the Cell and Developmental Biology programme of the CRG.
What differences are there between here and the US?
Americans are goal oriented and very driven. They want to solve problems whatever the cost. They are aggressive and critical. And that’s how they have managed to advance so much. I have the feeling that in Spain people are scared of criticising. Consequently they cannot deal with criticism very well. Healthy criticism is essential for change and success.
Are we talking about science?
Criticism is essential in all aspects of life, but especially important for science. As the Greek philosopher Thales said, biology, unlike maths, is not complete, accurate, and permanent. It is open to interpretation, today’s proposal may need to be revised later on based on new knowledge and one should be willing to accept that.
Why did you come to Barcelona?
After 23 years in California I was bored. And even though I took a salary cut I am very happy here. At the CRG, I am able to do science at the same level I used to. I can see myself staying here for the rest of my career. The only thing that scares me is the general ’laissez faire’ attitude to the long-term potential of basic science. Spain needs to invest more in education, long-term and at all levels: school, university and research centres. There are now good research centres in Spain, but far too few. Jordi Camí deserves a lot of credit for building up the PRBB. If we had 2 or 3 more Jordis who could build 2 or 3, or even one more centre like this in the next 5 years, it would be terrific.
What is the best advice you have ever received?
“Work on something you think you might be able to solve in your lifetime”. I have followed this suggestion and focused on key aspects of protein secretion. We have made significant discoveries, some of which could lead to the development of therapeutics for chronic obstructive pulmonary diseases. Drug development, however, is not for me. I dislike the corporate aspect of science.
What is a normal day for you?
I walk to work, which takes about 25 minutes. This gives me time to focus on the key issues for the day. When I get to work I talk to the people in my lab, and in fact I keep on doing that all day. On average every 10 mins I abandon the computer and walk around the lab and my floor, and generally bother people by repeatedly asking if they have anything new. Most people hide when they see me coming but the brave and passionate ones take the bait and we have fun talking. I do not have a set routine but I try to communicate regularly with my friends both here and in the US. My iPhone is always on. If I am awake at 3am and come up with a useful idea I send an email right away to my lab members. So there is no time limit for work. However, I am learning to keep my evenings free for my family.
This interview was published in the PRBB monthly newspaper, Ellipse.
You can also read an earlier post about his talk here.
Figuring out how the brain works is the obsession of Rodrigo Quian, professor at the University of Leicester (UK). This challenge led him to apply his physics training and a PhD in maths to neuroscience. With the discovery of the “Jennifer Aniston neurone”, or concept cells, it seems we have taken a step towards the understanding of memory.
How can we “see” neurones?
We work on patients with epilepsy requiring hippocampus surgery. As part of this they have electrodes attached to the brain for several hours. This allows us to talk to them and detect how the neurones respond to stimuli we present them with.
Why the Jennifer Aniston neurone?
We did experiments where we showed patients people close to them like relatives and celebrities. The first neurone I found responded to pictures of Jennifer Aniston. It was a shock to discover that somewhere in the brain are neurones that respond in such a specific way to abstract concepts.
Did it only respond to photos?
It responded to various photos of Aniston, images as different in colour and format as we were able to find. The same with her name when written or spoken. Specifically, to the ‘concept’ of Jennifer Aniston. We found neurones that responded to different famous people depending on the person. The only neurones that did not respond were in an autistic patient.
One neurone per concept?
If I could find one neurone that responded to Jennifer Aniston, there must be more because if it was the only one, the probability of me finding it among the thousands of neurones in that area is practically zero. There has to be a network of neurones that encode a concept. These concept cells can quickly generate associations, so there are neurones that respond to two concepts, but they are always related to one another. This is a key mechanism for generating memories. I think they are the building blocks of memory and the link between perception and memory. This is a radically different idea to what was believed until now, that the basis of memory was distributed networks of millions of neurones.
Can you locate complex thoughts like phobias?
Often a complex thought is an association of simple thoughts. My old mentor at Caltech, Christof Koch, said it was necessary to break down the difficult problem of consciousness into related problems that are simpler and easier to attack. The consciousness of self is a very complex thing. One must first understand how the flow of consciousness works. That is, that one thing makes me think about another thing and that about another and so on. This can be studied in the neurones generating associations between two concepts and, from the moment we have made this association, we can see if the neurone also responds to the association and encodes it. In a few tests we have found that these concept cells begin to respond to the association we have created.
What other experiments are you working on?
We want to know if neurone response changes according to the presentation of the stimulus, for example the exposure time to the photos. The results demonstrate that neural response is closely related to the conscious perception of the patient. That is, if the patient believes that he has seen something, then the neurone is activated. In fact, it is even possible to predict beforehand when neurones will be activated and know what image a patient is looking at only from the neurone records.