Margarita Salas: "Cancer when detected in time would never be a problem"

  • “The biggest problem with Alzheimer’s is that it is a silent disease and so when diagnosed, the patient has already suffered a lot of neuronal degeneration”.
Madrid, 18 April 2012. We are interviewing Margarita Salas, Ad Honorem professor at the "Severo Ochoa" Molecular Biology Centre (CBMSO), the mixed research centre of the CSIC and at the Madrid Autonomous University, which has received the support of Banco Santander via its Santander Universities Global Division since 2004.
 
Margarita Salas, PhD in Sciences by the Complutense University of Madrid, is a renowned Spanish biochemist, born in Asturias, and disciple of Severo Ochoa. She is a member of the Royal Academy of Exact, Physical and Natural Sciences, the Royal Spanish Academy of Language, the European Academy of Sciences and Arts, the American Academy of Microbiology, the American Academy of Arts and Sciences, and the US National Academy of Sciences, among others. She is the Chair of the Severo Ochoa Foundation and Chair of the Royal Board of the National Library of Spain.
 
Which are the main activities pursued by the CBMSO?
First, to perform research of excellence in the five scientific areas of the CBMSO (Cellular Biology and Immunology, Development and Differentiation, Genome Dynamics and Function, Molecular Neurobiology, and Virology and Microbiology), and from this research to obtain applications that are useful to society. Another major objective is training personnel, both at pre- and post-doctoral level, and training laboratory technicians at the School-Workshop funded by the Madrid Autonomous Community via the Severo Ochoa Foundation. Training is also important at undergraduate level in Biochemistry and Molecular Biology bearing in mind that the CBMSO is a mixed centre of the Spanish Council for Scientific Research (CSIC) and of the Madrid Autonomous University (UAM). All of this must contribute to the social visibility of Science in Spain.
 
Which milestones would you highlight since the CBMSO was created?
I would highlight the major contributions made to developmental biology and genetics, based on the Drosophila (fruit fly) model since they have been key in understanding the activity of many genes in human physiology and pathology, the contributions to virology for the development of vaccines or drugs such as the case of African swine flu and viral hepatitis, the work related with the immune and inflammatory system applied to certain types of cancer, the description of an essential protein in the pathology of Alzheimer’s disease, and the discovery of proteins that are crucial in understanding how genetic material replicates, which has led to the development of patents of high commercial profitability.
 
How has the CBMSO contributed to the discovery and solution of diseases and ailments?
I would highlight the close collaboration with the pharmaceutical industry in the development of useful drugs in Alzheimer’s, the development of anti-inflammatory drugs through “spin off” companies arising from the results obtained in the laboratory, and the contribution to the development of antiviral vaccines and drugs.
 
On the personal level regarding your research, what would you highlight?
My laboratory work focuses on the study of the replication of the DNA of bacterial virus ø29. We have discovered a new mechanism that triggers replication that uses a protein as a “primer” of the DNA polymerases coded by the virus, instead of RNA or DNA which are used by most DNA polymerases. This has served as a model in the study of the replication of viruses of healthcare and economic interest such as the adenovirus, hepatitis B and C viruses, the poliomyelitis virus, the encephalomyocarditis virus, the foot-and-mouth disease virus, and several viruses that infect plants.
 
Moreover, ø29 DNA polymerase has properties that make it ideal for use in biotechnology to amplify DNA. That is to say, starting with minimal quantities of DNA, making millions of copies for use in genetic analyses, in forensic medicine, in archaeological studies, etc. In fact, the patent we filed at the time has contributed 50% of the royalties obtained during the years that the patent has been exploited to the CSIC. This is a good example of something that Severo Ochoa used to say: “There is a need for quality, basic research, because that research will lead to results that are not foreseeable a priori, but which will end up benefitting society”.
 
How would you describe the situation of scientific and research pursuits in Spain?
We have good research in Spain if we refer to the quality of the science, but we are lacking in quantity due to the low budget allocated to research if we compare us with the average for the European Union. In these times of crisis, there is a clear danger of losing human capital as well as suffering a reduction in the amounts financed per project and the number of projects funded. Now it is difficult to achieve the stable integration of a highly promising generation of young researchers.
 
Breakthroughs in the fight against cancer
 
What are the CBMSO’s most significant breakthroughs in the fight against cancer? Will they help to bring forward and improve diagnoses or to find new, preventive formulas and treatments for the disease?
The CBMSO has several groups devoted to studying the underlying genetic and epigenetic mechanisms in the development of several types of cancer and in the development of gene therapy trials. Among the most recent contributions we could highlight the demonstration that the interleukin 7 receptor (IL7R) behaves as a key oncogene in the development of T-cell acute lymphoblastic leukaemia, or the demonstration that one of the most potent oncogenes known, the c-Myc oncogene, is controlled by a group of genes called microRNAs, which were unknown until very few years ago. The results of these investigations are enabling new diagnostic and therapeutic approaches.
 
Well into the 21st century, with funding that support and is made available for cancer research, what most impedes or hinders preventive vaccines like the one used in the prevention of cervical cancer?
The development of vaccines for some types of cancer has prospered in some cases, such as cervical cancer, which are usually caused by certain types of virus. This is not, however, the most usual situation. For most cancers, new chemotherapy strategies are being developed aimed at correcting specific molecular alterations that are essential for the development of each type of cancer. They would be strategies of targeted therapy, which are usually used in conjunction with others that have general effects.
 
In the coming years, will we see light at the end of this tunnel that so terrifies people? Could you make a prediction? Are we sometimes given hope irresponsibly? On a path of 1 to 10, how far along would you put current research?
Current research into cancer is showing the enormous complexity and heterogeneity of tumours. Contrary to what was previously thought, tumours are highly heterogeneous. In each advanced tumour there are different types of tumour cells which, moreover, can be distinguished by the accumulation of genetic and epigenetic changes. In a paper dealing with the mass exome sequencing of renal cell carcinoma recently published in the New England Journal of Medicine, it is shown that genetic differences can exist between cells taken from different parts of the same tumour. That means that not only would there be a need for customised therapy for each person suffering with a tumour, but furthermore, we would have to take into account more than likely intratumoral heterogeneity. On the other hand, in many tumours it has also been possible to show the existence of “cancer stem cells” which may be the cause of many relapses following apparently successful treatment. And, in addition to the stem cells per se, there are other accompanying cells that form what is called “tumoral stroma,” which may be decisive for the development of the tumour. Thus, our greatest hope is that the comprehensive knowledge of the genetic and molecular alterations that characterise the onset of cancer will enable developing preventive strategies. What I mean is, in the definition of biomarkers or signals that warn us in time. Signals that could sometimes even appear in body fluids, such as blood. A tumour when detected in time would never be a problem. When cancer is highly developed, the availability of new therapy strategies would come into play, which, if they could not be used to cure the cancer definitively would at least allow extending patients’ life or turn cancer into a chronic rather than a fatal disease.
 
Some noteworthy research performed by the CBMSO is that of Dr. Juan Alfonso Ayala on the resistance of bacteria such as Salmonella to antibiotics. How might this work be developed socially?
Infections by Salmonella enterica are the second biggest cause of the diseases produced by gastrointestinal bacteria in the European Union. Nevertheless, most Salmonella infections result in a mild, self-limited illness, and may not require antibiotic treatment in most cases. This might be the reason why a greater effort has not been made by the pharmaceutical companies to obtain new antibiotics. However, treatment with a suitable antimicrobial could save lives in the case of immuno-compromised patients and in invasive diseases, such as bacteremia and meningitis.
 
Despite having identified over 2,500 different serotypes of this bacteria, most cases of human infection are caused by a highly limited number of serotypes. In the last ten years, a marked increase has been observed in the prevalence of a serotype of S. enterica that is resistant to ampicillin, streptomycin, sulphonamides and tetracyclines in infections transmitted via foodstuffs and by pigs or pork meat in several European countries, including Spain.
 
Normally, the food products are analysed at source, and clinical follow-up is only performed when resistant or multi-resistant strains appear in hospital isolates. There is an urgent need for the competent authorities to increase the control of distribution in order to reduce the propagation of the infection to humans via the food chain and prevent the propagation of the possible pandemic of this serotype as happened with S. typhimurium DT104 in the 1990s.
 
The fight against Alzheimer’s
 
Another important task is that performed by various researchers at the CBMSO into Alzheimer’s disease; neuronal degeneration and repair processes. Will we hear in the short term of any therapy that is effective in neuronal repair or regeneration in order to reverse or palliate the consequences of this disease that affects some 700,000 people in Spain?
The biggest problem of Alzheimer’s disease is that it is a silent disease and so when diagnosed, the patient has already suffered much neuronal degeneration with neither the patient nor those around him or her even realising. This is why it is necessary to find out about the early stages of the disease as soon as possible. This is taking place through the use of animal models and, in addition, disease modifying agents are being sought in order to prevent its progression once neurodegeneration has commenced in patients’ brains.
 
How can potential sponsors be encouraged to collaborate with this important institution, as is the case of Banco Santander?
The aid provided by Banco de Santander, whose contribution is basic for the research carried out at the CBMSO, could help encourage other sponsors to support the work done at our Centre. Knowledge of our work is essential for that to occur and is a first step towards seeking the collaboration of other institutions.