Today my blog post will be devoted to a very controversial topic not just in physics, but also in biology. For those who do not know, both biology and physics have what we call “dark matter”. Whereas cosmological dark matter represents the gravitational effects that cannot be explained by known bodies in the universe, genomic dark matter emerged from the application of new technologies to the analysis of the transcriptome (all genes expressed in a genome), and could not have been inferred from any known biological principle. In physics, it represents everything that is not matter (basically, matter is any substance which has mass and occupies space in the universe such as the planets, us, etc; and the “dark matter” represents everything else). In biology, it corresponds to regions of the DNA in living cells, especially humans, which are noncoding or do not code for proteins (our building blocks in the cells). The dark matter in both fields account for more than 90% when compared to matter in the case of physics and to regions of the DNA that produce functional elements such as proteins and regulatory RNAs in molecular biology. The term “dark matter” was postulated by a researcher named Fritz Zwicky in 1934 to account for evidence of “missing mass” in the galaxies. At first, researchers thought that both “dark matters” had no function or did not represent anything important, just something that was there. Nobody knew why. However, it is becoming clear that “dark matter” plays a central role in state-of-the-art modeling of structure formation and galaxy evolution in astronomy. The same way, in biology, parts of DNA that were considered “junk” probably have functional importance. Studies have been showing that more than 50% of eukaryotic genomes is transcribed into RNA, but these are not translated in proteins. A recent editorial piece from BMC Biology (“The noncoding universe”, BMC Biology 2011, 9: 52) have discussed this topic claiming that the “dark matter” of genomes probably have function and are evolutionarily important for humans. Maybe they could also explain human complexity (for more details see the article that I wrote about this topic – “Non-coding RNAs, epigenetics and complexity”. Gene 2008, 410: 9-17). The debate on the functionality of “noncoding” parts of genomes recently took central stage in several debates in the scientific community with articles and editorials covering this topic. Some believe most of the transcribed regions of genomes represent by-products of the transcription itself and have no function. Others believe non-coding regions generating non-coding RNAs are important for gene regulation and even in evolution. Growing evidence with examples of RNAs coming from the “dark matter” of the genome that are functional and have roles similar to that of proteins have surfaced. But what function really means in genomics? What can be a good definition for function? Well, if gene expression control relies on the expression of non-coding regions for genome stability, maybe genome stabilization could be assigned as a function. The controversy will continue for some time, but in my opinion the noncoding regions probably have roles we do not even imagine yet. Similarly to the “dark matter” of the universe in physics, noncoding parts of genomes are still full of mysteries. This is a very philosophical controversy – the same way the universe, which is big, has a “dark matter”, the very small in the cells, specifically the DNA, have the same conundrum. The next years will be very exciting since researchers in these fields will try to understand both “dark matters”. The future is promising for astronomy and molecular biology…I am excited with this debate!
The dancing “noncoding” universe
July 31st, 2011Genetic Tests: facts and fictions
June 23rd, 2011
Are you more susceptible to developing cancer? Are you getting heart disease? Is obesity in your future? Your risk for many diseases and health conditions is just partly written in your genes. One day soon we will be able to visit our doctor and find out more about our health risks for the next years through genetic testing. But scientists (and I am included in this category) have many things to learn about genes before this becomes a reality. Genetic Testing regulation turned into a controversial topic after the FDA in the USA blocked some Over The Counter Predictive Tests and started paying more attention to this market. Several companies have been offering predictive genetic tests (examples are 23andme, Navigenics, Pathway Genomics, and others); however the tests they offer can be misleading in some cases. This is mainly because the environment plays a role in complex conditions. Genetic Tests for monogenic disorders such as Cystic Fibrosis, Huntington’s disease, etc are well established and reliable in most of the cases. In monogenic disorders, the affected individual will have a mutation or a genetic defect in a single gene or just a few making it easier to detect the underlying problem. In the case of predictive tests for complex diseases such as diabetes, cancer, arthritis, and others, several genes and the environment can affect the condition making it more difficult to get conclusions. I am not saying the consumer should avoid doing these tests; they just need to be careful and if some defect is detected they need to verify the veracity of it. Predictive Tests in some cases have a lot of support in the literature for the analyses, but in most of the cases there is no scientific evidence. Some say these tests are “recreational”. I think this is a start for an area that is not very explored yet. The companies offering these services have to mature and the beginning is always difficult. I believe that what needs to be done is a better explanation to the consumer on how these tests work, what they are really paying for and a better support after they get the results. Whole Genome sequencing companies such as Knome offer the sequencing of a person’s genome with a follow-up to explain the findings. In my opinion this is good; however there are a lot of regions in the genome that we do not understand yet. In fact, these companies are offering services coupled to research. The person that pays for whole genome sequencing will sign a consent form if he/she wants that the sequenced genome become public and available for research. Maybe that is a good way to better understand human genomes. In the case of genetic tests, the results could be a “Yes” or “No” answer but for most of them it will be a “Maybe”. This happens mainly because we are realizing that the environment has a big role in interacting with genes. In conclusion, the increasing need for regulation is a fact and there is still a lot of fiction in several of these tests that companies are offering (one example is the Genetic Tests for Sports Performance; well, genes are important, but the environment that can be exemplified by nutrition and training are also important factors). I believe we need to start somewhere and that is what is happening right now. Let’s see how the regulation will shape the genetic tests’ market from now on. I am curious…
Notes from a scientific meeting
April 8th, 2011
This blog post will be devoted to some thoughts and notes from a scientific meeting I just came back. It is always good to leave the laboratory environment and go to an international meeting full of new discoveries that can revolutionize fields such a cancer research. I am talking about the biggest cancer research meeting in the world, which is held every year with the objective of uniting cancer researchers in one place to share and discuss ideas. This year it was in Florida, the sunny state in the United States. There are some points that I always like to take notes after coming back from such meetings. This year it was not different. The first topic for discussion is novelty. I have been going to this cancer research meeting for at least 5 years and I always see that there are not a lot of exciting discoveries and/or new drugs in development. I see old drugs being used in different ways or in combinations and also old compounds that are modified to cause less toxicity. This fact could be due to the cost of developing new drugs, what they say – the cost from bench to bedside. It is not new that blockbusters are in extinction and both pharma and biotech industries have to adapt to personalized medicine, that postulates the use of specific drugs (or a combination of them) for each patient or group of patients. In the last five years, I saw a big boom and trend towards RNA interference and microRNAs for drug development, but now it looks like things are changing again. Some years ago the promise was the anti-angiogenic approach, which was able to decipher angiogenic pathways that cancer cells use, but was unable to “cure” cancer. Well, science is in “waves”, I like to say. One researcher discovers something that becomes a field with a initiation, a high peak (or boom) and then fall into oblivion. Second note is something I am against: every year in this meeting (and other meetings I have been going to) the same exact researcher who is a leader in that field will be giving talks. There has not been a big change in the last years and “new” scientists with novel ideas and interesting things to say remain with a small space to talk or to present a poster. The scientific world needs a change. Maybe the fact that there have not been big discoveries and new exciting drugs under developed is because the same people will be always “dictating” the rules. The third and last note is intimately linked to the “wave” effect in science. One example is the fact that talks from renowned researchers will have a line and people standing in the room to watch while “new” fields that just emerged will have an empty room. A field that I saw crowded rooms was epigenetics and next generation sequencing applied to cancer research. Emerging trends that I saw empty rooms: long non-coding RNAs in cancer research (not microRNAs) and genetic syndromes that have as a consequence increased frequency of cancer in people that is affected (eg.: Li-Fraumeni Syndrome and cancer). The lesson I took home: waves are important but we have always to watch for the empty rooms. Maybe one of these topics will be the crowded room in the next five to ten years or so. Who knows…Let’s wait and see.
Translational research and applied medicine – are we all lost in translation?
March 5th, 2011
In this blog post today, I will share some experiences in my day-to-day life doing (or trying hard to do…) translational research. Just to be clear there are two main types of research: 1) basic, which tries to understand the fundamental principles and phenomena that drive cells, organisms, systems and the world we live in; and 2) translational, which is the application of the basic research to solve specific problems, aid in diseases and help the society at different levels. In health sciences, translational research has its focus on removing barriers to multidisciplinary collaboration between scientists and physicians helping to “translate” basic discoveries in new drugs to treat diseases and/or the identification of better ways to manage chronic diseases such as cancer, diabetes, etc. Importantly, translational research has the potential to drive the advancement of applied science. It is also an attempt to bridge the medical and scientific domains to move discoveries “from bench to bedside” or from laboratory experiments through clinical trials to actual point-of-care patient applications. Well, it is pretty and fancy to say that you are doing translational research, since the chances that your research will help improve patient care are always higher. I can tell using my personal experience that this is a very complicated and entropic process. As in any field, communication is key to success. For example, in project management, business, finance, and etc, communication has to be the most important feature in the path to success. The same applies to multidisciplinary projects involving scientists, project managers and physicians. The problem is that it is not like this. Physicians have different expectations compared to scientists and I have a feeling that I am always “lost in translation” and vice-versa. The success of any project depends not just in commitment from the personal involved but also good communication skills between the people that are involved. It is like in the cartoon above, there is a “valley of death” between both parts mainly because the exchange of information is faulty. Well, we are in need for better ways to facilitate the communication between professionals with different backgrounds, especially when doing translational research. The physician needs to understand and be interested in the scientific side of the project (read more, study more, be curious about science which sometimes is not the case…) and the scientist has to understand the physician’s needs and the problems he or she wants to find answers in order to increase the rates of success. My feeling is that none of this happens and the environment between both sides is indeed entropic with constant miscommunication. Improvements in both sides for a better information exchange are crucial to develop multidisciplinary projects with impacts for patients suffering from diseases. New discoveries doesn’t depend just on working hard towards a goal, there might be a synchrony between researchers and doctors so the rate of success will increase extraordinarily. Finally, I believe that both parts need to learn more about Project and Finance Management, especially in though times with shortage of money for research. I think this is not an isolated case and this may happen in a lot of institutions around the world. So, let’s step back for a while and think on how to maximize our chances of better communication and, consequently, of success in translational research.
The impact of charity in Science and Medicine
February 12th, 2011
I was always told that the power of a country is measured by several factors, but especially by its scientific and technological accomplishments. For years, the United States was the world’s science and technology leader. Graduate students like me wanted to come here to study, and often to then work. This was the “status quo” for a professional that wanted to get higher positions in their fields – come to the United States to do a specialization, MBA and even a Ph.D. However, this has been slipping as industrializing countries enhance their own R&D (Research and Development) capabilities and universities, and as terrorism fears make it harder to come here. In addition, the economic crisis that started in 2007-2008 in the United States has severely affected scientific funding and the advancement of technology and medicine, among other fields. The federal government squeezed R&D funding and this is affecting several fields that the United States has always dominated. One example is the National Space Agency (NASA) and the cuts in the budget that have impacted in the retirement of the Space Shuttle with no substitute for it. On the other hand, countries like China and India, had increased budgets in science and technology and have been threatening the United States. Even Brazil, as discussed in an article in Science Magazine (Regalado A. Brazilian Science: Riding a Gusher. Science. Vol. 330 no. 6009 pp. 1306-1312, 2010) is in the right direction, despite some social problems. All of these turnarounds in the United States economy has brought up something that American people do better than anybody – donation of huge sums of money to charity from foundations. Examples of Foundations with impact to the American society are the Bill and Melinda Gates Foundation that have been distributing grants to emerging countries for vaccine development for cholera and other diseases that are epidemic in third world countries, The Lance Armstrong Foundation that funds cancer research, The Michael J. Fox Foundation that donates money for Parkinson’s disease research, among others. We need to recognize that Americans do this better than anybody. They can intervene in political problems, get into conflicts that are nonsense such as the Iraq and Afghanistan wars, but they are authentic patriots. So now let me tell a little about my history as a researcher here in the United States and how charity has changed my scientific life. Four years ago, when I was in Chicago doing research in cancers, a family that had lost their daughter for an aggressive brain tumor (she died when she was 3 years old – see video here) came to my boss since they had started a Foundation under their daughter’s name. The Maeve McNicholas Memorial Foundation, this was the name of the Foundation since their daughter’s name was Maeve, had just started and wanted to help researchers working studying brain tumors. Their child was treated in the institution I am working now so they came to us to talk about our research and visit the laboratory. Since this day, they had donated to our research almost half a million dollars (approximately 500,000.00 dollars) during 4 years. They gave me the honor to be the Maeve McNicholas Memorial Foundation Scholar and every year they promote an event to raise money for our research. The event is in a Park under Maeve’s name in the neighborhood that she lived in. This year they have donated 110,000.00 dollars to our research (see picture below).More importantly, this Foundation was initiated by a medium class family (not a rich family) and it was able to grow and spread the word not just in the Chicago area but in all the Illinois state. If it were not for their donations, we would be in financial trouble. These days are though times for researchers in the United States and charity plays a big role in maintaining several groups up and running. I believe that government agencies are still big players, but donation of money for research has grown since the economic crisis hit science and technology here. This is an example of something that americans do better than any country in the world, even in though times. Even with all the hate for americans all over the world because of the wars and their international political policy, americans are the most patriotic nation in the world. We should (and by we I mean the rest of the world) learn with these positive things Americans do. This is just one of the examples of the impact of charity in Science and Medicine in America. If you or your family have a story like this please post a comment here in this blog!
Web 2.0 and the democratization of science
October 10th, 2010
Science was supposed to be all about collaboration to achieve our main goals – try to understand the basics on how organisms and cells work and use this information to aid in the wide range of diseases that affect humankind. Unfortunately, the scientific world is not all about sharing information. In fact, it was always the opposite; a big competition in which the ones with more resources get to the discoveries first and prevail. To be able to do a nice discovery in science and make it available to the whole scientific community is more difficult than anyone would imagine. Scientific journal article evaluation and peer-revision, as I already pointed in my previous blog posts, is an unfair and frustrating process that can take months and even years. There is a lot of competition and the journals are not accessible to all scientists in the world since they charge for article download. This is somehow changing with the revolution of the Web 2.0 in which there is more interaction of the individuals with the information available online. Free social media networks such as Podcasts, YouTube, innumerous blogs, Twitter, Facebook, and others have been facilitating the “spread” of the scientific discoveries faster than it was imagined let’s say 10 years ago. The current “migration” of the printed media to the virtual world is indeed facilitating the democratization of science all over the world. Several scientific journals that are Open Access and free of charge have emerged, so everyone is able to download articles and commentaries about specific topics. The trend is that even the more “traditional” journals will need to find ways to get revenue and become freely available so everybody can have access to “first class” scientific discoveries. This type of democratization is not necessarily new, but now it will occur faster and will affect people all over the world in an era that information is the most valuable product. In a large enterprise like science, this can make a big difference. Web 2.0 is already changing the scientific community and I hope this will positively impact in the evolution of our field and facilitate the application of our discoveries.
Popularity x Prestige in science – what matters most?
October 3rd, 2010
In my last blog article I wrote that science is in a moment of “transformation” like any other field mainly because of the Web 2.0 revolution – which implies that the user has the power to insert and delete whatever he wants in websites, mainly social networks and information sites such as Wikipedia, Facebook, blogs, and etc. Society is dealing with a lot of privacy issues concerning these new internet advances. Some people think this is not a good sign, however any evolving field brings good and “evil” outcomes and society has to deal with it. In its early years, for example, the company Google stated that they would never play “evil” and collect private data from people using their search engine. It looks like this is not the case now that we know they are facing some problems with privacy, especially in China and in Europe. In the same fashion, Facebook faces increasing privacy issues and problems. Anyway, the point of this new blog article is focused in the scientific field. The point is that our research and reputation (and by our I mean every scientist in the world) is basically measured by the research we do. This means that if we can get our results to be published in high impact scientific journals our “prestige” in the scientific community will be good. The Impact Factor or IF of a journal was developed by Eugene Garfield of the Institute for Scientific Information (ISI) and it has been the main method to determine the impact of a scientific research discovery. However, in the “Google age” we have been facing a very interesting trend which is the fact that the search results or ranking that Google gives for a specific article or journal is different from the IF calculated by ISI. This is explained by the fact that these two sources use different methods and algorithms to calculate the impact of articles and journals. It is clear now that “popularity” that Google searches gives us does not overlap with the IF provided by ISI. The conclusion is that we need to come up with different methods to calculate the impact factor of research discoveries and journals. In that regard, currently available methods for evaluation of the quality of scientific papers and status are undergoing a profound re-evaluation. The question now is what matters most? Popularity or Prestige? A recent article is proposing a formula for this complicated issue (for more details see: “Impact Factor Page Rankled” by Hascall, Bollen and Hanson, 2007). A new formula that takes into account the algorithm from Google for web searches and the IF from ISI can be combined in a very elegant manner. Larry Page, one of the Google founders published the algorithm (see article: “The anatomy of a large-scale hypertextual Web search engine” by Brin and Page, 1998) they use in Google Search Engine. The ranking used by IF is mainly based in their own method for calculation which evaluates the number of citations a journal receives over a 2 year period divided by the number of research papers and reviews published in that journal. It is becoming clear that as the scientific material becomes available for free download in the Web 2.0 era with Open Access Journals popping up everywhere, and hence become searchable through Google, our perception of article popularity will change as a result of the recently suggested Page Rankled and not the IF alone. I am quite sure that a new revolution in the journal and article classification industry has already started. Now we just need to search our articles using Google and see how popular they are independent in which journal they were published in…
Peer review in science – “politically” correct?
September 3rd, 2010
This is a very interesting and controversial subject for scientists: why peer revision of scientific articles is so frustrating and time consuming? Like the cartoon illustration above, publishing our findings is not a very pleasant and enjoyable process. After spending months and sometimes years doing experimental procedures and collecting data (which are not easy tasks either…) we, as scientists, need to deal with decisions such as the journal that we will submit the article and the anxiety of acceptance or rejection of our work. Most importantly, some sort of “help” from politics is always needed. By this I mean that when you know the editor of the journal or somebody inside the editorial board it is much easier to get your article accepted for publication. It is like in any community; you need to be inside or even join the “club”. Metaphorically speaking, it is like in sports, journalism, or any other profession (well, not just in professions, but also in religion such as religious groups in which individuals help each other). It does not matter if your research and results are outstanding (and please I am not generalizing here); the most important component for success is who you know and how they could be of any help. Rejection of articles is part of the scientific game and like in anything in life sometimes it is not fair. I always question myself on why we spend a lot of effort and time to get the best results (luck is a very important factor here too) and the reviewers “kill” or destroy your article when you submit it for publication. Well, I believe that now there is no other way for the evaluation of science quality and importance; however we will need to come up with better and faster ways than the ones used by the system at the moment. Another disturbing fact is that sometimes you send the article for revision and the points of view of the reviewers are completely different. How could this be even if they have a different formation and opinion? Imagine that: you have nice results, write the article in a very concise way, and send it for publication expecting good suggestions to improve your research even if the article is rejected. Differently from expected, we get revisions that are nonsense from reviewers we don’t even know (peer revision is “confidential” – are they really confidential? I am starting to question that too…). You can suggest to the editor of the journal specific names of scientists that you want to revise your article (mainly people you know and that are respected in your field to give credibility to your work) and even tell the editor that others should not get the article in any circumstance mainly because of conflict of interests or the fact that they are competitors in that field among other reasons. Isn’t this too much of a political process? From my understanding pure science should be more independent from politics. Let’s go back in time and discuss Einstein’s theories and how he became famous. Of course at that time we had no globalization of social media like today; these were old times. Einstein wrote the “Theory of Relativity” when he was working in a Patent Office in Zurich (he wasn’t even linked or working in a laboratory or a major university at that time, but he always had this passion for physics and related fields). Of course, physics is all about theories, but other scientists needed to prove with experiments if he was right. At that time, he had trouble to publish his theory since he was unknown by the scientific community (or as I say here “club”). In fact, he was an outsider that struggled to make his ideas and theories accepted and even published. In the end, he was able to publish it and several years after that other scientists in the field started to show experimentally that he was right in mostly every detail. Some years after that, Einstein won the Nobel Prize and he was in the cover of several newspapers and magazines around the world. Using this example, what I want to show is that “the club” sometimes is so politically closed and incorrect that it does not give space for younger scientists that could have new and revolutionary ideas. The theories that Einstein proposed at that time changed paradigms and helped other fields to evolve improving our understanding of the world we live in. I believe that we, as a scientific community (and by “we” I mean both young and well-established researchers) have to come up with new ways for peer-revision. A trend that has just started is the “open access” publishing in which the access to articles is free, easier and less political. Articles are peer-reviewed in a different way and published faster. This could be the answer to a better and faster system for peer revision with less politics – a kind of “Science 2.0”. It will not be an easy task to change the system, but something has to be done. There is too much politics in science right now and this affects a lot of good researchers that are emerging out there. Not just in peer revision for article publication but also to get funding for research. Many scientists are giving up since they cannot expose their ideas easily, there is too much bureaucracy – in general it takes 6 months to 1 year (sometimes even more) to get an article published from submission, peer revision to acceptance and print (if it is accepted by the first journal you sent it). Young fellows like me are starting their careers and are unknown with no connections to “clubs” or any politics that could help them publish their research and spread their ideas. I can tell by personal experience that it is not easy, but this is how the system works for now. I can only evoke others like me and say: Young scientists unite – let’s change the peer review system right now! It is time for a change!
Think Different and challenge the “Status Quo”
August 29th, 2010
Steve Jobs back in the early days of Apple…
After watching this video from Steve Jobs back in 1997 when he was addressing the media about the new Apple “Think Different” advertisement it got me thinking… He was right more than 10 years ago. Nice marketing and products of quality are a combination close to perfection in technology (and probably in science too) and for a company to be successful. Like he says in this video: always “Think Different” and challenge the “Status Quo”. The best minds in history did this and entered to eternity. They were always questioning the beliefs and the things that general people thought were “correct”. Just doing a parallel or metaphor with the scientific world, i think that the great minds always thought different and chellenged the “Status Quo”. This is why they entered to history, to science books and some got Nobel Prizes, etc. Another parallel is the history of the company Google. In the early days of the company, Larry Page and Sergey Brin were doing Ph.D.s trying to find a way to come up with a matematical formula or model that could be applied in searching terms in the web and also to rank the results (they were lucky to give up their Ph.D.s and found Google at that time – a company that now is threatening Microsoft and even Apple). At that time nobody though this way and some books now telling the history and what happened when they had the “Google idea” describe that some of their peers were skeptic thinking they were crazy and a search engine like that would never work. Well, Google is a giant now not just in search engine, but also in other areas such as marketing, software development among other technologies. Thus, we definitely need to move forward and fight for our ideas, specially when other people or even peers tell us we are crazy and our ideas are nonsense. Sometimes, these ideas are too far ahead of time (like 10 years or more) in the general public’s mind. This is why iconic people such as Steve Jobs are geniuses and it does not matter if they present a conference to the media wearing shorts back in the 1990′s (see the video above to believe in what i am saying…). Well, our ideas need to be good, but we have to be brave to “sell” them!
The battle between our genes and the environment: our DNA isn’t our destiny
May 15th, 2011Posted in Biology | No Comments »