Updates & Lessons for a Post-pandemic World

November 16th, 2020

As I write this blog post there has been a lot of updates related to the coronavirus pandemic in the world. We are approaching the end of 2020 and there is currently a second and third waves of coronavirus infections in Europe and the United States, respectively. In the United States the number of daily confirmed cases are reaching the 200,000 mark and in Europe several countries are locking down and imposing restrictions again. The testing of the virus is still messy with misinformation and lots of false positives and false negatives. Doctors and healthcare practitioners are struggling to understand (or don’t have time) which is the best applicable test for each phase of the viral infection. For example, if the person is in the peak of the viral infection and did not develop antibodies against the virus yet, a serological rapid test will not detect the virus (false negative). If the PCR (“gold standard” test) is done after the infection phase and the body has cleared the virus, we will also see a false negative. Very confusing indeed. Regarding treatments for the infected people, I believe the healthcare systems are evolving but there is no “global protocol” to be followed by healthcare practitioners in all the countries. Thus, what we see is a trial and error, use of drugs that are not approved for viral infections, use of antibiotics in the wrong phase of the infection. Bottom line: It is still a big mess. Regarding the vaccines, in the last week we had several good news of vaccines from big pharma companies such as Pfizer, CoronaVac and the Russian Sputnik V having good efficacy (above 90%), Today I just read that Moderna Therapeutics released a statement in the media reaching almost 95% efficacy (check the NYTimes Vaccine Tracker and some other news here). I hope until the first quarter of 2021 we will have more good news for the vaccine research. However, the problems after the approvals will be the logistics to deliver it to people in poor countries (we already know that vaccines based in RNA are unstable and need very low temperatures to transport). Prices, country policies to distribute, who will get it first are also open to discussion. Well, there are several lessons we have been learning “on the go” with this pandemic. When I think in a post-pandemic world, I see a lot of people affected mentally mainly because of the restrictions, a generation of kids that will be living with fear, confused and probably still using masks (this is not going away soon). I think governments in the world need to join forces to overcome another pandemic if it comes; the response to this one was a disaster in my perspective (and from a lot of other people). With all the technological innovations and scientific accomplishments we have in the year 2020, we will probably see  around 2 million people dying (or even more) of the coronavirus globally with at least 100 million+ infected (unfortunately I have been reading a lot of reports of recovered people with long-term problems in the brain, heart, chronic fatigue, weird syndromes that will take a while to understand). Societies and political leaders will need to join forces in a world that is so divided right now. I am not talking about rich and poor, I am talking about us, humans, the human race as a whole. The world will never be the same after 2020. A “brave” new world will surface with more compassion, empathy and hope – I am trying to be an optimist. This pandemic affected everyone (of course differently) from Hollywood stars to people living in slums, from billionaires to middle class people. The world of sports such as NBA, MLB, soccer, car racing (I am a fan of Formula 1 and Indy Car Racing) were all affected in some way. Live TV shows were affected. All businesses were somehow negatively affected (exceptions are technologies such as videocalls, and retail with delivery such as the tech company Amazon, etc). The world economy is broken, a lot of people unemployed, kids having virtual classes and other changes that will need some years to go back to “normal”. And what this “normal” will be? I do not have the answer yet, but I hope next year will be better than 2020.

Why Information and Speed Matters in Industry

October 1st, 2020

We all know how competitive markets can be, especially when there are billions of dollars in stake. Both pharmaceutical and biotechnological sectors are indeed very competitive. Companies spend millions (sometimes billions) of dollars to get drug approvals and place a new medicine, drug or treatments in the market and it can take a decade to get the proper approvals. Regulation and approval are always a hurdle, but these are very important steps to evaluate a drug’s safety, toxicity, and the effects in the population in general, thus several clinical trials in different populations have to be done before any approval. We can see this going on with treatments and vaccine development for the coronavirus disease (for more information please check my previous blog posts). However, today in my blog post I will shift gears a bit to discuss about an area that has become very important for pharma companies: Immuno-Oncology (IO) and the drugs associated with cancer treatment. In fact, these drugs in a simple explanation, use the person’s immune system to attack cancer cells and shrink the tumor (sometimes even cure the patients). Thus, several tests and “facts” need to be checked before these types of treatment could be applied. I will discuss today about Business Intelligence (BI) and competitive advantage in life sciences. The example here will be two specific treatments that have been approved by the American Food and Drug Administration (FDA) to treat various cancer type. Immunotherapy combo drugs such as Opdivo or Nivolumab (developed by Bristol-Myers Squibb – BMS – NASDAQ: BMY) and Keytruda or Pembolizumab (developed by Merck – NASDAQ: MRK) have changed the cancer treatment landscape, but it’s becoming increasingly clear from clinical trial results that these potent therapies need to be targeted to the right patient populations to have the best clinical results; something named precision medicine. Both treatments use specific genetic profiles and background of the patient’s immune system to be successful, which is the expression of two proteins by patients’ immune cells: the so-called “check point” proteins PD-1 and PD-L1. These treatments actually block PD-1 with monoclonal antibodies (mAb) helping the patient’s immune system to kill cancer cells. That is the basic concept (for more information on the molecular biology of these treatments check “A molecular and preclinical comparison of the PD-1 targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab”). In that regard, the brand names Keytruda from Merck and Opdivo from BMS mainly function by blocking the PD-1 ligand protein and have several structural similarities. In fact, both were approved in the same timeframe by the FDA in the end of 2014. However, Keytruda (Pembrolizumab) is projected to generate at least U$22.5 billion in revenue by 2025, according to an analysis by Global Data, a data and analytics company. In 2019, Keytruda generated more than U$7 billion in revenue and, based on more than U$5 billion it earned in the first half of 2019 it could hit U$10 billion or more by the end of 2020. Keshalini Sabaratnam, a pharma analyst at Global Data, said Keytruda has developed into Merck’s biggest product since it was first approved by the FDA in 2015. On the other hand, BMS’ Opdivo (Nivolumab), a rival checkpoint inhibitor to Keytruda, is expected to be in fourth place for global revenue and AbbVie and Janssen’s Imbruvica will take the fifth position, according to Global Data’s prediction. In 2018, Opdivo earned U$5.7 billion (for more information check “Keytruda Set to Become World’s Top-Selling Drug, Forecast Shows”). Why is that? Well, trying to understand why this market share change occurred in such a small timeframe (3 years or so) since both treatments were approved by the FDA in about the same timeline, I started digging in the approvals for both treatments since then. The main points I want to discuss in order to answer why Merck’s treatment is “winning” the competition now are: 1) Merck started combining biomarker identification to stratify groups of patients that would respond better to their drug, even in the clinical trials before approval, especially patients with high expression of both PD-1 and PD-L1; 2) big data analytics probably helped Merck to gain more information and faster approvals, so maybe people working for Merck were paying more “attention” to the advancement and developments of “targeted therapies” in immuno-oncology, which means that speed in getting information and data makes a big difference in business intelligence for big pharma and 3) it seems that Merck’s treatment can now be applied to several types of cancer and the one from BMS is a little more “restricted” to specific cancer types in terms of FDA approval. Thus, the take home message here is that we are in need of better tools, especially for life sciences’ companies, to get trustful information faster and use it smarter. There are already some solutions that can help big pharma in the market such as the Elsevier database (NYSE: RELX), Thomson Reuters Corp. database (NYSE: TRI), etc which are bringing revolutionary tools to speed this process. Indeed, sometimes being the first is not enough; keeping track of the information and the evolution happening in the scientific and biomedical fields are the differentiation factor to “win” in such a competitive market.

Understanding SARS-CoV-2 and COVID19

September 14th, 2020
Image Source: Ann Kiernan for “The Washington Post”, June 18, 2020

Here we go: another blog post on the coronavirus pandemia that is ongoing globally. The race to a vaccine continues (will discuss a little about that below), however this post will be focused on the virus that caused the disease COVID19 (Coronavirus Disease 2019), named SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), its biology, complexity, how changes in its genetic material could make harder to develop vaccines against it, the latest reports on tropism to specific human cells and organs and how the outlook for the near future looks like. In addition, I will discuss cases being reported of secondary infections in the same person and people that was “cured” from a first infection developing complex syndromes (especially children) and long-term neurological problems in older people. This pandemia is ongoing for more than 6 months, and I am very happy with how the scientific community is collaborating worldwide (collaboration in science is key, totally opposite to the system we were used to before) accelerating our understanding on the invisible enemy we are dealing with. Unfortunately, it is still not enough to eliminate it yet, but we are on the right track.

Biology of the Virus

What is the best way to understand a virus and its biology? First, we need to isolate the virus from patients and sequence its genetic material. With this information, we can use the databases available to scientists to compare its sequence and even identify how it is evolving comparing different strains in different places of the globe. The second thing to do is to study how the virus “attacks” the host (yes, us, humans). The good news are that both information is getting out fast with several scientists studying both topics very deeply. There is already a catalogue of SARS-CoV-2 mutations available and comparisons to see which genetic changes facilitate the infection and how it will affect the disease course (for more information check the article describing it here). To date, more than 100,000 isolates have been sequenced and made public (www.gisaid.org). Two SARS-CoV-2 viruses collected from anywhere in the world differ by an average of just 10 genetic letters out of 30,000 (the virus genome has 30 Kilobases or 30,000 bases) that could confer evolutionary advantages. Based on these studies, it is a possibility that the virus will acquire mutations that could change its susceptibility to antibodies and immunity affecting treatment and vaccination. The second way to understand the disease is to analyze the the tropism of the virus when it enters the human body. Tropism is which cells it binds to and in which organs it affects when inside the body. A recent report just released from a group that evaluated thousands of cell types (a type of “coronavirus cell atlas”) and organs from patients infected identified that the virus enters our respiratory system, however it has tropism to several other cell types and organs – see the Figure below. The idea here is that all these cell types in different organs in the human body have a protein (lock) that binds to the virus “spike” protein (key). When the key unlocks that lock the virus enters the cell and multiply, killing it and causing all the signs and symptoms that we see in the disease. Based on this study, we can tell how complex is the spread of the virus in the human body and why each person has a different reaction to the disease.

Source: Figure from article entitled “A single-cell RNA expression map of human coronavirus entry factors” published in the journal “Cell Reports”

Re-infection Cases

Another problem that worries the research community, especially for a successful vaccine to work, is the recent reports of cases of re-infection with the virus. Most of these are probably re-infection with other strains, very similar to the common cold or flu virus that we can get it more than once in a year, for example. The first report was in Hong Kong (see article here) and now we see a lot of reports with cases of re-infection. Most people who are infected with the coronavirus produce detectable antibodies that would be expected to protect against a second infection by the virus. Even people who had only mild symptoms may also have immune “memory” that prevent symptoms on a second exposure. It is clear now that is not the case. Even though it is early to make conclusions, this could impact vaccination when a vaccine is ready.

Post-COVID19 Syndrome

The last important issue that have been reported since April of this year when the spread of the virus started and now it is much clearer is that people considered cured developed neurological problems and other signs and symptoms that persist until today. Remember (check the Figure above) that the virus infects cells from the brain and the nervous system, so neurological problems would be expected. For the sickest patients, infection with the new coronavirus is proving to be a full-body assault, causing damage well beyond the lungs. And even after patients who become severely ill have recovered and cleared the virus, physicians have begun seeing evidence of the infection’s lingering effects (check the article for more information here). Another worrying post-coronavirus effect that has been reported is a mysterious, new disease called multisystem inflammatory syndrome in children (MIS-C, and also known as pediatric multisystem inflammatory syndrome or PIMS). It has affected hundreds of children around the world since it was first discovered earlier this year. Other syndromes have been reported everywhere now and that is concerning. What is causing these post-COVID19 syndromes? Why in children? We still do not have the answers to these questions. Let’s hope the scientists can uncover this mystery.

Updates on the Vaccine Race

Finally, let me discuss a bit about the “pause” that the AstraZeneca/Oxford University vaccine had last week because of a severe side-effect in one patient that had inflammation in the central nervous system. First, that is common to happen, especially when you are dealing with a fast-track vaccine trials and with people with different genetic backgrounds. Second, the “pause” was important to show to the world that this vaccine is trustworthy since the researchers from both places coordinating it are using the best scientific guidelines with very strict rules (trust is important!). Third, side-effects will happen, the severity of them that will be key for a successful vaccine. Finally, the vaccine race continues and I just read that AstraZeneca and the University of Oxford is going forward with their trial after the “pause”.

Final remarks

All the information I just discussed here is just the tip of the iceberg on the complexity of this virus and how it infects humans. We are starting to understand several processes on how the virus infects human cells, which cells and organs have the tropism for it and how people with different genetic backgrounds from different places react to it. Post-COVID19 effects are getting clear (it happens) but we still have lots of WHYs to focus on right now. I always finalize my posts with some advices: the best thing to do now is still social isolation, take the measures to avoid getting infected and stay mentally sane. I confess that I am already having mental issues (don’t leave the house for almost 4 months!). Stay strong. We will overcome this crazy pandemia. And let’s thank the scientists and healthcare professionals everywhere that are making it possible to gather all the information we have to date on this disease. A brighter future is closer… I hope!

Coronavirus Pandemia and the Vaccine Race

September 1st, 2020

This blog post will be focused on the race for a coronavirus vaccine that is happening globally. My main objectives here will be to explain in a general way how a vaccine works, to give some examples of successful ones, and the difficulty to develop specific vaccines for viruses. In addition, I will discuss some of the vaccines in the last clinical phases for the coronavirus and last, but not least, how it will get to you, me and to all global citizens when it is ready; this is the most complicated part. Just as a reminder today, September 1st, we have at least 850,000+ deaths and 25.5+ Million people infected by the coronavirus globally (data from the “Johns Hopkins University COVID19 Global Tracker”). We really need a vaccine to decrease the spread of this virus otherwise things will definitely get worse. Vaccines typically require years of research and testing before reaching the clinic, but scientists are racing to produce a safe and effective coronavirus vaccine by probably the beginning of next year (best estimate). To date, the number of vaccines under development worldwide are in the hundreds, however I will focus here on the ones that are in later stages in clinical trials with more possibilities of being successful. Researchers are testing 36 vaccines in clinical trials on humans, and at least 89 pre-clinical vaccines are under active investigation in animals (to see more information check “The NY Times COVID19 Vaccine Tracker” updated daily).

Types of Vaccines

Vaccines consist of five specific types: live attenuated microbial particles, inactivated microbes (by heat or any other methods), toxoid vaccines (part of the virus or bacteria that cause an immune response and immunological “memory”), conjugated or hybrid (most of it will be a non-pathogenic virus/bacteria with parts of it as targets) and new technologies such as nucleic acids (DNA & RNA) vaccines (for more information on vaccine types check this article). One example of a vaccine that used the attenuated virus is the polio vaccine that was able to almost eradicate the disease from the world (eradication just happened in Africa this week thanks to a lot of efforts from the WHO and its partners, but we still have isolated cases – check the article here).

Viruses and The Challenges Ahead

There are two types of viruses: DNA and RNA ones. They differ in the way they use our cells to produce more viral particles. The trickier ones are the RNA viruses since they use the cell machinery in a more successful way to “reproduce” and kill cells. For instance, the HIV virus is an RNA virus and until today researchers were not able to develop a vaccine mainly because HIV infects directly our immune cells, the ones that should “remember” and kill them in a second infection. For viruses causing infection in the respiratory tract such as the common flu, the H1N1 and now the SARS-CoV-2 it is not easy to develop vaccines. These viruses mutate a lot and the way our immune system “attacks” viruses can be different from other pathogens such a bacteria, for example. Additionally, each person has a different genetic background, thus different immune responses. This is why we are in this situation right now.

Vaccines Under Development

Let’s discuss some of the vaccines that probably will come first in the race and how they work: the AstraZeneca in collaboration with the University of Oxford in the United Kingdom (UK) and the Moderna Therapeutics in the United States of America. These are among the handful in Phase 3 clinical trials. Others include vaccines by Merck, the University of Queensland, GSK, Pfizer, Sinovac, Casino Biologics – the Chinese vaccine that was just reported, amongst others. Well, the AstraZeneca/Oxford and the Chinese Vaccine (their clinical study was just published on the well-respected journal The Lancet) use an adeno-associated virus genetically engineered as a “Trojan Horse” with an immunogenic protein (or an immunogenic part) of the Coronavirus (COVID19). It is difficult to explain right, but genetically engineered viruses have been used in research and clinical laboratories for research for decades. The idea here is that our immune system will fight “lightly” this foreigner hybrid virus and “create” a memory against it. The “secret sauce” for a vaccine efficacy and efficiency that we still do not know for the coronavirus is how long this immunological memory will last. For the polio virus one shot can last almost our whole lives, for the common flu and H1N1 we need to take it every year and probably from what I am reading about the coronavirus, we will need several shots during a single year based on the reports showing that the immunological “memory” doesn’t last too long. The Moderna vaccine uses a different approach based in nucleic acids. An RNA vaccine uses viral genetic material (in this case the coronavirus RNA) to produce antigens that would allow the body to learn to respond in a second infection by it. This is the first of this kind, that is why there is a lot of skepticism and concern. The last one that I wanted to write about is the “russian” vaccine that the media is discussing a lot recently. For me, as a scientist, if there is no data, no publication, no clinical trials and no information available I do not trust. The russians did not disclose anything: how the vaccine was developed, how it works, the tests that were done, if it is safe enough or not, etc.* To finalize, the most problematic part after all clinical and toxicological tests are cleared and the vaccine is ready is to produce it in large scale and distribute it globally.

What The Future Holds?

Several questions are still open to discussion based on the clinical scientific facts we have until now: Which country will get it first? How much a dose will cost per person? How many immunizations we will need to be safe and start walking around going back to normality? How the governments will deal with the bureaucracy to buy and distribute it to its citizens? We never had in my lifetime something involving so much money and interests in healthcare in a global scale like this. A lot of people can get filthy rich with the outcome of a successful vaccine, that is for sure. Thus, what the future holds in this race? Who will win? And, most importantly, when the first vaccine is approved what will be its immunological efficacy? 50%? 60%? Meaning that some people will not get the expected immune “memory”. Other factors that should be taken seriously are side effects of the vaccine (for example, in the Chinese vaccine study more than 90% of the group that received it had at least one side effect). Well, we are just watching this race and rooting for a good winner. I hope we will have something until the end of this year, and that it could reach every single person in the globe. A little utopic to think like this but we need to be positive. To close this post we still have an open question: Who will be the winner? What do you think?

*Footnote: An article describing a non-randomized phase I/II clinical study from Russia was published today, September 4th, with 76 people after my post was published. The strategy used was based on an engineered adeno-associated virus with an immunogenic protein from SARS-CoV-2. Even with a very low number of participants, the study is encouraging; however as stated in the Conclusions, the authors make it clear that further clinical investigation will be needed to test effectiveness. To check the full article in the journal “The Lancet” click here.

Please send your comments, questions, ideas or some information that you think is important to my email at fcosta@genomicenterprise.com or contact me at genomicenterprise.com/contact_us.

Coronavirus Tests: what you need to know

August 21st, 2020

This blog post will focus on the tests that have been offered for the coronavirus pandemia in order to evaluate individually and in geolocations how the virus is spreading. I am writing this post since most people do not really understand how these tests work, their differences, specificity, efficacy and also what means to have a positive and/or negative test depending on the technology used. I would say that 99% of people is “blind” when it comes to information on the tests and how to proceed after receiving a result. Well, since I am a researcher and have been reading a lot about the types of test, I will try to describe the ones in the market in an easy way to understand with no technical jargons. The main problem, like everything related to this coronavirus pandemia is misinformation or lack of it; this is expected since people in general know nothing about virology and the technologies used in research and clinical laboratories. In addition, most governments are not helping at all with confusing guidelines. There are two main ways to detect viral infections: immunoassays and by the PCR technique. Immunoassays are the widespread ones since they are cheaper and need just a droplet of blood or body fluids. PCR which means “Polymerase Chain Reaction” is a classic technique used in molecular biology since the 1990s. It was invented in 1989 and I have been using it since my undergraduate academic studies; this is not new at all. However, the way it is used and the type of it can impact the results. I will start with the immunoassay tests and then discuss PCR. Lastly, I will give my take home message with some guidelines and remarks on how people should proceed.

Immunoassays

Immunoassays have been used in laboratories for a while. I will not discuss the types of tests but how it works. These assays will detect an immune reaction caused by a pathogen, such as the virus, since our immune system generates what we call antibodies against the pathogen and a cellular “memory” against it in some cases.  One of the problems with this coronavirus is that we still do not know how long the immune cells will “remember” the virus and generate a better response in a second infection (the base to develop an efficient vaccine). This is still open to discussion. There are several ways to do immunoassays, but the best way is to detect indirectly the presence of these antibodies. Most antibodies are created against proteins in the outside part of the viruses. Thus, this type of test is indirect and will detect a response against the virus. Here that the problem happens. Most tests are binary: yes or no for the presence of antibodies against that specific virus (in this case the coronavirus). Just to make sure people understand: these tests are not measuring the virus, but a body response to it which will vary individually. The main problems that can happen are what we call false positives and false negatives. False positives happen when even without coronavirus infection you have a positive test. The main explanation for this is a cross-reaction with other viruses that the person was infected in the past that are very similar to the current virus. Another important point is that immunoassays will only detect the reaction of the body to the virus after the infection when the body was able to create antibodies after getting in contact with the virus. So, if you do these tests early in the timeline of the infection you can get what we call false negative. Finally, the pros to these tests is that they are fast, cheap and need just a few people and reagents. These are the ones that most people are doing now globally.

PCR and qPCR

The basic steps of the PCR test start with sticking a long swab far into a person’s nose (body fluid) or getting the person’s blood. To clean up the starting material, most test protocols then call for performing an assay that extracts out just the genetic material, clearing away all the debris and inconsequential bits. This requires time and specific reagents, which can be in short supply. PCR, like I wrote before, is not a new technology. However, in this case PCR will measure directly the presence of the viral particles (the nucleic acids or genetic material of the coronavirus) in the blood and/or body fluids. Thus, this test is mainly indicated during the infection period timeline since it will measure directly if the viral particles are circulating in the body. If you do the PCR test before the infection or after it, most likely it will be a negative test. The “upgrade” so to speak of the PCR is the qPCR or quantitative PCR, which can measure the number of viral particles per volume of blood and body fluid. For example, this is the test used to detect and to administer HIV viral infections in AIDS patients. That is the “state of the art” method indicated to detect the virus, even in small amounts. In this case a false negative will be very unlikely since it is designed for that specific virus. False positives could happen if the PCR test was badly designed and gets the genetic material of other viral particles infecting the person. These types of test have lots of pros since they are very specific; false positives and false negatives will be almost impossible. The cons are mainly the time it takes to get a result (generally days to a week), it is laborious, involves more people, reagents and it is expensive to be used for big populations. Moreover, most health insurance companies probably will not cover it, especially in the US. Recently, new technologies based in PCR were improved to decrease the costs, increase the specificity and efficacy making it more accessible (see this article for more information).

Take home message

The main message for the readers of this post is that there is no test that is 100% efficient and reliable, however as shown above in a very clear way qPCR is the best test if you are looking for a reliable result. However, be careful, the PCR tests should be used during the timeline of the viral infection since it will measure the viral particles directly. On the other hand, the immunoassays (there are several fast tests based in immunoassays) will measure indirectly the response of the body to the infection. Thus, these tests would be indicated maybe in the end of the timeline of the infection and after some time to see how long we can detect antibodies against the virus. All this information is very complex to understand but I believe these simple tips I am giving here are important to the general population and even governments to make decisions. Last, but not least, independent on the test you did or will do please do it at least 3 times, especially the immunoassays. For the PCR if you got a positive test it means you have an infection by the coronavirus at that moment. Then protect yourself and others and stay alert to symptoms. The tips I am giving here could be helpful so you won’t be confused by all this deluge of information (most times “fake news”) about tests and their results. Be aware and good luck – to all of us. We are in this together.

Coronavirus Pandemia: Why Science Matters Now?

August 3rd, 2020
Image Source: Chemical & Engineering Society

This is my fourth blog post on the coronavirus pandemia and I will focus on science and how general people are getting more interested in biomedical research. I’ve written in several occasions that the scientific system is broken, and I’ve criticized how the scientific funding system works, the peer-revision process, the low salaries and long hours of work, etc. In fact, let me just remind the readers how the scientific cycle works (I’ve already discussed this in an old post – check it here): First, when you want to get into academic research you need to do a Ph.D. in a very “famous” laboratory; this is the “business card” to get a Post-Doctoral Training in an even better laboratory (either in the US or in Europe); second you will need to publish your research after long hours of work (working like a “slave”, Pardon my French…) with a very low salary – not very exciting right?; third, with good publications in high-level journals you will need to bring in research money from well-respected funding agencies since this will enable you to start your own laboratory in a different Institution. If that does not happen you are already “out of the game”; fourth, if you are successful in all the first 3 steps, which are tremendously difficult, you can start your own laboratory and get funding  (the statistics are terrible: less than 5% of Post-Doctorates get to this stage, so what happens to the other ~95%? Do another Post-Doc, become jobless, change profession or go into the private sector). Thus, it is very competitive and the “big labs” always get the funding and grants. It is a very old-fashioned system. Another interesting fact is this: when you do experiments, draw an hypothesis out of them, write an article with your own intellectual skills, most times you will need to pay to publish (and a lot; we are talking depending on the publisher and journal at least 1,500 US Dollars) and give all copyrights to the publisher (well, there are some “open source” options, however it is not working well mainly because the big publishers are not happy, they want to keep getting their profits). Then, after giving the publisher all the rights for your work, paying a lot to publish, getting nothing in exchange financially – just “scientific prestige” (check my old blog post on this subject here), the publisher charges people to download the article (a range of 30-50 US dollars per article!). This is outrageous. Another fact: the private sector has full access to all these scientific articles (paying for downloads) and use them to develop “products” that they will come back and sell to Academic Centers and Laboratories for a very high price. It is a terrible cycle. Even Nobel Prize scientists are not happy at all with how science works (see my blog post about it here). It is a win, loose, loose, loose game. The only one winning here is the Publisher and eventually biotech and pharma companies. The most important aspect that will be the focus of my post: general people that pay taxes (part of it go to the funding agencies to finance research) have no clue how science and the scientific system works. Now, with the coronavirus pandemia, I believe everyone in the world is trying to understand how this system works. I always get questions like: Why there is not a medicine for the virus? Why there is no treatment? Why it took so long for governments all over the world to catch up and we are still in this mess? Simple answer: Scientific Systems are unprepared for any global pandemia. The system definitely has to change. Science communication has to come out strong after that (please stop the “fake news”!). Why is it so difficult to deal with the spread of the disease and lack of trustful information from the media and the governments? I don’t know. Lots of politics involved here. However, I think the positive point is that general citizens all over the world are trying to understand the scientific system, how we respond to pandemic situations such as this one and are demanding answers (true answers!). Now we see strong collaborations between Academic Centers and pharmaceutical companies (i.e.: University of Oxford and AstraZeneca) for a vaccine (this already happened before, but it not the rule). I will discuss the race to a vaccine for the coronavirus in my next blog posts (coming soon…). Let me give, as I always do, a personal example on how the scientific system is slow and old-fashioned: I just had an article accepted in a journal recently and we got the Cover of the Journal. I will not cite names here to avoid problems, but we (mainly my ex-Ph.D. student) took our creativity, time, resources and designed a “masterpiece cover” for the journal. We sent it to the Editorial Office and got the reply saying that the Cover was very nice and we would need to pay a fee of 1,700 US Dollars to have it published with our article. I said what? I wrote back questioning that we took our time, resources and creativity to design a cover and would have to pay to give them our copyrights – no thank you! The Editor wrote back apologizing and waiving 100% of the fee. This is a “toxic” business that is really affecting careers of young scientists. Another important fact: several if not most scientific articles published are already “old-news” since it takes an average of six months to a year if you are lucky to get your study published anywhere. Thus, now that this pandemia has impacted the globe, I see a “fast and furious” race both in academia and in the private sector to develop vaccines and treatments. I hope after we get an efficient treatment and/or vaccine the whole scientific system changes for the better. In addition, I defend that all the scientific community find better ways to communicate with the general public, mostly non-scientists, with trustful information in a way they can understand – no technical stuff, please. Science communication is key and it has to change for the better. People say that there is always a good side for every history and I hope this pandemia changes the whole scientific system for the better. We will see. I have my fingers crossed: to overcome this global pandemia and for changes in the way science is done everywhere!

Coronavirus Pandemia New “Normal”: Now and Then

July 20th, 2020

Image Source: World Economic Forum, 2020

On my last blog post I wrote about the misinformation that we are having to deal with in a daily basis with the coronavirus pandemia (see my blog post here). I also discussed how this misinformation is negatively affecting our society and the individuals, especially people that are not very careful in selecting trustful media and/or social media sources to gather information. This blog post will be more “positive” since I will discuss something that I see people asking everywhere: what will be the new “normal” after the pandemia? I mean, when things get in a stage that we can be more comfortable in going out and there is a vaccine that is efficient enough in the future (hopefully!). Well, there are five specific things happening right now that we could use as examples on how things will be after the pandemia. Actually, these factors have been accelerated by the pandemia since all of them were already happening “organically” in a slower fashion. I will try to discuss and show examples on how these areas have been affected and will be completely changed forever. First, let’s talk about remote work or working from home; something that most people in countries with “lockdown” have been currently doing. I am one of these people. Actually, I have been working remotely for more than a decade now. Remote work came to stay. Some companies before the pandemia were already using the option of “working from home” for one day a week or more, however from now on I believe that this will became more of a rule than an exception. I have examples of working remotely with Teams of people in South America, Europe, Asia and other places. The technology and faster broadband internet are already here. This came to stay, however how people that needs to go to an office or a laboratory or even a production line of a factory to work will do in the near future is still a question mark. Second, in the same way remote work came to stay, telehealth and digital healthcare solutions are expanding. I see people having videocalls with their doctors, psychiatrists, family doctors, etc. Solutions and technologies that are facilitating this connection between the patients and their healthcare professional also came to stay. Of course, that a lot of things need to evolve, and the patient privacy is still an issue, but this will be the new “normal” in medicine. Third, the impact of this pandemia on education (high school and college/university levels): EdTech (or virtual education) and education online is becoming more widespread now. Before, it was just a small percentage of the schools and colleges/universities that offered online courses. Now, all students from the globe are facing a different way of getting classes via internet. This trend was already in place by companies such as edX, Coursera, Udemy, the Khan Academy, etc. During and after this pandemia, online education has become more widespread as the technology evolves and the students get more used to it. I do courses online since 2015 and I really like it; I do not see any problem here. I think that the old-fashioned “medieval” education “on-site” is gone forever. Fourth, is the e-commerce sector and how big players such as Amazon are monopolizing it and will dominate (check this article entitled: “How the coronavirus and retail closures are accelerating the rise of Amazon”). Well, commerce in general has been affected by the pandemia and now we see all the companies (small, midsize and big ones) improving their websites, apps and other ways for online sales. Since nobody is able to go to the stores, the products have to come to us. Well, this trend started more than 20 years ago and now I believe it will become something “normal”. Unfortunately, owners of stores and commerce that are or were not prepared to move their sales online will be disappearing. That is a fact. Fifth and last, I think the bigger impact now and after the pandemia will be on the way we relate to each other. The consequences of social distancing will not disappear soon. One interesting personal example is that I went to a store the other day to buy groceries (of course with a mask and hand sanitizer in my pocket) and what I felt and saw was every single person getting far away from me and the other people around. When asking questions to people that worked in that specific place, I saw fear in their eyes and trembling hands when getting “closer” to others. Social distancing came to stay for a while, and it will affect even more the way we lived before – connected all the time with our mobile devices in our hands and not socializing at all. In my opinion, this will really affect social interactions between people for some time, I would say years if not forever. These are some of my perspectives on the new “normal” that we are facing and will face from now on. The world will never be the same, that is for sure. A “brave” new world and ways to deal with people came to stay. Let’s just hope that people will become more distant socially but closer in a general perspective, aware of the human species fragility, the nature around us and our planet. We need to take really good care of our “home”; and by “home” I am referring to the globe. The virus will be controlled at some point. However, how we as humans will live after that will change completely.

Coronavirus Pandemia: Facts and “Fiction”

July 2nd, 2020

In this blog post I will discuss about the current situation of the coronavirus pandemia and how misinformation and the so-called “fake news” is really a problem for our societies and the world in general. For those who follow my posts and read them, last month I wrote about a cousin I’ve lost in the North of Brazil for this disease (check the blog post here). My family members and his family like several other families in the world are still overcoming the sadness and trying to understand what is going on. The questions I currently see are: Why? How? When we will get a ‘cure”, an efficient treatment and/or a vaccine? The fact is that there is no “magic bullet” yet, especially when the pandemia is in the current stage. Today, the latest numbers are that at least 10.7 Million people were infected worldwide and at least 515,000 people died of complications of the coronavirus infection (for more information check the trustful website from the John’s Hopkin’s University here). Well, first of all, as a scientist I get lots of questions about the virus, how it infects people and mainly why it kills people in a current rate of 5-10% depending on the place, country and/or region. First of all, what kills is not the virus itself: the viral infection in the respiratory tract, especially the lungs (other organs are infected too, it has been already reported) causes a hyper-reaction from the immune system of the person that destroys the lung cells and open the “doors” to bacterial infections such as the one that causes pneumonia. Thus, what kills is the “auto-immune” response to the virus and not the viral agent COVID19. In this context, the age, sex, health, presence of a complex disease (diabetes, cancer, etc) will be important factors that will affect morbidity. In addition, since everyone is genetically different, even in immune response to viruses, this is probably why we see young people dying, not just elderlies. One thing is for sure: my generation and probably the one before me (my parents) and the next ones never lived through a situation like this. That is why now more than ever, the use of correct and trustful information are very important. Let’s get to 3 main important points that I would like to explore as facts and fiction: 1) Current tests that are being advertised everywhere. There are several types of tests that work very differently. The most common and fast is to check for antibodies against the virus or against proteins of the virus in the plasma of people, that is a fact. However, testing negative doesn’t mean that you are free to go outside without a mask and live like nothing is happening. I’ve had a very interesting personal experience last week since I went to the pharmacy where these “fast” tests are being offered and people have to pay (not cheap by the way…). When I was in the line waiting to get my medication, a lady got a negative result for the test and jumped saying to the pharmacist: “so now I am free and can go outside without a mask!”. The pharmacist very gently told her: “Well, please understand that having a negative result for this test doesn’t mean that you could get the virus or that you’ve already got it and have no antibodies against it”. The lady turned to him very angry and said; “Then why I am doing this test and paying for it!”. This is the main problem right now: people do not understand that the tests are not a way of “getting out and living free”. The other tests that are more specific for the virus such as the “famous” PCR are more expensive and laborious. Not a lot of people can afford to do it. The summary in this first example is that I do not trust any of these tests since we are still understanding how the virus works. So why bother?; 2) Treatments for the virus. Fictions: there is no “magic bullet” yet like I’ve wrote above and the treatments are much more complex than “advertised”. It is and will be a combination of drugs to block the hyper-immune reaction, block the virus and also antibiotics for the worst phase when people get pneumonia and/or other bacterial infections. So, please people do not believe any of these “miracle drugs” being advertised everywhere, especially in social media and last 3) the vaccine: well there are at least 140 vaccines in several stages of tests (please check this article from “The Guardian” for more information) and just 2 of them are in the latest phases of the clinical trials. There is another problem here with facts x fiction: a vaccine against a virus is not easy to develop. For example, we still do not have an efficient vaccine against HIV till this day (and HIV is an RNA virus such as the coronavirus; the only difference is the cells they infect and the way they spread). Vaccines could be of the attenuated viral particle, proteins of the virus, nucleic acids of the virus, etc. I believe that we need to be pragmatic: it will take time to get an efficient vaccine. Several groups are working toward this goal, that is a fact. However, let’s be “real”: it will take some time, maybe a year or so. The main fact right now that I think everyone in the world should believe is that the only way to fight this pandemia is avoid being infected by the virus. How? Social distancing and isolation, unfortunately. People working in healthcare and services that are essential need to use masks and be careful. There is nothing else we can do right now. Last, but not least, I wrote before that “Science is Broken: How, Why and When?” (see my blog post from some time ago) and other critics to how the scientific system is in its medieval times. My hope is that people in general, now being directly affected, see how important science is and give scientists such as myself and several others some respect. I also hope that the system changes. In this type of situation I see people, even my family members telling me: why no scientist was studying this type of virus? Why is it so difficult to overcome this? I tell them in an ironic way: ask the governments and the academic system that does not work for the people. Finally, based on all the facts I have been reading and know until now my last piece of advice to everyone reading this post is to stay home and take the measures that prevent the infection (use masks, disinfect everything, etc), independent on what governments and other people tell you or you see in social media. The fact is there is a pandemia, we do not completely understand the coronavirus, there is no treatment and no vaccine 100% yet. Thus, take care of yourself and people you love. Let’s try to overcome this pandemia together (but socially isolated…) with facts and not anecdotal information that we get every day through the media. And most important: let’s stay mentally stable and sane. This is my message to all.

Pandemic Times, Healthcare & Family

June 4th, 2020

The blog post I am writing today is a sad and tragic one. This past weekend I just lost my beloved cousin, Bruno Falconi Fontoura. He was a Medical Doctor, a healthcare practitioner, anesthesiologist, and more than anything a husband and a father of two beautiful kids; a son and a daughter. Well, the title of this post embraces all the craziness we have been living this year: the coronavirus pandemia, how people that are in healthcare have been dealing with it and about family, the most important piece of this puzzle we are living right now. Bruno has been a Medical Doctor for almost 20 years in my hometown in Brazil, named “Beautiful Horizon” (“Belo Horizonte” in Portuguese, because it is located in a nice valley and the sunrise and sunset are just beautiful). He has devoted most of his life to medicine, working overtime for years, not being able to celebrate birthdays and family gatherings mainly because he was always on call. The last couple of years have been tough for him, depression came and sank in. This year, he decided to go to the north of Brazil to help in the “front lines” against the coronavirus pandemia and unfortunately died suddenly. Brazil is now the second in the world in number of cases and deaths because of the coronavirus. We don’t really know the cause of his death (it was ruled as cardiac arrest and respiratory insufficiency), but since he was dealing with a lot of coronavirus patients, I suppose it had something to do with it. We have been talking from far using technology (whatsapp, phone calls, etc) constantly and in one of the last messages I have received from him he desperately asked: “What is going to be of all of us, our and the next generations, after all this pandemia ends if we survive?” I replied with a long voice message since I felt his anguish. The short summary of my message to him was to keep doing his work the best he could, protect himself and I told him to focus in four main things. The four things I mentioned were: 1) take care of our general health: exercise and eat well; 2) avoid getting this virus since we still don’t have a lot of knowledge about it; 3) take care of our mental health, since we (and him personally with his profession) are dealing with deaths and a global pandemia – basically keep yourself sane – and last and the most important 4) be with relatives and family at all costs (of course, taking the measures to avoid spreading the virus, etc). These four itens I told him a couple of weeks ago are still what I believe in, but now more than ever I believe we need to gather with our closest family and stay home. The governments and society are not and will not help at all. We are losing this battle. This virus is an invisible enemy and not being a pessimist, it will take time to understand it and to develop a treatment and/or vaccine. Now, more than ever, scientists have to work just like healthcare professionals to help. After this loss I’ve really got shaken. When things like these that you see in the news and media get close to you, especially to a family member that you’ve grown up together, young, full of life and energy, a dad, a professional and the most important: a human being. Loss is always tough, but when there is neglection like what is happening right now it is called genocide. But I will not get into politics in this post, maybe later. Bruno, wherever you are I hope you are well. And my message to all that are reading this post is stay safe, stay healthy, stay home (if possible) and stay mentally strong. It will not be easy, but I think we can do it. For the people we are losing and for the next generations.

*In Memoriam of Bruno Falconi Fontoura, my beloved cousin. He is lived through his wife Katia, his daughter Ana Beatriz and his son Benicio. Photo Source: Personal album of me and Bruno, circa 1989 in our “golden years”.

Portuguese version:

Pandemia, Saúde e Família

O “post” que estou escrevendo hoje é muito triste e trágico. Neste fim de semana, perdi o meu amado primo, Bruno Falconi Fontoura. Ele era médico, especialista em anestesia e, mais do que tudo, marido e pai de dois filhos lindos; um filho e uma filha. Bem, o título deste “post” abrange toda a loucura que estamos vivendo este ano: a pandemia global do coronavírus, como as pessoas que estão na área de saúde estão lidando com isso e sobre a família, a peça mais importante desse quebra-cabeça que estamos vivendo agora. Bruno foi por quase 20 anos médico em minha cidade natal, no Brasil, chamada Belo Horizonte. Ele dedicou a maior parte de sua vida à medicina, trabalhando horas extras por anos, não podendo comemorar aniversários e reuniões familiares, principalmente, porque estava sempre de plantão. Este ano, ele decidiu ir para o norte do Brasil para ajudar na linha de frente contra a pandemia de coronavírus e, infelizmente, morreu repentinamente (insuficiencia respiratoria e parada cardiaca, que sao as principais causas de morte pelo virus…). Realmente não sabemos a causa, mas como ele estava lidando com muitos pacientes com coronavírus, suponho que tenha algo a ver com isso. Nós conversamos usando tecnologia (whatsapp, telefonemas, etc.) constantemente e uma das últimas mensagens que tenho dele foi: “O que será de todos nós, da nossa e a próxima geração, depois que toda essa pandemia terminar, se sobrevivermos?” Respondi com uma longa mensagem pois senti sua profunda angústia. O breve resumo da minha mensagem para ele foi continuar fazendo o seu trabalho da melhor maneira possível, proteger-se e acho que agora devemos nos concentrar em quatro coisas principais. As quatro coisas que mencionei foram: 1) cuidar da nossa saúde geral, exercitar-se, comer bem; 2) evitar pegar esse vírus, pois ainda não temos muito conhecimento sobre ele; 3) cuidar de nossa saúde mental, já que nós (e ele pessoalmente com a sua profissão estressante) estamos lidando com mortes e uma pandemia global – basicamente mantenha-se são e por último e o mais importante 4) esteja com parentes e familiares a todo custo (claro usando as devidas medidas para evitar a propagação do vírus). Esses quatro itens que eu disse a ele algumas semanas atrás ainda são o que acredito, mas agora mais do que nunca acredito que precisamos nos reunir com a família mais próxima e ficar em casa. Os governos e a sociedade não estão ajudando e nem ajudarão como deveriam. Estamos perdendo a batalha. Este vírus é um inimigo invisível e não sendo pessimista, levará algum tempo para entendê-lo e desenvolver um tratamento e/ou uma vacina. Agora, mais do que nunca, os cientistas precisam trabalhar, assim como profissionais de saúde para ajudar. Após essa perda, fiquei realmente abalado. Quando coisas como estas que você vê nas notícias e na mídia se aproximam de você, especialmente de um membro da família que você cresceu junto, jovem, cheio de vida, pai, profissional e ser humano ficamos assustados. A perda é sempre difícil, mas quando há negligência como o que está acontecendo agora, isso se chama genocídio. Bruno, onde quer que esteja, espero que esteja bem. E minha mensagem para todos que estão lendo este texto é permanecer seguro, saudável, ficar em casa (se possível) e se manter mentalmente forte. Não será fácil, mas acho que podemos fazê-lo. Principalmente, em homenagem as pessoas que estamos perdendo e para as próximas gerações que ficam.

*Em memória de Bruno Falconi Fontoura, meu amado primo. Ele deixa sua esposa Katia, sua filha Ana Beatriz e seu filho Benicio. Foto: Album pessoal, Eu e Bruno, ano de 1989, nossos “anos incríveis”.

Chimeric Bio (CBC) and Genomic Enterprise join forces to tackle big data

January 21st, 2020

This blog post will focus on the announcement of the two life sciences’ companies that will start to work together to provide new, user-friendly, and revolutionary mobile access of big data to biotechnology, pharmaceutical, life sciences and technology companies. There is a new trend highlighting the need for new technologies to address the big data challenges and associated opportunities at pharma right now in drug development, biomedicine and healthcare. This is mainly because there is a need to develop and use big data analytics tools’ from hundreds of thousands to millions of patients and samples throughout the drug development process. That is what the CEO of Novartis (NYSE: NVS), Vas Narasimhan, started to implement at the company when he became CEO. This new trend is important to accelerate drug discovery, the development of new treatments and target identification applied to complex and rare diseases. However, there are several challenges associated to the current tools’ in the market and changes in the pharma “culture” to adopt new technologies as discussed by him and others at the JP Morgan Conference in San Francisco in January of 2020 (check the article at Forbes “Novartis CEO Who Wanted To Bring Tech Into Pharma Now Explains Why It’s So Hard”). Thus, Chimeric Bio (CBC) and Genomic Enterprise will start a “joint venture” called MobileBiOS to provide the best in class scientific solutions, services and support to customers identifying specific medicines and treatments to various diseases combing it to the development of solutions for mobile devices. “I think this will be a very nice opportunity for clients that are looking for state of the art consulting services in biomedicine and healthcare. Tristan’s expertise and my experience after founding and co-founding four companies and being the Head of one of the Apple Labs Program in Brazil, South America will definitely make a difference that the market needs right now” said Fabricio Costa about joining forces with CBC. “ModbileBiOS will allow biopharma professionals to have immediate access to new big data analytics tools’ and the corresponding actionable results culminating from these analysis. CBC already offers a number of powerful big data solutions across various types of data including curated scientific and biomedical content, patient data, single cell data, clinical trials’ information, biomedical conferences, publications, regulatory information and patents.” remarks Tristan Gill about the new Joint Venture.

Genomic Enterprise’s mission is to provide consultancy services in several different fields involving STEM (Science, Technology, Engineering and Math) for the government, academic centers, universities, start ups, mid-size companies and big corporations globally. In addition, Genomic Enterprise creates awareness on the new scientific discoveries and technologies that will impact society worldwide or even locally. Fabricio Costa is the founder and CEO of Genomic Enterprise and he has more than 20 years of experience in top academic labs and companies such as The Ludwig Institute for Cancer Research, Harvard University, Northwestern University, University of Chicago, Start Up Health Academy, Singularity University, 1871 Chicago, MATTER, Shire Pharmaceuticals (acquired by Takeda – NYSE: TAK), Google (NASDAQ: GOOGL) (Ventures, Higher Education and Start ups), Apple (NASDAQ: AAPL) and others. Fabricio is also a serial entrepreneur (co-founded and founded four startups; two were successfully sold).

Chimeric Bio (CBC)’s main mission is to support a complimentary set of innovative life science offerings and deliver first class consulting services to customers. CBC accomplishes this by understanding the pharmaceutical customer’s challenges and offering solutions to help customers’ achieve these critical needs. CBC can define unique solutions that best meet the scientific and business needs for customers.  Chimeric Bio’s founder and CEO Tristan Gill is an accomplished life sciences professional. Prior to founding CBC Tristan has 25 years of experience in top labs and companies including Cold Spring Harbor Laboratory, California Institute of Technology, Paracel (a subsidiary of Celera Genomics acquired by Quest Diagnostics – NYSE: DGX), Rossetta BioSoftware (a subsidiary of Merck & Co.- NASDAQ: MRK), Ingenuity (acquired by of Qiagen – NASDAQ: QGEN), Bejing Genomics Institute (BGI), and Thomson Reuters (NYSE: TRI).