[Science/Stem Cells] Stem Cell Therapy and Age-related Macular Degeneration – A Tale of Two Cases Reports

Yesterday, a breaking news in the stem cell field came from a case report published in the New England Journal of Medicine (a respected journal in medical research) (http://www.nejm.org/doi/full/10.1056/NEJMoa1609583?query=featured_home).
What is probably the most intriguing about this case report from a stem cell clinic, that had a clinical trial submitted to the FDA and subsequently withdrawn in 2015 (https://clinicaltrials.gov/ct2/show/NCT02024269?term=NCT02024269&rank=1).
This case report focuses on three patients, elderly patients (70+) and all three suffering from age-related macular degeneration (AMD).
They all three being injected with mesenchymal stem cells. For those not familiar with stem cells, stem cells comes into different flavors depending on their origin and potency abilities. The most pluripotent type of stem cells are the embryonic stem cells (hESCs) that are derived from embryos. Following in their pluripotency comes in the induced pluripotent stem cells (iPSCs). Unlike hESCs, iPSCs are reprogrammed somatic cells (usually skin fibroblasts). Then we have bone marrow stem cells (from bone marrow) that have a narrower pluripotency but proven efficacious for treating patients with leukemia. Finally we have the mesenchymal stem cells (MSCs) obtained from the stream fraction of adipose tissue. Usually these cells are obtained by liposuction and isolated from the fat tissue via defined protocols.
Now this last type of cells has a certain classification that allows to use a loophole. In order to conduct a clinical trial, you have to submit an investigative new drug (IND) application to the Food & Drug Administration to show evidence of safety and efficacy from pre-clinical studies. These are safeguards that ensure patients and medical researchers enrolled in such trials.
Now, when you are dealing with MSCs, these stem cell “clinics” can exploit some loopholes and apply for a non-IND application if your trial follows two criteria: it is an autologous procedure (you are injecting cells from yourself back into your body) and there is no procedures that modify the material used (in that case, the purification steps are not altering the MSCs identity and function).  In addition, these trials have to be done without any financial link. In academic institutions, you neither ask the patient to pay for the clinical trial nor  provide the patient with a financial compensation (only a possible therapeutic outcome, if the treatment work). In this case reports, all patients paid $5000 to that clinic. it is also important to note a certain level of deception from the stem cell clinic as this registration at the ClinicalTrials.gov website appeared to these patients as a clinical trial were it was not. It is even mentioned by the authors of this case report that none of the consent form signed by these patients displayed “clinical trial”.
There is also report in the consent form that the patient were informed of the risk of blindness and were requesting to have the procedure done in both eyes.
These patients rapidly developed post-operative complication including retinal detachment, increased ocular pressure and hemorrhagic events, such complications were not taken care by the clinic involved in the stem cell procedure and were done in eye clinics in patients domicile.

By coincidence, NEJM also published another case report of the use of stem cells in AMD in a clinical trial in Japan (http://www.nejm.org/doi/full/10.1056/NEJMoa1608368?query=featured_home). This procedure was done using iPSCs from patients and derived into retinal pigmented epithelial cells (RPEs). These cells are lining the outer side of the retina and serve as a barrier for protecting the retinal neurons involved in vision. This is the famous “iPSC clinical trial” from Takahashi and colleagues that had to be halted due to some safety issues that were corrected (https://ipscell.com/2016/06/good-stem-cell-news-as-takahashi-ips-cell-trial-to-resume/).
So far, the encouraging part is the absence of post-operative complication and graft rejection and the patient showed an improvement in her vision.Yet, this is a single report and the authors were also very cautious about to make overstating conclusion.

These two cases report should inform into two things: we are making little steps but confident steps in stem cell based therapies but it is also important to raise awareness and vigilance about the methods of some stem cell clinics making unrealistic claims of stem cell therapies or posing as clinical trial center.

My recommendation is if you decide to jump into a clinical trial is to verify the affiliation of the center (avoid any private firms and check the credentials of any institution supporting this trial), ask your doctor to help you read through the consent form and never ever be asked to pay for the procedure. The trial is funded by research grants, if it is requested that you cover the expenses of such procedures run away!

 

[Sciences] First clinical trial using the CRISPR/Cas9 in China.

You may have heard about the news on the first clinical trial in China that was consisted of inoculating cells modified by the CRISPR/Cas9 technique. In this post, I relaying the original article published in Nature online about the trial (source: http://www.nature.com/news/crispr-gene-editing-tested-in-a-person-for-the-first-time-1.20988?WT.mc_id=SFB_NNEWS_1508_RHBox)

For many of you, CRISPR may not be much explanative except the word that sounds like something being “crispy”. Indeed the technique is.
But let’s understand the technique to better understand why it is a breakthrough. There is a nice video made by iBiology and featuring Dr. Jennifer Doudna (the co-discoverer of CRISPR/Cas9) explaining very nicely exhaustively in lay terms the CRISPR/Cas9 technique that I will quickly resume to keep that post short

 

CRISPR/Cas9 acts as a little genetic scissors, that permit us to cut and paste genetic data into cells. Stricto sensu it is not new and we have doing it in bacteria, yeasts, plants, fruitflies, zebrafish and mice for a while now. But one thing we have been facing is editing genomes in bigger animals like rats, primates and humans. It is extremely difficult and very poorly efficient.

With CRISPR/Cas9, we suddenly have a magic wand that now makes the impossible-possible by making the gene edition in higher mammals much more easier. Also CRISPR/Cas9 allows us a more targeted editing, precisely.
However the technique has known some possible off-target gene editing, such caveat is enough to raise concerns for patients safety. However, as science goes, there is a rapid interest in the technique and improvements are coming in the fast pace.

In this trial, the investigators have taken immune cells from a patient suffering from a lung cancer and removed a gene called PD-1. PD-1 is a receptor for a molecule called PD-1 ligand, a protein secreted by cancer cells. Upon interactions with PD-1L, PD-1 results in a immune suppression and shutdown of the immune system. By removing PD-1, the immune system is no more silenced and now can target and strike cancer cells. This is a new concept in fighting cancer cells called immunotherapy.

This trial will tell us two things. First if the technique is safe and second if it is efficacious. The treatment appears safe (because the cells have been engineering outside the body and reprogrammed in a dish before being reinserted) but we cannot exclude any severe if not fatal side effects.
The second is the efficacy. There are evidence of PD-1 targeting being a novel treatment that showed promising results in Phase II and III clinical trials. But that will work with lung cancer? We will have to wait and see….

If it works, that would be fantastic and open the possibility to revive the gene therapy that has been mostly stuck in limbo by our lack to insert and correct defective genes in patients.

[Science] What if cancer was just a series of bad luck?

10885528_856688584354383_5301852488791619441_n

Source: C. TOMASETTI, B. VOGELSTEIN AND ILLUSTRATOR ELIZABETH COOK, JOHNS HOPKINS UNIVERSITY, The Scientist magazine.

Since the “war on cancer” decorated by Richard Nixon in the 1970s, where are we after 40 years of research on cancer and why do not we have a cure for cancer?
We have learned a lot about cancer:

* We referred to cancer as a single disease, but it is indeed  an umbrella for many different types of diseases. A brain cancer is different from a lung cancer.

* We have been classifying cancer based on the tissue of origin (carcinoma, sarcoma…),

* We have identified many genes that once mutated result in cancer, we have identified many environmental factors capable to increase your risk of cancer (tobacco, smoke, obesity, polyaromatic compounds, ionizing radiations….). http://www.ncbi.nlm.nih.gov/pubmed/24816517.

* We learned that cancer is a disruption of a physiological balance, for instance we thought that an excess in oxidative stress and free radicals were promoting cancer. http://www.ncbi.nlm.nih.gov/pubmed/25496272.

* We have highly improved the way we detect cancer, remove surgically cancer and found new chemotherapy that really improved survival rate in many cancer. Yet, malignant brain tumors (glioblastoma multiform and brain metastasis) remain the most deadly form of cancer, in partly because we fail to deliver therapeutics across the blood-brain barrier. The tragic case of Brittany Maynard as well as children with aggressive form of medulloblastoma makes me feel helpless because I know how powerful the blood-brain barrier is in blocking the delivery of these agents. It will be hard to untangle a evolutionary trait to protect our brain from neurotoxic and poisons to deliver it.

* Stem cells and malignant cancer cells seems to share a dark common origin. If you inject stem cells in an animal, they become wild and form teratomas, just as cancer cells would do. But they also share similarity and I like to refer that stem cells keep “the primitive cell phenotype” in a evolutionary standpoint. I like to think that cancer are cells that “accidentally” turn on the time machine and reverse their biological and evolutionary clock back to the time were LUCA (the Last Unicellular Common Ancestor) were swimming in the “Primeval soup”.

So now, we now that “one size fits all” approach to treat cancer and we really need to think about treating it as a personalized approach, using modern technology (genomics, epigenomics, proteomics….) to dress an identity card of the cancer for each patient to find which approach is the best.

Cristian Tomasetti1,*, Bert Vogelstein2,* Science 2 January 2015:  Vol. 347 no. 6217 pp. 78-81  DOI: 10.1126/science.1260825

Source: Cristian Tomasetti, Bert Vogelstein. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 2 January 2015: Vol. 347 no. 6217 pp. 78-81. DOI: 10.1126/science.1260825.

The recent study from Tomasetti and Vogelstein indeed show that incidence of cancer is “bad luck”. We know that each time our cells divide, the duplication of our genome is not “fool-proof” and introduce a mutation (1 base pair mutation for every million replicated). This is a handicap (because you loose your information over time) but it is also a blessing because this is how evolution works and what we are. Just a bunch of lucky mutations spanning over a billion of years of zillions of cell divisions. Under normal circumstances, we have “safe-fail mechanisms” (tumor suppressors) that are here to send defective cells into apoptosis (a sort of auto-destruction mode or if you like the cellular version of “hara-kiri”). But sometimes these defective cells do not follow that path and keep proliferating. This is all about. More you have cells within a tissue that keeps dividing, more you increase your risk to increase your pool of potentially tumorous cells. At the end, it is just a long equation of probability in which risk factors just increase the probability to success of the event.

My recommendations? Stay healthy (exercise often, follow the nutritionist recommendation for calories intake), stay safe (especially if you are working in a risky environment, follow your safety and OSHA guidelines), keep a regular check on your health and if you feel something weird do not hesitate to further investigate. And please, follow your physician recommendations.

Happy new year y’all.

[Sciences] My Top 10 Sciences Discoveries of 2014

Here I am, a couple of hours before the end of 2014 and lots of excitement in science this year. Here are my top 10 discoveries that marked me this year. It is surely biased (stem cells, blood-brain barrier) but hey I am a scientist after all. There is no particular ranking, so do not use the numbers as a rank.

Note: I will update this blog post by adding additional contents.

1.STAP Cells

The latest blog post from Dr. Knoepfler on the STAP cells debacle

STAP cells: stimulus-triggered acquisition of pluripotency. This was certainly the buzzword of January. Imagine that. Cell reprogramming (following the Yamanaka protocol) of somatic cells into iPSCs is a daunting experience. It is long, expensive and low yield (0.1%). When the technique came, it brought 30% yield and sounded as easy as prepping kosher-dilled pickles. Yep, just that, plunge the tissue into some acidic bath (that is a scientific iteration of the pickling process) and you get 30% of iPSC-like cells (or STAP cells). Sound as easy as ABC, no? Well indeed it was not. And it turned sour very fast indeed with over 10 labs trying without success. First came some statement similar to “it’s complicated”, then inquiry from RIKEN university in Japan followed by obvious scientific misconduct and paper retraction as the first author failed to reproduce the original data. In addition, the senior author committed suicide. A tragic ending for a flawed study, a “too simple to be true”.

2. The first stem cell clinical trials for retinal macular degeneration

This year have seen the first stem cell clinical trials using hESCs and iPSCs in patients suffering from macular degeneration. Preliminary results are showing a relative safety of the technique (no tumor observed so far) and some reports of improvements in certain patients. It is still not known if such improvement is a “placebo effect” or real effects. Similar studies are ongoing for other cardiovascular diseases and for neurological disorders such as Lou Gehrig’s disease or Huntington’s disease at the Mayo Clinic. However, I would like to remind people that there is yet no stem cell cures or proven stem cell therapies. Please, please, please do not listen to those claiming “stem cell therapies” that are working. There is not such thing and there is not yet any FDA-approved guidelines for such. A lot of labs are working to bring stem cells from the bench top to the patient’s bedside but still a lot of way to go.

3. The gut-brain interactions: the blood-brain barrier as the middleman

Diffusion of an IR-dye across the blood-brain barrier in a “sterile” mouse compared to “pathogen-specific free” mice. Note the fluorescence intensity showing a leaky BBB. Courtesy Karolinska Institute.

This was the most interesting and the fast-pacing rise. Until a few years ago, we mostly believed that the gut microbiota would only affect the GI tract without any incidence on the rest of the organism. I was stunned by two studies: one study showing the impact of microbiota composition in the gut flora on autism-like symptoms (http://www.ncbi.nlm.nih.gov/pubmed/23307560) that shows how the alteration of the flora composition resulted in the display of autism-like phenotype. The mechanisms are unknown but it seems the presence of a leaky intestinal tract may trigger neurobehavioral changes. The second comes from http://www.ncbi.nlm.nih.gov/pubmed/25411471, in which they show that the absence of a gut microbiota results in an increase leakiness of the blood-brain barrier. It took 60 years for neuroscientists to admit the presence of a blood-brain barrier. Hopefully, by 2020, neuroscientists will finally understand how crucial the BBB is for the brain well-being and the salute of treating neurological diseases will only come when they will understand that we BBB scientists are as important as them.

4. Human induced pluripotent stem cells as disease modeling and drug toxicity screening

If one biomedical research field that quickly emerged in the last decade, it is certainly the field of induced pluripotent stem cells (iPSCs). For those who are not aware about iPSCs, this is an important discovery of this century. Once the egg is fertilized, it quickly divide into 2, 4, 8, 16 cells up to reaching a stage called a “morula” stage that ultimately evolve into a blastocyst. This blastocyst will eventually become…YOU! Interestingly, all these cells are called totipotent as they can form any type of cells. These are the classical “embryonic stem cells” that have raised hope and fears among the public.
All of our cells have the same genetic information but what makes a neuron from a muscle cell is the number and types of genes that are ON and OFF. This is what we call the epigenome. By reverse-engineering it, we can bring reverse the clock on these cells to bring them into a pluripotent stem cell stage. Once pluripotent, we can reprogram these cells into any type of cells. This dedifferentiation stage was developed by Yamanaka in 2006 (Nobel Prize 2013) and applied to human cells by Jamie Thomson in 2007. Since then, a lot of effort have been done to differentiate these cells into various cell types including neurons. This open a new perspective as we can now try to understand human diseases in a dish by directly having access to patients cells. And this have been successfully applied in these last five years for different types of neurological diseases. If we have to show a poster-child for personalized-medicine, that would be its first iteration. There are numerous studies showing the ability to differentiate neurons from patients suffering from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, ALS, frontotemporal degeneration, Dravet Syndrome, Fragile X Syndrome, schizophrenia….
As we are just starting to understand the mechanism of diseases, we can now foresee the possible usage of these cells to identify novel compounds capable to slow or even relapse the disease.

5. The Edna Krabappel and Lisa Simpson peer-reviewed study

http://www.sciencealert.com/two-scientific-journals-have-accepted-a-study-by-maggie-simpson-and-edna-krabappel

This was one of the big bust, especially when you are in the academic field and know the calvary of publishing your manuscript. Getting your study is a long and patient process in which you have to deal with peer-review process, in which other scientists (anonymously) review your study and give their decision to the editor-in-chief about if your study is good for publishing or not.

In the classical model, the journal charges the authors of the study for publishing the study and the readers to access to the full journal. And having access to journals can be very expensive especially if you are in a small university or if you are located in a developing country. Still even with the best peer-review system, there are still flawed study that made it to publication and get retracted (http://retractionwatch.com). Since these last few years, an important step have been done to provide open-access to scientific papers. The authors pay a publication fee (usually higher than the traditional journal) but the paper is freely accessible to read it.

This new model has of course brought some interest for some people seeing “easy money” to be done, by accepting ANY studies, even from fictional characters. The fact that a paper authored by Edna Krabappel and Lisa Simpson filled of non-sense text fillings raise concerns and make a call to establish some guidelines and ways to select the “good open-access journals” from the bad ones. Also this year, the NIH Library of Medicine, the Pubmed portal (a well known scientific articles search engine for biomedical scientists) has launched the Pubmed Commons to provide an open, post-publication review mechanism in which anyone can comment on any paper presented in Pubmed.

I believe this is the first case of many uncovered and we are expecting to see more. It is a time we have to decide if we keep our science straight and well-sounded or if we let hijacked by flawed and manipulated studies.

6. Rosetta Stone and Philea probe

This was the biggest achievement of the European Space Agency (ESA). Can you imagine sending a remote probe, have it land on an asteroid. You have to imagine piloting a RC buggy car through a screen with 10 minutes delay between the time you see the obstacle and the time the command is executed. Imagine you drive your RC buggy see a tree in front of you, send the command to turn right and have to wait 10 minutes to get it done.

If I have one rant to make, it certainly on some trolls that pointed on Dr. Mark Taylor’s shirt and ignored the scientific achievement accomplished. Yes, having this shirt on live broadcasting was a terrible PR move, but putting on that shirt to blame the problem of women in science is wrong. The problem is much bigger than a shirt and those that are putting bars in the wheels of women in scientific careers are not wearing such shirts. We need to re-think about the whole system to better retain women in sciences, set maternity leaves and adapted schedule to have them the possibility to adapt their work to their schedule, tailor the tenure process to take in consideration that women have to deal with two important choices in their life in the same time and should not be forced to choose one  for the other.

Although Philea landed in a wrong place and rapidly died from low battery, it gave us some information. For a moment, I fell in love with Philea, like a real-life WALL-E. I am looking forward to have it back on track and running up soon.

The also interesting projects are the Mars Curiosity roving over the red planet and found some bursting methane (that could be some microbial life) and of course the Pluto mission coming in early this year.

7. Prosthetic arms and cyborgs

As a kid, I always got fascinated by robots, cyborgs and giant mechas. I grew up watching “UFO Grendizer”, “Star Wars”, “Transformers”, “The Terminator”, “The Million Dollar Man”, “Robocop” but also got frightened by “Galaxy Express 999” in which in a distant Earth future, humans have most of all acquired immortality by replacing their biological parts into robotical parts. Those who failed to afford or refused to become cyborgs are considered as sub-humans and hunted as preys.
Human-mechanical interfaces sounded like science fiction 20 years ago. As we have been progressing in neurosciences, we also have considerably improved in mechanical engineering and electronic. We are just assisting in the first trials in which prosthetic limbs are directly connected to the brain surface or capable to transduce electrical impulse from nearby muscles to execute movements. Two trials especially caught my attention: the one depicted in the picture and currently run at John Hopkins University in the Department of Applied Physics. The two robotic arms can sense muscle activity from the chest and transduce into complicated movements. Watch the video it is really impressive to see this man capable to regain functional from lost limbs.

http://bcove.me/vst8dnvp

The second one from the University of Pittsburgh allowed a quadriplegic woman to gain control of a robotic arm through a brain-connected interface. Look at the fluidity of the arm, the dexterity. Remember this is a robotic arm connected to the patients brain, it is just  awesome to see the improvement of such discipline over the years.

8. The lady with no “Little Brain” (Cerebellar agenesis)

Source: Cerebellar agenesis Luigi Titomanlio, Alfonso Romano and Ennio Del Giudice Neurology 2005;64;E21 DOI 10.1212/WNL.64.6.E21

Source: Cerebellar agenesis
Luigi Titomanlio, Alfonso Romano and Ennio Del Giudice Neurology 2005;64;E21
DOI 10.1212/WNL.64.6.E21

The cerebellum (or little brain in Latin), is an important piece of the central nervous system. Its function is essential in the locomotion and in the coordination of movements. This is also the primary target of ethanol, the active component of alcoholic beverages (or booze if you like it). Thats why when you are drunk you loose your reflexes and have the typical walking pattern of a drunk person.

We may think that the absence or severe malformation of this organ may significantly impact the locomotor function. Seems not according to a recent study from Fu and colleagues (http://brain.oxfordjournals.org/content/early/2014/08/22/brain.awu239.long). Apart from having trouble to keep an equilibrated statute and some episodes of nausea, the patient appears to have a normal life as she is reportedly married and has one daughter. It shows one thing: the brain appears very plastic and can rewire some of its functions if needed. The most interesting aspect now is how the cerebellar function is re-wired and compensated by the other brain area and which areas?

World Stem Cell Summit 2014, wrapup and impressions

0c0cfa2

Just coming out the #WSCS14 conference that was held in San Antonio this year. Oh boy, three days of intense scientific contents and networking, three days of running from one conference room to another and looking at the program to be sure to pick the most relevant one. Time to metabolize and put some thoughts on a blog.

This was a great meeting, especially for one that I just got introduced. Lots of good speakers, interactions with the exhibitors and with other presenters. It was a truly unique experience to get to know the San Antonio biomedical research area and strengths. It clearly seems to me that UTHSC San Antonio branch really try to built a strong research on stem cells research, including non-human primate based research. It was for me a particular chance to identify possible collaboration within the state of Texas.

The second aspect that i appreciate was the eclecticism of attendees at this meeting. Typically, you have conferences designed by scientists for scientists. Here I had the chance to discuss with scientists (sure it is a scientific meeting) but also with fundraising agencies, core facilities managers, patients and patients advocacy groups. And that is unique to have such patients advocacy groups that brings us back to what is our research is about: finding cures for patients because patients outside are suffering from their conditions and the medical advances are not reaching them. This is where as an outreach enthusiast I can grasp the need to scientists to reach out to the community and understand why their tax dollars means and how it get used.

Another session that i particularly appreciated was the “Ethics and Scientific Misconducts in Stem Cell Research” hosted by various speakers including “Retraction Watch” Ivan Oranovsky and Graham Parker, Stem Cell Development Chief-Editor. The stem research is a promising research field, a fantastic boat to sail on but because it has enormous potential and impact on medical research that can be easily hijacked by snake oil sellers (those claiming to have working stem cell therapies beyond the stage of clinical trials) and the forgery (remember the embryonic stem cell cloning fraud from South Korea in 2004)?

Here I am, waiting for my flight back to the Panhandle, now boosted more than ever to push on my research interests, developing new avenues of collaborations and hopefully developping the stemming stem cell research community in Texas.

Link

http://www.nature.com/news/history-great-myths-die-hard-1.13839?WT.mc_id=FBK_NatureNews

Joseph Lister bringing the concept of anesthesia and aseptic conditions, Alexander Fleming miraculous finding of Penicillin, Pasteur discovery of the anti-rabies vaccine…..Science is full of these unexpected findings and discoveries that brought us these heroic moments. But are these stories really true?

Read the latest scientific history article co-authored by Dr. Heloise Dufour, a remarkable colleague here at UW-Madison, also a talented HHMI teaching fellow and proven science out-reacher. A must-read.

Link

Supreme Court: Natural DNA is not patentable (but cDNA is)

The recent decision of the Supreme Court is a big relief for scientists like me, following the battle engaged between Myriad (the company behind the BRCA test and Angelina Jolie’s story). It clearly stipulates that natural DNA cannot be patented, but artificial (cDNA) can.
What are the differences and how it would impact us? Lets take the BRCA gene as an example.

Mutations in the BRCA genes (BRCA1 and BRCA2) are linked to increased risk in breast and ovarian cancer (thus explaining Angelina’s decision for the double mastectomy that I would argue against but this not the topic of this blog). Before the decision, Myriad had the exclusivity of the BRCA gene including the gene product (protein), thus making the development of detection kit and assays exclusive to Myriad (at least in the US). The problems of this test? Very expensive ($3000-6000 per screening) and not 100% reliable. On the other side of the Atalantic Sea, French have also a BRCA kit that is slightly cheaper than the US one but also more reliable. Thus, we can clearly understand that having the open access to the genome would help the development of new technologies and at the end decrease the cost of this kit, good for your health and your wallet.

The proof of my reasoning? Look at the cost of DNA sequencing. You even have a company called “23 and Me” that sequence your genome for $100 (but also opens another genie contained in the bottle).

In the other hand, artificial DNA is still under patent. What does it mean? For the general public not much but for scientist, that means now virtually everyone can patent any cDNA or recombinant DNA (for example someone that created a hybrid of the BRCA gene fused with a green-fluorescent protein contained in a plasmid could apply a patent on it). That can be a no-problem for scientists (as patents most of the time protect the intellectual property by the scientist that formulated that cDNA and you have to acknowledge them in your publications at minimum) but may become a hassle for all these companies like Affymetrix, Illumina or Agilent that heavily rely on cDNA for the DNA microarray analysis (the next BIG THING is personnalized medicine). So let’s how things are going in that direction….