Category Archives: Tibor’s Blog

Sex As a Biological Variable, what could represent this better than the clitoris: that was how I opened my last posting 3 years ago. Sex As a Biological Variable, what could represent this better than the penis, I would start my assay today.

Now, I am a little bit confused, on one important side I am trying to follow my higher authorities in science, the National Institute of Health, they say we need to govern biological experiments in regard of gender. I design cancer genetic tests, however we do not consider gender in our scientific conduct, we should do better, I agree. On the other very important side of my confusion, my daughter is an Ivy League graduate and a competitive swimmer. She used to swim in the same pool as Lia does. I follow the news and I see the images of a beautiful young man in a skimpy female swimsuit with a very visible graphic contour of some protruding entity at his frontal middle body. In my confusion I am trying to disconnect from my profession as a biologist and I am trying to be a very compassionate human being to understand how in your case, Lia, indeed there are no biological differences between male and female genders. You are a very good human person, you can feel as a woman, you can feel as a man, you can feel your nonbinary third gender status. As a matter of fact the very liberal German society represented by the German Parliament passed the law recognizing the third gender. Unfortunately, we don’t have this law here at home in the USA but I assure you I will vote for it when it comes. Until that you are still protected. Nothing is going to happen to you, nobody will hurt you, don’t worry about those narrow minded conservatives trying to force you to be a man.

Really, I thought I was confused, but thinking harder, I am reaching at my opinion that actually Lia, you are confused. You are too young of a man you don’t understand that we men cannot do almost nothing as good as women, at the best case scenario we can do equal. The only thing we have is the penis that women don’t have and what makes us real men, including you. You may feel like a woman but you are not a woman with a penis. You are a man with a penis. Lia, please cut your penis, I mean the whole package, the sack and the balls and just leave a little chunk for peeing.

As for myself, I am a 65 year old man, I would qualify for medicare and social security benefits plus I could have started to withdraw my 401K sawing several years ago. I tell you, I am confused, it is all right to be confused, I feel like a 45 year young man. Just to tell you two things, I go to work every day very diligently and I design cancer genetic tests like a younger man. Also, I can walk on my hands like very few even very young man can do. That is true, I used to be a gymnast when I was a kid, we were competing after the training sessions how far we can walk on our hands. I never stopped doing it as of today more than half a century later. When I turned into my 60-ies I wanted to legally lower my age to match my biological age. Believe me, I really considered to do that. Eventually, I realized that I would encounter unwanted complications with my mis-matching legal age and birth age. I chickened out. I did not do it. I made peace in my mind, the fact is I am an old man but more importantly I feel like a young man and with this peace I can live hopefully a long and healthy life ahead of me.

Lia, don’t be confused like me, don’t be a chicken like your old-man-friend. You are young and your whole life is ahead of you. Stand up for yourself and be who you are: be a woman, cut your penis.

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin
“Possideo genes ergo sum”—Anonymous Roman Philosopher

Sex As a Biological Variable, what could represent this better than the clitoris. I found this publication at the Experimental Biology annual meeting in Orlando Florida presented by Dara Orbach, a Postdoctoral Scientist who conducts her research in Patricia Brennan Laboratory. They study dolphin’s reproductive biology.

“Dolphins copulate year-round despite short estrus periods. Copulation may be pleasurable for female dolphins through clitoral stimulation, as they have large and well-developed clitorises.” “In dolphins, the clitoris is positioned at the entrance of the vaginal opening and in direct contact with the penis during copulation, unlike the external position of the clitoris in humans,” said Orbach. “The location of the clitoris near the vaginal opening indicates it can potentially be easily stimulated during copulation.”

In my previous essay about SABV, I was describing the top to bottom recently introduced science policy by the NIH to include gender in the scientific experimental design. Dr Brennan’s laboratory has been doing this for long time. Her laboratory does important research regarding reproductive biology and because of her study subject she also has public visibility. She was booed by the public, 89% of the people questioned by Fox News poll disapproved her research about the reproductive biology of the ducks including the study of the ducks’ penis and vagina, called cloaca for birds.  Dr Brennan is blamed for using public support from the national science foundation to study the penis and the vagina.

As a scientist, this makes me very concerned but as a man I think I understand this uproar. Listen to me, I’ll tell you the story of the guy who goes into the hat store and says, good morning, I would like buy a hat. So, what do you have in your mind, what would you like to have, Sir, asks the hat shop attendant. The guy hesitates for a second and he says, well, my beloved woman is in my mind and I would like to have sex with her. However, in this moment I actually would like to buy a hat. 

I don’t pretend to be different from this guy in the hat shop. I am trying to give my science based opinion about the gender issue, but when you say clitoris I can’t help thinking about my beloved woman and having sex with her. 89% of Fox News poll respondents are thinking about having sex when they see Dr Brennan’s research describing the ducks’ penis and the cloaca and the copulation. The picture of the duck is very graphic and the Fox News poll respondents are ashamed that they think of having sex when they see the duck’s penis penetrating into the cloaca. They are hypocrites and they are convinced that it is Dr Brennan’s fault that they have this shameful feeling, so they simple disapprove this type of research.

Maintaining our existence we have to eat, maintaining our species we have to have sex. Simple, it is. Look at the food and restaurant industry, all based on our first biological priority. Nobody questions that, nobody denies the necessity and the accompanying pleasure of having food.  I was in Rome last year and I am fascinated by the ancient culture of the Roman Empire. I spent half a day in the Colosseum  imagining my fight as a gladiator in the arena and die in glory. Yes, sure, that was my imagination but after that we were sitting in a restaurant overseeing the Colosseum in full view through the huge panorama window, the Colosseum lightening up in all colors mounting in full spectacle as the night fell and I had my best pasta in my life and I finished up the night with the best Italian Chianti. If we fully accept and cherish satisfying our first priority biological need by having food why don’t we fully accept and cherish satisfying our second priority biological need by having sex, keep it in the marriage to procreate the children and yes, have sex thousands more times for pleasure.

Do these biology related questions about food and sex have anything to do with the gender issue that is widely discussed in today’s social and political environment? Does Joe Biden think of food and sex when he is touchy-feely? I have no idea how to answer these questions, and I am not even trying to pretend answering these questions. All I can say here is I am saluting to my daughter, to Dr Orbach, to Dr Brennan and to all the extraordinary, high achiever women including my scientist female co-workers who should take leadership to connect the biological gender differences to the social, political and legal aspect of gender equality.

What I will do next Christmas for sure is to ask Dr Brennan professional help to determine the gender of my traditional Christmas Duck, I will purchase two ducks one female and one male, roast both of them and compare the taste of the female and the male duck if there is any gender specific biological difference.

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin
“Possideo genes ergo sum”—Anonymous Roman Philosopher

Sex As a Biological Variable, I would rather say gender, because sex can be a dangerous word in professional environment, not in social media, but we are serious scientists, talking to my co-worker, who said she would take Christmas climbing vacation in Ecuador, I asked you mean rock climbing or high elevation hiking, she said high elevation hiking, I said you still need crampons and ice axe. Somebody overheard what I said without the context, all the other person heard was “I sex” (ice axe). I still have a job no worries, but I am trying to avoid the word s** instead to say gender.

In 2016, the National Institutes of Health (NIH) implemented a policy which requires grant applicants to “consider sex as a biological variable (SABV)” in vertebrate animal and human studies. I do not write grants, I did not know about this NIH policy but I found this publication the other day, a follow up study, a peer-reviewed article describing that indeed in the last 2 years there was a significant increase in the proportion of grants that considered SABV in the research strategy and applicants who adequately addressed the incorporation of SABV into the experimental design, analysis and reporting.

When I started my career in the early 80-ies we did cancer immunology in-vivo experiments randomly and indiscriminately on male and female mice, we did not think there was any difference. Later I did monoclonal antibodies, I did not think of the spleen of the immunized male or female mice were different, either. Science is so advanced today since I did my first experiment, we recognize now that males and females are reacting differently as a result of different molecular mechanism,  after all the gender difference in the spleen might generate different antibodies. We have just never studied that, it is time for the NIH to address it.

Well, I know for sure the taste of the male chicken is better, plus we all eat the un-balled male beef. As I did not consider of this gender difference in my scientific experiments, same way I did not consider the gender difference in the meat I eat, so I have to admit NIH has the right to warn me. It raises a new issue for me however, my traditional duck that I roast for Christmas is already in the freezer, all cleaned up, will be defrosted on the day before it jumps into the oven. I have no way of determining the gender of my Christmas Duck, so when I bite into the delicious meat of the upper thigh of the bird I will definitely contemplate about the open question of those are female or male. We must lobby for the gender identification on the food labeling of the meat we eat.

Good, the ice axe has no gender.

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin
“Possideo genes ergo sum”—Anonymous Roman Philosopher

In early 2015, I wrote an article about the making of designer babies. I was referring to the CRISPR gene editing technology that would make it possible to do them. I said it would happen by the year of 2042, which is obviously symbolic in the meaning of accuracy. More importantly, you fully understand that my article was about supporting, cherishing and never ever let obstructing scientific development. Also, that article was about my deep and sincere belief that we would never use scientific advancements in a wrong way.

The CRISPR gene editing technology is exploding, scientists are using its potential to make great progress in science. Just to mention, in our laboratory I did a next generation sequencing experiment to find the successfully gene-edited mouse tumor cell line for research purpose. We reverted the tumor causing mutation to the normal wild type status. Should you have very little imagination if you think this would lead to cure cancer. Let me not indulge myself into telling you in what year, let the realistic future success show us when it will happen.

Since early 2015 there have been several scientific reports about human embryo gene editing. Chinese scientists changed the mutant β-globin gene to normal variant to prevent the development of sickle cell disease. Next year, another Chinese group made the normal wild type CCR5 gene into a mutant variant rendering it resistant to HIV infection. Recently, from the Oregon Health and Science University in Portland, the 3rd paper about human embryo editing described the correction of germline mutation of the MYBPC3 gene, a mutation that causes hypertrophic cardiomyopathy. All these described experiments are truly only scientific experiments, the embryos were destroyed with no intention to be implanted. There are more than ten thousand monogenic inherited disorders. Cystic fibrosis could be the next one trying to fix, and ten thousands more to go, what a great way to progress science and save lives. Ask the parents of the child with cystic fibrosis. Should these experiments progress into perfection avoiding off target alteration in the genome and avoiding the unwanted mosaicism in the edited embryo, soon controlled, regulated and legally supported clinical trials will begin. Once demonstrated that the human embryo genome editing is clinically safe, medically justified and fully beneficial to the patient, authorities will approve it.

We are not going to make designer babies, we are not going to make GMO sapiens as it would be depicted in fake-news outlets or maybe more forgivably in Hollywood movies. Jude Law is great in Gattaca. The movie is about a eugenic society in the not so distant future, actually in about the present time, as the movie was made in 1997. Eugenics is the idea that with artificial genetic control we can improve the genetic quality of a group of people or even the entire human society. Eugenics idea might get a boost from the CRISPR genome editing technology in belief of making the perfect designer baby to produce the absolute superhuman. The idea of eugenics is a real danger, has been around since the ancient Greeks and sporadically practiced infamously throughout our entire human history. Yet, there is no real eugenics practice exists today. When the practice of eugenics happened in the past, it became crime against humanity and our entire humanity stood up against it, punished eugenics and eliminated eugenics.

Fire is dangerous, yet we use fire after almost a million year since we discovered the taste of the delicious meat roasted on fire and enjoyed the warmth of the fireplace in the cold caves. Where would be our human society now without fire if the Homo erectus tribal elders, the smart ones, would have said no-no-no to fire, because fire was dangerous. The smart elders would have said we could accidentally burn ourselves or worse we could use it to burn other people. Fire could be used as a lethal weapon of mass destruction, they would have said. The Homo erectus tribal elders definitely would have been wrong to ban fire, despite of the tragic fact that indeed we burned, roasted, cooked and boiled alive many people over the civilized part of our human history. We burned at the stake Giordano Bruno because he said the stars are actually distant suns surrounded by their own planets like Earth even with possible life on those distant planets. We burned at the stake Joan d’Arc, the Virgin of Orléans because Archangel Michael and Saint Margaret appeared to her. Giordano Bruno, the martyr of science lives today and guaranties the freedom of thoughts, and Joan d’Arc herself is a Saint.

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin
“Possideo genes ergo sum”—Anonymous Roman Philosopher

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More than 100 years ago Élie Metchnikoff said that “the dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes”.

Ever since Metchnikoff for over 100 years in the modern era of biological science we have an increasing interest of the important role of our symbiotic microbiota. Next generation DNA sequencing certainly accelerated the study of metagenomics, the genetic background of a complex living system.  We are all ascertained as a commensal life-entity, we just simple cannot ignore those microbial cells that overgrow our human cells by 10 times and it would be very un-scientific to ignore those millions of microbial genes interacting to influence human health and disease. Our commensal life with microbiota is a true symbiosis, we help and nurture each other, but I would say we, humans might have an upper hand, after all we look like humans and not bacteria. To support this, in 2015 (Ref-1) the first and so far only GWAS, where they study the association between genotype and potential phenotype at a genome wide screening level, they found that a single SNP, a human genetic variant is associated with the number of Akkermansia muciniphila bacterial cells harbored in the gut. Akkermansia muciniphila is smart, listens to the host genetic constellation.

Akkermansia muciniphila made itself interesting in 2004 to the scientific community when it was isolated for the first time (Ref-2) and the discovery group in the Netherlands and Belgium has been working on this bacterial strain very intensively, ever since. They have found out that Akkermansia muciniphila plays a crucial role in the symbiosis between the gut microbiota and the host that controls gut barrier and other physiological and homeostatic functions during obesity and type-2 diabetes. In the coming years they demonstrated (Ref-3) in purely laboratory setting using well controlled mouse experiments a dramatic decrease in Akkermansia muciniphila in both genetically and diet-induced obese and diabetic mice. Also, by restoring the physiological abundance of this strain in these experimental mice they were able to reverse the obese and diabetic pathological phenotype. Finally, they identified and isolated a protein (Ref-4) in the bacterial wall and they called it amuc-1100 that is associated with the host metabolic health. Amazingly, amuc_1100 is a drug candidate in human clinical trial by now, well tolerated and now paves the way for future human therapeutic tools of microbial origin.

Growing research interest in this field of metagenomics has resulted in the discovery of amuc_1100 and its role in human obesity and type-2 diabetes. This is the first bacterial protein linked directly with human disease. This is the first one and there are million more to discover and as a result of our research we are going to be able to curate microbial genes that are associated with human phenotype. This first direct scientific link between the bacterial gene and human phenotype proves that indeed we, scientists need to go into this direction in our research efforts. If we do any research, most importantly with the aim to cure cancer we must study bacterial genetic association with cancerogenesis, otherwise we are not serious in our effort.

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin

“Possideo genes ergo sum”—Anonymous Roman Philosopher

Reference

1. Genome-Wide Association Studies of the Human Gut Microbiota; Emily R. Davenport, Darren A. Cusanovich, Katelyn Michelini, Luis B. Barreiro, Carole Ober, Yoav Gilad; PLOS ONE | DOI:10.1371/journal.pone.0140301 November 3, 2015
2. Akkermansia muciniphila gen. nov., sp. nov.,a human intestinal mucin-degrading bacterium; Muriel Derrien, Elaine E. Vaughan, Caroline M. Plugge and Willem M. de Vos; International Journal of Systematic and Evolutionary Microbiology (2004), 54, 1469–1476
3. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity; Amandine Everard, Clara Belzer, Lucie Geurts, Janneke P. Ouwerkerk, Céline Druart, Laure B. Bindels, Yves Guiot, Muriel Derrien, Giulio G. Muccioli, Nathalie M. Delzenne, Willem M. de Vos and Patrice D. Cani; PNAS (2013), 110(22), 9066–9071
4. A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice; Hubert Plovier, Amandine Everard, Céline Druart, Clara Depommier, Matthias Van Hul, Lucie Geurts, Julien Chilloux, Noora Ottman, Thibaut Duparc, Laeticia Lichtenstein, Antonis Myridakis, Nathalie M Delzenne, Judith Klievink, Arnab Bhattacharjee, Kees C H van der Ark, Steven Aalvink, Laurent O Martinez, Marc-Emmanuel Dumas, Dominique Maiter, Audrey Loumaye, Michel P Hermans, Jean-Paul Thissen, Clara Belzer, Willem M de Vos and Patrice D Cani; Nature Medicine advance online publication, published online 28 November 2016; doi:10.1038/nm.4236

Literally, you can make your beer belly and you don’t even need to drink beer over decades. You can do it just for tonight. You can swallow yeast, the bakers/brewers yeast, Saccharomyces cerevisiae and eat chips, your beer will be fermented in house, it would be personally artsy-crafted, healthiest, fresh-bio-beer you could ever have in your life.

Well, it was not so easy for Joe (Doe, no real name) for long time until they found out what was going on with his frequent, strange, drunken behavior. His wife was looking for hidden bottles, suspecting him to be a closet alcoholic. Finally, he went to the hospital and his gut meta-genome got sequenced. They found out that Joe suffered from auto-brewery syndrome, his stomach harbored 400% more yeast than normal people’s stomach do.

Generally, the diseases we know as cancer, diabetes, cardio-vascular, autoimmune and mental diseases might represent only the small pictures in our broken health. We suspect that the picture is bigger, more like when the balance of our body falls, our health falls, as well. But why would the “balance” fall? Just because we have a sedentary life style with lots of cheeseburger from fast serving restaurants and chips munching on TV bound sofa? Is that enough? But what if the “balance” of the commensal nature of our body falls.

Normally, we have bacteria, yeast and other microbial cells in our body, even “parasites”. Scientifically, it is proven that the total number of these microbial cells is more than the number of human cells. Well, here I am not going to argue whether we are in fact a multi cellular micro-organism or a complex one-unit human body, but I would say we are certainly a meta-biome, we are certainly a gaia-organism that is governed by our brain. The total mass of micro-organisms make up only about 2% of our body, even if they outnumber our human cells, because microbial cells are 10-20 times smaller than human cells, in general. Microbial cells are less diverse in our body, represent only about a few thousands distinct types, not comparable to the human cellular diversity that carries all the characteristics of human cellular biology.

So, what are these microbial cells doing with us, together? We have a commensal life with them that benefits for all. We feed them and they help us maintain our healthy balance. Sporadically, we do know for long time, if we take antibiotics, we need to eat yogurt, so we will not have stomach ache, I remember this from my childhood, like 50 years ago. If you are in the nutrition-supplement business, you can’t even open your store if you have no probiotic products containing Lactobacillus acidophilus. We know that Candida albicans live in my mouth and to question a two-sided, nasty yeast infection is not about how they got there, but what the problem could be with my immune system, why my un-balanced body let her overgrow.

In a disease related context, we also know from recent advancement of meta-genomic science that our microbes regulate the population and density of intestinal immune cells, and if something goes wrong in this process it could lead to ulcerative colitis, a type of inflammatory bowel disease. Scientific research discovered that microbiota imbalance would lead to other serious diseases, to complex metabolic disorders, to diabetes, to all kind of autoimmune diseases and to Parkinson’s disease. Recent study showed in a mouse exploratory model, that bacterial metabolic products would pass the blood-brain barrier and influence the behavior of mice, in experimental settings.

I love to bake home made pastry and I love to drink beer in microbrewery. I love the smell of the bakers/brewers yeast. I am already planning my next experiment calculating the minimal dose of yeast cells to swallow and feed them in my stomach with the right amount of carbohydrate food, Italian bread, my favorite, to brew three units of the best beer I ever have in my life, in my belly.

If you are interested more in your commensal life, listen to this video clip, but viewer discretion advised, Greg Foot from BritLab has a heavy British accent: why you are more bug than human!

Tibor Gyuris

Personal Genomics Blogger

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin

“Possideo genes ergo sum”—Anonymous Roman Philosopher

Surprising study came out the other day in the prestigious medical journal, The Lancet Diabetes and Endocrinology (Ref-1). You are fat, I mean obese, you get hugely reduced risk of developing Alzheimer Disease. The authors followed up 2 million people for over 20 years, simple recording their BMI and the date of onset of dementia if that happened. Out of the 2 million, 45 thousand people developed dementia during this time. Underweight people had a 34% higher chance to get into the Alzheimer Disease group. From lean to obese, the risk of developing dementia gradually decreased. When the doctors analyzed the obese group, BMI above 40, they found that the chance of getting demented got reduced by another 29% compared to the average not skinny and neither obese group of people.

Alzheimer Disease, yeah well, next generation sequencing is my baby and that is growing into numerous medical applications. In my personal opinion the most anticipated breakthrough would be happening in cancer research, but I accept any argument what any other scientific and medical field including dementia are revolutionized by the sophisticated sequencing machines. Just think about the ABCA7 (Ref-2) gene. There is a brand new discovery that suggests this gene to be associated with the development of Alzheimer Disease. This ABCA7 discovery came from the shear force massive genomic sequencing and microarray genotyping of 100 thousand people in Iceland.

What do I say about this Lancet study? Is fat some kind of protecting factor from dementia? We do know about several genes that play a role in Alzheimer Disease development and naturally, we have to look at the environmental factors as well, like being active, especially in social context, having responsibility, never stop working and finishing your day with a crossword puzzle. Common wisdom regarding environmental factors is that the major villains are attacking from sedentary life style and obesity and putting you in the group of developing the so called “sitting diseases” including cardiovascular diseases, diabetes, reproductive deficiencies, cancer and dementia.

So why does obesity lower your risk of dementia? We don’t know. This new discovery does not fit into the previously predicted list of risk or protective factors of dementia. What we know about the molecular mechanism of dementia is that the aberrantly folding beta amyloid protein leads to aggregation and plaque formation in the brain. There are different types of approaches how to treat Alzheimer Disease like braking up the aggregated, harmful Alzheimer plaque structure or even better, try to prevent the formation of the Alzheimer plaques. There is one clinical trial that does not attempt to cure it, not even tries to treat it, just wants simple to delay the onset of Alzheimer Disease. So now, based on this Lancet study, I tell you, do it yourself at home: get fat. Really, just relax, indulge into your wildest eating adventure, if you don’t like physical exercise, just sit on the sofa. You would greatly reduce your risk of getting demented and most reasonable you would die sooner from cardiovascular diseases, diabetes or cancer.

The good news is that we also have serious choices in our life. Yes, I am still strongly advocating of your genetic testing to find out what possible known genetic risks you might have that would be associated with the development of certain diseases, consult with your doctor and learn what kind of lifestyle changes you could make to reduce the potential manifestation of your genetic bad luck. Besides eating whole nutritious food, you would still stick to other aspects of healthy lifestyle, like going to the Fruit Street or learning the Latin language at old age, but hey, if you already put up some pounds, don’t worry about loosing them. Enjoy the moment of life and have sex even if you are in the nursing home for elderly. And continue eating well.

Ref-1: BMI and risk of dementia in two million people over two decades: a retrospective cohort study; Nawab Quizilbash et al.; The Lancet Diabetes and Endocrinology, Published Online: 09 April 2015

Ref-2: Loss-of-function variants in ABCA7 confer risk of Alzheimer’s disease; Stacy Steinberg et.al.; Nature Genetics, Published Online 25 March 2015

Tibor Gyuris

Personal Genomics Blogger

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin

“Possideo genes ergo sum”—Anonymous Roman Philosopher

This picture is created that it can be seen either way. It is an illusion -visually- but it reflects the relative realty of life, certainly the relative perception of life. I saw the cat going down, but in the next fraction of the second I saw the cat going up. For me it is both way in the same time.

This picture was created in 1915 by the cartoonist W.E. Hill. Yeah, I married my young wife in 1974, but I knew it was a package deal, she came together with my mother in law. Like the cat, up and down, young and old in the same time.

But the dress, I don’t get it. It is blue and black.

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”There is not the slightest indication that nuclear energy will ever be obtainable. That would mean that the atom would have to be shattered at will.” Albert Einstein, 1932.

“Nuclear-powered vacuum cleaners will probably be a reality in 10 years.” Alexander Lewyt, president of the Lewyt Corporation, 1956.

Let me side with Mr. Lewyt, the inventor of vacuum cleaner: we will have designer babies by 2042. We have the tools to do it now, but let’s say it will take another 15-20 years by the time the scientific protocols will be developed into standard operating clinical procedures and another 10 years with clinical trials and finally the FDA approval. If I am wrong, like Mr. Lewyt, it is not because we cannot do it but because we don’t want to do it.

Almost twenty years ago I was making molecular constructs for transgenic and knock out animals. Mice, precisely, we generated transgenic mice to give them a gene to over express it in order to study that gene by the principle called gain of function. Also, we knocked out other genes in order to study those genes by the principle called loss of function. We made the mega-mouse, the size of a rat, in which we inserted a transgenic growth hormone gene to over express in her body. It was about the time when Dolly was cloned. Our mouse genetic group was composed of the embryonic stem cell laboratory, the microinjection and in vivo transgenic animal facility and the molecular design lab, which I conducted. All together, we could have cloned a human, more we could have inserted an extra trans-gene into her genome or we could have knocked out a gene in her genome. We never did it, because we loved her. In that time the technology was not developed into routine, the outcome would have been a disaster, but even if we succeeded, her life would have been a misery, think of it, for god’s sake in heaven why would we do that. Now, 20 years later we still don’t do it. It is not because we cannot do it but because we don’t want to do it. I don’t know why we would do human cloning, because cloning procedure simple makes a copy of one genomic constitution into another human life. We want genetic diversity, not copies.

However, think of disease. Huge effort we are making to cure diseases. We are devastated when we have children born with genetic disorders. We would do anything to save our children. So why not prevent genetic diseases for our children.

Today, we have the technology in human clinical practice called pre-implantation genetic diagnosis (PGD). In vitro fertilized human embryos are screened for healthy genetic constitution, by microarray technologies and yes, you might have guessed, by next generation sequencing. Choose the best embryo and implant it for a happy delivery of a beautiful healthy baby to delight the parents for the rest of their life.

Today, we have a technology in research practice called clustered regularly interspaced short palindromic repeats (CRISPR) based genome editing. This is so simple, that makes my highly qualified molecular expertise obsolete, I am like an antique furniture, beautiful to look at, very expensive, but who needs those type of things, maybe a museum. Edit the genome, knock in what you want, knock out what you want, reverse a disease mutation to a healthy normal variant, or add a mutation that makes my neck longer and I can graze on higher level. You know, like messing with the evolution.

However, keep it simple, let’s do just the regular in vitro fertilization. We already know the whole genome sequence of both the mother and father, we know what we are doing, we are all prepared with the CRISPR genome editing protocol design, we have the genes and the mutations exact locations to correct them in the embryo’s genome. In cystic fibrosis, the most common mutation is a deletion of three nucleotides which results in a loss of the amino acid phenylalanine at the 508th position in the protein. Would you re-insert those 3 simple nucleotides, a TTC triplet into your baby? Where those TTC’s are missing? Not to have her being born with the cystic fibrosis terrible disease? I would do it for my baby. I will. Certainly.

We will have designer babies, soon. Nothing is wrong with that. We have atomic energy and we still don’t destroy each other because we love each other. We could prevent genetic diseases, we could even manipulate evolution but we will not use it for the wrong reason because we love our humanity.

Tibor Gyuris

Personal Genomics Blogger

2015. January 23

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin

“Possideo genes ergo sum”—Anonymous Roman Philosopher

Most of the scientific and medical community would agree that cancer is a genetic disease. Recent scientific publication (ref-1) went deeper to point to this direction, even further, cancer is also a “statistical” disease, a result of  genetic gambling bad luck.

Think of the six billion nucleotides that must be replicated in each cell at each cellular division, multiplied by the billions of cell divisions every minute of our full length of lifetime. Something must go wrong, just by the sheer number of events, nothing is perfect, there are always some wrong nucleotides that are incorporated into the newly formed stretch of DNA in the newly formed daughter cell. There is of course a massive effort of the countless proteins monitoring the cell division and the DNA replication to catch the error and repair the mistake. But there is just one point, when just one DNA replication mistake is not corrected and the new incorrect peace of little nucleotide remains in the replicated stretch of DNA and keeps being replicated through the subsequent cellular divisions. This change in the DNA sequence might be irrelevant, just becomes a variant, just a variation, part of our diversity. This change in the DNA sequence might be good, like changes a protein function resulting in a physiological change, in other words change in the phenotype, resulting in an advantage for the individual, like a longer neck of the giraffe, reaching higher level of leaves on the tree, more delicious food, making the giraffe being better fed, stronger body, longer survival and healthier babies, all carrying the new variant for the longer neck, sounds familiar, they are making the evolution.

Just sometimes, this change in the DNA becomes a “mutation”, that is a bad word, we know that something is wrong with mutation. What if a mutation happens in a protein that promotes cell division or growth and that mutation makes that protein super active, than cell starts multiplying like crazy. Or what if a mutation happens in a protein that slows down cell division or growth and that mutation makes that protein totally inactive, that cell also grows faster because nothing to stop it. In the very complex cell there are many proteins that carry either of these functions, promotion of growth or arresting the growth. What if there are 50-100 or even more of these proteins are mutated as it is shown in the Cancer Genome Landscape study (ref-2). Bad Luck: Cancer. The recent study (ref-1) says 65% of cases of cancer is associated purely with the number of cellular divisions characteristic of those type of tissues, more division, more errors, more cancer. The other 35% of cancer cases are still could be linked with environmental or inherited factors.

So, what can we do? I thought environmental factors make us sick, you know, tobacco as the first villain, or the sunshine with the ultra violet irradiation, alcohol, processed food, chemicals, pesticides, the mercury in the fish and arsenic in the soil and the bad air we breathe in, you read the media, how to avoid these abrogating factors and instead how to lead a healthy life style. Oh come on, it is only bad luck, I will indulge in the half a pound medium-rare red juicy hamburger, and I will have the beer today, even if it is weekday, instead of my regular sugary sodas, than I will have my Cuban cigar (it is legal by now) on my beautiful, sunny California patio, to get some suntan, it looks good on my face.

There are half a million unfortunate death from cancer every year in USA. Something like 150 thousand of the cancer deaths can be linked with environmental and inherited factors but the other majority of them is linked with bad statistical luck. Even the 150 thousand cancer deaths like the smokers and the suntan worshipers must have extra bad luck, because most of the smokers and most of the beach goers don’t die from cancer or don’t even have cancer, so these are the people with the good luck.

There are 1 in every 3 people diagnosed with cancer in their lifetime, about 100 million people in USA. What can we do with these people, including myself, 1 in 3 is huge, I am included, for sure. Maybe I can fine-tune my odds by not smoking, avoid sun, eat healthy food, drink some red vine (that is part of good diet) and do my regular exercise. But we have just seen from the brilliant publications referred, that it is still better to have good luck than to have bad luck.

I am not a doctor, not a holistic healer, not even a lifestyle coach, but I am a next generation sequencing scientist with major interest in cancer research. Scientists are making huge progress in cancer research, however, we are not curing cancer yet, probably we don’t even understand exactly what the molecular mechanism of cancer is. So what can scientists say, only the scientific facts, what they find, even if it sounds scary, bad luck or good luck. Yes, we can say that cancer is a statistical genetic disease. The best we can do right now is to do early diagnosis, including for example next generation sequencing of our circulating blood DNA to catch the early signs of our bad luck, identifying the cancer associated mutations in our blood DNA sample and take preventive actions. Cancer maybe not curable right now, but cancer death could be avoidable by early detection of actionable mutations and by potential targeted therapy .

Reference:

1. Variation in cancer risk among tissues can be explained by the number of stem cell divisions; Cristian Tomasetti, Bert Vogelstein; Science 347:78, 2015

2. Cancer Genome Landscapes; Bert Vogelstein, Nickolas Papadopoulos, Victor E. Velculescu, Shibin Zhou, Luis A. Diaz Jr., Kenneth W. Kinzler; Science 339:1546, 2013

Tibor Gyuris

Personal Genomics Blogger

2015. January 5

“Knowledge is always good and certainly always better than ignorance”–Sergey Brin

“Possideo genes ergo sum”—Anonymous Roman Philosopher Continue reading →