Monthly Archives: January 2015

”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 →