The Creature

English author Mary Shelley was the mother of science-fiction genre and an unlikely heroine of the horror fiction genre. In the early 19th century, Mary traveled through Europe with her future husband Percy Shelley, Lord Byron and John Polidori. They traveled along the River Rhine in Germany and had a stop in Gernsheim which is about 15 km away from Frankenstein Castle, where, two centuries before, an alchemist was allegedly engaged in sinister experiments. Later on their journey, they traveled in the region of Geneva in Switzerland where the topic of galvanism (contraction of a muscle stimulated by the electric current) was the latest fade due to the recent discovery of electrical current and its role in the human body.

The group decided to have a competition to see who could write the best horror story. Several days after the wager, Mary had a dream about a scientist who created life and was horrified by what he made. Mary said that this dream was the inspiration for her novel “Frankenstein”, one of the best horror stories ever and the first true science-fiction novel ever.

“Frankenstein” is the novel about young scientist Victor Frankenstein coming from a wealthy family who created an artificial creature – the Creature – that turned against his own creator. The story revolves around “mystic” scientific experiments, creating life from the non-living matter, and ultimate evil and perversion of such life.

It is the story I absolutely love and love to read. The novel was much ahead of its time, the writing style is superb, characters are interesting and the story is griping. It is the work of art that keeps you on the edge, entertains you while making you feel uneasy. It is a horror story after all.

It is also the story I absolutely hate. Not because of the story, but because of the lasting impact this story has. While imagined as a fictional horror story, most people treat Frankenstein novel as a documentary novel which documents futility of scientific progress, corruptness of science and ultimate evil of what comes ahead of us.

To summarize, I love the story itself but I do profoundly resent its impact on public opinion, as it is grossly misunderstood novel. And the story of the Creature (that most people call Frankenstein) is very popular nowadays.

It is especially popular in the debate concerning genetically modified organisms (GMO). The newly coined term “Frankenfood” is heard more often than not, projecting (on purpose) irrational fear of unleashing unthinkable evil upon the world by using genetically modified plants, animals and microorganisms. It is with a picture of The Creature that various organizations (varying from religious institutions to so called environment protectionists) sow fear and distrust towards organisms created using tools of modern molecular biology.

So, what’s the big deal with genetically modified organisms? Why are they the topic of THE most heated public debate all around the world for the last 30 years? Why do people fear this technology? How did humanity feed itself through the history, and why do we need (if we need) this technology today? How is humanity using this technology today, and what does the future hold for the genetically modified organism? This is the topic I will write about in this and future posts.

Personally, I believe that the most significant number of people who distrust GMOs and are afraid of GMOs distrust and fear GMOs because they are fundamentally not educated enough. I am NOT stating that they are stupid or ignorant, or that they cannot be educated, I am simply stating that this group of people have not received, up to this point, the most basic education in biology of human body, or biology in general.

To start off with, anti-GMO group does not understand even how digestion works. I was shocked, on more occasions than I would like to admit, when I was talking to people fighting the introduction of GM food how little they knew about the inner workings of human body. I did not know whether to cry, laugh or both when I was told that by changing the DNA of an organism that is being eaten our own DNA will be changed and “god knows what will happen to us then”. Upon first conversation of such sort, I personally thought that that one man was crazy, but surely other members of community engaged in these discussions know better. How wrong I was.

First of all, DNA is a static element of heredity – it does not change on purpose by itself at absolutely no occasion. DNA can be changed only in two occasion. First are random mutations, which happen all the time, and most of them are repaired by our own inner mechanism of DNA repair. Mutations are random and are caused by accident, that is, by DNA replicating machinery not being perfect. Most mutations that are not repaired are either dormant mutations that have no effect on human body, while the rest of mutations are either “bad” mutations that lead to cancer or other diseases, or “good” mutations that have some beneficial effect to a man and its offspring. We have absolutely no control over these mutations, we cannot induce it, except by treating people with excessive amount of radioactive emission (e.g. nuclear waste emissions, Chernobyl disaster). The only other way to change human DNA is by retrovirus exposure. Those viruses insert their own DNA into host cell (e.g. human T4 lysozyme cell) and use the hosts’ machinery to replicate its DNA. That is the way HIV virus work, for example.

Second of all, DNA by itself does absolutely nothing in the cell. It is simply a material that other parts of the cell use as a template for proteins. By its composition, DNA is an acid – deoxyribonucleic acid.

To make the picture clear, I will use this example: you want to bake a cake. You have absolutely no idea how to bake a cake. What do you do? You take a cookbook, find a recipe you fancy, buy ingredients which recipe requires, bake the cake following the recipe, and woila! A cake.

That exact thing happens in our bodies. DNA is the cookbook of a cell. The cook from the example (that is, you) is the RNA machinery (RNA + proteins regulating RNA) that reads the DNA, takes the necessary information (what is necessary and what is not is the topic of epigenetics), “buys” required ingredients (base pairs), brings the ingredients to the ribosome (the “oven” of a cell), and ribosome assembles (“bakes”) the protein (the cake). That is, in the simplest possible form, that. All other “nuances” are topic of cellular biology, and each little detail in the story is a field of science by itself.

As you can see, DNA does absolutely nothing. It is a passive component of the cell. Proteins control DNA replication, DNA repair, shape (state of condensation) of DNA, etc., and RNA machinery is the link between DNA and proteins. Proteins do everything else in the cell as well. Proteins can be defined in the simplest way as a working class of the cell and of all life on Earth. Energy your cells have, functions your individual cells have, structural integrity of your cells, communication between and inside your cell – all that and much, much more is done by proteins. They do absolutely everything in every cell, and proteins are the final expression of DNA.

Composition of every cell can be summed in five main components: water, proteins, fats, carbohydrates (sugars) and everything else.

Proteins are, as stated before, the main actors of life.

Fats and carbohydrates are mostly used as energy source, but they are also essential for structural integrity of the cell. For instance, every cellular wall is built mostly from phospholipids bilayer and cholesterol (that is, fats).

Everything else is contained in traces. We would not be able to live without those elements (e.g. minerals, vitamins, DNA is an acid, etc.) but most of those elements cannot be found in the abundance. One notable exception here are fibers, and then only in some plants, and plants only.

Now, let’s get back to our food.

Remember those labels on the food you’re buying? Yes, the one that list how many calories per serving there is, how many grams of protein per 100 g does you food contain etc. You can see on those labels that the great majority of your meal contains of proteins, fats, and carbohydrates. These components are what your body digests and what your body stores.

So, how digestion and metabolism function?

First of all, digestion and metabolism are two completely separate processes.

Digestion is the process of getting the food in your body and getting unprocessed food out of your body. Its main role is to mechanically (by chewing) and physically (using stomach acid) break down big chunks of food you eat, bring it to the inner intestines, let intestines do its job and take the nutrients it can process, and then excrete what is left out. What happens in the intestines and then in the blood, and then in the other organs is the job of metabolism.

Metabolism is the process of breaking that food down to the simplest building blocks – that process is called catabolism – and storing these building block and then using them to assemble every molecule of your cells – that process is called anabolism. Catabolism and anabolism together form metabolism. There are three main purposes of metabolism, and those are the conversion of food to energy to run cellular processes, the conversion of food to building block for proteins, lipids (fats), nucleic acids (building blocks for RNA and DNA), and carbohydrates (sugars), and elimination of nitrogenous wastes. Metabolism allows us to grow and reproduce, maintain our structure, and respond to our environment.

Every food you ever ate and every food you will ever eat was and will be disassembled to its most basic components and all proteins, lipids, carbohydrates and DNA of your body was and will be assembled within your body, using your own cellular infrastructure. All carbohydrates you ever ate and you will eat were disassembled and will be disassembled to glucose, fructose or galactose. That means that every potato, corn, wheat, and soybean you ever ate was disassembled to glucose. No matter whether potato came from USA, France, Poland or Croatia. No matter whether that potato was grown “organically” or industrially. To your metabolism, all potatoes are the same and all hold virtually the same nutritional value. Every citrus you ever ate was to you body just a big ball of water with a lot of sugar and some vitamins and fibers in it. All meat you ever ate was a bunch of proteins and fat to your body. And everything was disassembled, stored in your body and used by your body, when needed, as energy or building blocks for our own proteins, fats, and carbohydrates.

Knowing and understanding these facts renders most of the GMO vs. anti-GMO discussion unnecessary. Knowing and understanding these facts also exposes raw food advocates as simple scams, but I will devote separate blog post to this topic.

So, how does GM food fit into all of this?

To start off with, according to the World Health Organization, genetically modified organisms (GMOs) can be defined as organisms (plants, animals or microorganisms) in which the genetic material (DNA) has been altered in a way that does not occur naturally by mating and/or natural recombination. The technology is often called ‘modern biotechnology’ or ‘gene technology’, sometimes also ‘recombinant DNA technology’ or ‘genetic engineering’. Foods produced from or using GM organisms are often referred to as GM foods.

Genome is changed not because of the DNA itself; new genes are inserted, or genes inherently present in the organism are deleted, in order to change the proteins in the organism of interest. The idea is to change proteins in the organism of interest. And all proteins, absolutely all proteins you eat, are disassembled in your body to its most basic building blocks. Therefore, even in its idea and theory, digestion and metabolism of the GM food is absolutely identical to the digestion and metabolism of non-GM food. There can be no safety issue for human health arising from the introduction of the GM food to our diet.

Genetic engineering is a tool just like any other, just like a hammer is a tool, just like a dynamite is tool. Using genetic engineering, scientists can take any trait from organism A and implant that trait into organism B. It does nothing less, and nothing more. Just like any trade and industry, it takes a lot of knowledge and experience to deliver perfect merchandise, in this case plant, animals or microbes. And just like in any industries, there are companies and individuals that are in the business of genetic engineering because they want to change the world and make it a better and safer world. There are companies and individuals who are in this business to make money, and there there are companies and individuals who are in this business to make money the dirty way.

If we take the example of dynamite, its inventor, Alfred Noble, invented it to make the mining industry safer. Instead of sending hundreds of workers with pickaxes in claustrophobic holes to build tunnels and extract the ore, or sending hundreds and thousands of workers to collapse buildings – manually, you could just send a couple of workers with these funny looking sticks and make the job fast, easy and without casualties. Alfred Noble intended to use dynamite solely in non-violent, commercial activities, and Noble saved untold thousands of lives with his invention.

Much to Nobles’ dismay, other people concluded that dynamite can be used for other things, not only non-violent and commercial activities.

Armies started to use dynamite in defensive and offensive actions, but bandits also started using dynamite in train robberies and bank heists.

The same argument hold in the business of genetic engineering. Genetic engineering itself is a noble mission to better the world, and most scientist envision a better, safer, cleaner and better fed world than it is today. Unfortunately, GMOs can be abused, just like dynamite.

I just ask of all of you reading this not to put the sign of equation between bank robber and a dynamite stick.

As I figured out that this topic cannot possibly be covered in just one blog post (it would be more of a blog booklet), I decided to make this post a multi-part series. In the next blog post, I will write more about GMO usage and what business models are used in the business of genetic engineering. I will also start debunking anti-GMO arguments, one by one.

The Silence of the Lambs

Think of your special, happy places and your happy memories. Birthday parties, Christmas family dinners, weddings, romantic dinners with your partner, fancy company dinners… These are all special events and everyone celebrates them in their own, special ways. Some like their birthday parties quiet and intimate, some like them big and rowdy, some people like small weddings, while other people like their weddings to be a fairytale-like events with 600 people on board. But all of these events have two things in common: that special feeling of happiness and meat consumption.

Just think about it: have you ever been to a special event that didn’t have some exquisite meat meal? Every household has its own special recipes for their special occasions and they mostly revolve around special (read as costly) piece of meat that family eats once or twice a year. It is in human nature to associate big, fat, juicy (and costly) piece of meat with a sense of accomplishment and happiness, all the way back to prehistoric era.

The best hunter, the man who could bring home the most and the best meat (or meat carcass), was always the leader of the tribe; kings, pharaohs, emperors and leaders of all kinds celebrated their power with unending feasts that included a lot of sex and a lot of meat. Public displays of sexual or sexualized acts and food (mostly meat) abundance were always used (and still are) to showcase ones power and satisfy primordial survival instincts.

Throughout the history, any kind of meat was considered to be a luxury. Situation changed dramatically in the second halve of 20th century. Until then, meat was consumed only in those special events I mentioned in the opening of this blog-post. Staple of human nutrition was made of dairy products, wheat products such as bread or wheat porridge, stews made from cabbage, beans, potatoes or other available vegetable. Typical person ate less than fifty meat meals in their entire life. That is two to three weeks of meat consumption average person consumes today. So, why was meat such a luxury in times past and what made transition from meat-as-a-luxury to meat-as-an-everyday-commodity possible?

Common people lived in autarchic communities – each household, each farmstead had to provide every necessity for itself. Each household had to grow its food, process its food, make its own clothes, building materials, weapons etc. In those conditions, if you wanted to grow pigs, cows, sheep, chicken or any other animal, you had to build a special building for them, feed them with food you grew yourself, nurture them, kill them, process them in special buildings you had to build, treat them with spices that were extremely expensive at that time and store them in, again, specialized building for that – remember, there were no fridges back then. As you can see, it was a time consuming process that required a lot of ones effort and material investment. As a result, most people kept a couple of chickens (for their eggs) and a couple of sheep (for their milk and their wool). Some people grew rabbits for their meat. Owning one cow or one fully grown pig was medieval equivalent of owning an upmarket sedan like Mazda 6 or VW Passat nowadays.

Technological innovation of the 19th and 20th century, sociological changes that occurred during industrial revolutions (population moving from villages to great cities) and economic revolution (wide adoption of free market economy) ended autarchic communities and gave rise to the civilization of specialized individuals organized in nuclear families. With emergence of specialized manufactures and factories, with specialized bureaucratic machinery, with emergence of blue collar and white collar jobs, farming and husbandry became specialized, industrial activities. Law of the big numbers did its thing and farming output started to grow exponentially. Introduction of internal-combustion and electrical machinery gave birth to corporate farming and that transition made abundance of fruits, vegetables and meat reality we live in today. There are arguments if corporate farming industry is a good or bad thing, but reality is that without those great corporations operating in a free market economy, we would still live in a world where any kind of meat is a luxury and our diet would consist of season-available fruits and vegetables.

So, how does the husbandry look like today?

Most of our food comes from great, unending agricultural fields, be it from French and Ukrainian wheat-lands, USA Midwest with stretches of hundreds and hundreds of kilometers of farmlands and husbandry fields, Chinese or Argentinian steppes. Most of your food doesn’t come from some farmer that has two cows and five sheep, the food on your table is an end result of a fine tuned global industrial process. But is that whole process sustainable and ethically acceptable?

I will not go into the discussion whether meat consumption is an ethically acceptable or not, it really depends on your religious background, your empathy, desire to eat meat and plethora of other subjective reasons. I do not want to discuss these matters, I want to talk about science, about objectively measurable facts on the subject of sustainability of modern husbandry, whether there is a problem and what would solution to the problems, if there are any, be. I am using data collected mostly from USA, and I apologize for all the gallons and pounds mentioned in this post. The emphasis of this post is not on the actual numbers but on the orders of magnitude and ratios. I would like to point to the fact that the country that has the most “invisible” and lightweight bureaucratic system in the Western world has the most complete and up-to-date data on just about anything.

These are the facts about modern husbandry and agriculture.

Our food consumption is killing this planet, and this way of life, this way of growing our food is completely unsustainable. The data is irrefutable, the amount of evidence is overwhelming. In the face of this data, will I, and the most of the population, give up on meat diet?

To tell you the truth, no.

The fact is that we do eat too much meat and the amount of meat that we consume can certainly come down. We do not need to consume meat for breakfast, lunch and dinner, one meat meal a day is certainly enough. If all people on the Earth would cut down their meat consumption to one healthy meat meal per day, environmental damage of husbandry would certainly be diminished. However, in the face of growing population numbers, continuation of desertification of our planet and increase of living standard in the Third world, no amount of meal-size decrease would stop us from driving ourselves to the complete and utter doom.

Would going back to the roots save us, as “environment-friendly” groups such as Greenpeace suggest? Would complete disbandment of modern agricultural industry (usage of pesticides, herbicides, GM crops, etc) save the planet?

Well, it would certainly make humans healthier. If a large portion of the population would start to farm again, without using the pesticides, herbicides or fungicides for their crops, without using antibiotics in raising their animals, we would eliminate a significant portion of the chemical pollution we’re causing today.

Most of the Earth’s population would starve as well. Personally, I don’t consider that solution to be most effective or the most happy one. Advocates of going-back-to-the-roots idea suggest then that we should just farm more land. That means that more forests, more swamps, more coastlines would have to be destroyed. As I pointed out earlier in this text, our ecosystem is on the point of breaking and we’re facing complete and utter loss of biodiversity as is. To further accelerate habitat destruction is no less than signing a death sentence to the entire humanity.

The next question is, what can we do? Can we save ourselves without going vegan?

Luckily, we can. And the solution for these problems is the whole reason why I started to write about this issue.

You see, there is a new revolution brewing right in front of our eyes, and it coming from the field that had nothing to do with agriculture or husbandry. Using the same techniques that are used in tissue building and 3D printing of the human organs from stem cells, we could theoretically grow animal meat and hide from animal stem cells. Take a vial of bovine (cow) stem cells and grow 100 pounds of beef in a matter of days, using nothing else than a container full of water, some hormones and a vial of bovine stem cells. Sound like science fiction?

Well, it was up until 2013 when a team of scientists made a hamburger-from-a-tube, first in vitro hamburger. A famous chef made the burger, the public could taste it and rate it and it was a smashing success. There was just one, small detail that still made in vitro burgers a topic of science fiction – that one small burger cost 250 000 €. That was about 300 000$. Nobody actually expected that in vitro meat will be commonplace in our lifetime.

And everybody was wrong. In just a year, the scientist managed to greatly optimize the process and they made a new public tasting event. This time, the burger did not cost 300 000 $. The cost of the burger was just 11$, or 80$ per kilogram of in vitro meat. The best part is that they can now produce over 10 000 pounds (over 5 000 kg) from just one small piece of meat.

Let that sink in.

Today, we have the technology not just to increase our husbandry output for 10% without causing environmental destruction, we have the technology to increase our meat production by 5 000 times, that is 5 000 000% (five million percent) without causing further environmental damage.

We are entering the new era of food production.

Welcome to the era of cellular agriculture.

There is a growing momentum in the scientific world regarding research and optimization of in vitro meat production. Plethora of research groups and organizations are doing their best to bring the artificial meat to our tables as soon as possible. There is a lot of hard work to be done, but in vitro meat will be a commonplace commodity in our supermarkets by the middle of this century.

And it is not just about the meat. We can already make perfect milk without cow or sheep, we can make (real) animal hide and leather without killing any animal and we can produce eggs without chickens.

With the birth of cellular agriculture, we once again have the possibility of growing healthy food for everyone without killing the planet and decimating species. We no longer need to slash jungles and rain-forests, we no longer need to pollute our air, water and soil with tonnes and tonnes of antibiotics. We can make Earth a healthy, vibrant planet once again and we can do it in our lifetime.

I fully expect Luddite-like organizations to raise up against the in vitro meat, I fully expect those you’re-playing-God(s) nonsensical argumentation and I fully expect that road from industrial agriculture to cellular agriculture will be a rough one. You can count that I will fight with every fiber of my being for cellular agriculture. And the reason for that is pretty clear; there are only 3 viable options regarding our future food production: (1) we will either continue to do what we’re doing today and kill our planet (and us with it) in the next 100 years, (2) we will revert to the “organic” farming and let majority of the world population to starve to death, or (3) we will embrace scientific advancements and make our planet a better place to live on, without sacrificing our modern way of life.

We all have that same choice.

On the Shoulders of Giants

“I have seen a little further it is by standing on the shoulders of Giants.”

– Isaac Newton

We live in a very, very exciting and intriguing times. Technological progress is moving forward on a scale never seen before, society has changed immeasurably in the last 20 years and it is continuing to do so. We are truly living in one of the Golden Era of Humanity.

One foundation of this era is a discovery of basic physical unit of heredity – deoxyribonucleic acid, better known as DNA. For thousands of years, humanity was baffled with how a (wo)man comes to life, what magic is involved in creating a child and how do our bodies even function. Science finally lifted the veil of mystery of life in 1950’s with the discovery of genetic code. It was the single most important discovery Homo sapiens made since the discovery of fire.

We felt like gods.

Suddenly, everything was in our reach – humanity figured out how does it procreate, we understood how we grow, we confirmed that cell is a building block of life. We learned that genes encode proteins (life’s building blocks) in a very simple and elegant manner. We finally understood diseases and we thought that cure for all diseases is just around the corner. First obstacle was decoding of our great code. Back in the 1950’s and 1960’s, mapping 3 billion base pairs (by hand) was impossible task. Another great foundation of this Golden Era – computers and computer science – helped us to overcome this obstacle and at the beginning of new millennium, we decoded human genetic code. New era of medicine ushered, giving birth to entire new scientific fields: bioinformatics, chemoinformatics, molecular medicine, clinical genetics, biotechnology, medicinal chemistry, etc. It also revolutionized pharmaceutical industry – era of serendipity-based research ended (“luck-based” research – most of the drugs developed in the 20th century were developed by chance, not by systemic research), and era of molecular design, era of rational drug design (targeting of specific target – protein – with known structure and function) started. Multi-billion dollar industry per year emerged and impact on the world is tremendous. But this is only the beginning of the great transformation that is to come.

Key to this transformation is recombinant DNA (rDNA). Recombinant DNA molecules are DNA molecules formed by laboratory methods of genetic recombination to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in the genome. For instance, you can take gene from a fruit fly and insert it in genome of a tomato. Recombinant DNA is possible because DNA molecules from all organisms share the same chemical structure and they differ only in the nucleotide sequence within that identical overall structure. We were aware of this possibility ever since the 1970’s and we are able to do this for quite some time now. The trouble is, it is still very complicated, it is quite expensive and it is mostly limited to lower life forms. Back in the 1970’s, people had a ‘what if’ debate starting at Asilomar Conference Grounds on the subject of recombinant DNA and possibility that it would be easy, cheap and very fast. Preeminent genetic researchers of the time went to Asilomar to grapple with the implications of being able to decrypt and reorder genes. It was a god-like power – to plug genes from one living being into another. Used wisely, it had the potential to save millions of lives. But the scientists were also aware that their creations might slip out of their control. They wanted to consider what ought to be off-limits. Asilomar was about establishing prospective guidelines, a remarkably open and forward-thinking move.

David Baltimore, young genetic researcher from MIT, and four other molecular biologist stayed up all night writing a consensus statement. They laid out ways to isolate potentially dangerous experiments and determined that cloning or otherwise messing with dangerous pathogens should be off-limits. A few attendees fretted about the idea of modifications of the human “germ line” – changing and introducing new genes into a human being that would be passed on from one generation to the next – but most thought that was so far off as to be considered science-fiction, strongly leaning on the fiction side. Engineering single-cell bacteria was a nightmare (it was really, really hard), engineering human being was considered to be impossible all the way through the next millennium. The rules of Asilomar scientists hoped biology would follow didn’t look much further ahead than ideas and proposals already on their desks.

Forty years later, much sooner than prophesied thousand years, Baltimore joined 17 other researchers for another California conference. Topic was, once again, genome engineering. The stakes, however, have changed.

Everyone at the meeting had access to a gene-editing technique called Crispr-Cas9. Remember that abbreviation, as it will turn your world upside-down. The first term is an acronym for “clustered regularly interspaced short palindromic repeats”, a description of the genetic basis of the method; Cas9 is the name of a protein that makes it work. Technical details aside, Crispr-Cas9 makes it very easy, very cheap and extremely fast to move genes around – any genes, in any living thing, from simplest bacteria to full grown human being. These are monumental moments in the history of biomedical research.

Using this new technique, researchers have already reversed mutations that cause blindness, stopped cancer cells from multiplying, and made cells impervious to the HIV virus. Agronomists have rendered wheat invulnerable to killer fungi like powdery mildew, hinting at engineered staple crops that can feed a population of 9 billion on an ever-warmer planet. Bioengineers have used Crispr-Cas9 to alter the DNA of yeast so that it consumes plant matter and excretes ethanol, promising and end to reliance on petrochemicals. Startups devoted to Crispr-Cas9 have already launched. International pharmaceutical and agricultural companies have spun on Crispr-Cas9 Research and Development (R&D). There is also a great TED talk from the creator of technology itself about usage and implications of Crispr-Cas9 and I highly recommend it, although I don’t agree with take away message of the lecture.

This technique is revolutionary, and like all revolutions, it’s perilous. Crispr-Cas9 goes well beyond anything the Asilomar conference discussed or even dreamed of. It could allow genetics researchers to conjure everything anyone has ever worried they would – designer babies, invasive mutants, species-specific bioweapons and a dozen other apocalyptic sci-fi tropes. It will, however, not come to that. Promising new research suggest that we could, using this technique, end world hunger within 30 years, completely eliminate blindness, deafness, genetic disorders of the face of the Earth, we could end polluting oil industry and still keep (clean) petrochemical industry etc. And it will cost us peanuts. World will not be the same place in 30 years, it will be nothing like we can even dream of at the moment.

Great inventions, especially ground shattering inventions like this one, comes with its own great intellectual property battle – who invented it first and who will make most money out of it? As media covered it, there are two groups of scientist battling over it – one that filed a patent request first and one group that claims it invented it before the first group. I will not go in the specific details of each group arguments, you can read all about it on this link. I see two great problems in this story.
First problem I have with this patent lawsuit is the patent right itself. On political and economic scale, I’m a libertarian (economic scale) liberal (political scale). I firmly believe in capitalist system and patent right is a core tenet of it. Quite simply put, patent rights systems is one of the pillars of capitalist system and it is a great concept of assuring that you, and you alone, will reap the benefits of your hard work. If you put your entire wealth, time and integrity in a project – be it a new product, music album, molecule, anything – and you make a breakthrough or develop new and never seen before product, you deserve to make a profit out of it. Patents are a great driving force of development, technological advancement and cultural renaissance we are currently living in. It is also a great concept of protecting “small” players (for example, small biotech start-up) from a “big” player (pharmaceutical giant) and ensuring that big player will not just take someone else’s research and develop new product line-up without honoring, recognizing and, ultimately, paying small player’s share.

However, there are some things that should not be patentable. Basic knowledge, basic techniques (basic does not mean simple) should be free for all. I’m a great advocate of the open source philosophy and I firmly believe in open science. Human genome project was approached in open science manner and it brought billions of dollars of revenue to the world economy per year, while every bit of information that was discovered on that project was published freely and stored on the databases that were open and accessible to each and every man on Earth – literally every gene, every protein, every piece of knowledge about DNA, RNA and proteins is on the Internet and you can access it now whenever and wherever you are on whatever piece of hardware, be it a supercomputer or 100$ smart phone.

Why am I drawing this parallel? Story of Crispr-Cas9 is very much like Human Genome Project. It is not a discovery made by a deliberate private investment. Crispr-Cas9 research has been an ongoing story for over 30 years across the globe and it was mostly funded by public money on public universities. That means that you (we) funded this project. It shouldn’t belong to the two or three persons alone, not when this discovery was possible due to collective work of thousand of researchers funded by general public. What was paid by general public should be freely accessible to general public – we have already payed for the discovery of the Crispr-Cas9 system, we should not pay it once again for every new product that will be made using this technology.
Second problem is that Crispr-Cas9, however revolutionary, belongs to the sphere of general techniques. That is not a final product – it is a mean of developing new products. For instance, genes are non-patentable category, no one can patent certain gene (believe me, many have tried). Imagine that every laboratory in the world should pay a fee just because their research somehow involves certain gene – entire field of modern biology and biochemistry would be non-existent. All this progress that we have seen in the last 20 years would not occur, we would still treat diseases as we had treated them in 1970’s, with the same success. If Crispr-Cas9 gets patented, we might lose decades of research in the same manner.

However, all is not so grim in this case. I had already mentioned that Cas9 is a protein, and Crispr is a technique. New proteins have been found recently that do the same thing as Cas9, some even better. Most prominent one is a Cpf1 protein. These proteins are in fact an antiviral defense mechanism in simplest bacteria and Feng Zhang, researcher behind Cpf1 protein, had said that there are many more defense system proteins like Cas9 and that “he has a feeling it’s just the tip of the iceberg”.

So, now we have a situation where a tip of the iceberg can turn our world upside-down. Even if this and all future proteins (like Cpf1) are patented, we will have a market competition between them. That means that every team will try to deliver this technique at the lowest price, best precision and greatest speed. Situation simply cannot be better for scientific community and Humanity as a whole. We will either have great market competition of different genome editing techniques or every research will be done in the open science manner.

I would like to add up just one more thing. This entire patent battle of Crispr-Cas9 gets science all wrong. We have a situation where two labs have made a groundbreaking discovery. The sociologist Robert Merton, who made a career out of studying scientists, writes about how every field of research builds upon an “accumulated cultural base”. What he means is that discoveries don’t drop out of the air: they’re the products of their time and incremental increase of thousands of contemporary researchers.

Two teams that are now bickering over the patent rights and potential (probable) Nobel prizes have come to the same conclusion in the early 2010’s having approached the problem from two different sides. From the early 2010’s onward, it was a race of who will polish and publish these results first. My point is, work of both of these laboratories should be acknowledged and applauded, as they have independently came to the same conclusion and the same final genome editing technique.
This situation has actually been pretty common throughout history. Isaac Newton and Gotfried Leibnitz independently discovered calculus in the late 17th century and then spent years fighting over who got there first. Charles Darwin and Alfred Russel Wallace both came up with the theory of evolution through natural selection, though these two had a more amiable relationship. Back in 1922, the sociologists William Ogburn and Dorothy Tomas catalogued 150 examples of independent discovery and invention. Scientist naturally flock to the interesting scientific problems of their time, and again naturally, they use the tools of their time to solve them. No wonder they often come up with the same solutions.

Science, more than every other field of human activity, is all about cooperation and communication. Amount of knowledge is massive and there is no living human being that can revolutionize scientific field all by himself. We all depend upon our peers and the ones that came before us, be it Giants like Darwin, Einstein, Tesla or “ordinary” scientists of their time that didn’t make it to the spotlight of history.

So, in the light of this, I would like to end this blog as I have started it, with Isaac Newton’s words that every true scientist, and every true man, should live by:

“I have have seen a little further it is by standing on the shoulders of Giants.”

The Good, the Bad and the Stupid

Before I start writing new post, I just want to say out loud that if any of the facts you read on this blog prove to be wrong, I would be very happy if you point them out to me. Mistakes can be made, facts can be overlooked and I don’t balk from apologizing if I’m wrong. This applies to this post and every post from now on.

So, as I promised in my last post, I will be talking about the mess with the Daraprim treatment and Turing Pharmaceuticals. As they tend to do, the press covered the story with the usual shallowness and they missed their target far and away. Yes, Martin Shkreli is a douche-bag and, yes, his move with Daraprim pricing is borderline, psychopathic villainy, but the main issues in this story remain unresolved, undiscussed and, mostly, unmentioned.

So, let’s start from the beginning. Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii and infections with toxoplasmosis usually cause no symptoms in healthy adult population. Rarely, it might involve mild flu-like illness for a few weeks. Problem is, it can cause severe symptoms (such as seizures) in population of weak(ened) immune systems, such as newborns and patients with AIDS. Preferred treatment is pyrimethamin, better known as Daraprim in both USA and EEA area, taken alongside folic acid. The thing is, AIDS-infected patients often have to take that medication for life. There are other treatments, such as sulfadiazine or clindamycine, but doctors prescribe Daraprim because the side effects of Daraprim are well known and they feel safest when administering that drug. Other reason is that they avoid prescribing antibiotics if they aren’t absolutely necessary. Usage of antibiotics leads to development of antibiotic resistant bacteria and that might be the greatest health care issue of 21st century. I will talk more about it in a separate post. Daraprim is on the market since mid 20th century, patent protection ran out in ’70-ies and it was pretty cheap and easily accessible to the patients and everyone were happy until now.

GlaxoSmithKline was the holder of Daraprim up until 2010 when it sold the rights for selling of the Daraprim in the USA (and the USA alone – GSK still holds the rights on Daraprim in all other EEA countries AND Canada) to CorePharma. CorePharma sold it to Impax Laboratories. Impax laboratories did not do much with the drug, only major thing they had done with Daraprim was a change in distribution system – they went from typical wholesale distribution to a smaller and more tightly controlled, specialty drug distribution network, making development of new generic drug virtually impossible. Making generic drug is pretty straightforward process and there is only one critical step – you have to prove that your new (generic) drug has absolutely the same properties as the original drug (originator). If you cannot acquire enough of the originator or if owner of originator gives you “bad” drug (drug from production batch with some error or outright wrong formulation) and you embarrass yourself (and lose hundreds of millions of dollars in the process) in front of regulatory agencies, you cannot develop novel generic drug. Impax Laboratories did nothing with Daraprim per se, they only made making generic version of Darapim virtually impossible.

Enter Martin Shkreli.

Impax Laboratories sold the Daraprim market rights to Turing Pharmaceuticals, start-up company led by a young hedge fund manager Martin Shkreli. Right after acquiring market holding rights of Daraprim in the USA, Turing Pharmaceuticals raised price from $13.50 a tablet to $750, shocking 5555,56% increase in price. Mass hysteria ensued, Skhreli was dragged in the mud all across the Internet, pharmaceutical industry was (once again) vilified, everyone had all of a sudden had (the same) opinion about the pharmaceutical industry, American presidential candidates had speeches about it and promised to end the outrageous pricing of drugs. Yes, Martin Shkreli is an idiot devoid of all sense of morality (and if we were all wrong, and he did have a plan to make good use of the money he had intended to plunder with this Daraprim pricing, I will publicly apologize and cover the story about good guy Martin Shkreli) and that is where this story should end.

First of all, he is not the first to do this and he is not the only one to do it this year. Second of all, he is not a scientist, he is not an engineer, he is not a leader and he will never build anything except his bank account. He is hedge fund manager and his (and all the other hedge fund managers) interest is in short-term monetary gain. Players like these do not understand how does the pharmaceutical industry work, they do not understand the principles in building pharmaceutical empire, they do not understand that you have to spend 10 to 20 years on one (ONE!) drug to start making profit. These players enter the field of pharmaceutical industry, they wreck havoc for a couple of months, they sell the market holding rights back to pharma-savvy (yes, I made this phrase up right now) company and situation normalizes afterwards.

What is most important fact in this story, patients are not and will not be endangered by this move. First of all, there are stocks of Daraprim in hospitals (although they are dwindling). Second of all, in November 1992, the US Congress created the 340B program which is codified as Section 340B of the Public Health Service Act. This law protects specified clinics and hospitals from drug price increases and gives them access to price reductions. This law requires pharmaceutical manufacturers participating in the Medicaid program to enter into a second agreement with the Secretary of Health and Human Services – called a pharmaceutical pricing agreement (PPA – btw, hello Ubuntu users) – under which the manufacturer agrees to provide statutorily specified discounts on “covered outpatient drugs” purchased by government-supported facilities, known as covered entities, that are expected to serve the nation’s most vulnerable populations.

In other words, Medicaid patients and hospitals who service those patient, are protected by American Federal law from the burden of large increases like this. The 340B program is one of the most powerful contractual pharmaceutical pricing systems in the world to protect those people who are in need of expensive medications that are on those contracts. Moreover, Medicare and private insurance patients also have access to those prices if they can demonstrate need.

In other words, only population that would bear the burden of this increase is rich population covered by platinum level health insurance, even if Shkreli had not backed down on his decision to increase the price. I’m sure that those pitchforks would not be needed.

Shkreli’s failure was actually not of business logic, his plan was actually perfect on that side. He bought the drug that was in use for more than 60 years, there are no generic version of it and previous market holder had made virtually impossible to develop generic drugs. Poor and middle-class population is protected by the Federal law and Shkreli was to make money on perversely rich and AIDS infected population. Great plan. And it would have worked if Shkreli invested in one thing – marketing. His failure was not of business strategy, his plan flopped because he had lacked proper PR.

People brought pitchforks up because of overpriced medication that is mostly used by a very tiny percentage of AIDS infected population (that really is a niche of a niche on pharmaceutical market) but no one is bringing pitchforks to Apple headquarters for overpricing their technology. Moreover, for absolutely the same business strategy, Apple is applauded as the best tech company and it is currently ranked as world’s greatest company and the most profitable one. OK, that might be completely wrong example, iPhone or iPad are matter of luxury, not survival. Let’s try to find more suitable example.

Pricing of bread – in ideal world, ration of price of wheat to flour to bread is 1 : 2 : 3. First part of the equation adds up and ration of price of wheat to flour is about 1 : 2. Things completely break down in other part of the equation. Currently (in Europe), ration is 1 : 2 : 10. OK, let’s say that bakeries have many expenditures, they are bogged down by regulations just as anyone else and the ratio would be 1 : 2 : 5. Where are other 5 parts of the price? Pure extra profit. Where are the pitchforks? Why is there no public outcry for this example of profiteering?

The answer is simple – we are used to it. That is just the way things are and we live with that fact and for all of our lives, we are overpaying the commodity that is essential for all of our lives. Just as drugs are. If Shkreli had had a pinch of patience and good PR team behind him, he wouldn’t have raised anyone’s eyebrow.

Now, on to the other points that remained under the radar. Daraprim is on the World Health Organization Model list of Essential Medicines. Daraprim tablet cost in USA was $13.50 and nobody had had any problems with that fact. Nobody had mentioned the fact that the same drug in UK costs 13£ for 30 tablet pack – that is approximately 0.43£ (0.65$) per tablet, making Daraprim treatment around 2800% pricier in USA than in the rest of the world – BEFORE Turing Pharmaceuticals’ price increase. Even worse, there are various pyrimethamine tablets in India for the price of 0.08$ per tablet. Now, one could say that unregulated markets of India and southeast Asia where drugs could kill you just as they could cure you are not comparable to the market of USA, but markets of European Union are comparable to the market of USA. Difference in price of 2800% is unjustifiable. So why is there such a difference?

People and media are accusing capitalistic system and pharmaceutical industry as a whole, saying that drugs can’t be commodities. The problem is exactly lack of capitalism in this case. How could it be allowed that Daraprim – drug on WHO’s list of essential drugs – became commodity under monopoly of one company that closed the wholesale distribution of Daraprim and made it harder to obtain than the high quality crystal meth or cocaine on the street?! This situation is prime example of what happens when competition is stifled. This is not the story about greedy capitalist (although it is caused by one), this is story of failed system, system that became bogged down with unending sea of bureaucracy, system that actively discourages investment, competition and progress – system where it was non-profitable to develop generic version of a drug that was overpriced for 2800%. Just imagine, margin of 2800% was not enough to make a profit. That is the state of the legislation of pharmaceutical industry today, that is the amount of money the state takes for itself for every drug. And government of USA knew that and subsidized that drug, consciously overpaying each treatment for 2800%. I don’t know how you call that, but I call it cartelization – and that is not a sign of a healthy, capitalistic system, it is a sign of corrupt, bureaucratic (one could even say fascist) system.

And what was the reaction of politicians and policy makers? They want to regulate and dictate the price of drugs EVEN MORE! And what happened after those remarks? Whole sector of biotechnology fell and lost millions of dollars of worth in just one day.

At this point, I’m not worried about price of Daraprim treatment increase one bit – I’m more worried about politicians meddling in the affairs they are not qualified one bit, potentially destroying entire sectors of research in biology and chemistry that will improve all our lives. Every meddling of politicians in pharmaceutical industry resulted in destruction of entire companies and slowing down of research in certain areas for entire decades.

To conclude this post – yes, Martin Shkreli is a shortsighted, greedy man and Daraprim price increase is, to say the least, sickening. He will wreck havoc in this sector for a month or two and he will become history. I’m far more concerned about increase of the state legislation and start of the dictated economy, similar to fascist and communist economies, that will ultimately destroy years of research, years of hard work and the greatest victims of this event will be you and every one of us, all children, all men and all women. Innovation and progress cannot be dictated. We should keep hedge-fund managers out of pharmaceutical business, but we should not forget to keep out the politicians as well.

So, the question remains – why are drugs so expensive?

That will be the subject of my next blog post.

‘Till then,

Goodbye.

Hello World!

Hello World!

That might be the most generic greeting in the world. Every computer scientist, web specialist, database administrator and, lately, every kid that is remotely tech savvy programmed it in multiple computer languages as its first tutorial. Yet I chose it to be the greeting in my first blog post ever. I consider it to be one of the most empowering greeting ever and one that evokes most beautiful memories one person can have. For most of you, simple “Hello World!” evokes the memory of when you programmed your first program, your first masterpiece, one of the first thing that made you feel powerful and proud, and it was probably one of those aha-moments and wow-moments in your life. So I cannot think of the more appropriate greeting for this occasion.

Yes, I decided to write a blog despite swearing that I never will write one. It was in a time when blogs filled the role of todays Facebook or Twitter, when blogs were mostly hurt teenagers diary and litanies of doomed loves or other world shattering problems of 12-year olds. Meanwhile, blogs matured and we had matured with it. Heartbreaking drama of 13-year old girls has moved to Facebook, Twitter and other services I have already lost track of, while blogs became special, very personal form of education, communication and news-sharing place. In the world where we’re flooded with bits of informations, but the picture as a whole is blurred more often than not, in the world where communication was never easier, people have lost the ability to properly communicate. What is even more frightening, people have lost the will to communicate. To really communicate, to exchange ones views, opinions and/or facts, to appreciate different viewpoint. We as a society have became a mass of entrenched, bickering people with depth and knowledge about our world that can fit as a logo on a T-shirt. In such a world, blogs became lighthouses of knowledge, a place where enthusiast and people of good will invest their time (a lot of their time, I might add) to be a positive change and to influence small part of their, and our, world for the better. One of the best examples might be WaitButWhy blog. There is no better place to spend your extra time on. Honestly.

I can thank Vedran Miletic for talking me into writing this blog. I will be writing about the things I consider I’m well versed in and the goal of this blog will be to bring scientific topics (mostly pharmaceutical science) closer to you. I might wander off into some general topics over time, but I will tend to write about the things that are my profession and bring them closer to all of you.

My first story will be about all the hustle and bustle with Daraprim and Turing Pharmaceuticals. I believe that this event should be given a proper context and thorough background check. More on that in the following week.

‘Till then,

Goodbye.