The hope of personalized medicine

After being gone from the blogging scene for a while, I decided to write about what I was doing in the meantime. Specifically, how an exciting new technology will soon bring a new era of personalized medicine into existence.

When I started my undergraduate studies in molecular biology at the end of the last century, my hopes and dreams were no less romantic than any of my young colleagues’. Yes, we were the ones who were going to get those Nobel prizes, solve mysteries of the Universe and find the cure for cancer. Well, at least we thought so. Around our third year, after learning basics of biochemistry and genetics, we realized that – while we still might have a good chance for that Nobel prize – the cure for cancer just won’t happen. EVER. Now, a decade later, I am starting to change my mind. Let’s explain.

The biggest misconception non-scientists have about cancer is that this is one specific disease. Or several diseases: skin cancer, lung cancer, breast cancer, etc – until you counted all your organs. But actually, there are over 100 types of cancer. And to be completely honest, no two cancer patients have the same disease. As much as our DNA is unique and personal, defining what we look like and many aspects of who we are, every cancer and every tumor is also unique and personal.

How does cancer become so personal? Well, each tumor arises from our own cells, which have accumulated DNA mutations and no longer behave as normal cells. The biggest difference is that tumor cells divide without control, eventually spreading to all the organs and basically eating the patient alive. Those mutations happen for several reasons: 1) some are inherited from our parents, 2) some happen naturally (as we grow older, mutations in DNA accumulate due to imperfections of our body chemistry), 3) and some arise due to avoidable external factors (such as UV radiation from the sun or chemicals in cigarette smoke). These mutations arise randomly and are all over our DNA.

Now let us go back to my days as a young undergraduate student. How did I know we can’t really cure cancer? The answer is that all drugs have to target specific mutations. If every patient has different mutations, how can we find the universal cure? It’s impossible. The other problem is – we didn’t even identify all the genes and what they do, let alone all of those that, if mutated in certain ways, can give rise to cancer. The future certainly didn’t look very bright to me. I realized that, even if we cure all other diseases, every human will eventually die of cancer – some sooner, some later (depending on lifestyle as much as pure luck).

But something else was happening at the end of the last century: The Human Genome Project. A huge international effort, worth 1 billion dollars, to identify chemical properties of human DNA. (DNA molecule is a chain of 4 different chemical components – named A, T, C and G – which are linked to one another in a certain sequence. This project was about “sequencing”, identifying the sequence of these letters, over 3 billion of them. Any change in the original sequence is called a “mutation”.) If we know the complete sequence of human DNA (human genome), we can identify all genes – and much more. We could, one day, identify all genes involved in cancer!

After the Human Genome Project was completed, people started dreaming about looking into the cancer genome. If we knew the DNA sequence of a tumor, and we compared it to normal DNA, we could find mutations that caused that particular cancer. And if we identify the mutations, we can start developing highly effective, personalized treatment for this tumor.

This all was nothing but science fiction until a new, “next generation” sequencing technology was developed several years ago. This cheaper and faster technology led to the sequencing of the first cancer genome in 2008, making an impact on basic science and medicine comparable to the impact of Internet on communication. The cost of whole genome sequencing dropped from initial 1 billion dollars 10 years ago to about 10 000 dollars today, making personal genomics almost affordable. And the price continues to drop! In fact, there are already companies like Knome (Cambridge, MA) that sequence genomes of private clients, making it possible to know, for example, the risks one carries of developing a specific disease.

Since last summer, I was fortunate enough to attend this big sequencing party. I was offered to work on a project that aims to sequence tumors (lymphoma) in mice, which we use as model organisms to help us understand leukemia and lymphoma in humans. Sequencing is still expensive, but we found a cheaper way to get information we want by modifying our method a little bit. One of our goals is to identify mutations that “drive” the growth of a tumor. Since majority of mutations we see in tumors (usually tens of thousands) are harmless, looking for those important “driver mutations” (between 5 and 20) is a bit like trying to find a needle in a haystack. Still, we are hopeful – and all the necessary tools are here.

Does this mean we will have our cures for cancer very soon? Not really. Identifying all cancer genes and developing drugs that target them is a long and tedious process that will take many years. There is no technology that can speed up traditional biological research that still has to be done. But the benefits of sequencing tumors in patients are enormous. First – by knowing the exact mutations in your tumor, doctors will be able to prescribe targeted therapy, using those drugs that already exist. Second – more tumor sequences we have, the better we will become in understanding the biology of their growth, identifying those “driver mutations” and using them as novel drug targets. So, even though no miracle will happen over night, we will surely see some impact on healthcare in about a decade. And who knows, by the end of this century, we might look at cancer as we look at small pox today.

Freedom we will never have?

Nad Wolinska (Painters for Human Rights)

“[Free speech] ranks with the privilege of committing murder: we may exercise it if we are willing to take consequences. Murder is forbidden both in form and in fact; free speech is granted in form but forbidden in fact. By the common estimate both are crimes, and are held in deep odium by all civilized peoples. Murder is sometimes punished, free speech always – when committed. Which is seldom.”

This is an excerpt from an essay written by one of the greatest (in my opinion) American writers and intellectuals: Mark Twain (1835 –1910). An essay he was afraid (yes, afraid!) to publish while still alive… And which he entitled “The privilege of the grave”. It took 99 years after his death for this text to get published, along with other previously unknown work (of which some is unfinished), in “Who is Mark Twain?”, the book I’m currently reading.

Before I read this essay, for me, Mark Twain was merely an author of two famous children’s books (The Adventures of Tom Sawyer and The Adventures of Huckleberry Finn) – or at least two of his books I have read as a child. But now I came to respect and admire him as a man well ahead of his time. In fact, well ahead of our time too…

In this essay, he describes how society restricts free speech, a privilege he considers to be a “good thing”. Out of fear of social isolation, most people will never say what they really think – if their opinion is not aligned with the majority:

“When an entirely new and untried political project is sprung upon the people, they are startled, anxious, timid, and for a time they are mute, reserved, non-committal. The great majority of them are not studying the new doctrine and making up their minds about it, they are waiting to see which is going to be the popular side.”

Twain is hilarious: he notices that, since no one really says what he thinks, we can never know which party really won the elections! (Scary thought, or comforting one, depending on the party currently in power in your country.) Most people join, or support, the same party as their parents. Even if they realize they changed their beliefs, they will never leave the party. By that time, most of their friends will be in same party, and no one wants to be left alone and excluded.

I think this phenomenon is very natural and human. Most of our opinions and beliefs are not actually ours. They belong to the society, our collective minds. Few people ever question them, most never even become aware of it. It all comes from education. A small child asks many questions, hundreds a day. As soon as the child starts formal education, he learns NOT to ask questions. He must accept all those opinions presented – because who has time to explain everything? Even more so: does the teacher really know? Or is he too just repeating, as a parrot, what ever he (or she) was told to say?

The real problem here is not even freedom of speech, but freedom of thought. Or – freedom to think. We are all victims of it. None of us has this freedom, not really. We are all educated to think in a certain way and we were rarely encouraged to think for ourselves. Still, I can’t help but wonder: what if more people would think for themselves?  We would certainly have a more just world. If people are guided by empathy, a most beautiful innate human quality, how could we ever have wars? How could we ever leave someone deprived? We would also be happier in our personal lives. We would live to fulfill our own dreams, not do what we are “expected” to.

Recently, there was an example of this phenomenon in New York City, where I currently live. Some time ago, a 13-floor Islamic community center was presented that was to be built in lower Manhattan (there are many similar community centers in the City). No one had a strong opinion about it at the time. It took months until a heated discussion developed – and until headlines appeared in the newspapers: “A mosque to be built next to Ground Zero”. As it turned out, for those who cared to learn the facts, it was neither a mosque (the center was supposed to have one Muslim prayer room, along with classrooms, theater, art school, swimming pool, etc), nor it was next to Ground Zero (it’s two blocks away – close enough, perhaps). The opposers claimed that it’s a bad idea since it could upset the families of 9/11 attack victims (just because the attackers were Muslims). It was really interesting to watch how some people took sides – and aligned perfectly with their relatives, friends and parties they support… (including those 9/11 families). I consider many of those people capable of studying the matter and making up their own mind. They are all able to emphatize, simply by being human beings. But they didn’t bother – even if they would form their own opinion, they would be severely punished for expressing it.

Maybe it’s Utopian to believe that all people will be willing, or even capable, of studying great problems of our society. At least in our time. Struggle to survive and troubles of everyday life are more than enough work for most. But those few who can afford the time to think, to study, have moral duty to use that time well. And they must gather courage to speak now, not in 100 years.

How are you intelligent?

Sir Ken Robinson appears to be one of the most impressive thinkers in the field of education today. I read his book “The Element” after being intrigued by his TED talk, filmed in 2006: “Ken Robinson says schools kill creativity”. (The talk ended up being one of the most e-mailed and “favorited” TED talks ever, translated to 41 language so far – check it out.)

So, what is the Element?

“The Element is the point at which natural talent meets personal passion. When people arrive at the Element, they feel most themselves, most inspired, and achieve at their highest levels.”

In his book, Sir Robinson introduces a revolutionary idea – a different view of intelligence. Rather than a number you are given after taking an IQ test (whose inventor, French psychologist Alfred Binet, himself didn’t think that intelligence is a fixed, measurable quantity), Sir Robinson proposes that intelligence is diverse. We think about our world in all the ways we experience it: visually, kinesthetically, emotionally. And we have all those brilliant people from different domains of human activity to prove it. Intelligence is also very distinctive – it’s as unique for every person as a fingerprint. Together with our interests, it makes an essential ingredient of our Element.

Sir Robinson then explains how from very early age, kids learn about the hierarchy of subjects: math/science and language are the most important, then humanities; arts are at the bottom. If they work hard at math and science, kids are rewarded. If they like drawing, they are likely to be discouraged: “You can’t make a living as an artist.” As a consequence, many people end up never finding their Element, thinking they are not particularly good at anything. Others end up studying science and forgetting about their childhood dreams of becoming animators at Walt Disney studios (that’s me). They spend a lot of time in universities where they are brainwashed to think that university professors are the highest form of human achievement.

Being a person who spent 22 years on her education, mostly focusing on areas that would indicate my “high” IQ score (I never took the actual test), I wasn’t supposed to be thrilled about these ideas. I felt cheated and misguided by my teachers, mentors and various other intellectuals whose opinions used to matter to me. As a young student, I had deep belief in the intellectual superiority of scientists. And yet, I intrinsically felt Ken Robinson was right. Even the famous physicist, Richard Feynman, said:

“I believe that a scientist looking at nonscientific problems is just as dumb as the next guy.”

When trying to understand where these widespread beliefs are coming from, we should go back in time. Public education didn’t exist before 19^th century – schools and universities were available only to rich people. Educational systems today are relics from the industrial age – and they reflect its needs. In another great book, “A Whole New Mind: Why Right-Brainers Will Rule the Future”, Daniel Pink discusses this issue. He notices the world has left the industrial age a long time ago. It was followed by the “information age”, a time of great technological advances that changed our world dramatically (just think about the Internet). Indeed, when I was in high school, kids were advised to become computer programmers in order to succeed. Now, Mr Pink argues, the Western world is moving towards the “conceptual age”. If your job can be done faster by a machine, or cheaper by someone abroad, it’s time to re-examine your career choices. For example, even medical diagnosis can now be done using a computer – but it is harder for a machine to replace a caring human being. The author concludes: due to increased automation, abundance of goods and outsourcing to Asia, the only way to stand out in a market as is to develop your “right-brain” senses: big-picture thinking and empathy. Isn’t this in complete disagreement with our educational system where arts and humanities are undervalued?

Society depends on the diversity of human talent. There is no need to educate everyone to become doctors, lawyers or scientists. This is not the recipe for success any more either. The world is changing fast, much faster than ever before. Who knows what the markets will be like when today’s 6-year olds will be looking for a job? According to UNESCO, more people will graduate from universities in the next 30 years than from the beginning of humanity. Suddenly, our degrees mean nothing (I certainly have many jobless PhD friends to prove it). But there is a need to give kids the opportunity to discover their Element: only those who understand their talents and are confident in their abilities will always be able to adapt.

Each of us has a unique set of strengths and talents, as well as different interests. The purpose of education should be to help us find them, not to help us forget about them. In order to live successful and fulfilled lives, we must first change our backward views. As Ken Robinson proposes, let’s start by asking: “How are you intelligent?” rather than “How intelligent are you?“

From here I saw what happened… and I cried

(“Pictures by Women: A History of Modern Photography” – exhibition in MoMA)

It was another hot and humid New York Sunday. In a desperate search of air-conditioned spaces (my Brooklyn apartment was boiling), I found myself in the Museum of Modern Art.

Whenever I visit a museum, no matter how long I stay, I tend to remember only one piece. I stare at it obsessively and come back to see it over and over – or hope never to see it again. This time the piece was “From here I saw what happened and I cried” by Carrie Mae Weems.

The artist re-photographed old pictures of African slaves from 19^th and 20^th century, most of them originally taken in the attempt to show Africans as different species (!!!). She enlarged them, printed them in red tones, and added her own text to each photograph – emphasizing one aspect of their suffering and humiliation, the prejudice (“some said that you were the spitting image of evil“) and de-humanization (“you became a scientific profile, negroid type, an anthropological debate”). The collective effect is heartbreaking. From left and right, they are framed by an old picture of a (free?) African woman, in blue tones, saying: “From here I saw what happened… and I cried”. She is the only figure not robbed of all dignity. She sees the injustice and she’s angry. She makes you want to apologize to her, even if you or your ancestors had nothing to do with the slave trade (mine were serving feudalists in Europe at the time). I see this expression on many faces of African-Americans here in New York City. They are still angry.

Here’s what the author says about the piece:

In some ways I think, From Here I Saw What Happened is perhaps one of the more painful pieces that I’ve made. When I look at it, when I study it, I cry. It is a very sad piece, and, at the same time, of course, there’s always hope that’s located within sadness, as well. The hope that in the end our mutual humanity will be understood and embraced.

Speaking of “our mutual humanity”: so easy is to detach oneself from those who are suffering (we are all guilty of it), in our own worlds, running from one place to another, one job to another, in search of “power, gold or bread” (“za vlascu, zlatom il’ za hljebom” – as Croatian poet Dobrisa Cesaric put it). Because we can’t help them anyway. Or can we?