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about a year ago

Director of National Human Genome Research Institute Updates on Medicine, Calls for Help

Galacidalacidesoxyribonucleicacid

Since the era of recorded history, thinkers as early as Aristotle have philosophized on the nature of heredity. Hippocrates believed that hereditary material was collected throughout the body and then passed to offspring, not unlike Darwin’s speculation thousands of years later. An Arab physician described the heredity of hemophilia  in 1000 CE.

In the 19th century, a gardener by the name of Gregor Mendel proved using tens of thousands of pea plants that traits were heritable. Around the same time, a Swiss physician discovered a microscopic structure in the pus of discarded surgical bandages, what he called “nuclein” because it was found in the middle of a cell, but what we now know to be DNA. Francis Crick and James D. Watson published a paper in 1953 detailing the double-helix structure of DNA, inspiring a generation of scientists (and at least one artist) to try to understand how that encoded information could lead to the complexity that is a human being.

You probably have at least a vague awareness of the Human Genome Project. For those who don’t, it is a project that began in 1990 spearheaded by the (descriptive yet awfully named) National Human Genome Research Institute at the National Institutes of Health, an institute that Eric Green, speaker at Saturday’s lecture, is now directing. The project began with the promise to “provide foundational information that will allow us to provide better care to patients on an individual basis,” said Green. Exactly 50 years — and $1 billion — after the discovery of Watson and Crick, the project ended after sequencing over three billion protein bases (abbreviated by letters) that comprise the genetic code.

The collaborative effort was hailed worldwide by scientists and politicians alike as proof that humanity can come together and do some good from time to time. But all it really accomplished was three billion letters that nobody understood. What does it all mean for average Joe?

In Green’s lecture, titled “Bringing Genomic Medicine into Focus”, he presented on what areas need further research before we can really have something to be proud of, the end of disease through the use of individualized medicine. The five domains of research are the structure of genomes, the biology of genomes, the biology of disease, the advancement of scientific medicine, and the use of that medicine to improve the effectiveness of healthcare.

The structure of genomes is well-researched, i.e. we are fairly certain we have an accurate human genome sequenced. But “we don’t know the grammar, we don’t know the words, and we don’t know the syntax,” said Green. That means we need to better research how our bodies translate those letters into commands. So far, we are pretty sure that we understand protein-coding sequences, or “the bricks and mortar” as Green put it. That accounts for a whopping 1.5% of the total genome.

Whats about the rest? “The fact of the matter is we will be trying to understand the genome for a long time,” said Green. What makes this so difficult is that every gene is different. The vast majority of your gene is identical to everyone else on the planet, but in around 1 out of 1000 places, you might have a T where I have an A. That’s it. In fact, of your six billion nucleotides (of the 3 billion you received from both parent’s DNA), an estimated 150,000 are not in the database, which was assembled on average from many people. Sixty of your ‘letters’ are not in either parent.

After we manage to understand all that, which will likely take decades, we must understand how that applies to human disease. Monogenic diseases like hemophilia, cystic fibrosis, and sickle-cell anemia are rarer, but because they are influenced by only one gene they are easier to trace to one coding mutation and subsequently prevent. It is the common diseases like colds and cancer that are the most complex and influenced by many genes as well as the environment.

One way to understand how the structure and biology of our genes tie in with disease is through routine genetic testing. Remember way back at the beginning of this article, where you learned that the first sequence cost $1 billion? That would be pretty tough to incorporate on a large scale. Green and colleagues made waves when they published a paper forecasting technological leaps that sounded impossible. The paper became famous, maybe more as a joke at the time, when it predicted that the human genome could one day be sequenced for $1,000 or less.

If there’s one thing the people of my generation know, it’s that the progress of technology is inevitable. The first sequence, the Human Genome Project, took about eight years and $1 billion.In those years technology had gotten a little better; a human genome could be sequenced in 3-4 months for just $10-50 million. And today? The human genome can be sequenced for under $10 K, in just two to three days.

Not quite $1,000, but it’s not bad. These improvements are possible through better equipment, and improved methods. One method proposes to implant a small device in a skin pore, and read the stream of DNA as it is removed from the cell in real time. We’re not there yet, but it’s being designed. “Technology will be the driving force of the genomic revolution,” said Green. One the same slide was a USB which plugged into a computer that could analyze the DNA on any laptop. “Perhaps the greatest feat,” said Green, “is that it will be compatible on both Macintosh and PC.”

Understanding all of this data will be “like trying to drink water from a fire hydrant.”

Once this data has been analyzed, one of the first areas on which it will be used is cancer. Another area that needs immediate attention is how to better prescribe medication to individuals while avoiding side-effects. The hope is that, while applying individual care may not be in the very near future, research in the domains necessary to get us there will steadily improve, hopefully before funding dries out.

What Green said that stuck with me the most is, “We don’t have the workforce. We need new people trained in new ways.”

Which brings me to that curious painting you see as the featured image in this post. Some of you might not recognize the name of the piece (Galacidalacidesoxyribonucleicacid), but you undoubtedly recognize the artist (Dali). The great thing about art is that it is subjective. When I look at that painting in the context of the presentation, it speaks volumes.

The circles on the left are molecules as well as people fighting a war. To me that is the background, those who have chosen to drift through life doing whatever is easiest. The squares on the right are actually arranged in a double helix, while also being people with guns pointed at the adjacent person, in a more civilized and dare I say bureaucratic manner. It makes me think of government, who would cut science funding in order to fund a war, or the potential of this genetic information to be used as a weapon (see this post). And lastly, the person in the middle, who is actually Dali’s wife, to me represents those in life who ask questions, and who are not satisfied with simple answers. The scientists, writers, and, yes, innovative businessmen, who think creatively to solve problems.

One thing is for sure: it is a very exciting time to be a geneticist.

This is the third in an ongoing series entitled: “Your Genes: How They Contribute to Who You Are”. Last weekend’s lecture was titled, Life’s Little Problem: Determinism vs. Chance in the Complex Ways of Genomes”. Next week’s is titled, “Personalized Medicine: Are We There Yet?”. The lectures take place at 11:00 a.m. every Saturday through February 23 in 100 Thomas. Video recordings of previous lectures are available here. Sorry for the length!