Aug 15 2011

MS and the Promise of The Genome Project

The Human Genome Project  (HGP)- the project to map the entire human genome – was one of the big public science endeavors that captured the imagination. It started in 1990 and took 13 years to complete, completing the map in 2003 (but certainly not ending the project). Unusually for most such big projects, it was completed ahead of schedule and below budget. The project benefited tremendously from improved techniques and advancing computer power. Sequencing the first genome took about 300 million dollars. Today we can do it for about 10,000 dollars, and the price continues to fall geometrically (about half every 9 months).

By all accounts the HGP was a huge success. But 8 years after the completion of the first human genome map there is the vague sense in the public that the promise has not been fulfilled. The public was promised that the HGP would allow us to identify genes associated with diseases, and then craft cures based upon that knowledge. So where are all the genetic cures we were promised?

What is really going on is that even a big-picture successful science project like the HGP can be overhyped by the press. By mapping the human genome scientists were given a powerful tool with which to investigate disease. It still takes, however, a tremendous amount of research to translate that tool into specific knowledge about an individual disease, and then further translate that specific knowledge into a proven treatment. The pipeline for translating the basic knowledge of the HGP into an actual treatment is about 15-20 years optimistically (and that is after a specific disease is pursued genetically.

The effect of media hype is to make the public impatient, as if results were right around the corner, and then feel disappointed or cheated. But have patience, and the promise will likely be fulfilled. I think there is a good analogy to the internet and the world wide web. Around the same time as the HGP was started, 1990, the web started to come into existence and public awareness. It was, of course, hyped by the press with the promise that it would transform the economy, the way we communicate and do business. Then, a decade later (after the tech bubble burst) it seemed like the promise of the internet was mostly hype – a few killer online services had emerged (like eBay) but overall the web seemed like a fizzle. Now here we are another decade later and I think it’s fair to say the promise has been fulfilled. We have social media, internet businesses, free online communication, and much more. You can also carry it all around in your pocket. If the internet was a disappointment in 2000, I would say in 2011 it has exceeded expectations.

I suspect the HGP will be the same (perhaps not as quickly). Give it another decade or two and we will look back at the amazing success of mapping the human genome.

Here is one nugget to whet your appetite. Recently it was published in Nature the results of an international effort to examine the genetics of multiple sclerosis (MS). Previously we knew of about 15 genetic variants that increased the risk of developing MS. The latest study increased that number by 29. MS is a complex set of diseases, and there are environmental factors as well. But now we have over 40 genes, genes that are involved with the regulation of the immune system, that are known to make one susceptible to the disease.

This will not lead instantly to a treatment or cure. But it does provide a powerful window into understanding the disease. What proteins to these genes code for, and what are the functions of those proteins? How are the immune systems of people with genes that predispose to MS different from those that do not? This might provide an insight into how we can tweak the immune system to turn off the attacks of MS.

Now don’t get too excited – it may take a decade or two to fully realize the benefits of this new knowledge about the genetics of MS. Research takes a long time to grind slowly forward. But it is nice to celebrate the occasional big milestone – like the HGP and this latest advance in understanding the genetics of MS.

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11 responses so far

11 Responses to “MS and the Promise of The Genome Project”

  1. daedalus2uon 15 Aug 2011 at 10:25 am

    There seems to be a disconnect between what the science says and what those pushing the research as a source of potential cures say.

    If there are 40 genes involved in MS, then MS is not one disease, it is many diseases that by coincidence have common symptoms that lead it to be called MS. That there are similarities in symptoms but not in genetics suggests to me that the problem(s) and the solution(s) do not lie in genetics at all.

    I am not saying that the HGP should not have been done, or was a waste, but the genome is much more complicated than was initially believed and the observed correspondence between genotype and phenotype is not what was expected.

    A large part of the problem is the wrong idea that every similarity in MZ twins is due to their shared genome and not to their shared in utero environment where they grew from a single cell to 10^11 cells. If MZ twins were exposed (unknowingly) to a teratogen in utero, their shared response to that teratogen would be considered to be “genetic” and not environmental.

    I appreciate that many humans have a blind spot, where they want to perceive differences in adult humans as being due to differential genetics and not to differential environmental effects, as a justification for eugenics.

    This systematic bias in imputing genetic causes to disease is (IMO) slowing progress.

  2. locutusbrgon 15 Aug 2011 at 10:35 am

    I cannot deny the bust of boom attitude of media related to scientific advancement.
    I would like to point out that the HG project’s perception as a disappointment is multi-factorial. Science fiction and entertainment has been portraying genetic manipulation as simple well before the genome project was a tangible reality. Even reasonably educated persons grasp of genetics does not usually extend beyond Punnett squares and dominance/recessive traits. The complex nature of applying the knowledge gained by the project is beyond most lay persons knowledge. People do not understand that you can have a detailed set of instructions all the tools and still have no idea how to put it all together. Mapping the genome is exciting, using it is exciting. Developing the uses is incremental and unexciting.
    I always say this to my patients “my experience with new science is baby steps, not leaps, in the end it will probably not be as good as you hoped or as bad as you fear.”
    It is more than news reporting and headlines. In my opinion we have a culture that has been watching people shocked back to life in entertainment for 70 years. Asystole you do not Shock. Culturally the attitude is ” What do you mean you can’t cure my arthritis, I just saw Dr. McCoy fix anoxia with a shot in the arm Tuesday night”.
    We all are waiting for fusion power, cloned body parts and flying cars. I mean I see it on TV and at the movies every weekend it must be coming soon. ( Although I will admit the the thought of drunk drivers crashing their Delorean into my bedroom at night gives me pause.)

    As a personal note my aunt suffers from advanced MS and is wheelchair bound. I certainly hope that something restorative my develop from this.

  3. PharmD28on 15 Aug 2011 at 2:48 pm

    As a clinical pharmacist I am very excited that in my lifetime we may see some movement in these areas. We see scatter plots of data points and a line of best fit, but there are significant sub groups that have strangely specific responses to therapies….not that genetics will be the all encompassing defacto cause, but I can only presume it as another piece of data in clinical trials will shed so much more light, and perhaps its own confusion at times….

  4. Kawarthajonon 15 Aug 2011 at 3:39 pm

    It is convenient to always blame the media for the exaggerated effects of a particular technology or advance in science, but I recall that the HGP researchers themselves also contributed to the hype as well. Competing for research grants is often fertile ground for exaggeration, as is the scientific journals’ quest for readers. The research granters also want to promote the fact that their money was well spent, so will contribute to the hype, as will universities who want the exposure. There are multiple layers of hype built into any major scientific advance and it is convenient to blame the journalists, but it can miss the bigger picture.

    BTW, there was a recent success with gene therapy in treating leukemia – they altered the genes of t-cells to hunt down and destroy cancer cells and it worked!

  5. Draalon 15 Aug 2011 at 3:57 pm

    Captain nit-picker here.

    Today we can do it for about 10,000 dollars, and the price continues to fall geometrically (about half every 9 months).

    Depends on the size of the genome. This data applies to re-sequencing a human sized genome. If the genome is brand new, additional downstream data processing is required and increases the cost. In addition, the drop in cost has been much faster than Moore’s Law (www dot genome.gov/sequencingcosts/).

    And an observation regarding writing style:

    By all accounts the HGP was a huge success. But 8 years after the completion of the first human genome map there is the vague sense in the public that the promise has not been fulfilled. The public was promised that the HGP would allow us to identify genes associated with diseases, and then craft cures based upon that knowledge. So where are all the genetic cures we were promised?

    Replace ‘the public” with “the American people” and you have a political stump speech. These kind of broad sweeping statements that declares a group of people think this or want that raises my skeptical eyebrow. Is it really known that the public has a vague sense of unfulfillment regarding the HGP? If surveyed, would the majority of the public even know what the human genome project is?

  6. PharmD28on 15 Aug 2011 at 4:52 pm

    “BTW, there was a recent success with gene therapy in treating leukemia – they altered the genes of t-cells to hunt down and destroy cancer cells and it worked!”

    Worked in 3 patients right? Not sure if this may be another exampmle of media hype: “new cure” is the headline, but the final paragraph may say something like “well, but there is still much uncertainty and more research is warranted”….

    What a cool treatment though – simply amazing – hopefully it is replicated and has similarly awesome results without killing folk :D

  7. SteveAon 15 Aug 2011 at 5:55 pm

    Draal: “Is it really known that the public has a vague sense of unfulfillment regarding the HGP? If surveyed, would the majority of the public even know what the human genome project is?”

    I’d tend to agree. It’s true that the Human Genome project was hyped up as a Holy Grail in some circles (mostly by know-nothing reporters). But I’d guess that 95%+ of the population regard it as just background ‘sciency-type’ stuff that isn’t going to do anything that dramatic very quickly.

  8. son 27 Aug 2011 at 2:06 pm

    Wholly agree with daedalus2u comment.

  9. surfiemicon 28 Aug 2011 at 7:03 am

    Another example of how reductionist science can be interesting, exciting and help with understanding ofcourse – but fail to have much of an impact when its comes to putting things together and understanding the whole complexity of such diseases. The basis of such research is still overly reliant on the o so outdated linear cause and effect model of science ‘this gene does this’ mentality. Unless it is complemented by some dynamic thinking, we will reduce ourselves to oblivion! Thank god for the couple of refreshing truly forward thinking neuroscientists in my field of motor control, they give me a reason to stay in this crazy world!

  10. rezistnzisfutlon 28 Aug 2011 at 2:21 pm

    “Unless it is complemented by some dynamic thinking…”

    What kind of dynamic thinking are you referring to?

  11. surfiemicon 30 Aug 2011 at 9:04 am

    Dynamic as in non-linear; moving beyond obsession with linear cause and effect, beyond the idea that complex systems exist as the sum of their parts… Another way of looking at things, which accepts that most processes exhibit circular causality.

    Not in anyway implying that research other than this is not creative/dynamic/brilliant, just that, it has it’s limitations – naturally both aspects of the coin must be polished.

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