Wednesday, October 22, 2014
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Humanizing the Human Genome Project

COLD SPRING HARBOR – Since the human genome was first sequenced in 2000, genome science has accelerated at a remarkable rate. Rapid advances in DNA-sequencing technology mean that affordable decoding of the human genome is not far away. In fact, human genomes could be sequenced for as little as $1,000 in the next few years. Unfortunately, the current biomedical research establishment is entirely unprepared for such a scenario.

Researchers often believe that their mission is to uncover new biology and genetics, and that someone else will translate them to the clinical arena. Accordingly, many geneticists have worked on “big-science” genomics, including genome-wide association studies focused on common genetic variation in the human species.

But it is widely known that certain mutations can run in families, increasing dramatically the risks of certain diseases – for example, breast cancer, sickle-cell anemia, and cystic fibrosis. Unfortunately, many human molecular geneticists have abdicated any responsibility for trying to decrease the overall burden of such diseases.

While this trend has many causes – most of which have been debated extensively – one very important factor is rarely discussed. Scientific research – and biomedical research in particular – largely resembles a race. Human geneticists, like big-game hunters, specialize in finding disease genes – the “prize.” Once they succeed, they usually do not continue to develop their findings; instead, they move on to their next target.

Today, scientists are rewarded for how many papers they publish, and in which journals. In the United States, several major genome-sequencing centers exist primarily to conduct research – including the Centers for Mendelian Genomics, which seek to find the genetic basis of “simple” Mendelian disorders (diseases caused by a single mutation in the structure of DNA). Many other countries are undertaking similar programs.

But the discoveries and published papers rarely benefit the people who enable this research by donating their blood and other tissue samples. As Michael Nielsen discusses in his recent book Reinventing Discovery, the “publish or perish” mentality that dominates the field means that many substandard or incomplete papers are published, while those people who are supposed to benefit from the research are often little more than an afterthought.

Indeed, research volunteers rarely receive their genomic data, which betrays the trust that participants place in researchers to use their findings not only to increase the stock of scientific knowledge, but also to deliver actionable results.

The personal genomics and biotechnology company 23andMe has created a useful interface for returning results, which could easily be built upon to deliver complete genome data to participants – as long as the sample collection and sequencing are performed to a sufficiently high clinical standard. The company’s model laudably calls for research participants to help in the analysis of their own genomes, thereby relieving researchers of the burden of returning all results at once.

With expanding knowledge, analyzing genomes becomes easier. The hope is that, as technology develops, more researchers will recognize the importance of returning results – especially those that could have a significant medical impact – to participants.

Because there is no regulation requiring that initial sequencing of human genomes be performed to clinical standards, most sequencing does not meet laboratory-test criteria. Indeed, results are often not reproducible – badly conceived, poorly conducted, or outright fraudulent. Criteria must therefore be established to ensure that sequencing is performed in an appropriate clinical environment, with rigorous standards in place, including for sample collection.

Researchers today face the wrong incentives, which results in the failure to translate findings into meaningful action for research participants. Only by improving clinical standards and returning results to participants can human genome sequencing truly serve its purpose – to help humanity.

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  1. CommentedCher Calusa

    Thank you for re-iterating the true motivation for our exploits into the scientific arena. We are perhaps, too underdeveloped as a species to be engaged in science. Intellectual pursuit motivated by an immature ego is certainly not proving to be a benefit as we can see by the conditions that prevail among us. The fact that we can think should lead us to better conclusions but we're thinking in a vacuum of self benefit and we have a dangerous tool in our hands. The solution is to develop our knowledge of each other and the system in which we live. The entire network of living systems from the microscopic to the macroscopic level cooperates and favors development, growth and balance. Organisms which are out of balance and/or don't contribute to growth and development of their own colonies are creating an opportunity for their own destruction. We are the "human organism" and we are not immune to the laws that dominate living systems. We can establish balance among ourselves through mutual concern. We won't win at competition because in the natural world collective cooperation always trumps competition.

  2. CommentedFrank O'Callaghan

    A great article. Much needed. What motivates researchers? Fame ? Career structure? Money? Curiosity?

    Where is the structure within the research environment to motivate research to benefit humanity?

    If a researcher in a pharmaceutical company developed a drug that cured all forms of cancer. If it had no side-effects. If the drug was cheap to produce, easy to formulate and stable in all conditions. If it would work on a one dose basis. Would it be produced? Given that it would make all other cancer drugs obsolete?

  3. CommentedZsolt Hermann

    Although I fully agree with the findings of the article, the researchers are not to blame.
    They are just another symptom of what has been influencing all areas of our lives.
    Basically human evolution is the evolution of the human ego.
    This evolution has reached its maximum potential today, resulting in a completely fragmented, separated, polarized human society where each and every thought, plan and action is performed solely based on self interest without the smallest consideration of others, or the system we exist in.
    Besides science we can observe the same in politics, finances, economy where the leaders in more privileged positions completely disconnect from the rest, we can watch it live at the Olympic Games, where we cannot even find the last shards of the initial Olympic spirit, it is all about winning, personal or national pride and legacy, triumphing over the others by any means possible, and we can keep continuing with the examples.
    On one hand humanity achieved unprecedented capabilities, we can dissect ourselves down to the gene level, while quantum physicist can find the smallest, most obscure particles, but in the meantime we have lost sight of the whole picture, we do not see the forest from the tree.
    Which is especially tragic today, when we evolved into this closed global, totally interdependent network with each other, we simply cannot exist without each other, like cogwheels in the same machine.
    The global crisis is the representation of this huge tension between the self calculating, totally introverted, self obsessed human ego, and the external reality where we are locked together with iron chains.
    We should devote all our capabilities, talent and adaptability towards solving this tension, controversy before and explosion takes place.
    One important note: the system around us is not going to change, the only element that can change is ourselves.

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