Sunday, November 29, 2009

Genomics – The Global Opportunity

Genomics is particularly interesting as a candidate area for possibly making the most difference the most quickly to the most people worldwide by contributing to developments in energy, food and public health.

A full understanding of genomics, the instruction set for life, could mean a more comprehensive ability to manipulate both the world around us and the world within us. Biology evolved to be just good enough to survive and genomics provides the critical next-generation toolkit for its greater exploitation. With the possibility of a complete understanding of biology and the ability to engineer life to be optimum, traditional limits can be overcome, moving from the gene therapies of today (replacing or silencing one gene) to working with whole genomes and possibly creating new ones.

The global challenge and opportunity is for humanity to move safely and expediently into the genomic era of biological manipulation.
The agricultural applications of genomics have been underway for some time in the form of genetically-modified crops. Energy applications of genomics are in development using synthetic biology to generate fossil fuel replacements and are estimated to be ready for commercial launch in 2011. The public health application of genomics is especially promising, using genomics to further understand and eradicate disease. Genetic information is already starting to be medically actionable and is likely to become increasingly useful over time. Its two main current uses are in pharmacogenomics, personalized therapeutics, categorizing drug responders and non-responders for tailored treatment, and in routing higher-risk individuals to earlier screenings for chronic diseases such as prostate cancer and breast cancer. It is estimated that each individual is in the upper 5% risk tier for at least one chronic disease and that $100,000 per person per condition could be saved as a result of earlier detection. By 2010, according to a World Health Organization (WHO) report, cancer will surpass heart disease as the world’s greatest killer, and in fact, developing countries could be at the highest risk due to smoking and high-fat diets.

As our molecular understanding of disease progresses and genomic technologies continue to decrease in cost and become increasingly medically relevant, the use of genomics could become quite widespread. Physicians could start to see the precise, additive information conferred by genomics as a means of improving the care now delivered, finding themselves initially encouraged and eventually regulated into incorporating genomics in care regimens. Pharmaceutical companies are already using genomics as a means of improving efficacy in drug discovery and delivery, providing much-needed assistance to their ailing cost structures. Individuals worldwide could have unprecedented access to their health information which could prompt a much greater level of responsibility-taking and health self-management.

Sunday, November 22, 2009

Humanity: hedgehog or fox?

Isaiah Berlin discusses an interesting paradigm for understanding different kinds of thinkers, the hedgehog and the fox. The hedgehog operates under a single vision while the fox incorporates many ideas into a worldview. Philip Tetlock applies this framework to an analysis of political predictors and finds that while all expert predictors are bad, foxes are not as bad as hedgehogs. The success of the fox is perhaps partly due to Bayesian updates, adjusting the synthesis-oriented worldview per new information, as opposed to the hedgehog being stuck trying to fit all new developments into the same model.

Humanity: hedgehog or fox?
It could be argued that so far all of human history has been organized around certain grand hedgehog visions such as mastery over matter, immortality or evolution, to name a few.

Mastery over Matter
Over time, humans have been continually demonstrating increasing mastery over matter. The current focus is on improving control of biology and indeed reengineering it with genomics and synthetic biology, matter with 3D printing and eventually molecular nanotechnology, the brain with fMRI technology and smart-drugs and space with a next-generation understanding of physics. Perhaps the most intense version of mastery over matter is the present focus on the biomolecular interface, the integration of organic and inorganic matter. However mastery over matter may not persist as a paradigm, a future redefinition could include mastery over information.

Immortality is another grand vision, persisting from the time of the Pharaohs and earlier to long-established religious beliefs to the contemporary notions of life extension, uploading and cryonics. In some sense, immortality is just another kind of mastery over matter.

Evolution is a strong paradigm, explaining many things, and connotes a higher order than just mastery over matter since not everything is matter. Evolution can examine more phenomena, including the progression of intelligence, possibly across substrates as is contemplated with artificial intelligence. However, despite myriad application attempts, it is not clear yet whether evolution can explain everything, for example the laws of physics and how the universe developed.

Since even in a simple analysis, no one model can explain everything and there are multiple ideas relating to a composite explanation of human activity, the conclusion would be that humanity bears more resemblance to the fox model than the hedgehog model. Tetlock’s finding that the multi-viewed more adaptable foxes are better could likely hold true for societies and humanity in general as well as for individuals.

Sunday, November 15, 2009

MMP inhibitor to kill senescent cells

Important work in the understanding and remedy of aging at the Buck Institute’s Systems Biology Symposium of Aging held November 10-13, 2009 was presented by Judith Campisi in a keynote talk, “The Four Horsemen – Damage, Inflammation, Cancer and Aging: Integrating Aging and Age-Related Research.”

Campisi has found a common biological explanation for the related phenomena of aging, degenerative disease and cancer: the senescence-associated secretory phenotype (SASP). Senescent cells produce the SASP, essentially inflammation, which can then trigger degenerative disease (aging) and hyper-prolific disease (cancer). A potential solution is to remove the 10-15% of senescent cells that are not naturally killed by the immune system by using matrix metalloproteinase (MMP) inhibitors.


Humans are much longer-lived than other organisms such as flies because they have evolved cell-dividing mechanisms for tissue regeneration and repair. However, mistakes in the form of mitotic mutations occur during this process and build-up cumulatively which can cause cancer. To counter the build-up of mutations, tumor suppressor mechanisms evolved. One action of gate-keeper tumor suppression mechanisms is to direct damaged cells to senesce, or lose function.

Senescent cells are not harmless, they amass at sites of inflammation and pre-cancer and secrete up to 40 different cytokines (immunoregulatory proteins) which together can be thought of as the SASP secretome. All major age-related diseases share an inflammatory pathogenesis including atherosclerosis, myocardial infarction, stroke and metabolic syndrome. The build-up of senescent cells can lead to both degenerative disease (aging) and hyper-proliferative disease (cancer).

The purpose of the cytokines is to repair tissue. In the SASP secretome, they are perhaps trying to summon the immune system, communicating to the rest of the tissue that there is a problem. The immune system does arrive and kill most senescent cells, but 10-15% survive, perhaps due to the over-expression of matrix metalloproteinases (MMPs) which can cleave the ligands off the cell surface where natural killer cells would bind, allowing the cell to escape the immune system.

Extending the existing research and application of matrix metalloproteinase (MMP) inhibitors, chemicals that mimic the binding site, Campisi’s lab has been able to drive senescent cell killing to 95%.

Sunday, November 08, 2009

Ubiquitous information technology fields

The broadest thematic point in futurist Ray Kurzweil’s opening keynote at Singularity University on November 6, 2009 was that once any area becomes an information technology, it starts conforming to the exponential curves of Moore’s Law progress that have defined the computing and communications industries since 1900 or earlier.

Health is well on its way to becoming an information science with genomic sequencing and synthesizing, bioinformatics and continuous automated biomarker capture. Energy is starting to be an information science with the smart grid, essentially an electron routing network allowing on-demand ingress and egress of diverse flows. Many other fields could behave in the networking and packet-routing metaphor, directing fungible quantized resources to where they are needed and requested like people in driverless cars, neurons in a brain, clean air and water molecules, disease management and health care delivery. Since demand varies, market principles could be used for unobtrusive resource allocation in automatic markets that meet and transact per digitally-inferred demand profiles and pre-specified permissions.

All science is in some phase of becoming or has already become an information science in the sense of using computational models, simulation and informatics.

With computation and communication becoming increasingly embedded in every manufactured object, it is obvious that many more if not all fields could become information technologies.
Intelligence, for example, is becoming an information science. With the exponential growth of computing, it is likely that at some future point, machine intelligence could surpass that of humans. One path forward is to reengineer life into technology that can keep pace with technological advances. There are already three dimensions of progress towards this goal: understanding the existing examples of the brain through neuroscience, simulating and building de novo intelligence in software and robotic forms and integrating human and machine capabilities with brain-computer interfaces, creating the biomolecular interface of integrating organic and inorganic material.

Social sciences
The question arises about how seemingly subjective and nuanced fields like politics could become information sciences. In the short term this is already happening with citizen journalism and collective organization through social networking (examples: flashmob protests and Twitter Iran election feedback). In the longer term, it is imaginable that political artificial intelligences, pleasantly absent the agency problem and special interests of human politicians, could start to perform low level political tasks and over time be used to a much larger degree in policy formation, public resource allocation and administration of nation state affairs.

Sunday, November 01, 2009

Synthetic biology enables green petroleum

The good news about the number of worldwide vehicles, approximately 1 billion at present and expected to double in the next few decades, is the number of fossil fuel alternatives feverishly underway, many of which have established pilot projects and are expected to launch in selected commercial markets in 2011.

Synbio enables green petroleum

The current killer app of synthetic biology, the programming and engineering of biology, is green petroleum.
Several companies are developing improved versions of fossil fuels which can be easily substituted into the existing worldwide fuel infrastructure for autos, planes, etc. at approximately the same cost of fossil fuels (oil is presently $80 per barrel). Pilot plants are underway and commercial introduction is expected in 2011. Sapphire Energy and Synthetic Genomics are working with algal fuel, ramping the highly efficient natural process of algae creating petroleum through photosynthesis.

Other companies such as Amyris Biotechnologies are using synthetic biology to generate ethanol, and LS9 is synthesizing carbohydrates into petroleum with designer microbes. In the farther future, late-generation biofuels are contentious but already being envisioned by companies like Craig Venter’s Synthetic Genomics, employing carbon dioxide (CO2) as a feedstock for bacteria to convert into methane using molecular hydrogen as the energy source.

Green petroleum vs. electric vehicles
There may be less of a competition between transportation fuel alternatives and more of a market suitability analysis governing which choices arise in which areas. Large markets like the U.S. are already showing signs of both, or all, alternatives arising. Markets and countries with other parameters such as smaller size, increased government involvement and more stringent emissions regulations my make a strategic commitment towards certain choices, for example an interesting train and EV-sharing program announced in Denmark.

International electric vehicle leader Better Place notes that the ‘Goldilocks’ markets for greenfield electric vehicle networks are countries that are not too big to risk the introduction of such a disruptive solution and not too small such that economies of scale would not work. The poster child market for the company is Israel, with has networks of charging stations already installed in Tel Aviv and plans to build another 100 in Jerusalem for the mass availability of electric cars in 2011.