Recombinant DNA, Synthetic Biology,and Nanotechnology, oh my!

There is an interesting article on Synthetic Biology in last week's New Yorker. Though I just gave it a skim, and didn't read the ending – the topic is intriguing and describes a field of science devoted to developing the capacity to build and manipulate biological systems as if they were Legos. According to SyntheticBiology.Org their goals begin with identification of the parts that “have well-defined performance characteristics and can be used (and re-used) to build biological systems” and end with “reverse engineer and re-design a ‘simple’ natural bacterium."

Wow. Should they succeed, they’d bear a hefty biological, ethical, environmental responsibility. Were these people nut jobs? Nascent Frankensteins? Or were they just being realistic about the future of their science? As I thought about what this all meant it dawned on me that Synthetic Biology, being an extension of Genetic Engineering, in some ways wasn’t so different or separate from nanotechnology.

I don’t mean that they’re similar in how the products of these technologies interact with living systems, all threats of “grey goo” (a worst-case scenario hypothesized by Eric Drexler, popularizer of nanotechnology, whereby nanobots run a muck, literally mucking up the world) aside - one science proposes to build biological systems while the other builds chemicals. Although, I suspect, as time goes on these two technologies will mingle if not marry (if they haven't run off to Las Vegas and done so already.) Biological systems after all are nothing more than chemical building blocks – so once those building blocks are better understood, and once we have the capability to not only engineer one cell at a time, but also to build chemicals one atom at a time, why not?

As a toxicologist observing the emergence of nanotechnology it has been easy to ask what nanotechnology can learn from past practices of chemical production, regulation, use and disposal. But beyond toxicology, biotechnology, has also laid some groundwork as to how to proceed with – or not-- development of a new technology that will impact all of our lives for better or worse, in ways we cannot fully understand.

Genetic engineering, the cornerstone of biotechnology, has been around since 1972 when scientists including Paul Berg of Stanford University first recombined pieces of DNA – the molecule which holds the secrets of all live on earth. Two years later, Berg and others raised serious concerns about unfettered recombinant DNA research, eventually calling for a temporary moratorium on certain types of research. Berg’s committee proposed that, “…until the potential hazards of such recombinant DNA molecules have been better evaluated or until adequate methods are developed for preventing their spread, scientists throughout the world join with the members of this committee in voluntarily deferring the following types of experiments....” the authors then listed specific research that they considered most risky, acknowledging that…”our concern is based on judgments of potential rather than demonstrated risk since there are few available experimental data…and that adherence to our major recommendations will entail postponement or possibly abandonment of certain types of scientifically worthwhile experiments.” A year later, the first conference on “Recombinant DNA molecules” widely referred to as Asilomar for the idyllic conference center by the sea, took place, and is still referred to, and reflected upon as a model of “self-regulation” by the scientific community (the meeting included scientists from around the world, lawyers, government officials and journalists as well.)

Of course the concept of self-regulation may be an oversimplification since the conference purposefully focused on health and environmental safety only. The ethics and legalities of recombinant DNA were not on the agenda, “This choice of agenda,” wrote Berg years later, “was deliberate, partly because of lack of time at Asilomar and partly because it was premature to consider applications that were so speculative and certainly not imminent.” Perhaps. I imagine, like my district’s school committee meetings which I’ve sometimes referred as “adults behaving badly” – if we stuck with the nuts and bolts rather than the deeper questions – we too might be more successful.

Berg revealed one other key to success on at a symposium celebrating the 25^th anniversary of Asilomar: molecular biologists weren’t yet heavily invested in the science and the public knew very little – so that there was still room for fluidity in the conversation. Positions on the recombinant DNA were not yet “hardened,” and scientists were primarily academic. This was a time when government funding was flush, when there was separation of academia and industry and the biotechnology industry with all its promises of the next million dollar drug was more “Jetsons” than reality.

Which brings me back to nanotechnology - a field developing under incredible public, government, and scientific scrutiny. Even industry, as I’ve read and heard, wishing to avoid the genetically modified foods fiasco (which is either ironic or inevitable considering Asilomar), seems willing to tread carefully when it comes to development of nanomaterials. A recent report by the DEEPEN (Deepening Ethical Engagement and Participation in Emerging Nanotechnologies) project – emphasizes a role for increased public participation in governance decisions related to nanotechnology development. In part because nanotechnology is poised to affect everyday life – so why not include all participants -- those who deliberately participant and those who are incidental nano-tourists in the conversation?

There's one caveat to suggestions by DEEPEN and others. There have been so many meetings, and project reports on how best to move forward conscientiously with nanotechnology, that there is some concern there’s too much talk and too little action. Meanwhile, nanomaterials find their way into more and more consumer products (1000 and counting,) and the body of research papers continue grow like a bacterial culture in log growth phase. But that's no reason not to broaden the conversation.

Perhaps comparisons between nanotechnology and Asilomar are unfair for nanotech.

As Berg noted, in 1975, neither Joe Public nor Joe the Plumber were invited members of the 'Recombinant DNA steering committee,' the focus of the meeting was strictly focused, and recombinant DNA was, and still is fairly easily defined. Isolating and rejoining segments of DNA – that was recombinant DNA. Today we have the world wide web of information where the public, if they wish can be informed, NGOs following and reporting on nanotechnology, a technology that is already in use, and scientists who can’t even agree on what constitutes a nanoparticle. Are they particles with one dimension measuring 100 nm or less? Or, should they be much smaller, encompassing particles in the 30 nm or smaller range, particles most likely to exhibit new and different physical-chemistry?

Then there are nanodots, nano-metals oxides, nanotubes and other nanos – all very different chemically although they may share some basic properties in terms of size, or increased reactivity as a result of decreased size, but how much do we know of their differences in terms of how nanoparticles will move and react inside a living being, or outside in the big wide world?

Our best hope right now, is that nanotechnology as a field is still young and flexible. Hopefully the talk with turn to action before nanotech’s arteries begin to harden before, as Berg observed twenty-five years after Asilomar – the issues become “chronic.”

(For the results of a recent poll on public understanding of nanotechnology and synthetic biology click here. )

Lining Asbestos-Concrete Drinking Water Pipes with Vinyl: Its enough to make you wonder

I’ve been a “lurker” on the TCE List serve – a gathering site for those impacted by this old industrial solvent and one of this country’s most important groundwater contaminants. Unfortunately it is an incredibly active list because so many people are affected by this legacy pollutant. Often, I let the emails pile up - shifting them into my TCE folder - in case, one day, I might have something useful to offer the list. But today one email caught my attention.

It began with a posting by Lenny Siegel, Executive Director, Center for Public Environmental Oversight – and list host. The subject line was “PCE in pipes - this is new to me.” If something about these chlorinated solvents is new to Lenny it’s new to a lot of folks, activists and scientists alike, because Lenny really knows his stuff. So I took a look.

According to the Cape Cod Times article posted by Lenny, a study by Boston University epidemiologist Ann Aschengrau, found an association between exposure to PCE (perchlorethylene, or tetrachlorethylene – a solvent most commonly associated with dry cleaning) contaminated drinking water, and an increased risk for birth defects in offspring of Cape Cod women exposed to the water back in the 70's and early 80's.

That PCE was in drinking water wasn’t surprising – it’s a common contaminant in groundwater near old dry cleaning sites . What was surprising was that an old leak, landfill or dry cleaner wasn’t responsible for contamination this time around. The culprit was the municipal drinking water pipes.

Apparently back in the good old days (in this case the 1960’s and '70's) according to the Aschengrau, who was interviewed for the article,

“…water pipes in several towns on the Cape and elsewhere in Massachusetts were purposely sprayed with vinyl plastic and PCE to improve the taste of drinking water.....

Manufacturers wrongly assumed the PCE would disappear during the drying process, but large amounts remained and slowly leached into drinking water in Barnstable, Bourne, Falmouth, Mashpee, Sandwich, Provincetown, Brewster and Chatham, ……Once the PCE contamination was detected, authorities cleared the pipes through a flushing process, saying replacing hundreds of miles of vinyl-coated pipe would be too expensive..”

Reading the chatter on Lenny’s list, I learned that back in the early 1980s Avery Demond, an MIT master’s student studied leaching of PCE from those vinyl lined pipes. Back then Demond wrote that while his focus was on the hydrodynamic factors controlling release of the toxicant, it was “difficult if not impossible” to ignore the social context of the problem. Meaning, people were drinking the contaminated water. As Demond noted, PCE was a common contaminant in drinking water a levels of 1 part-per-billion (ppb) or below. But then a 1976 survey of organic chemicals in water (with a focus on water treatment byproducts) turned up PCE concentrations ranging from 6 ppb to upwards of 1000 ppb in water from a Newport RI state park, warranting a closer look. After seeking potential industrial sources, municipal pipes eventually came under suspicion.

Wrote Demond, early on,

“...the PSWB [water board] tested the liner in May 1968 and contemporary analytical tests and techniques could not find anything undesirable in the water that might have arisen from the water’s contact with the liner. (The sophisticated powerful gas chromatography equipment in general use today was either unavailable or not thought to be needed.) The development of the liner predates the current widespread concern about organics.”

That last statement about sums it up, if you were wondering what they were thinking using pipes recently treated with a solvent combined with a plastic matrix allowing it to leach out over time. They weren't, because they didn't have to. Smell no evil, taste no evil, measure no evil.

Although by the time Demond wrote his thesis, organic solvents were losing their innocence, as residents of Woburn, Massachusetts were realizing the possible linkages between high incidences of childhood leukemia and water contaminated with PCE's chemical cousin, TCE.

Unfortunately for New Englanders, according to Demond, the vinyl-lined asbestos-cement pipes produce by Johns Mansfield Company (of asbestos fame) were used primarily in New England to control alkalinity-related corrosion of the pipes. Over 600 miles of vinyl lined asbestos-cement pipes were laid in Massachusetts, with the majority on Cape Cod. A few years after the leaching problem was identified the company stopped production.

While some pipes were replaced, remediation more often consisted primarily of flushing, until concentrations fell below levels of concern at the time.

Twenty year's later, Aschengrau’s paper in the journal Environmental Health reports finding “large increases in the risk of gastrointestinal defects (particularly oral clefts), neural tube defects (particularly anencephaly) and, modest increases in the risk of genitourinary defects (particularly hypospadias),” and concludes

“The results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who identified by independent records.”

For more, check out Aschengrau's paper.