Building a living organism

Carolyn Abraham on lab-made DNA

Globe and Mail Update

Assembling bits of lab-made DNA, researchers at the J. Craig Venter Institute in Maryland say they have — for the first time ever — built the full genetic structure of a living organism from scratch.

The announcement was greeted with both elation and fear.

As Globe reporter Carolyn Abraham wrote in her article: Lab-made genome gives new life to ethics debate

"The feat marks a historic and controversial milestone in the fledgling field known as synthetic biology.

"It uses chunks of synthetic DNA like Lego blocks, with an aim to create life forms that can be genetically programmed to perform useful tasks.

"Its proponents envision making micro-organisms that gobble up pollution, produce hard-to-make drugs, pump out clean energy, or, at the whimsical end, flowers designed to bloom on your birthday."

Ms. Abraham also wrote that "bioethicists and some scientists allege that the researchers have applied for such broad patents on their human-made genome that, if granted, they might give the group a monopoly on the making of all synthetic life forms — which some believe will fuel the next industrial revolution."

The idea that lab-made DNA can be assembled to create new life forms is fascinating and a bit frightening.

What is the next step? How far are we from a breakthrough in the lab to something we can use in our daily lives?

Ms. Abraham joined us online to take your questions on her article and on the issues it raises.

Carolyn Abraham has been the medical reporter at The Globe and Mail since 1998.

She has written extensively on developments in genetics, stem cell research and neuroscience, focusing on the science as well as the social and ethical issues they raise.

She is a four-time winner of the Canadian Science Writers Association national award for medical reporting and has twice won the Edward Goff Penny Memorial Prize from the Canadian Daily Newspaper Association for investigative work and feature writing.

Ms. Abraham is the author of the internationally published Possessing Genius: The Bizarre Odyssey of Einstein's Brain (2001), winner of the Canadian Science Writers national book award and a finalist for the Governor General's Award in non-fiction.

She was born in England, and is a graduate of the journalism program at Carleton Unviersity, where she also specialized in political science.

Before joining The Globe, she was a feature writer for Southam News and a Queen's Park correspondent for The Ottawa Citizen.

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Christine Diemert, globeandmail.com: Carolyn, thanks for joining us today. The subject of synthetic creation is broad and sweeping and we've got a number of questions and comments for you to tackle. But before we begin, one of the things you wrote in your story last week caught my eye: "With advances in computer technology, making bits of DNA from scratch has become relatively easy and cheap in recent years. Even amateurs can type up genetic code with keystrokes, e-mail it to a commercial lab that spits it out as chemical dots on a glass sheet, synthesizes it, tucks it into a bacteria for transport and returns a live version to the customer."

Does this happen now and in what way?

Carolyn Abraham: Hello Christine and thanks for having me.

For the last several years, research groups, corporate scientists and students alike, have been able to "make" stretches of DNA from scratch. As described in the article, at least half a dozen companies exist that essentially take orders from customers to produce "base pairs" — which are nucleotides, or the chemical units that make up DNA. The companies, of which Blue Heron is the best known, synthesize these DNA stretches and send them back out to customers, and the price has been dropping steadily over the last several years, from $20 per base pair in 2000/2001 to less than a dollar today. Making DNA has become a regular part of university-student science fairs, and in one case I know, an expert has even fielded "how to" questions from a teenager in Grade 10.

Martin Duhamel, from Vancouver Canada writes: Agree or disagree: It would be in the public interest to prohibit patents on "synthetic life" until we know enough to craft a policy that prevents overly broad patents. The purpose of patents is to provide an incentive for innovation. For now, at least, we don't have a problem with that. The Venter institute is not-for-profit, and so evidently has its own motivations.

Carolyn Abraham: Hi Martin, Thanks for your question. I agree there is definitely a public interest in blocking overly broad patents on the making of synthetic life forms. However, since the field is so new, it would be difficult — even for the experts — to define what is "overly broad." As a result, it would probably be dangerous to innovation to issue a blanket prohibition on the patenting of all synthetic biology work. The Venter project has certainly brought the patenting issue to the forefront. But debate remains even among those in the field as to whether or not the patent applications would indeed prevent others from trying their hands at similar creations.

There has been a general sense in the field that synthetic biology should be an open-source technology, or at least at the basic research stage. However, as the field moves closer to commercial applications, as with drug development, few companies would be willing to invest in research unless they were assured their efforts could, in the end be profitable.

I think the motivations of the Venter institute are to pioneer these novel technologies through their not-for-profit institute, patent the work and then strike a very favourable licensing agreement with Venter's company, Synthetic Genomics. Certainly, if the institute does manage to be the first to create a synthetic life form, this will draw investors to the corporation that holds the license to develop this technology.

Bob ImamI from Canada writes: I have a paint by number set. I have all these paints in little jars and each jar has a number on it. My picture of the mona lisa has a bunch of regions with corresponding numbers. I then make a recognizable but very poor rendition of the mona lisa by putting paint in the regions.

The accomplishment in this lab is no different. After DNA sequencing … deriving the numbers, it should be simple to place the GATCs in order … simple but very small. Consider the genius of da Vinci in creating the mona lisa by observing the beautiful woman. Consider the beautiful woman!

Paint by numbers is no accomplishment. Copying reality isn't either. The genius of creation. Now that would be something. But that wasn't done in the lab. They were just playing copy-cat … no big wow … yawn.

Carolyn Abraham: I agree completely that "copying" the genetic recipe of an organism is no display of creative genius in and of itself. I suppose, however, that the creativity comes with figuring out how to assemble such large stretches of DNA successfully. In the case of the Venter project, it did take much longer than expected and several tries before they pulled it off. But only in doing this first can they get to the stage where the design element comes into play — that is making a life form that does not exist in nature, but one with functions that researchers invent. For example, for fun, University of Toronto students tried their hand at making E. coli colonies that act like a mood ring, changing colours at different temperatures. This seems like small-fry stuff, but it is an example of a "novel" creation. Whether it's art, however, would probably be best judged by the eye of the beholder …

Christine Diemert, globeandmail.com asks: In addition to the questions about whether or not science should be replicating life forms, the other dispute is whether one person, or company should be able to patent the work.

Here's part of a comment from a post on globeandmail.com, referring to J. Craig Venter, the upstart U.S. biologist and businessman who heads the not-for-profit institute behind the project: "Obviously, the guy has an interest and love of science and he should be applauded if he thinks he can create whole industries from it. It really doesn't bother me than Bill Gates or Henry Ford became wealthy, the fact is that I now have a computer (with OS) and a car."

What are the some of the concerns being raised about who owns a project such as this and where will some of those arguments be settled?

Carolyn Abraham: It has played out several times in biotechnology that there are disputes over what could or should be patented when it comes to biological materials. Among the most contentious debates have been those arising from the fact that hundreds of genes have been patented. The genes were not themselves invented, they were simply found. But companies arguing "the find" has commercial potential have been successful. Two of the gene mutations involved in breast cancer, for example, were patented by the U.S. biotech firm Myriad and in theory, this means every time someone is tested for these genes, the company is essentially owed a royalty. This has been hugely controversial, but unresolved — to the point that some jurisdictions simply refuse to pay.

Patent disputes are traditionally settled by the court. The most prominent example being the case of the Harvard mouse. Developed by researchers at Harvard University, the genetically engineered mouse is considered a terrific lab tool because it develops cancer. While the Harvard patent was upheld in the U.S., Canada's Supreme Court refused to recognize it.

At the end of the day, the truth is that patents have a huge impact on research and development. You see this play out all the time with so-called orphan drugs. If a medication is no longer patentable fewer companies are interested in developing it as a product.

Frank N. Stein from Canada writes: The only problem is we cannot already contain species to local habitats — zebra muscles, West Nile, fish species, killer bees. …What happens when one of these escapes the bottle? Nice science, but there is always a fool who likes playing with a loaded gun.

Carolyn Abraham: Thanks for your question Mr. Stein — it's a good one.

It's definitely true that one of the key concerns that haunts the field of synthetic biology is what kind of control humankind could actually wield over their creations. DNA is organic, it evolves, it changes as it copies itself — so that no two generations, with the exception of clones and identical twins (and even that is disputable) — share exactly the same genetic code. So let's say that researchers do manage to "make" new species of microbes, there is no way of knowing how that lab-written genetic code will eventually mutate. I've heard that the idea generally is that lab-made life forms will be kept in specially built bio-factories to do human bidding — such as pumping out biofuels, anti-malarial drugs. … But there is also work under way to develop microbes that could be used like drug-delivery systems inside a patient's body. For now, however, the research is nowhere near the point of actually releasing any of synthetic creations out of a controlled environment. I suppose the outstanding question is how will that bridge eventually be crossed.

IB from Canada writes: I wonder if this creates a convenient loophole to restart bioweapons research and development into synthetic bacteria and viruses?

Carolyn Abraham: Hello IB — It is true that governments, ethicists and researchers are all concerned about the potential to use synthetic biology to produce new weapons of bioterror.

For starters, the work is so comparatively simple and cheap. In 2003, the Venter group reported that they could assemble an entire virus genome in just 14 days. Then a research group from New York showed they were able to assemble a fully functional polio virus. Obviously both of these feats forced government bodies, etc., to review the safeguards. But ultimately, the decision so far has generally been that the potential benefits of synthetic biology could outweigh the potential risks of misuse. The bottom line is that anyone interested in building weapons of bioterror need not invent something from scratch … certainly anthrax taught us that.

David Guy from Canada writes: Hi Carolyn, Thanks for an interesting story on the new development. As a journalist, you were careful not to include your personal opinion, Since you agreed to answer questions and discuss everything here, however, let me put you on the spot — what do you personally think? More specifically, are you for or against this?

Carolyn Abraham: Hello David, Thanks for your question, and the hot spot … I personally think that synthetic biology is a field worth pursuing, largely because it has the potential to help solve some of the world's most profound and insurmountable problems — finding a renewable, clean energy source, combatting pollution, revolutionizing the way our factories operate and, of course, using microbes to make crucial medicines that are just too expensive and tricky to make by chemical means.

The question become less clear, and more uncomfortable, when the talk turns to ideas of "making" trees designed to grow into tables or bridges … of course, I suppose there's even an argument to be made that this could put an end to clear-cutting.

The concerns around the technology are completely legitimate. Anyone with a credit card can have access to mail-order DNA parts and the "recipes" for things such as the Ebola virus are freely available online through Genbank along with 40 million other bits of code. But that said, all technology has a sinister flip side … you can use a match for a cooking fire or arson, synthetic chemistry gave us panty hose and poisonous gases. A few years back there was a CIA document that concluded synthetic biology was particularly worrisome because it could lead to pathogens too deadly to even imagine, and what's worse, it could be pioneered by a kid sitting in Starbucks with a laptop. I suppose my feeling is that so much of this happens out of public view, and that the only way to "police" this is to make sure that what is happening stays in the public domain so that people, and policy makers, are aware of what is going on and can at least try to maintain safeguards.

One other thing: When genetic engineering first became possible in the 1970s, and researchers gained the ability to add or delete genes in an organism or fiddle with DNA, people feared Frankenstein creatures would escape and destroy the planet … but it turned out that such altered species don't really survive well in the wild. Many of those initial fears are now considered to be terribly overblown, while the benefits — in medical research, particularly gene discoveries, have been genuinely beneficial.

Globefan EH from Canada writes: I read recently that there are no safety standards in place for many of these new technologies, nanotechnology being one, this being another. The technology moves faster than drafting the safety standards to protect workers from it. As we sow …

Carolyn Abraham: Hello EH — This is a critical question. In 1975, after genetic engineering became possible, about 140 of the world's top biologists met in California and hammered out a policy that set down rules of containment and safety regulations under which scientists could police themselves.

The emergence of synthetic biology has since raised calls to review and update those policies. In particular, it might be worth policy makers taking a look at the safeguards in place at the mail-order DNA companies — what identification do they require of their customers? Should there be age restrictions? What sorts of orders, if any, raise red flags? In the same way that since 9/11, flight schools would now be immediately suspicious of any student not interested in learning how to land. Who, if anyone, should decide what gets mailed out? Should the genetic codes of dangerous pathogens be freely available online? These are the kinds of questions that some esteemed body should be tackling at an international level.

Christine Diemert: Thanks Carolyn for joining us today. Just before you go, is there anything you'd like to add?

Carolyn Abraham:Thanks Christine, I've enjoyed the discussion. I'm sure so much of this kind of work conjures "science fiction" scenarios to many readers. But genetic manipulation and engineering of one kind or another has been a part of human life and civilization for a very long time — from the domestication of dogs to the frost-resistant tomato. I think it's worthwhile to keep raising the questions and concerns and keep the discussion flowing. A true synthetic life form could be announced in the not-to-distant future.

Cheers, Carolyn

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