W. Ford Doolittle Cell Biology

Contributed to our understanding of where mitochondria and chloroplasts came from by conducting experiments supporting the endosymbiont hypothesis. He has also demonstrated the importance of horizontal gene transfer in prokaryotic evolution.

"If you come up with a hypothesis, what’s your next job? Not to prove it. To try and disprove it."

The Story

Doolittle came to Canada in 1971 when he landed a job at Dalhousie University in Halifax, after falling in love with Nova Scotia while on holiday there. “To tell the truth, I had not heard about Dalhousie before that, because I was an American and Americans don’t know much about Canadian universities other than McGill and UBC,” he says. “I’ve been here for 43 years, and Dalhousie has changed enormously in that time. It wasn’t a serious research university at that time, but it was hoping to be, and now it is.”

The work Doolittle has done over the past four decades played a role in that. His first major contribution was helping to prove Lynn Margulis’ endosymbiont hypothesis – the idea that the mitochondria and chloroplasts in eukaryotic cells were actually once free-living bacteria that had become trapped as symbionts within the cells of their hosts, and degenerated into their present form of energy-generating organelles.

Doolittle is also a proponent of the selfish DNA hypothesis, which describes the vast amounts of repetitive DNA in genomes that appear to have no function contributing to the reproductive success of an organism.

Doolittle has earned a reputation as a contrarian, a trait that he embraces. “I think I have a kind of ornery streak in me, so if you come at me with a hypothesis the first thing I’m going to do is say well now let’s see, maybe that’s wrong, what could an alternative explanation be?” he says. He thinks that too much of science has become about verification, about proving that the people who came before you were right. “I think that scientists should be much more self-critical, and science has lost some of its self-criticalness,” he says.

That dedication to falsification and the scientific method is apparent in the way he talks about his career. Included on his list of scientific contributions of which he is most proud is one - known as “introns early”, the idea introns were present from the earliest stages of early pre-cellular evolution, and had been lost in bacteria but regained in eukaryotes - that has since been disproved. He sees that failure as equally important to science as any of his work that has withstood scientific testing. “We should be trying to falsify hypotheses, not prove them,” he says.

Author: Brian Owens

As A Young Scientist...

W. Ford Doolittle almost didn’t become a scientist. Growing up in Urbana, Illinois, he had a summer job washing glassware in the lab of molecular biologist Sol Spiegelman, who was the father of one of his high school friends. Though he found the lab exciting, and showed a keen interest in biology, when he enrolled at Harvard University as an undergraduate he was torn between majoring in biochemistry or English.

What decided him was just the luck of the draw. Harvard had a seminar program for freshmen, which involved small groups of students “sitting at the knee of some famous person in the field” for tutorials and encouragement, and Doolittle applied in both fields. “I didn’t get into the one in English, I got into the one in biochemistry. So here I am,” he says.

The humanities’ loss was science’s gain. Doolittle has had a remarkably successful career over the intervening decades. He is a fellow of the Royal Society of Canada, a member of the US National Academy of Sciences and in 2014 won Canada’s prestigious Herzberg Gold Medal for Science and Engineering.

 

The Science

Doolittle used RNA cataloguing, a sort of primitive form of sequencing, to show that ribosomal RNAs encoded in the genomes of chloroplasts and mitochondria are more similar to the ribosomal RNAs of bacteria than the ribosomal RNAs of their hosts. “That was a testable implication of the endosymbiont hypothesis, and there weren’t really that many other things which were testable in a quantitative way,” he says. “It got some attention because it was the first logically adequate proof of the hypothesis.”

That bit of solid experimental work aside, much of Doolittle’s reputation is based on his more theoretical work. He is known mainly as an ideas man, who advances or challenges hypotheses about how the genome works, and how it has evolved.

In the early 1980s he was one of the early proponents of the “selfish DNA” hypothesis, that stated the vast majority of DNA in the genome was essentially useless junk, or “clean fill” DNA, composed of transposable elements that had integrated into the genome and persisted because they did no harm to the organism, but served no useful function other than replicating themselves. In 2012 this idea was challenged by the ENCODE project, which found evidence that as much as 80% of the genome served some purpose after all.

But Doolittle is not convinced. There certainly is activity going on in those stretches of DNA, but there is no evidence to suggest it actually contributes to the fitness of the organism. “I’d say that most of what people in the ENCODE project measured were accidental consequences of there being DNA there, and its not evidence that it’s there because natural selection wants it to be there,” he says.

Doolittle has also challenged the received wisdom on the shape of the evolutionary tree of life, particularly for bacteria and archaea. The extent of lateral gene swapping that goes on between microbes means that it is virtually impossible to reconstruct meaningful evolutionary relationships between prokaryotes based on their genetic similarity. “If you look at a typical bacterial genome, the fraction of its genes which have been in place since the last common ancestor of bacteria is probably less than a few percent, and all the rest of the genes will have come in from lateral gene transfer at one time or another in the intervening 4 billion years,” he says. “It may well be that you can construct a tree, because the data are not totally randomised, but it doesn’t necessarily mean that that tree is a reflection of any of the history of organisms.”

Career Advice

According to Doolittle: “The pressures now are quite different from what I experienced. I’m not even sure I’d go into science now if I had it to do over again because the pressures to produce applicable results or translational research or something that’s going to make money quickly are very strong, and I don’t like that. The management of scientific research for perceived governmental and social goals is, to my mind, antithetical to the free development of any scientific discipline. So I would not encourage someone to go into science now unless A: they want to do that, or B: they’re prepared to fight hard to keep their values, the values of science as a basic human need to understand the universe, rather than science as a way to spur innovation.

To be what I call a scientist--a scientist who is pursuing science as a vocation--I think you have to be quite dedicated to the enterprise itself. Sort of like being an artist or something. I’m not opposed to innovation, obviously, I just think that that’s not science.”

 

The Person

Birthdate
November 30, 1941
Birthplace
Urbana, Illinois
Residence
Halifax, Nova Scotia
Family Members
  • Spouse: Paddy (Patricia) Muir
  • Children: Emily Doolittle, Adrian Doolittle
Favorite Music
Blues
Other Interests
Photography
Title
Professor emeritus
Office
Tupper Building, Faculty of Medicine, Dalhousie
Status
Semi-retired
Degrees
  • BA, Biochemical Sciences Harvard University, 1963
  • PhD, Stanford University, 1967
  • BFA, Photography, Nova Scotia College of Art and Design, 2013
Awards
  • Fellow of the Royal Society of Canada, 1991
  • Member, US National Academy of Sciences, 2002
  • Herzberg Medal of the Natural Sciences and Engineering Research Council of Canada, 2014
Mentor
A.M. Pappenheimer. Jr. (Harvard), Charles Yanofsky (Stanford), Norman Pace (Colorado)
Last Updated
April 11, 2014
Popularity
1109

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