Science in Public

Medical research can be intensely competitive—and, as a result, surprisingly secretive. Researchers can be reluctant to share data or describe what they’re doing because they’re afraid their ideas might be taken and they’ll be scooped. In science, there’s no second prize: Whoever makes a discovery first gets the credit. Although scientists agree in theory that collaboration and data-sharing is more effective, many don’t do it.

So when Rachel Harding, a postdoctoral fellow at the Structural Genomics Consortium (SGC) in Toronto, suggested making all of her HD research public while it was still in progress, some told her she was taking a foolish risk. “A lot of traditional academic scientists believe it’s mental,” she says. “Why would you do that? Everyone could steal all your data.”

She and her boss, CEO Aled Edwards, aren’t daunted by the skeptics. They calculate that the potential benefits are bigger than the risks. “We’re big believers in open-access data, working in collaboration rather than competition,” she says. “So we decided it’d be fun, and a new experiment for us, to see how the scientific community and wider community react to this more radical open data publishing approach.” SGC is cooperatively funded by governments, pharmaceutical industry, large foundations and smaller disease-focused foundations (including CHDI). All the work it produces is not patented but shared openly to speed up the process of science.

Harding and Edwards anticipate that the open science experiment will encourage new collaborations, and also improve the flow of information so that other research teams learn from her experiments immediately, rather than waiting a year or more for her to publish her findings in a research journal. That will prevent the unnecessary duplication of efforts that are sometimes an unfortunate consequence of research secrecy. Harding and Edwards also hope that it will display the scientific process to people who may not know much about it, especially patients and their families.

The shape of HD

Harding’s major goals is to figure out the structure of huntingtin (HTT), the protein produced from the HD gene. This protein, present in every cell in the body, is still something of a mystery; researchers have a limited understanding of what the normal, non-mutated version of the protein does, and they don’t know exactly how it causes damage when it’s mutated in HD.

“The more time we waste repeating each other’s experiments, the more time we’re losing.” —Rachel Harding, Structural Genomics Consortium

In modern biomedicine, researchers often look to understand what a protein does by mapping out its 3-dimensional structure. “If you understand what something looks like, you can work out what it’s doing,” says Harding. “Given that we have a conflicting hodgepodge of data about what huntingtin is doing in cells, actually knowing what the molecule looks like would hopefully provide insight into designing next phase experiments that could lead to therapeutics.” It’s a massive effort that requires access to extremely expensive instruments—and it means collecting and manipulating enormous amounts of data.

Many such experiments are done by teams working independently. If they don’t succeed—and most don’t— the results may never be published, meaning that other groups won’t know that the approach has already been tried and didn’t work. In addition, many nationally-funded efforts all focus on the same questions, yet don’t share information. “We don’t know a lot, and yet we keep studying the same things over and over again,” says Edwards.

That’s one reason that inspired Harding and Edwards to go public. “We want to find out more about huntingtin as quickly as we can,” she says. “The more time we waste repeating each other’s experiments, the more time we’re losing.”
As she’s been working through all the steps for her experiments, she regularly blogs to describe her experiments and uploads the protocols she’s perfecting, as well as data from her experiments. She invites anyone to comment on her posts or email her about the work.

In the last few months she’s been tinkering with a method to use insect cells to make certain parts of the protein. This step is necessary because it will permit her to make large quantities of the protein fragments in the lab. Once she gets this method fine-tuned, she will purify the protein fragments—another tricky step that involves testing out many different methods. Only then can she begin the structural studies.

Bumps and warts

Science is inherently prone to failure, since the whole point of research is to discover what we don’t already know. False starts, do-overs, and confusion are common, but most researchers don’t advertise that fact. By blogging about it as it happens, Harding reveals all the highs and lows.

Edwards says he is proud that she is willing to take the risk, and is confident that she will be able to handle any potential downside. “She’s the right person—incredibly confident, talented, and gregarious,” he says. “She’s taken a career risk— somebody could scoop her, and she will make mistakes,” missteps that anyone following her posts might see.

“We want more people to take this up, but scientists don’t do anything unless you give them hard evidence.” —Rachel Harding, Structural Genomics Consortium

Some senior scientists have in fact contacted her about the work with critiques as well as comment. But Harding hasn’t been intimidated; instead, she’s found it useful. People from HD families have also contacted her. “It’s really nice,” she says. “It’s really motivational to hear people’s stories, and why they’re interested in any research.”

The risk of having her hard-won data simply stolen by other teams is mitigated by the way she makes it public. It’s published under a “Creative Commons” license, meaning that anyone who uses it is required to credit her.

Edwards and Harding treat her open-lab project as an experiment of its own, to see if this approach can accelerate discovery or produce better results. They are tracking several outcomes: Whether other scientists use her data and tools and acknowledge her contribution to the papers they write, and whether the approach sparks an unusually high number of new collaborations with other scientists in academia and industry.

They plan to compare these statistics against a project conducted with a more traditional approach, in order to measure whether the open-access model significantly increases collaboration or accelerates research. If it does, Edwards wants every project that is funded by a disease-related nonprofit foundation to be open in a similar way.

“At the end of the day, what we want to do is compare this project to another project where we used conventional methods,” she says. “We want more people to take this up, but scientists don’t do anything unless you give them hard evidence.”

Researchers are basically conservative: They want proof that something works before they are willing to make changes. Harding and Edwards hope that her open-lab project will begin to provide some of this evidence. If they demonstrate that the approach was effective, they’re betting some open-minded groups might take it up as well.

This story was originally published in the Autumn 2016 issue of Enroll!