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CRISPR, ‘CANCR’ lead 2013’s top scientific advances

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By Anette Breindl,
Science Editor

Science and Nature offered their year-end roundups of the most important scientific advances of the year and the people behind them, respectively, this week. Those lists are not exclusive to biological science, nor to applied science. But there was plenty for the biopharma industry on this year’s Christmas list, starting with Science’s breakthrough of the year: cancer immunotherapy.

Cancer immunotherapy is an unusually mature area of study to be named a scientific advance. Immunotherapy has two approved therapies to its credit – Provenge (sipuleucel-T, Dendreon Inc.), approved in 2010, and Yervoy (ipilimumab, Bristol Myers Squibb Co.), approved in 2011. Several other drugs are in Phase III trials, including Merck & Co Inc.’s MK-3475 and Bristol-Myers Squibb Co.’s nivolumab (formerly BMS-936558).

The technology is still new enough, however, and 2013 saw scientific advances in immunotherapies, especially in engineered T cells, which show great promise but whose toxicities remain to be worked out. (See BioWorld Today, Dec. 12, 2013.)

Both Science and Nature had another scientific advance that is likely to have wide-ranging applications in the biopharma industry prominently on their lists – the CRISPR/Cas genome-editing system. (See BioWorld Today, Jan. 17, 2012.)

In nature, CRISPR is a sort of primitive bacterial immune system – bacteria use it to target and degrade foreign DNA. Scientists can use that targeting system to direct CRISPR to a desired DNA sequence, which can then be cut and edited.

2013 marked some significant advances for the CRISPR technology, the most significant of which was probably the January demonstration that this bacterial enzyme could be used to edit mammalian cells. (See BioWorld Today, Jan. 4, 2013.)

By year-end, scientists were using CRISPR for whole-genome editing, and Editas Medicine had become the first company based on the technology, raising a respectable $43 million is a Series A round. (See BioWorld Today, Nov. 25, 2013.)

But CRISPR technology is still new enough that significant limitations, too, were uncovered in 2013. Targeting can be very precise – or quite imprecise. Scientists showed that in some cases, the enzyme would edit sites that were mismatched at a quarter of the targeting base pairs. The findings do not kill the methods’ promise – RNAi, too, can be imprecise, a limitation that researchers work around by using pools of RNA with shared on-target but different off-target activities. But for now, the method is definitely not ready for clinical use, and even in research, off-target effects need to be accounted for. (See BioWorld Today, June 30, 2013.)

Another technology development that made strides in 2013 were the organoids, three-dimensional cell cultures consisting on multiple cell types that allow scientists to study cell biology in a setting that’s simple enough to be experimentally tractable, yet complex enough to be much more realistic than single-layer monocultures.

The biggest media buzz of the year surrounded the announcement of a brain organoid in August. But organoids of the liver and kidney also exist, and scientists are using it to model tumors, which also consist of multiple cell types that are structurally bound in specific ways. (See BioWorld Today, April 10, 2013, Aug. 28, 2013, Dec. 9, 2013, and Dec. 16, 2013.)

Finally, one scientific advance has the distinction of not only being on the breakthrough of the year list for the second time, but also of having its supporting data questioned after publication yet again.

That advance is the cloning of human embryonic stem cells. Such cloning was reported in May, but post-publication peer reviewers quickly pointed out that there were errors with several of the figures in the publication announcing success. (See BioWorld Today, May 21, 2013.)

That quick pall on the data brought to mind the first time the cloning of human embryos was reported, in 2004. That achievement was named a breakthrough of the year in 2004, and then a “breakdown of the year” in 2005, after the claims turned out to be fraudulent.

Ethically speaking, there is no comparison between Woo-Suk Hwang’s overtly fraudulent claims of embryonic cloning and what appear to be a few honest mistakes with respect to the figures used to support Shoukhrat Mitalipov’s work.

But the sequence of events does illustrate an issue that was named by Nature as one of the key factors affecting scientific progress in its 2012 year-end roundup, and that continues to be on the minds of anyone considering the big picture of basic research – that its quality control procedures are poor to nonexistent, and as a consequence, its reproducibility rate is stunningly low. (See BioWorld Today, Dec. 21, 2012, and Dec. 13, 2013.)