Single-cell breakthroughs let scientists see exactly what we’re all made of

In Israel for Broad Institute conference, Eric Lander, pioneer of Human Genome Project, marvels at speed with which ‘new genomics’ opens ways to fight disease

David Horovitz

David Horovitz is the founding editor of The Times of Israel. He is the author of "Still Life with Bombers" (2004) and "A Little Too Close to God" (2000), and co-author of "Shalom Friend: The Life and Legacy of Yitzhak Rabin" (1996). He previously edited The Jerusalem Post (2004-2011) and The Jerusalem Report (1998-2004).

Two years ago, when mathematician and biologist Eric Lander was in Israel for an innovative gathering of researchers and students, he took a break from his conference to describe to The Times of Israel how scientists had completed the sequencing of the human genome — a person’s “parts list” — and were now working on the “wiring diagram,” setting out how those parts work together.

Back in Israel recently for the third of his Broad Institute’s annual conferences, Lander enthused over the “amazing” pace at which science has moved on since that last visit, most especially in the study of single cells — what he called “the new genomics.”

One of the founding fathers of the Human Genome Project, Lander has dedicated his work to understanding what makes us tick, the better to keep us ticking. To underline the significance of this work for all of us, I headlined my 2013 interview with him, “This man’s work will change your life.” What’s unfolded in the last two years, he said, is a growing ability to identify what we humans are made of at the most fundamental level — the level of a single cell — with extraordinary potential benefits for understanding, observing and treating the diseases that afflict us.

Lander, 58, is the founding director of the Broad Institute of Harvard and MIT, which is devoted to utilizing human genome research in medicine. He was back in Israel for the “Third Annual Broad-Israel Science Foundation (ISF) Cell Circuits Symposium” — which brought together experts and students from the Broad Institute, from Harvard, and from Israel’s universities, on the cutting edge of human genome research and its applications for medicine.

Eric Lander (Tony Cenicola/The New York Times)
Eric Lander (Tony Cenicola/The New York Times)

Capitalizing on an Israeli scientific community that is very strong when it comes to combining biology and info-technology skills, the Broad-Israel partnership encourages Israeli and American trailblazing in an increasing number of joint projects, all designed to speed our progress toward thwarting cancers, Alzheimer’s, diabetes and other diseases.

Explaining the rapid advances in single-cell research, Lander said that as recently as two years ago, scientists had only what you might consider “a pixelated, low-resolution image” of our cell structure. They really didn’t know how many different types of cells there are in the body, and they couldn’t identify the differences between them.

“In the past we had a kind of blended big picture, a ‘smoothie,'” said Lander, finding another metaphor to enlighten this non-expert. “Now, because of new laboratory techniques and maths and advances in DNA sequencing,” he went on, “we have the ability to study single cells. Folks spent 40 years working to identify the cells of the retina, the back of an eye,” he said by way of an example. “Now you can do that in an afternoon.”

And why should we care? Because, Lander positively sparkled, “the ability to do single-cell analysis, to get the identities and states of each of the cells, is the final revolution in this field. It’s the equivalent of an amazing new microscope” — a microscope that offers remarkable potential for improving our health.

Human cancer cells with nuclei (specifically the DNA) stained blue. The central and rightmost cell are in interphase, so the entire nuclei are labeled. The cell on the left is going through mitosis and its DNA has condensed.  (TenOfAllTrades/Wikipedia)
Human cancer cells with nuclei (specifically the DNA) stained blue. The central and rightmost cell are in interphase, so the entire nuclei are labeled. The cell on the left is going through mitosis and its DNA has condensed. (TenOfAllTrades/Wikipedia)

For instance? In the old days — that is, until a couple of years ago — scientists struggled to understand what constituted a tumor. What common genetic features do tumors have? How might tumors be tackled most effectively? “Now we can see the commonality, the types of cells, the proportions, the logic,” he said. “This has major implications for our health.

“You want to kill a tumor? Well, maybe our treatments work on one type of cell. We were blind to that. Now we can test a treatment on the few different types of cells.”

The new microscope, in other words, enables an unprecedentedly precise understanding of disease. “It tells us what we need to solve.”

‘The ability to do single cell analysis, to get the identities and states of each of the cells, is the final revolution in this field. It’s the equivalent of an amazing new microscope’

“Imagine medicine before gross anatomy,” Lander suggested, as he sought to put the dramatic recent progress into historical perspective. “Then comes anatomy, and you can describe the organs of the body. You can see something problematic, say, in the lung, or in the heart. Well, this is the ultimate anatomy. It will penetrate every type of medicine. Not bad for two years. This just didn’t exist last time we spoke.”

Another area of rapid progress cited by Lander is the ability to “precisely edit” the genome of human cells, which has massive potential to help treat certain diseases. Just two years ago, Feng Zhang, a researcher at the Broad, invented this power gene-editing technology by harnessing what Lander described as “an ancient bacterial mechanism” — called CRISPR-Cas9 — that can cut genomes in any place and thus enable editing.

Already an Israeli researcher at Broad has published a paper “editing” each of the 20,000 genes to find those that are essential to particular types of cancer cells – in effect, identifying the Achilles Heels of these cancers.

These advances also might open up possibilities of altering the human gene pool, of working to create less-diseased humans, even super-humans. “There’s talk of editing the DNA of embryos to alter our gene pool,” he acknowledged. “It’s being discussed.”

Then he added dryly, “I’m not sure it’s a good idea. Eugenics hasn’t worked out too well for society. Moreover, changing DNA for one purpose can have unexpected bad consequences.”

Where the advances are clearly positive is in the capacity — as genetic mapping becomes more affordable and more sophisticated — to identify the genes that predispose to Alzheimer’s, early onset cancer and many other diseases. (A personal genome map now costs about $3,000, he said.)

In some cases, genetic information can be important to parents. “Today, doctors can check two folks getting married for some mutations that would cause a disease if it was inherited by their children. In the future you would do checks for more.”

The partnership between Broad and Israel, Lander stressed, works particularly well because of Israel’s strong information technology and bio-science communities. “Israel is such an intersection of those skill sets,” he said.

And Israel’s ever-strained public health system, he added, actually has very good electronic medical records — “a 20-year history,” he said — which makes it well-placed to utilize new advances as they become available. “In the next decade we’ll collect a lot of information, and we’ll figure out the best uses. We’ll assess the risks of disease, the possibility to intervene.”

For all of that, you need groundbreaking scientists and good data. Like the United States, said Lander, Israel has both.

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