The cells come from the early embryo of a mouse, three and a half days after conception. It’s when the embryo looks like a beach ball, explains Mitch Weiss, a hollow ball, and inside that ball is a small mass of cells that are destined to become the embryo, the whole embryo, every part of it from the head to the feet.’’ The cells are known, in the technical jargon of biology, as undifferentiated. Weiss, who is a physician and a researcher at a Cambridge, Massachusetts, biotechnology company known as Ontogeny, Inc., uses the word naive to describe them. They haven’t become educated to become heart, liver, lung, blood, whatever, he says. They are identical, at least for the moment.
Before coming to Ontogeny a year ago, Weiss spent a decade at Boston’s Children’s Hospital and the Dana Farber Cancer Institute treating and studying blood diseases and cancer in children. He also studied, he says, the basic biology of how blood is formed. In the human body, red blood cells survive 120 days, white cells anywhere from 24 hours to 10 years; platelets, which help blood clot, will last 5 or 6 days. All of them are constantly being regenerated from a single type of cell in the bone marrow known as a hematopoietic stem cell. If you knew the chemical signals—referred to as growth factors or, more generally, inducing molecules—that your body uses to incite a hematopoietic stem cell to differentiate, Weiss says, you might use them to help your body replenish blood and bone marrow quickly after chemotherapy. You might create red blood cells for patients undergoing bone-marrow transplants, or white blood cells for cancer patients whose immune systems are impaired by chemotherapy. If we could find factors like that, says Weiss, we could help a lot of people.
The catch is that maybe 1 in every 10,000 cells in your bone marrow is a hematopoietic stem cell, which makes it difficult to find and study. Another huge challenge is finding the inducing molecules that turn it on and off. So Weiss is showing off his naive embryonic cells under a microscope, pointing out how they grow into tiny clumps of incipient tissue, composed of a whole gemish of fat cells, muscle cells, blood cells, and nerve cells.
By taking one such gemish, breaking it into single cells, and then seeding those cells onto a plastic laboratory dish with some nutrients and the right growth factors, he can generate pure colonies of blood cells in the laboratory. The first time I did this, says Weiss, I looked in the tissue-culture dish and I said, ‘Whoa, I’m making blood.’
The idea that you can learn how blood or other tissues are formed in the embryo and then apply that knowledge to re-creating them in an adult is one of the hottest new ideas in medicine. Developmental biologists have demonstrated that the same growth-inducing molecules that spur the differentiation of cells, tissues, and organs in the embryo serve critical roles throughout life. These molecules represent a gold mine of pharmaceutical promise: if used correctly, they could make not only blood but also nerve cells, for instance, to replace ones that are dead and dying in people with Parkinson’s disease. They could make the insulin-producing pancreatic cells that are missing in patients with juvenile diabetes. They could make bones grow faster after they’re broken and perhaps someday, although not particularly soon, regenerate entire organs. Liz Wang, who works with Weiss at Ontogeny, calls such plans the Star Trek fantasy: You’ll have this Star Trek library of tissues, so you can say, ‘Well, I need this kind of cell and this cocktail of growth factors, and this will give me this new kind of tissue.’
