In June the International Society for Stem Cell Research held it's annual meeting in Australia's tropical city of Cairns. It was a fitting location. Outside, lush vegetation covered sea-hugging mountains and spilled out onto the streets.

And inside at the conference centre – a thousand flowers were blooming. There was stem cell research of every description: stem cells from placentas and amniotic fluid; stem cells from cloned monkey embryos or single parent embryos or stem cells made from embryo biopsies in a way that left the embryo unharmed. And there was the promise of clinical success around the corner with dazzling reports of stem cells that corrected mouse diabetes, blindness and blood vessel disease.

These diverse blooms had sprung up all over the place; fertilised by different soils: the soil of necessity, serendipity, medical need, and sometimes just the result of a brilliant pair of green thumbs. So let me take you on a conference tour.

Blooms grown on the soil of necessity

Kevin Eggan from Harvard University in Cambridge, U.S., looks like a college kid but he's already a star performer in stem cell science. For several years now he's been on a quest for the holy grail: namely to find the alchemy that will transform a patient's skin cell into a never-ending supply of tissue-matched stem cells; the seemingly magical cells able to fix whichever of a patient's organs is in need of an overhaul.

A couple of years ago, he partly succeeded. He fused skin cells with embryonic stem cells. But these hybrid stem cells were pretty abnormal. So Eggan turned to another technique which promises to deliver stem cells from skin cells, that is: therapeutic cloning. To carry out this controversial technique, he teamed up with his colleague George Daley, a haematologist at the Children's Hospital in Boston.

Human therapeutic cloning is an alchemy that transforms a regular skin cell into an embryo (and potentially an entire cloned human). And it is from that embryo, that human embryonic stem cells are derived. But the first step is the crucial one. It requires an unfertilised woman's egg to act as the alchemist's vessel. The egg's own chromosomes are sucked out, so removing its genetic instructions. They are replaced by the genetic instructions of a skin cell, carried by the skin cell nucleus. Inside the egg vessel, the skin nucleus starts developing into a clone embryo. After several days the embryo is destroyed to derive embryonic stem cells that match the skin cell donor.

The long wait

Eggan and Daley spent a couple of years just to get their University's permission to carry out the controversial technique. Then they waited for women to donate their eggs. As Eggan explained in his talk, it was a long wait. In fact not a single woman ever showed up. But it gave him lots of time to think. He realised that unfertilised eggs were very precious: a woman had no idea how many she would really need in order to conceive. On the other hand, fertilised eggs were often thrown away because they were faulty. So couldn't he use these readily available fertilised eggs instead?

Past evidence suggested not. Researchers had originally tried using fertilized eggs as cloning vessels, but only unfertilised eggs had ever worked in mice. But as Eggan sat there thinking, he realized what the problem must be. In cloning you have to start by removing the egg's own chromosomes. But the chromosomes of fertilised and unfertilised eggs differ in a very significant way. In unfertilised eggs the chromosomes float freely in the cellular soup like fish in an aquarium. And just as you can net fish from an aquarium while leaving the aquarium fluid intact; you can scoop chromosomes from the egg yet leave most of the egg goodies intact.

On the other hand in the fertilised egg, the chromosomes get bagged up in a sac called the nucleus. When you remove the sac, you not only remove the chromosomes you remove lots of other goodies as well. And some of those goodies must be essential for cloning. At least that was what Eggan guessed. If his hunch was right, there was still a way to use fertilised eggs for cloning. Because a few hours after fertilisation, just before the egg split in two, the sac around the chromosomes broke. In theory that should allow someone to fish out the chromosomes only and leave the other goodies in the egg. Eggan tested his theory on fertilised eggs whose nuclear sacs had just broken and it worked: these eggs turned out to be good cloning vessels.

Accepting the rejects

If fertilised human eggs can be used the same way, Eggan (a most fitting name) and lots of other researchers will be back in business. That's because fertility clinics in the U.S. throw away up to 50,000 fertilised eggs each year – because they're faulty; they carry more than one sperm. But reject eggs like this work fine for cloning. Eggan has stopped waiting for altruistic women and now plans to apply to the clinics to use these reject eggs.

Necessity has also been the mother of invention for Robert Lanza, a scientist at the company Advanced Cell Technology in Massachusetts. In 2001, U.S. president George Bush decreed that American researchers cannot use federal funds if their research destroys human embryos; even if they are surplus embryos from fertility clinics and destined to be thrown away. So Lanza thought of a way to make embryonic stem cells without destroying embryos.

It's known that at the eight-cell stage, an embryo can tolerate losing one or two of its cells, and go on to develop normally. That is the routine technique behind embryo biopsy—where the single cell is tested for genetic defects before the embryo is implanted. Last August Lanza announced in the journal Nature that he had managed to take one of these biopsy cells and turned it into an everlasting embryonic stem cell.

At first Lanza was lauded: he appeared to have cut the Gordian knot strangling stem cell research – embryonic stem cells could be made without destroying the embryo. Then he was vilified, because it turned out that in fact, the embryos he used to do his experiment had been destroyed.

But at Cairns, Lanza redeemed the promise of his earlier research. He described how he had, in fact, created embryonic stem cells from three embryos, without harming the embryos. After surrendering a single cell, they had been safely returned to the freezer, where they should still be fully viable (based on thousands of cases where healthy babies have been born from such embryos.) Lanza told me he has since applied to the U.S. National Institutes of Health, to see whether embryonic stem cells made by his technique would qualify for federal funding, since no embryo is destroyed in the process.

Blooms from the soil of medical need

The affable George Daley is the newly incumbent president of the International Society for Stem Cell research. He is also a physician-researcher dedicated to his child patients who have genetic blood diseases. Bone marrow transplants are the best bet for these kids, but this cure has a two to five per cent chance of killing them. The risk comes from the bone marrow graft itself which, because it is foreign, will sometimes attack the patient.

That's why Daley has been dreaming about using a patient's own cells as the source of their cure. He has achieved the dream in mice. In 2002, he took cells from the tail of a mouse, and using "therapeutic cloning", reprogrammed them to become embryonic stem cells. Then he fixed the genetic defect in those cells, turned them into bone marrow cells, and returned them to the mice to cure their disease. The hope is to repeat the trick in humans: that's why Daley and Eggan spent two years trying to get permission to carry out therapeutic cloning.

But Daley also has other balls in the air. Human therapeutic cloning is extremely difficult – nobody has yet succeeded. But there is another way to create an embryo that matches its donor. That's an embryo that develops from a single parent – a so-called parthenote. These embryos, of course, never develop beyond an early stage. They occur when a woman's egg starts developing without being fertilised. Or when two sperm fertilise an egg and the female chromosomes are kicked out.

It turns out to be quite easy to make these single parent embryos, and even though they don't develop very far, it is quite easy to make embryonic stem cells from them. It is certainly a hell of lot easier than therapeutic cloning. For instance in mice, only 1 per cent of clone embryos yield stem cells, but 70 per cent of parthenote embryos will deliver.

Woo Suk Hwang, the Korean cloning expert who defrauded his results, found this out the hard way. He used over two thousand human eggs to try therapeutic cloning. His only success was an embryonic stem cell line that came from a parthenote embryo. That was a genuine world first – but it's not clear whether Hwang realised what he'd got.

Daley is very eager to test grafts derived from single parent embryos for their therapeutic potential. Because in theory, they should not be rejected. In mice such cells have been trained to become bone marrow cells, and they are not rejected when transplanted back into the animal that donated the sperm or eggs.

Daley is also trying to get therapeutic cloning to work using cow eggs as cloning vessels. As far as pushing the research envelope for his patients, Daley is leaving no stone unturned.

Green thumbs

In this conference the exotic blooms kept popping up right till the end. Hongkui Deng from Peking University in China was one of the very well-represented Asian contingent: about a third of the conference attendees came from Asia. And his talk was a show-stopper.

Researchers have been getting closer and closer to converting embryonic stem cells into insulin-producing beta cells. These are the cells that die off in children with type-1 diabetes. Grafts of beta cells from donated pancreases can control the disease and prevent the side–effects like blindness and kidney failure. But there will never be enough donated pancreases to go around.

That's why embryonic stem cells, with their capacity to be grown by the bucket load, provide great hope. Many labs have now made cells that look and feel like beta cells. The problem is when they graft the cells into diabetic mice, they don't work. For some reason though the cells make insulin, they won't release it when blood sugar levels rise.

Not so for Deng. He used a slightly different method to make his beta cells, and when he grafted the cells into diabetic mice, they performed, releasing their insulin in response to rising blood sugar levels, and normalizing the blood sugar levels of the mouse. It worked when he used human embryonic stem cells too, and when he removed the grafts, the mice went back to being diabetic.

Scientists are cautious about research presented at a conference. Nevertheless, Bernie Tuch who heads the Diabetes Transplant Unit at Sydney's Prince of Wales Hospital In Australia in had to admit, " he seems to have progressed further than anyone else."

It turns out Deng has a reputation for having golden hands: Ten years ago, when he trained at New York University, he isolated a key receptor for the AIDS virus. Now at his lab at Peking University, he has a US$1.9-million grant from software tycoon Bill Gates, and uses stem cells to work both on HIV vaccines and diabetes.

At Cairns, one could at last move on from the politics and religion that has so distorted stem cell research – trying to wedge it into adult versus embryonic stem cells. Here all the disciplines were enjoying the fecund cross-pollination that science thrives upon – to allow a thousand flowers to bloom.

---