By Don C. Reed

When I first heard Brazil had signed a letter of agreement with the California stem cell research program, to support research collaboration, I could hardly believe my ears.  Brazil is a religiously conservative country: how could they achieve the necessary scientific freedom?

I wrote to a scientist friend, Dr. Lygia Pereira, of Sao Paulo, Brazil, who said:  “the road to legalizing embryonic stem cell research in Brazil  was  bumpy”…

In 2005, her letter read, the Biosafety Law approved in Congress had allowed the use of stem cells made from fertilized eggs left over from the In Vitro Fertilization procedure–  but only after being  frozen for more than 3 years. This was strict, and from a too-narrow population (primarily European ancestry) but perhaps workable.

Unfortunately, individuals associated with the Catholic church filed a lawsuit attempting to ban the research.  If they won their case, frozen fertilized eggs could be considered a full-fledged life with Constitutional rights–and embryonic stem cell research could be declared illegal.

Enter the scientists I will always think of as the three Musketeers of Brazilian stem cell research: Drs. Lygia Pereira, Stevens Rehen, and Mayana Zatz.

Lygia Pereira is a pioneer, the kind of scientist who takes giant early leaps of progress, on which others build. She began working with stem cells in 1992, and developed a mouse model for a condition called Marfan’s Syndrome, a potentially fatal disease. She wrote three books, five book chapters, and many papers.

Stevens  Rehen is a visionary, who looks at what is now, and asks: how can we do it better?  One improvement that may revolutionize the field is his method of increasing the number of stem cells. The old way was to put embryonic stem cells into a dish of feeder gel, and gently tap and shake the container. This “passaging” helped develop the stem cell colonies, but was awkward and time-consuming. Instead, Dr. Rehen developed an automatic spinning method, which might be called the “Rehen Spin”, reportedly seven hundred times as efficient as the older method–for half the cost.

And the third Musketeer?  Mayana Zatz is the ultimate patient advocate. Having visited the shanty-towns of Brazil, she saw children with muscular dystrophy born to families who could not afford to give them any medical treatment, not even a wheelchair. She fought for them, organizing and raising funds for the Brazilian Association of Muscular Dystrophy. And when they asked to be present in the court, so the judges could see who would be affected by the trial, it was Dr. Zatz who made it happen.  In 2001, she won the L’Oreal-Unesco Award for Women in Science.

The three scientists did everything they could: making literally hundreds of educational presentations.

At last, there was nothing further they could do.

On the day the Brazilian Supreme Court argued the case, the courtroom was packed with patients, many in wheelchairs, and their families beside them.

Embryonic stem cell research would either go forward, or be banned.

The final vote?  Six to five– in favor of allowing the research. Six to five… Without the efforts of Pereira, Zatz and Rehen, there would be no embryonic stem cell research in Brazil today.

Instead, Brazil has taken its rightful place in world science.

And what happened to the three Musketeers of Brazilian stem cell science?

Dr. Lygia Perreira established Brazil’s first embryonic stem cell line, BR-1.

“Once the legal aspects were sorted out, we started culturing the Harvard lines… using those cells as a model to study… and the Brazilian government decided to invest in cell therapy.  We got a grant to establish lines of hESCs, and in 2008 we reported the generation of our first line, BR-1.  Since then, we have established 4 additional lines, and provided cells and training in hESC culture to several groups in Brazil. When we reported… the first Brazilian line of hESCs, the public reaction was all positive…” -personal communication.

Mayana Zatz,  a member of the International Human Genome Project of the Academy of Sciences of the State of Sao Paulo, and of the Brazilian Academy of Science has been cited almost 9,000 times in peer-reviewed publications, and has had more than 150 articles published in magazines such as “Nature Genetics” and “Human Molecular Genetics”. Dr. Zatz is also a columnist for Brazilian Veja Magazine.

Stevens Rehen is Full Professor at the Federal University of Rio de Janeiro and Head of Research at the D’Or Institute for Research and Education.

FLASH! As this is written, Brazil’s Stevens Rehen has just taken “…an important step toward the implantation of stem cell-generated neurons as a treatment for Parkinson’s disease. Using an FDA-approved substance for treating stomach cancer, Rehen and colleagues were able to grow dopamine-producing neurons derived from embryonic stem cells that remained healthy and functional (in) mice, for as long as fifteen months, restoring motor function (muscle control) without forming tumors.”

Long life to the three stem cell Musketeers of Brazil! May they continue to enrich the world with their useful skills–and may they never need to take up their legislative swords again!

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