Profile of Rafael Palacios

Coming to America

In 1970, as is true today, it was common for Mexican Ph.D. students to go to the United States or Europe for postdoctoral work. There were few molecular biologists in Mexico, so it made sense for Palacios to attend a top American university like Stanford. However, he made a choice, unusual at the time, to pursue research at Stanford that was completely different from his Ph.D. focus. Schimke had moved on to work with messenger RNA (mRNA) in higher organisms. The question that Palacios, Richard Palmiter, and other postdoctoral fellows in Schimke's laboratory sought to answer was whether, in cells specializing in large-scale protein production, there are more copies of genes coding for that protein than there are in other cells. They used the chick oviduct, which produces ovalbumin, as their model. “The limiting step at that moment was the isolation of mRNA,” Palacios says.

The scientists had to invent a new technique if the experiment was to progress. Palacios used antibodies against ovalbumin to trap ribosomes in the act of translating the nascent protein from mRNA. Once he had identified the mRNA coding for ovalbumin, it was transformed into complementary DNA, which was used to probe the genome in chick oviduct cells, to find out how many copies of the gene existed. Despite the huge output of ovalbumin from these cells, the researchers found that both oviduct and liver have the same number of genes. The oviduct cells were able to mass-manufacture the protein by greatly accelerating the rate of gene transcription.

At Stanford, Palacios regularly encountered Nobel laureates, although not quite as abruptly as with Joshua Lederberg. “I was in pharmacology, [Arthur] Kornberg [Nobel Prize in Physiology or Medicine, 1959] was in biochemistry, so I saw Kornberg in the doorways, in the lobbies, in different places.” At one point, he even found himself competing with Paul Berg, future Nobel laureate in Chemistry (1980), for time on the centrifuge. With so many researchers in one place, the fire of innovation burned hot.

Palacios was impressed, but he felt that he needed to return to Mexico to advance science at home. “Looking at this panorama of so many good labs in a single place,” he wondered “How should we do research in Mexico? And I got a clear idea that we have to get together different scientists around a similar topic.” This goal drove him for many years.

In 1973, at the end of his postdoctoral term, Palacios announced that he would return to Mexico at the Biomedical Research Institute at UNAM.

As a new associate professor at UNAM, he began a partnership with Jaime Mora, the institute's director. They focused on the central enzyme of nitrogen metabolism, glutamine synthetase. “We started an academic collaboration and a personal friendship that have lasted up to this moment. He's actually my best friend, and we have done many academic things together,” Palacios says. He dedicated his 2007 Inaugural Article (1) to Mora.

Homegrown Expertise

One year after returning to Mexico, Palacios discussed with Mora how they might engineer the same sort of creative cauldron that Palacios had experienced at Stanford. They wanted to build a new facility dedicated to a single avenue of research based, of course, in an area in which they already had some expertise.

“We decided that nitrogen fixation was very promising because of the scientific interest and because of the possibility of helping agriculture. So we decided to dedicate ourselves and to commit several other researchers,” Palacios says. “It was a very planned decision.”

Schimke remembers Palacios' spirit of altruism. “He felt strongly that he should go into an area that would benefit the people of Mexico,” Schimke recalls.

“If we're isolated, everyone doing different work, it is very difficult to do interesting things.”

Securing support and funding took several years, a process aided by crucial support from Palacios' former Ph.D. supervisor Soberon, who was serving as rector (chancellor) of UNAM. In Mexico, university rectors are powerful figures. “In the university,” Palacios says, “we are highly protected from all these recurrent crises, economic, political, and social, that we have in Mexico.”

In 1980, with Soberon's backing, Mora and Palacios founded the Nitrogen Fixation Research Center in the city of Cuernavaca, far from urban sprawl in the hilly, picturesque countryside 50 miles south of Mexico City. Palacios was appointed as the first director of the center. At the outset, there were 10 researchers, 12 students, and assorted technicians and staff.

Under Palacios, the Center's researchers began to explore the genetics of Rhizobium. “It's a bacterium that interacts with the roots of legumes and then fixes atmospheric nitrogen and transforms it to ammonia and other compounds,” he explains. Rhizobium can enrich poor soil, acting as a living fertilizer. Along a path parallel to Palacios' earlier work with chick oviduct cells, the scientists closely examined DNA in Rhizobium that coded for key nitrogen-fixing proteins. Their efforts paid off when they discovered that these genes were repeated multiple times in long stretches. Stable reiterated genes are rare in bacteria, and the researchers found them conserved across several strains of Rhizobium, which suggested that the repeats serve an important purpose (2).

“And so we got interested in repeated sequences,” Palacios says. During mitosis, it is relatively common for the machinery of DNA duplication to make errors in copying regions with repetitive sequences. Sections of the repeated DNA can be deleted, amplified, or inverted by “genomic rearrangement,” which also became a specialty of the Center.

In a PNAS article published in 2000 (3), Palacios and co-workers describe how they leveraged these naturally occurring rearrangements in the Petri dish in a process they named “natural genomic design.” They predicted the rearrangements that could occur in a population of bacteria, and out of millions of cells, they were able to select the few—possibly only one—cells or cell with a particular rearrangement. Within the constraints of the experiment, they were able to obtain live bacteria with a custom rearrangement without inserting foreign DNA.

Unlocking the Potential of Youth

Palacios is not just a scientist, but an educator as well. Reflecting on his professional life, he is proudest of two things: his career-long research collaboration with Jaime Mora and the five-year undergraduate program in genomics that he helped found at UNAM in Cuernavaca. With the success of the Nitrogen Fixation Research Center, Juan Ramón de la Fuente, the visionary rector of UNAM, formed a committee of six scientists in 2001 to explore how the university might develop genomic science in Mexico.

Palacios served on the committee, which concluded that it is essential to establish a top-tier program that provides students with a solid background in analytical thinking. “It has to be at the undergraduate level because that is when students can learn math, statistics, computer science, and biology,” Palacios says. “We pushed a lot for this program.” The first generation of students began in 2002.

Palacios coordinates an international segment where fourth-year students meet face-to-face with researchers from other countries. Scientists from institutions such as Harvard and Stanford visit the center in Cuernavaca and give weekly seminars in genomics. Often, Palacios solicits his guests' opinions of his students, and the professors compare them favorably to graduate students from their own institutions. Selection for the program is rigorous; fewer than 40 of 400 applicants were admitted to the most recent class. Ten years from now, he predicts, these undergraduates will be the leaders in the field of genomics in Mexico.

In recent years, the scope of the institute has expanded. In 2006, the scientists sequenced the Rhizobium genome. “We changed the name of the center,” Palacios says. “It is now called the Center for Genomic Sciences, and we changed the mission. We expanded from nitrogen fixation to a larger scope on genomics. So we handle bacteria, plants, and now humans.” In fact, Palacios stopped working on Rhizobium two years ago.

In his current research on human cells, Palacios relies on undergraduate students. “They do all the bioinformatics,” he says. Twelve of them are listed as authors on his Inaugural Article (1), which covers genomic rearrangements in nucleated blood cells.

In bacteria, rearrangements in reiterated DNA serve as a mechanism by which the microorganisms can meet the challenges of their environment. Cells in the human body undergo similar changes, beginning in the embryo or fetus and accumulating through adulthood. Although the cells are not organisms themselves, the mechanisms that lead to evolution in bacteria remain active within them.

As odd as it may seem, Palacios concludes, “the genome varies not only between individuals but also within cell populations of a single individual.”

Genomic Nourishment

Palacios' goal has been to strengthen Mexican science, and he is convinced that international experience is invaluable. Palacios expects his students to travel abroad for postdoctoral work or to obtain their Ph.D. and then, on their return, “nourish the country with genomics,” he says. He recognizes, though, that some of them may remain in North America or overseas. “I know there are some decisions you have to make,” he says. “They will have a good academic life, and I also know that they will help us with this program of genomic sciences in Mexico. So it doesn't bother me if they end up living in northern California or in Paris or anywhere.”

The same holds true for his family. His wife Margarita Flores is also a geneticist and helps lead his laboratory.

Palacios and Flores live in Cuernavaca with their 16-year-old daughter, Kim. His two sons from a previous marriage, Rodrigo and Gonzalo, live in the San Francisco Bay Area and work at Genentech and Google, respectively. “These are difficult companies to get into,” Palacios says, “They have children, so I have four grandchildren. And they are happy. So I don't mind that they don't live in Mexico.”