Newsweek - National News, World News, Health, Technology, Entertainment and more... | Newsweek.com
SPONSORED BY
  • From 'Sins of the Fathers' to Virtues of the Mothers: Lamarck Won't Go Away

    Sharon Begley | Feb 3, 2009 05:19 PM

    Among the things that scientists don’t like is having their grant proposal denied, having their papers rejected by eminent journals, and not getting tenure. Among the things they really, really hate (based on the comments I got on my column last month on Lamarckian inheritance) is for a science writer to describe studies that show that the Modern Synthesis (the marriage of Mendelian genetics and Darwinian natural selection acting on random variation, which forms the basis of evolutionary biology) is not the last word. “Why is a creationist writing for Newsweek??!!” and “there is no evidence of Lamarckism!!!” were among the more polite comments.

    So it pains me to have to take note of a new study that describes—and here I’ll just quote from the abstract—how “qualities acquired from experience can be transmitted to future offspring,” and documents “non-Mendelian transgenerational inheritance” and a “‘Lamarckian’-like phenomenon.” In short, what scientists led by Larry Feig of Tufts University are reporting today in The Journal of Neuroscience is that when adolescent mice are exposed to an environment that improves the ability of brain neurons to communicate with one another and, as a result, improves their ability to learn and remember, that enhancement is transmitted to unborn offspring—offspring that never experienced the brain-boosting environment, that were not even conceived at the time their mothers did, and that are not even raised by the learning-enhanced mothers.

    Might a similar effect occur in people? No one knows. But if it does, conclude the scientists, “the effectiveness of one’s memory during adolescence . . . can be influenced by environmental stimulation experienced by one’s mother during her youth.”

    This result is so remarkable that the usual caveat—the study must be replicated by an independent lab—needs to be underlined. You get a sense that the scientists themselves are astonished by what they found, for they sprinkle their paper with words like “remarkably” and “dramatically.” “When we first got the results I didn’t believe them,” Feig told me.

    Here’s what he and his team did. They built on the well-established finding that when lab rodents are raised in an “enriched” environment, filled with toys and other animals and an opportunity to exercise, it enhances their learning and memory, promotes neuronal changes such as the dendritic branching and synapse formation that underlie cognition, and even stimulates neurogenesis. In 2006, Feig and colleagues showed that an enriched environment can overcome the effects of a genetic defect that otherwise impairs learning. What seems to happen, says Feig, is that a secondary pathway supporting neuronal communication is turned on, sort of like when surgeons bypass a blood vessel. Now he and his team have gone further.

    They housed adolescent mice (15 days old) in an enriched environment (plastic play tubes, cardboard boxes, running wheel, toys, friends—all rearranged every other day to keep it interesting) for two weeks. In the mice with mutations that impair memory (the underlying deficit is in the cellular process called long-term potentiation), the experience repaired the defect that kept brain neurons from communicating well, as Feig and his colleagues had previously found. But when the mice grew up, mated and had pups, the pups of the mutant/memory-impaired mice (the pups also carried the mutation) seemed to have benefited from their mothers’ acquired trait: their brain neurons’ communication capacity was as good as that of normal mice. As a result, they learned and remembered better: after experiencing an electric shock delivered through the floor of their cage, next time they entered the cage they froze, recalling the unpleasant experience. (The pups of normal mice that experienced the enriched environment had improved levels of neuron communication as well, but showed no improvement in their memory capabilities, at least as measured by the shock test.)

    Just to reiterate: the offspring still had the genetic defect that impairs memory. They never experienced the brain-boosting enriched environment. But their mothers’ experience of that environment—an experience the mothers had before the pups had even been conceived—repaired the biochemical glitch that the mutation causes and that impairs memory. “Transgenerational inheritance of the effect of enriched environment,” write the scientists, “occurs before birth. . . . Enrichment can restore . . . a genetically-induced memory defect in both mice directly exposed to an enriched environment and, more remarkably, in their future offspring.”

    To be sure that the pups’ improved memory was not the result of better nurturing by mothers whose own brains had been improved by the enriched environment, the scientists had foster mothers raise the pups. The foster mothers had never experienced the enriched environment. Yet the pups still had improved brains. “The effect lasted until adolescence, when it waned, suggesting that this process is designed specifically to aid the young brain,” said co-author Shaomin Li, who is now at Brigham and Women’s Hospital.

    And why do the scientists describe this as the inheritance of acquired traits, or Lamarckism? Because the mothers-to-be acquired a change in their genome as a result of an experience in the environment (a cage filled with goodies). That change was transmitted to—inherited by—their pups. The scientists don’t yet know what molecular mechanism achieve this magic, but Feig was willing to speculate about how it evolved: “We hypothesize that this evolved to let mothers pass on a signaling pathway that was turned on by the enriched environment, in case the pups were not themselves exposed to that environment.”

    There’s an interesting historical footnote to all this. A 1985 paper reported that when pregnant rats are exposed to an enriched environment, their pups are better at learning mazes. And a 1987 paper found that rat pups of moms exposed to an enriched environment before pregnancy “inherit” mom’s exploratory behavior and learning ability. Those studies, while occasionally cited, were so far ahead of their time that they essentially were lost to science. “People thought, how could this possibly be so?” Feig said.

    This study is the first to show that genetic defects in neuronal transmission and hence memory, caused by a mutation, can be at least partly reversed by an experience a mother has long before she is pregnant. Might this happen in people? Obviously it is way too soon to speculate, so let me leave it at this: the reflexive antipathy of many biologists to the possibility of Lamarckian inheritance reflects badly on the scientific community’s reputation for openness to new ideas and to data that challenge existing ones.

    More
  • Human Clones: One Step Closer

    Sharon Begley | Feb 3, 2009 01:00 PM

    The science of cloning and stem cells has been somewhat of an unholy mess, what with fraudulent claims (by a South Korean biologist) of generating custom-made stem cells lines and, sigh, of producing a baby through cloning. (The little cloned boy should be 5 now; we wish him well in kindergarten.) The latest advance therefore shouldn’t inspire headlines about cloned babies being right around the corner, but here goes: scientists have transferred DNA from an adult human cell into a human egg, and gotten the egg to “reprogram” the donor DNA back to its embryonic state, producing a pattern of gene activation like that in normal IVF embryos--and therefore, it seems, the pattern necessary to create an embryo.

     

    What this means, in a nutshell, is that if the study holds up, it will look increasingly likely that there are no known technical obstacles to reproductive cloning, the creation of human clones not for stem cells (in which case the clone never gets further than a days-old ball of cells) but for babies.

     

    Scientists led by Robert Lanza, chief scientific officer of the biotech company Advanced Cell Technology, have no such goal in mind. They just wanted to see whether putting adult human DNA into (non-human) animal eggs would send the DNA back in time, so to speak, to its embryonic stage. Such “reprogramming” could, in theory, produce a days-old ball of cells from which scientists could extract stem cells that, with some coaxing, could be used to treat patients with diabetes, spinal cord injury, Parkinson’s disease and other ailments. If the DNA came from the patient himself, the stem cells would be perfect and personalized genetic matches, eliminating the risk that they would be rejected by the recipient's immune system.

     

    The reason human DNA would be put into animal eggs rather than human eggs is that the latter are hard to get. Harvard’s Kevin Eggan, for one, has described “stomping around to different disease advocacy groups, tea circles, knitting circles, trying to find anyone and everyone who would donate their oocytes,” to little avail. The new study throws cold water on the hope of using animal ova.

     

    The scientists used standard methods to transfer DNA from adult human cells into ova (human, cow and rabbit) whose own DNA had been sucked out. All three kinds of ova yielded about the same success rate in getting the ovum to divide like a fertilized egg  (39%, 36% and 36%, respectively, formed balls of 12 to 32 cells). But when the scientists tested these embryos to see which genes were active, they found a stark difference. The pattern “was dramatically different” in embryos created from human ova and from cow or rabbit ova, they report online ahead of print in the journal Cloning and Stem Cells. The human-human clones had gene activity patterns that matched those of normal embryos created at IVF clinics—that is, they seemed to follow the recipe for baby making in that the adult donor DNA had been reprogrammed back to an embryonic state. The human-animal hybrids had a different pattern, Lanza told me: “The donor DNA just wasn’t being reprogrammed.”

     

    Several key genes were activated in the human-human clones but not the human-animal ones. Called Oct-4, Sox-2 and nanog, they seem to be the keys to directing the entire genome to revert to the embryonic state necessary to create both stem cells and babies. Called pluripotency genes, they had been “effectively silenced” in the human-animal hybrids, said Lanza, making it impossible for the hybrid to produce stem cells. “These data call into question the potential use of [animal ova] to generate patient-specific stem cells,” the scientists conclude.

     

    Now about those human embryos. There have been several previous claims (such as one in 2001, by a team that included Lanza, and one last year by a company in California called Stemagen). But although some of the balls of cells looked normal (others did not), there was no molecular evidence that the donor DNA had been reprogrammed back to an embryonic state. In the new study, gene chips that test for DNA expression confirmed that the donor DNA had been reprogrammed to a state “very similar to normal IVF embryos,” said Lanza. “This is the first real evidence that the donor DNA is reprogrammed, and the first time anyone has furnished hard evidence that human cloning is indeed possible, at least in terms of proving that the donor human cell was actually reprogrammed.”

     

    Ian Wilmut, who led the team that cloned Dolly the sheep in 1997, the first mammalian clone, is now director of the MRC Centre for Regenerative Medicine at the University of Edinburgh. He told me in an email that the study underlines “an important difference in gene expression from transferred human nuclei depending upon whether they were transferred into a human oocyte or a non-human oocyte.” Although it does not “absolutely rule out the use of animal oocytes, . . . the balance of probability is that transfer into human oocytes is more likely to work” for generating therapeutic stem cells.

     

    And if Lanza and his team are right, the idea that nature erects insurmountable barriers to human cloning will seem like a misplaced hope.
    More
  • Advertisement