segunda-feira, 16 de fevereiro de 2009

Evolution's Future Shock

February 12, 2009
by Alan Boyle

Recent advances in stem cell research - including the technique for reprogramming ordinary skin cells to behave like embryonic stem cells - could put human evolution on a pace that's much faster and wilder than we can handle, according to a pioneer in the field.

Advanced Cell Technology's Robert Lanza, who was one of the first researchers to work on human cloning, thinks someone better be ready to put on the brakes before the breakthroughs spin out of control.

Chalk this one up as just one more controversy for a scientist who has to be used to it by now. For more than a decade, Lanza has been on the forefront of cloning research - first with genetically engineered cows, and then with human embryos. More recently, he's been delving into other avenues for cell therapy - ranging from extracting single cells from embryos to the cell reprogramming trick.

Lanza and others involved in stem cell research are seeking to harness the marvelous ability of embryonic stem cells to transform themselves into virtually any tissue in the body - which could lead to new treatments for maladies ranging from spinal-cord injuries to heart attacks and Parkinson's disease. Other types of cells, such as adult stem cells and umbilical-cord cells, have some of these abilities, but embryonic cells are seen as "the gold standard" for future therapies.

Observers are expecting stem cell research to surge now that President Obama has moved into the White House. Just last month, the Food and Drug Administration gave California-based Geron Corp. the go-ahead to begin the world's first medical study of a treatment based on human embryonic stem cells.

But there are lots of scientific and ethical questions yet to be answered: Last week, Lanza and his colleagues made headlines when they suggested that egg cells from animals might not be useful for creating human stem cells. If those findings hold up, it would be bad news for scientists who want to use animal eggs to supplement the very limited supply of human eggs available for stem cell research.

The research also raised some questions about the reprogrammed cells - which are also known as induced pluripotent stem cells, or IPS cells. The technology was touted in 2007 as a way to solve the ethical problems associated with destroying human embryos, but it could carry its own brand of ethical baggage. Experiments indicated that IPS cells could be used to create clones of any individual, dead or alive.

Lanza's main concern is that the technology could let someone tinker with the human genome in such a way that the tinkering is passed down from one generation to the next through sperm, egg and embryo - an enduring genetic chain known as the "germline." That could be done for seemingly good reasons: to build in resistance to disease, for instance, or to make us smarter or longer-lived. But like most science-fiction plots, such good intentions could have undesired consequences.

This week, I spoke with Lanza about his latest research and his latest concerns about IPS cells, as well as his observations on evolution and the fresh perspectives he'll be putting forth in "Biocentrism," an upcoming book on a biology-based theory of everything. Here's a trimmed-down taste of the conversation, fine-tuned with some follow-up e-mails:

Cosmic Log: Last week you published some research that related to the implications of IPS cell research for animal-human hybrid cells, as well as the prospects for human cloning. I saw some reports about that study indicating that a type of reproductive human cloning is doable, and that could set some alarm bells ringing.

Lanza: Well, yes. I think the first point of this particular paper was that the animal eggs didn't seem to be a suitable substitute for human eggs. In our particular lab, we tried hundreds of experiments trying to create patient-specific stem cells using animal eggs. And we got beautiful little hybrid embryos, but it didn't work, no matter how hard we tried.

We've had lots of experience with this. We've cloned entire herds of cows - in fact, we cloned a couple of endangered species using cow eggs. But despite all the tricks we attempted, we were unable to have any success. Then we looked at what was going on inside the cells. Up until now, people generally looked at pictures or looked under the microscope, but we assessed the complete gene profile. And we found that basically the eggs from the animals turned the genes off that we hoped would have been turned on.

What we also showed here, for the first time, was hard evidence that human cloning is indeed possible, at least in terms of proving that the donor human cell was actually being reprogrammed. This may be very important, along with the new IPS cell technology, in that it furnishes us for the very first time with the ability to start tampering with the germline.

At this point, the only two possible ways to enter into the era of "designer babies" is through either cloning or the new IPS cell technology. These new technologies are very similar. The technology currently used to reprogram a skin cell into a stem cell could be used to make designer babies and possibly even super-athlete babies. So despite the enormous medical promise of SCNT [somatic cell nuclear transfer, the traditional approach to cloning] and IPS cell technology, it opens a whole can of worms.

Someone could use these techniques to produce a child that has most if not all their genes. The implications of this are enormously troublesome. It revives the same issues raised by reproductive cloning. And although the technology for human reproductive cloning still doesn't exist, with the IPS cell breakthrough, we actually do have a technology whereby anyone - young, old, fertile, infertile, gay, straight - could pass on their genes to a child, using just a few skin cells. Or, in fact, hair follicles.

So if you had a few hair follicles from Albert Einstein, or whoever, you could theoretically generate IPS cells. And since those cells are immortal, any couple in the world could have a child who is, say, 10 percent or 75 percent Albert Einstein by just injecting a few of those cells into one of their embryos. Perhaps you could mix a little Brad Pitt in there, too.

The potential to fast-forward the era of designer babies exists. Of course, it would be scientifically and ethically irresponsible to use this technology for reproductive purposes. People have not thought the whole thing through.

Let's go back to the parents who are obsessed with having super-athlete babies. They could conceivably have the myostatin gene knocked out in a few skin cells, and then inject IPS cells into one of their in-vitro fertilized embryos. That would be unsafe and unethical, and there's no guarantee to what extent those cells will contribute to a child's muscle mass. It might be 1 percent or 100 percent. There's also the chance that the child would want to play chess instead of becoming a super-athlete.

But this isn't science fiction. We know the technology already exists to increase an animal's body mass by knocking out this myostatin gene. In cows, for instance, it's been used to literally double the muscle mass.

There's a concern that this could contribute to the germline. We've got to think about this carefully. It's not just a matter of people wanting to make their children stronger or have a higher IQ. When you start tampering with the human germline, you're really crossing a line that's wrong. Remember, the human body is an exquisitely fine-tuned machine that took millions of years of evolution. I think it would be foolish and arrogant for us to think that we can engineer better people through science.

Q: Do you see a distinction between using these technologies to repair genetic flaws and using them to enhance abilities?

A: There are two things to consider here: One, you can simply generate cells to replace worn-out tissues or organs. I don't see any problem with that whatsoever. You're not tampering with the germline.

Now, when you consider genetically correcting some sort of disease, you're really crossing a line. A good example of that would be sickle-cell anemia, which we consider an awful disease. But that gene actually protected people from malaria for thousands of years - when malaria was killing literally hundreds of millions of people. So we can't even begin to understand what tampering with other genes could lead to.

It would certainly accelerate evolution. But for better or worse? That's the question.

Q: So this would speed up human evolution even more than it's speeding up today? Could it lead to some sort of radical retooling of our species?

A: Absolutely. That's the whole issue. Evolution normally occurs, even today. There are natural mutations, and the bad mutations are weeded out.

There’s another unrecognized but seismic shift occurring in human evolution. The wide scale intervention of science and modern medicine - drugs, vaccines, machines, and soon, stem cells and regenerative medicine - has allowed the survival of a large range of mutations, traits and genetic combinations that would never have been possible in the past.

For instance, someone like Stephen Hawking - or even Bill Gates - might not have fared as well in a hunter-gatherer society. New economic, political and behavioral pressures will shape this pool of gene-combinations in directions never before possible. Human evolution is occurring - and will continue to occur - at a rapid and unprecedented rate.

The problem with these new technologies is that we can now go in directly and modify genetics. We can knock out a specific gene. In fact, we've done this in pigs to knock out a gene that's associated with hyper-acute transplant rejection in humans. But we've also found that knocking out those genes has other, adverse effects. So with these new tools, we're entering into an entirely new era - which we don't completely understand.

Q: How do you wrap your mind around the pluses and the minuses? Is there somebody who should be appointed as a genetics czar to have people toe the line? What are you suggesting?

A: I think there are several things going on. One is that we need to enact laws, just as we did when we were considering xenotransplantation, when we were worried about pathogens crossing the species line. We were concerned that although we passed a law in the United States, there might be "xeno-havens" somewhere else. The same would apply here. A while ago, the United Nations was on the verge of banning reproductive cloning. We need to move on that right away. That should also incorporate other technologies such as the IPS technology.

In the more developed countries, we obviously have laws in place to prevent abuses from happening - and that will probably succeed there. But in some of the developing countries, we may not have that regulation, and there could be some abuse. We've seen this with AIDS and other genetically based changes that move quickly from one country to another. If this technology is abused anywhere, once it gets into that germline and those people immigrate or move, it's in us, it's in the DNA of our species. And God only knows how it will manifest itself down the line.

Q: If someone else were to receive tissue as the result of an IPS operation, might that work its way into the germline? Would you have to have a restriction on people reproducing if they receive IPS cells?

A: No, that's not an issue. You wouldn't inject the IPS cells. You'd inject replacement cells that are terminally differentiated, and they would not enter the germline. When the patient dies, so do the cells. The concern here would be if you place the cell either into an embryo or the germline - that is, a sperm or an egg. Only then could it be passed on to subsequent offspring.

Q: Are there points of contact between what you're doing on this subject and the topics that you'll be addressing in "Biocentrism"?

A: No, they're separate. But I think biocentrism does have something to say about evolution as well. From a biocentric perspective, Darwinian evolution is an enormous simplification. While a lot of the components are right, it's still far from the complete picture. Darwin's theory of evolution is helpful if you want to connect the dots and understand the interrelatedness of life in the past. For instance, we can follow the changes that occurred in our genome even before we were human. We can even map some of the mutations and blind alleys that life took to get us here. But it fails to capture the driving force that's really going on.

If you consider the universe, there's a long list of traits that make it appear as if everything the universe contains - from atoms to stars - were tailor-made just for us. If the big bang had been just one part in a million more powerful, the cosmos would have blown outward too fast for stars and worlds to form. The result, of course, would be no us. Even more coincidentally, the universe's four forces and all the constants seem to be perfectly set up for atomic interactions, the existence of atoms, elements, planets, liquid water and life. You tweak any of them, and we never existed.

At the moment, there are only four explanations for this mystery. One is that it's just an incredible coincidence. Another is to say, God did it, and that explains nothing, even if it is true. The third is to invoke the anthropic principle, meaning that we'd have to find these conditions if we're alive, because what else could we find? And then there's the final option, biocentrism, which is what I'm supporting. It says the universe is actually created by life, and no universe that doesn't allow life could possibly exist.

The same thing would apply to our own human existence. Probability-wise, there are millions of things that could have gone wrong in the history of life on Earth. We could have been snuffed out at almost any turn. For instance, the meteor that wiped out the dinosaurs could have missed the earth, and then we would have never evolved. The list goes on and on. Evolution might suggest that it's just dumb luck, that there's a 1-in-a-gazillion chance that we're here. But surely science can do better than the dumb-luck theory.

For additional food for thought on Darwin Day, take a look at these other Cosmic Log postings:


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