Oldest Art from the New World?

In a cave in Brazil, researchers have found what they claim may be the oldest known art from the western hemisphere. Dating from between 9,000 and 12,000 years ago, the simple petroglyph pictures a human-like figure that is roughly 30cm tall.

The report of the discovery is published in the February 22, 2012 issue of PLoS ONE, an open access journal. The team was led by Walter Neves of the University of Sao Paulo.

Caption: This is the oldest reliably dated petroglyph ever found in the New World.

Credit: Citation: Neves WA, Araujo AGM, Bernardo DV, Kipnis R, Feathers JK (2012) Rock Art at the Pleistocene/Holocene Boundary in Eastern South America. PLoS ONE 7(2): e32228. doi:10.1371/journal.pone.0032228

Early New World art is rare, and the oldest examples are not nearly as old as art discovered in Europe and Africa, which ranges back 30,000 years or more. But this finding is interesting nonetheless. Odd features of the drawing--is it human or a bird or reptile, and does it include an oversize phallus--are sure to fuel speculations about the religious or shamanistic origins of ancient art. The earliest expressions of symbolic culture in any setting or context provide additional insight into the cultural origins of modern humanity.

"Rock Art at the Pleistocene/Holocene Boundary in Eastern South America" is published in the February 22 issue of PLoS ONE and is available free to the public.

Single-Atom Transistor: Why Small Is a Big Deal

A tiny achievement with huge significance was reported today by physicists at the University of New South Wales (UNSW). They have created a transistor that uses a single atom. Their work is described in a paper and an editorial published in the February 19 issue of Nature Nanotechnology.

Using a scanning tunneling microscope—the essential tool in nanotechnology that allows researchers to visualize and manipulate single atoms—the UNSW group positioned a phosphorous atom between nano-scale electrodes. A video explaining the feat is available.

CAPTION:This is a single-atom transistor: 3D perspective scanning tunnelling microscope image of a hydrogenated silicon surface. Phosphorus will incorporate in the red shaded regions selectively desorbed with a STM tip to form electrical leads for a single phosphorus atom patterned precisely in the center. Credit: ARC Centre for Quantum Computation and Communication, at UNSW.

What seems to be most important about this achievement is the accuracy of the placement of the phosphorous atom. This opens the possibility that precisely placed atoms may be used to create a whole new generation of computer chips that are both reliable and smaller than anything used today.

"Our group has proved that it is really possible to position one phosphorus atom in a silicon environment—exactly as we need it –with near-atomic precision, and at the same time register gates," said lead author Dr Martin Fuechsle in a press release from UNSW.

The leader of the research group, Professor Michelle Simmons, claims that "This is the first time anyone has shown control of a single atom in a substrate with this level of precise accuracy." Simmons is director of the ARC Centre for Quantum Computation and Communication at UNSW.

According to the famous “Moore’s Law,” which argues from past achievement in chip design and predicts future a doubling in chip power ever 18 months, single atom or quantum computing should be achieved by the year 2020. Fuechsle and Simmons are speculating that because of this breakthrough, technology is ahead of schedule.

If so, then arguments advanced by futurists such as Ray Kurzweil take on added significance. As chips grow in power and shrink is size, more and more powerful computing becomes possible. Smaller chips are more implantable, bringing us closer to they day when they are implanted not just for medical but for other purposes (see previous post).

Even more significant is that smaller and more powerful processing paves the way for more highly intelligent machines. Kurzweil predicts that within a few decades, machines with greater than human intelligence will be produced. What then? Will our inventions become the inventors of the future, and will they still need us? The report, "A Single-Atom Transistor," is published in the February 19 is of Nature Nanotechnology.

Humans Beings, DNA Nano-Robots, and Implantable Chips

Technological devices inside the human body are fast becoming more fact than fiction, and two reports released on February 16 are significant milestones along that path.

In one study, appearing in Science Translational Medicine, microchips were implanted in women suffering from osteoporosis. Researchers at Harvard Medical and Case Western worked with MicroCHIPS, the manufacturer of the device.

Patients with advanced osteoporosis, whose bones have weakened and lost density, are currently able to give themselves with a daily injection of a drug that requires refrigeration. By implanting a device, researchers want to make the process easier compliance more consistent.

The microchips implanted in the study contain tiny reservoirs of the drug. The device releases a daily dose when it receives a wireless signal. It also monitors the release of the drug and reports back to the physician, who is able to modify the prescription by sending new instructions to the device from another wireless device, such as a smart phone. This is believed to be the first wirelessly controlled implanted drug-delivery device.

"This trial demonstrates how drug can be delivered through an implantable device that can be monitored and controlled remotely, providing new opportunities to improve treatment for patients and to realize the potential of telemedicine," according to Robert Langer of MIT and the cofounder of MicroCHIPS, Inc. "The convergence of drug delivery and electronic technologies gives physicians a real-time connection to their patient's health, and patients are freed from the daily reminder, or burden, of disease by eliminating the need for regular injections," Langer said in a release issued by the MicroCHIPS.

The drug delivery device (on right) next to an everyday computer memory stick. Courtesy of MicroCHIPS, Inc., Massachusetts.

The company also reported that it is currently developing new designs of its microchip-based implant to include as many as 400 doses per device providing daily dosing for one year or multi-year therapy for less frequent dosing regimens.

In another study reported today, a team of researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University report on their work in assembling tiny robots out of DNA.

Building on previous advances in what is popularly known as “DNA origami,” the Wyss team used a computer to fabricate a barrel-like structure capable of containing specific molecules for delivery to targeted cells in the body. For example, cancer cells could be targeted with molecules that cause them to self-destruct, much the way the body’s own immune system carries out its functions.

“DNA origami” allows researchers to use DNA as a construction material. They are able to fold it and weave its strands together. What’s more, since DNA is a chemical code, specific patterns or sequences in the DNA can be used to “read” a signal and “act” accordingly. In this study, researchers built a DNA “latch” or locking mechanism. Their DNA barrel kept its molecular payload safely under wraps until it arrived on the surface of the target cell. On the surface of the target cell is a protein that unlocks the DNA latch, releasing the molecule at just the right location.

Cell-targeting DNA nano-robots bearing antibody-fragment payloads. [Image created by Campbell Strong, Shawn Douglas, & Gaël McGill using Molecular Maya & cadnano]

"We can finally integrate sensing and logical computing functions via complex, yet predictable, nanostructures—some of the first hybrids of structural DNA, antibodies, aptamers and metal atomic clusters—aimed at useful, very specific targeting of human cancers and T-cells," said George Church, Ph.D., a Wyss core faculty member and Professor of Genetics at Harvard Medical School, who is Principal Investigator on the project.

One way in which the researchers tested their DNA nano-robots was by programming them to target and destroy cancer cells growing in culture, including leukemia and lymphoma cells. The results were promising. According to the study, ” These findings demonstrate that the robots can induce a variety of tunable changes in cell behavior. Furthermore, biologically active payloads may be bound indirectly via interactions with antibody fragments, enabling applications in which the robot carries out a scavenging task before targeted payload delivery.”

The work reported here is built on advances around the world in nanotechnology and synthetic biology. What is new is the way the Wyss team combined several of these advances for the first time. For example, the release mechanism used here responds to the presence of a protein, not just to the presence of DNA or RNA. That feature alone makes this work more immediately applicable for medical purposes.

Put together, these two reports are part of a far wider panorama of basic advances in biomedical research. They stand out in part because of what they promise in terms of future treatment strategies. But more than that, they catch our attention because advances like these continue to blur the lines between ourselves and our technology.

In the first case—a wireless implanted drug-delivering chip—we are not simply injecting a medication or implanting a device. The patients in this study are hosts to a high-tech subsystem implanted within them that interacts in sophisticated ways with another human being (their physician). What’s more, that other human being—even if half a world a way attending a medical conference—can send instructions that immediately cause an effect within the body (but perhaps without the knowledge) of the patient. Surely there’s a spy story here just waiting to be written. More than that, this seems to be another significant milestone on the way to the (post?-) human future.

In the second case (the DNA nanoscale robot), nothing is yet implanted, but that’s clearly a next step. What are we to make of this elegant piece of tiny engineering? It is so small that it can only be made using computers. It is built from the same sort of DNA that we have in every cell, but it's engineered to hold a desired shape and to respond to a specific signal. Then, if inserted in great numbers into the human body, it can emulate the human immune system but take it in directions far beyond evolution.

The report on the implantable chip is entitled "First-in-Human Testing of a Wirelessly Controlled Drug Delivery Microchip" and appears in the February 16 issue of Science Translational Medicine. The report on DNA robots, "A Logic-Gated Nanorobot for Targeted Transport of Molecular Payloads," appears in the February 17 issue of the journal Science. Both journals are publications of the American Association for the Advancement of Science.

Regenerative Medicine: Repairing the Heart

A breakthrough in the use of stem cells for regenerative medicine has just been reported by researchers at Cedars-Sinai Heart Institute. Patients who suffered heart attacks were implanted with cells derived from their own hearts. Some of the scars left by the heart attacks dissolved and new heart muscle cells re-grew, according to a report in the February 14 issue of The Lancet.

Patients involved in the study had all experienced recent heart attacks that damage heart muscle. The first step in the procedure involved inserting a catheter through a vein in the neck under local anesthesia. Using the catheter, researchers withdrew a small sample of healthy heart tissue. The tissue contains some stem cells, but the key step in the procedure is to multiply and purify the small number of stem cells so that they number in the tens of millions.

These cardiac stem cells, multiplied but originally from the patient’s own heart, were then infused back into the site of the heart attack. The result seems to be a nearly 50% drop in the size of the scar and a re-growing of healthy heart muscle, at least as far as could be determined using imaging technology.

It is important to note that this study is a Phase I clinical trial. Its main purpose is to show that there is no unwarranted risk in the procedure. The outcome of this trial, however, shows a real likelihood of benefit. The evidence is strong that scaring is reduced and heart muscle regenerated. It is too soon, of course, to know the long-term benefits.

What is new in this study is the strong likelihood of actual regeneration of heart cells. Whether the implanted cells produced the new muscles or whether they acted indirectly, triggering neighboring cells to divide and regenerate tissues, is still not clear.

The lead researcher in the study, Eduardo Marbán, made this claim about the finding: "This has never been accomplished before, despite a decade of cell therapy trials for patients with heart attacks. Now we have done it. The effects are substantial, and surprisingly larger in humans than they were in animal tests." Marbán is the director of the Cedars-Sinai Heart Institute who invented the procedures and technology involved in the study, including the procedures for multiplying the stem cells.

"These results signal an approaching paradigm shift in the care of heart attack patients," said Shlomo Melmed, MD, dean of the Cedars-Sinai medical faculty and the Helene A. and Philip E. Hixon Chair in Investigative Medicine. "In the past, all we could do was to try to minimize heart damage by promptly opening up an occluded artery. Now, this study shows there is a regenerative therapy that may actually reverse the damage caused by a heart attack."

The study itself concludes with this claim: “Our study provides an initial indication that therapeutic regeneration might indeed be possible in cardiac tissue.”

The goal of regenerative medicine—the use of stem cells to help patients regrow cells and regenerate tissues or organs—has long been central to the dreams that surround stem cell research. Even though this in only a Phase I study and still must be replicated, it seems to be an important step in the development of regenerative medicine.

Many of course will be especially delighted that no embryonic stem cells were directly involved in this procedure. Those who object to the use of human embryos in research will regard these cells as “morally unproblematic.” It is also very significant to point out that because the cells come from the patients, there should be no issue of tissue rejection.

At the same time, it should be noted that the field of stem cell research advances as a whole field. Knowledge gained from one area (for example, using embryonic stem cells) opens the door for advances across the whole field.

The article, “Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial,” appears appropriately in the Valentine’s Day issue of the medical journal, The Lancet.

New Hope for Alzheimer's Patients?

Working with mice, researchers at Case Western Reserve University School of Medicine are reporting a dramatic discovery in the search for a treatment for Alzheimer’s disease (AD). They treated Alzheimer’s-prone mice with a drug called bexarotene, which is already FDA-approved and available as the anti-cancer drug Targretin®.

The result, reported in the February 10 issue of Science, is nothing short of stunning. Bexarotene appeared to dissolve the excess brain-harming amyloid beta in the mouse brain. Amyloid beta (Aβ) is produced naturally in healthy brains, mouse and human. But when Aβ builds up and forms deposits, it seems to interfere with the function of the brain, including the formation of new memories.

Researchers found that just six hours after administering bexarotene, 25% of the excess Aβ was cleared from the brains of the mice. After 72 hours, 75% of the Aβ plaque was gone and the behavior of the mice was observably different. For more on these finds, take a look at this video released by Case.

So now the big question is this: If bexarotene works like this in mice, will it work the same way in human beings with AD? According to Gary Landreth, professor of neurosciences at Case and lead author of the study, that question is already researched. “We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment,” Landreth said in a press release issued by Case.

One interesting point about bexarotene is that it does not act directly on Aβ. What it appears to do is to stimulate the expression of gene, apolipoprotein E or apoE. Bexarotene seems to switch apoE back on to a healthy level, which produces a protein that helps clear Aβ from the cells of the brain.

This discovery about bexarotene is truly exciting news in the field of Alzheimer’s research. In the final sentence of the report in Science, the authors conclude cautiously that “The ability of bexarotene to rapidly reverse a broad range of deficits suggests that…[it] may be of therapeutic utility in the treatment of AD…”

If you know someone dealing with AD—and who doesn’t?—this is a promising advance. It is critical, however, to stress that there are still key questions that must be answered before this finding changes the way AD is treated.

On the positive side, part of the excitement is that bexarotene is already FDA-approved. What about side effect? As the study puts it, bexarotene has “a favorable safety profile.” In other words, we already know that this drug is reasonably safe for human use.

But will it work? And if so, how long will it work in an individual AD patient before the benefits of the drug are no longer strong enough to off-set the progression of the disease?

Time will tell. For now, however, there’s new reason for hope in the face of one of our most dreaded diseases.

The article entitled "ApoE-directed Therapeutics Rapidly Clear β-amyloid and Reverse Deficits in AD Mouse Models” is published in the February 10 issue of Science, the journal of the American Association for the Advancement of Science.

Designer Babies Revisited

“Designer Babies” are back in the news. Scientists and medical experts in Australia have asked the government to allow the use of a controversial technique to allow couples to conceive without passing on a genetic disease.

The technique is controversial, at least in the media accounts, because the child that is conceived would have three parents.

The truth is a little more complicated but a lot less dramatic. Most of the genes in our cells are located in chromosomes, which we get from both our parents. A very few genes are located outside the chromosomes in small structures called mitochondria. These genes—our “mitochondrial DNA”—are necessary for energy production in the cell. If they are defective, the result can be a number of diseases.

We get our mitochondria only from our mothers. That means that if a woman has a defect in her mitochondrial DNA, she will inevitably pass it on to all her children, who may be more or less ill than she has been during her lifetime.

But what if a couple could conceive a child using their own chromosomal DNA while using a donor’s mitochondria? That would give the couple the best opportunity to have a child that is almost entirely “their own” genetically while avoiding diseases associated with mitochondrial irregularities. That’s the hope that doctors in Australia are holding out.

In 2001, word leaked out that a fertility clinic in New Jersey was quietly offering this technique. The report triggered a bit of a flap, mostly over issues of safety and the utter lack of government oversight or public moral reflection. The best account of that episode is found in an essay by Erik Parens and Eric Juengst, “Inadvertently Crossing the Germ Line,” appearing in the journal Science in April of 2001.

Is the strategy safe? Should it be permitted? Is it moral? Is “germline” modification in general ethically defensible? Is it religiously objectionable?

I try to address some of these questions in my 2008 collection of essays, Design and Destiny: Jewish and Christian Perspectives on Human Germline Modification. Among other findings: Catholic teachings may object to specific techniques but not so much to the core idea. As long is “in vitro” techniques are not used, what could be wrong with helping a couple conceive a healthy child? (See my earlier post.) But for all religious people, is there a line to be drawn between germline modification aimed at avoiding disease and the very same technique that might be used to produce a “better” child—one that is smarter or healthier than normal?

To be clear, the Australian scientists are proposing no such thing. But as they know, these techniques will likely advance along a common front. The minimal modification to avoid mitochondrial disorders will help pave the way to germline modification to avoid other diseases. And those techniques will almost certainly lead in time to the possibility of enhancing our offspring.