FDA = Big Brother

The New York Times reports that last week the FDA announced plans to regulate commercial genetics companies like 23andMe and deCODE. The agency sent (and posted) letters to five major genetics companies, claiming their services fall under the FDA designation of a “medical device” and must therefore be regulated federally. The FDA is calling on each company to either apply for federal approval or explain why they are exempt, igniting debates over how the dawning age of personal genetics will fit into existing structures of medical regulation.

Among the letter recipients are 23andMe, deCODE, and NaviGenetics, all companies that test for genetic variations linked to ancestry, disease susceptibility, and potential drug responses. Also tapped was Illumina Inc., a company that sells DNA chips for other companies to use (e.g. 23andMe uses customized versions of their chips), and Knome Inc., which offers complete genome sequencing and has scanned more genomes than any other company in the world. This round of letters wasn’t exactly unprecedented; last month, Pathway Genomics Corp., which markets an at-home saliva genetic test, received a similar letter.

We often report about new frontiers in the genetics revolution – the amazing success of prenatal screening, the dawn of synthetic genomics, chasing the causes of autism and developing new cancer treatments. The acceleration of discoveries in genetic technology is dizzying, and not just for the curious layperson. Legal and legislative institutions have faced the new challenge of making unprecedented decisions about how to regulate these emerging technologies. Can you patent a gene? Can employers or insurance companies peek at your genome? Or, in the present case, does a DNA kit count as a diagnostic tool? These are social, ethical, and political questions that didn’t exist twenty years ago, and our government has been scrambling to address them as they emerge.

The issue at the center of the FDA’s crackdown – what qualifies for federal regulation – has traditionally been determined by how widespread a device or service is.  Generally, FDA approval is required for any medical device that is widely distributed for use in laboratories, doctor’s offices, or sold in stores (Pathway was attempting to sell saliva kits – which we previously described in detail here at the Hub – at Walgreen drug stores).  Companies like 23andMe argue that their genotyping takes place in-house, and should therefore be exempt from federal red tape (the FDA pointed out that the company’s saliva kits are sold on Amazon). Esther Dyson, a board member at the company, has even called the FDA’s position “appallingly paternalistic.”

But distribution isn’t the only issue at stake.  A more interesting question is whether your personal genome is currently a tool for diagnosis – and if not, when it will be. As we’ve covered recently, the state of the union is less than perfect. Commercial genetics companies interpret their customers’ genomes by means of correlation studies; any particular genotype is “associated” with a disease because it is found in higher proportions within diseased populations. This kind of probabilistic genetics isn’t the same as understanding the molecular mechanisms by which genes act, much less the environmental factors involved in a final phenotype. Today, with a few exceptions, a genome scan cannot diagnose much more than statistical likelihoods.

But this will change. As genetic testing gets cheaper, research will accelerate and begin to unlock how gene expression contributes to certain diseases. As a genome scan becomes a real diagnostic tool, it will need to be regulated just as other medical devices are. In this sense, the FDA’s move is preemptive to the changes which will come. I’m tempted to think that 23andMe’s resistance has more to do with the open-source philosophy it shares with its partner, Google. It’s your genome, you should have unregulated access to it, etc. Putting peoples’ health into their own hands resonates well with the brave new world these companies envision: less top-down control, no Microsoft-esque middle man, don’t be evil, all that. The FDA here plays the part of big brother, prying into what is frankly between you and your commercial genetics provider.

Do we want a wild zone of laissez-faire freedom when it comes to genetic technology? Probably not. The industry is changing so rapidly, and in such unpredictable ways, that regulation will be essential to addressing the emerging ethical and social concerns that accompany such powerful technology. But the danger is that regulatory systems are inherently conservative, notoriously slow to adapt to rapidly changing fields – information technology and biotechnology being prime examples. Outdated and sluggish regulation will restrict innovation, slow progress, and increase costs in a tangle of decades-old red tape.  The FDA must coevolve to meet the unprecedented needs of regulating a fledgling market without clipping its wings.

Even if a genome scan can’t currently determine very much, that doesn’t mean people aren’t already making medical decisions based on their results. This trend will increase as our understanding of gene expression gets better. The accuracy of these tests should come under closer scrutiny as they become more and more instrumental to our diagnostic processes and healthcare decisions. Commercial testing will need to be regulated eventually – what remains to be seen is whether the FDA can adapt to this new landscape as fast as it changes.

C'mon girl, help me get a stem cell treatment!

What are these treatments promising? According to anecdotes, the results are amazing. Old dogs with bad hips frolic like puppies. Race horses with injuries come back to become world class winners. One such racehorse, Be A Bono, won 16 out of 24 starts, earned more than 1.3 million in prize money, and was the 2004 World Champion Quarterhorse. All after a stem cell treatment. The success stories with dogs are equally remarkable, if a little tinted by emotion; check out the video from Vet-Stem after the break.

Most animals that have been treated with stem cells suffer from joint ailments. Damage to cartilage, tendons, ligaments, or arthritic inflammation top the list. Stem cells are seen as a way to provide almost magical regenerative healing to combat these ailments. The process is actually pretty simple. Rather than embryonic stem cells, adult stem cells are used. These adult stem cells are harvested in a veterinary office from fat cells in the animal, and then sent to a lab. Processing separates out the stem cells from other cells, and a concentrated dose is sent back to the vet (The turn around time for processing is only a day). The adult cells are then injected into the animal in the area that needs regeneration.

Regulation does not necessarily stop research, but it tends to slow it down as it navigates bureaucracy. That’s where the helpful word “autologous” comes into play. An autologous transplant is one where the donor and the patient are the same organism: like a fat transplant from your buttocks to your lips, or like the horse and dog treatments we just discussed. Autologous transplants of stem cells in animals are not regulated by the federal government and this has led two competing companies, Vet-Stem and Vet-Cell, to specialize in providing veterinarians with stem cells for their equine and canine patients.

From the Horse’s Mouth

The anecdotal results may be hyperbolic, but the clinical numbers are no less noteworthy. In clinical trials by Vet-Stem, 66 horses were treated and 77% saw marked improvement and a return to racing. Vet-Cell’s trials used 82 horses and had a success rate of 78%. Critics are quick to point out that company run experiments are a far cry from double-blind clinical trials, but both companies have treated thousands of horses and are making huge strides into the small animal market (read here: dogs).

Equine results from the Vet-Cell website.

Of the 1500 veterinarians that Vet-Stem has trained to perform autologous stem cell transplants, more than 60% specialize in small animals. That means that most of the transplants have moved from equine athletes to canine companions. With a price tag less than $3000, the stem cell treatment is actually cheaper than many hip replacements surgeries for larger dogs (as much as $10k or so). As Vet-Stem and Vet-Cell promote the efficacy of the treatment, you can expect more and more dog owners to be stepping up and demanding it for their pets. Considering the attachment between pet and owner, it’s an easy sell.

The harder sell would be to convince academia to validate the clinical findings…or so you would think. But of the four U.S universities that have veterinary stem cell projects (UC Davis, Colorado State University, U Penn, and Cornell) all have expressed cautious optimism about the success of treatments on their test subjects. CSU treated 15 race horses and saw 10 return to active competition. Not quite the 78% success rate of Vet-Cell, but still impressive. The UC Davis Regenerative Medical Laboratory is expanding to accommodate more work in the area as well.

Which isn’t to say that anybody really knows how these autologous stem cell treatments actually work. There’s a large debate between scientists whether the stem cells are actively reassigning to become mature cells of different types (bone, ligament, etc) or whether their presence promotes healing by releasing cytokines (cell to cell communication chemicals). There’s even argument over which kind of adult stem cells to use. Vet-stem favors fat cells, while most of the universities favor bone marrow cells. Fat cells are more plentiful, but perhaps less potent. Marrow cells are more potent, but have to be cultured to provide enough for treatment. Definitive answers to these debates may take years to resolve, but that hasn’t stopped animals from being treated today.

It Really Gets My Goat

The first equine autologous procedure was performed around 1995 by Douglas Herthel DVM. He was reporting regular success by 2001. Be A Bono was treated and then became a champion in 2004. It’s now half way through 2009 and Vet-Stem and Vet-Cell are going strong. They train new veterinarians every year in the procedure and they can process dozens of sample each week. This is amazing technology, which still needs more testing, but right now is one of the more miraculous cures in veterinary medicine. Similar treatments for humans don’t exist yet. So your horse or dog can benefit, but you can’t.

There’s a lot of really great reasons why this is so. Human test subjects are not animal test subjects, and clinical trials for humans have to be more rigorous and take longer. Collecting and isolating adult stem cells in humans still needs more time to be perfected. This technology is largely focused on joint ailments, which are important for humans, but not life threatening as they are for horses and dogs.

There are also a lot of stupid reasons why autologous transplants are years behind in humans, mainly bureaucracy, debate, and fear. I can’t help but look at these veterinary treatments and feel disappointed and angry that similar treatments are not available for humans in the U.S. Perhaps that’s an ignorant reaction. Look at the progress being made in the animal trial stages for organ replacement, or even the madcap use of stem cells in other countries, however, and you get the feeling that caution in the United States is stifling our development.

Still, progress is being made. The British parent company of Vet-Cell is starting Med-Cell, and hopes to bring the autologous treatment to humans suffering from problems in the achilles tendon. The National Institute of Health is funding programs that will focus on bone marrow stem cell treatments for arthritis, and musculoskeletal and skin diseases. ABC news Nightline recently did a report on the veterinary treatments that raised awareness and sparked a lively debate on stem cells once again.

Most of the controversy on stem cells seemed to stem from the use of embryonic cells. George W. Bush banned such research in 2001, Barack Obama opened the research again in 2009 both with great hullabaloo. The use of embryonic stem cells, however, is just one option. Adult stem cells are also viable for treating illnesses as autologous veterinarian joint treatments show. As the success of stem cell treatments continue, I hope that the bureaucracy works to adapt (or minimize) regulation so that it can promote research while still maintaining the safety of the public. That public is clamoring for better, faster, and cheaper treatments that stem cells could provide. Throw us a frikin’ bone here.

Check out Beike BioTech, a bio-technology company in China that has “…treated over 2,000 patients with stem cell injections for diseases like Alzheimers, Ataxia, Autism, ALS, Brain Trauma, Cerebral Infarction, Cerebral Hemorrhage, Cerebral Palsy, Guillain-Barre, Encephalatropy, and Spinal Cord Injury”.

In the engineering world there is a common and powerful custom of developing solutions to problems simply by trying lots of things and seeing what works. Because of intense regulation in the United States it is not possible to just try random procedures or drugs on people to see what happens. In many cases this is for good reason, but a huge price is paid for this as valuable treatments are delayed or not even attempted.

In China, on the other hand, we are witnessing the power of trial and error medicine when it is not denied by regulation. People from all over the world are flying to China to companies such as Beike to pay for experimental and unproven medical treatment for some of the world’s most terrifying diseases. Beike even admits on its own website that the benefits of their stem cell treatments may be questionable for many of their patients. But if you have the money and you have no other options to treat your severely debilitating illness then Beike is happy to give you that small glimmer of hope.

Using humans as laboratory mice certainly has its moral hazards, but it also holds great power as a tool for medical innovation. The United States might win the game of morals, but we can increasingly expect many of the greatest achievements in the game of medical breakthroughs to come from places like China where morals are seen differently.

On a related note I was recently speaking to my neighbor who is a specialist in developing drugs for cancer treatment. He will soon be moving back to China after living in the United States for 20 years. Why? Because he says he can’t get anything done here in the United States. By going to China he will have an ample supply of patients to try his drugs on and few regulations to limit his ability to experiment.