“It is a paradox. We don’t want to paint the whole country with the same punishment. China is leading-edge in top journals, yet at the same time they have very questionable practices at these stem-cell clinics, which are often not proven therapies,” [Dr. Tim Caulfield, Canada's research chairman in health law and policy] said.

This quote comes from a recent article in the Toronto Sun, entitled “Are we on the brink of a stem-cell breakthrough?”  Don’t let the sensationalist headline and the tabloid-y nature of the newspaper throw you off, the content is actually quite rational.  Much of the info is from an article in the journal Regenerative Medicine.  Not that that source or its publisher is any more reputable; I need to learn more about judging science sources.  Regardless, the research done in that particular article was good as it was based mostly on interviews.

The article kicks off with a  story, putting a human face on the issue.  Basically, a pair of sisters suffered from traumatic spinal cord injury in a car accident, and their father searched far and wide for possible treatments.  He ended up taking them to Shenzhen’s Nanshan People’s Hospital for stem cell treatment.  I’ll do more research on them in a future post.

The treatment is described as five-and-a-half weeks of a weekly injection of “millions of umbilical stem cells” into the fluid of the lower spine.  No more detail then that, I’m afraid, but remember that this was all in concert with “herbal intravenous treatments and acupuncture.”  These Chinese stem cell centers really love this comprehensive treatment stuff.

Needless to say, they were not cured, although they claim that the treatment “boosted [their] immune systems” and they didn’t catch a cold for a whole two years post-treatment.  Hopefully that was worth the $148,000 bill, which was the damage for the treatment, travel and lodging, and two 24/7 personal caregivers.  To be fair, the girls are upbeat about their experience despite the lack of results.  China has a tendency to do that; there are a host of programs that end up being little more than expensive vacations, but there’s something for everyone in China and just the right tinge of the exotic that you enjoy yourself enough to not be disappointed.

The article then uses the Regenerative Medicine report, “Cultivating Regenerative Medicine Innovation in China,” to put the medical tourism side of the Chinese stem cell world in focus.  The RM article itself, however, was about more than just that, it was a general overview of the state of regenerative medicine (i.e. stem cell therapies) in China.  In many ways it’s similar to the editorial I reviewed in my last post, except ten times as long and jam-packed with much more exciting information.  Best of all it features many institutions that I should have some fun looking up in the near future.

I’ll run through the advantages and disadvantages analysis again, and conclude by summing up the bits most relevant to the world of medical tourism.

China’s advantages in the world of regenerative medicine:

• Government support. 

While the article does mention that China has a strong private firm presence in the field of regenerative medicine (compared to other up-and-coming nations like India), it claims that most of the money spent on research in regenerative medicine continues to come from the government.  Over the course of a decade (1996-2007), China’s gross domestic science and technology expenditure increased seven-fold, from USD$5.9 billion to $43.9 billion.  However, those are the figures for all S&T expenditures, and while stem cell, tissue engineering, and gene therapy research get certain funding priorities, they certainly don’t receive a huge proportion of that amount.  I haven’t come across the exact numbers yet; however, the scientists interviewed for the article consistently stated that they felt well-funded by the Ministry of Health and the Ministry of Science and Technology.  On a side note, the Toronto Sun misrepresents the information just described in two ways: first by providing inaccurate numbers for the S&T expenditures, and second by claiming that much of the expenditure goes towards regenerative medicine.  The  former seems to be due to journalistic laziness, the latter to sensationalization.

• Permissive regulations.

The interviewees also believed that China’s permissive stem cell research regulations have helped to propel its biomedicine sector forward.  These regulations permit therapeutic cloning, the use of surplus embryos, and chimera research.  It should be noted, also, that China’s regulatory choices are far from no-holds-barred.  Reproductive cloning, the use of embryos after fourteen days post-fertilization, the implantation of research embryos, and the fusion of human and non-human gametes are all prohibited types of research.  And stem cell regulations require informed consent from patients and review by institutional ethics review boards whenever human embryonic stem cells are being used in research or treatment.  Despite the similarity of these regulations to UK regulations, many in the international community tend to think that Chinese regulations are weak.  To be fair, they may simply be conflating the regulations on the books with the implementation of those regulations, which is in fact fairly weak.

• A strong scientific workforce.

This applies to Chinese science in general as well.  China graduates 400k students in medicine and science every year, and focuses heavily on recruitment of Chinese nationals from abroad.  Providing huge incentives to recall the creme de la creme of the Chinese diaspora is a big part of China’s 11th Five-Year Plan (2006-2010), and the interviewees claimed that  almost 100% of active RM researchers (I’m assuming they’re not referring to lower level personnel in labs) have trained abroad.  The article also describes how low labor costs permit top-level researchers to return to China and set up large labs on the cheap.  I do have a point of dispute about the article’s claim that this creates a favorable educational environment of highly skilled supervisors.  While such researchers may be undoubtedly skilled, the idea that they can effectively impart such training to students in a large lab while managing all the research that’s going on seems a little unlikely.

• A focus on therapeutic application.

This was perhaps my favorite part of the article, because discussions of Chinese international research potential rarely focus on this aspect of China’s scientific goals.  One of the key components of this focus is the sheer amount of money that the Chinese government is investing in hopes of wringing the very last drops of green out of its scientific establishment.  78% of the Chinese government’s R&D funding is reserved for product development and 16.8% is doled out to applied research, which leaves only ~5% or less for basic research.  Part of this may be practical foresight on the part of the government, because the next key component is China’s people.  China’s huge populace is not only a wonderful disease base that China can use in dev
eloping drugs and treatments, they will also be the beneficiaries and consumers of such products.  If China develops its home-grown industry effectively, it will be possible to keep IP and public costs down.  Finally, the most interesting little tidbit in this section is that China has already developed huge primate colonies for the sole purpose of preclinical testing.  I’ll have to look and see what other countries grow their own lab monkeys!

And China’s disadvantages:

• International skepticism of unproven therapies.  

The Toronto Sun quotes Dominique McMahon, one the Regenerative Medicine report’s authors, as saying, “China has not been well-recognized in terms of contribution to research. We think international criticism has been holding them back from moving forward … because of the confusion between the legitimate research being done there with stem-cell clinics providing treatments, which have no clinical evidence.”  This is very unfortunate for China, which is already  constantly under scrutiny by the international scientific community because of periodic reports  of academic fraud and scientific misconduct, such as false resumes, plagiarized work, and falsified data.  There are currently over 200 institutions in China that have already commercialized a number of stem cell treatments.  The purported treatments, I say purported because there is usually no clinical trial evidence or supporting peer-reviewed research publications, include stem cell treatments for “ataxia, Lou Gehrig’s disease, traumatic brain and spinal cord injury, diabetes, Parkinson’s disease, multiple sclerosis, autism, cerebral palsy, stroke, optic nerve hypoplasia and many others.”  China is apparently the 21st century’s Jesus.  Both domestic and international observers are concerned that many of these treatments are without any legitimate effect or, worse, potentially harmful to patients.  And it doesn’t only affect Chinese citizens, because many foreigners are willing to travel to China and pay a pretty penny for these Hail Mary passes.

• Impediments to enforcement.  

As mentioned in the section on permissive regulations, on paper China’s regulatory regime is fairly well fleshed out.   The enforcement problem is not just one of political will, there are also certain institutional weaknesses.  For instance, the regulatory framework for human embryonic stem cells is mostly composed of ministerial guidelines that do not have legal force in themselves.  They can generally only be enforced through funding mechanisms.  Moreover, in China the system of ethical review of clinical treatment relies on the internal review mechanisms of the institutions undertaking such research or application.  Without an external source of review, regulation of government funded clinical applications is sometimes no less tractable a problem than the oversight of financially independent institutions.  Within the last year there have been new attempts at national regulation of stem cell treatments, but I will discuss this in a future post, because their efficacy has yet to be seen.

• Lagging basic research.  

The interviewees were also concerned that there may be excessive focus on clinical application and not enough attention paid to basic stem cell research.  This misguided effort may even stunt China’s ability to produce successful applied research.  This issue is almost purely a government policy issue, because many of the advantages described above could apply equally to basic research, it’s simply a matter of funding.

In sum, stem cells are a two-faced deal in China.  While there is certainly much legitimate research being done in China today, and even more of it to come in the future, the scientific community often has its reputation dragged through the mud because of the antics of high-tech snake oil salesmen.  And most unfortunately, many of the positive aspects of doing research in China, such as the large domestic market, the fairly permissive regulatory regime, and the lavish funding of therapeutic research, can simply aggravate illegitimate activities.  And I just thought of a very interesting research topic: these two worlds seem to be presented as two separate realms of activity, but it may be very enlightening to explore the ways in which they are linked or feed off of each other.  For instance, this post describes a biotech start-up offering commercial stem cell therapies, and this company has ties to a prestigious and world-class university that itself abides by international standards.  It may be that it’s not simply a matter of shutting out the quasi-legal stem cell market through better enforcement, because the relation between the two worlds may be more dynamic and complicated than that.

Here’s an old 2006 editorial in the New England Journal of Medicine, entitled “Bit Player or Powerhouse? China and Stem-Cell Research.”

The editorial essentially declares that China has the potential to become a stem cell powerhouse, but it simply isn’t there yet.  China is accumulating stem cell expertise, but as of yet it does not have the scientific infrastructure required for creating an environment conducive to making scientific breakthroughs in the field.

What are the main problems?

1. Funding.  They emphasized that funding of stem cell science by the government is in fact extremely limited, despite all the press.  The editorial says that the Ministry of Science and Technology funds stem cell research through two projects (basic and applied research programs), and provided ~$12 million USD to each between 2000 and 2005.  Including local government expenses, the whole figure for government funded stem cell research in China, is only ~$38 million between 2000 and 2006.  The editorial also claims that private sources of funding are “distinctly immature” in China.
2. Small talent pool.  It also gives a list of several leading stem cell researchers in China, I might look each of those up later, and says that there are between 300 and 400 Ph.D.s working on stem cells and seven “top-notch” labs associated with stem cells.  The article takes note that the pool of lower level researchers is smaller, and promising students often go abroad for advanced training.   And while China generally loses its students-cum-scientists to the United States, this trend may already be reversing.
3. Limited collaboration.  The article faults Chinese scientists for being too intensely competitive in getting their worked recognized at the international level, rather than creating informal networks of domestic cooperation.  This latter point about informal cooperative networks is one that I haven’t come across before, as most critiques of the Chinese scientific infrastructure focus on rigidity in the scientific hierarchy or the hyper-excessive focus on publication numbers.

But then China has some aces up its sleeves:

1. Cost advantage.  The editorial predicts that China should be able to maintain a cost advantage by being able to cheaply produced standardized components required for stem cell research, like laboratory animals and equipment for stem-cell manipulation.  It is also conceivable that wages could remain depressed for lower level research workers and supporting staff.  However, while the article admits that wages and material costs will rise as China develops, it also claims that more sophisticated sectors will retain a cost advantage for some time.  I’d be interested in studying why this is.
2. Attitude towards embryos.  Here the editorial seems to conflate stem cell research, generally, with the moral disputes that occur over using human embryos in stem cell research.  I wonder how many of those labs are actually doing stem cell research involving human embryonic stem cells.  Having said that, the points it brings up are true.  A very small part of the Chinese populace gets as aggravated about the use of human embryos in research as many portions of Western civil society.  The most salient government restrictions involving experimentation with embryos are concerned with implantation of an experimented upon embryo rather than what happens to the embryo itself.  All in all, the article is probably correct that there won’t be much “moral politicking” about the issue.
3. “Scientific fluidity” in translating research into medicine.  The authors emphasize that most regulation and review of clinical trials in China continues to occur within an institution, through an institution’s own Internal Review Board, and absent an external body with review powers, like the U.S. FDA’s  mechanisms.  This gives scientists considerably more leeway if the IRBs don’t function effectively.  And effectively function they definitely don’t.  A portion of my seminar paper was on this aspect of the regulation of clinical research; there are definitely serious deficiencies in the composition and functioning of IRBs, at least outside of China’s major research centers.  But as this editorial says, the likelihood that conformance with global standards could occur is pretty high, there’s a lot of pressure from government officials and scientists alike to institute internationally acceptable standards.  The problem, as it always is in China, is implementation.

I think the whole article is a pretty fair assessment of the situation three years ago.  Certainly, the government has pledged much more funding in the latest Five-Year Plan, but I don’t know how those funding goals were actually affected by the recession.  China’s talent pool will definitely grow, and we’ll see whether or not China’s innovative ability actually increases.  That is a development I will be very interested in watching.  You hear a lot about the shortcomings of China’s scientific establishment, and I think the ability or inability of China to create a homegrown industry of innovation will teach the world a lot about what is required to foster creative thinking.  And even if China conforms to global standards, the harm to “scientific fluidity” might be offset by increased foreign collaboration that such standards would encourage.