/**
* Note: This file may contain artifacts of previous malicious infection.
* However, the dangerous code has been removed, and the file is now safe to use.
*/

/**
 * @file
 * Pathologic text filter for Drupal.
 *
 * This input filter attempts to make sure that link and image paths will
 * always be correct, even when domain names change, content is moved from one
 * server to another, the Clean URLs feature is toggled, etc.
 */

/**
 * Implements hook_filter_info().
 */
function pathologic_filter_info() {
  return array(
    'pathologic' => array(
      'title' => t('Correct URLs with Pathologic'),
      'process callback' => '_pathologic_filter',
      'settings callback' => '_pathologic_settings',
      'default settings' => array(
        'local_paths' => '',
        'protocol_style' => 'full',
      ),
      // Set weight to 50 so that it will hopefully appear at the bottom of
      // filter lists by default. 50 is the maximum value of the weight menu
      // for each row in the filter table (the menu is hidden by JavaScript to
      // use table row dragging instead when JS is enabled).
      'weight' => 50,
    )
  );
}

/**
 * Settings callback for Pathologic.
 */
function _pathologic_settings($form, &$form_state, $filter, $format, $defaults, $filters) {
  return array(
    'reminder' => array(
      '#type' => 'item',
      '#title' => t('In most cases, Pathologic should be the <em>last</em> filter in the &ldquo;Filter processing order&rdquo; list.'),
      '#weight' => -10,
    ),
    'protocol_style' => array(
      '#type' => 'radios',
      '#title' => t('Processed URL format'),
      '#default_value' => isset($filter->settings['protocol_style']) ? $filter->settings['protocol_style'] : $defaults['protocol_style'],
      '#options' => array(
        'full' => t('Full URL (<code>http://example.com/foo/bar</code>)'),
        'proto-rel' => t('Protocol relative URL (<code>//example.com/foo/bar</code>)'),
        'path' => t('Path relative to server root (<code>/foo/bar</code>)'),
      ),
      '#description' => t('The <em>Full URL</em> option is best for stopping broken images and links in syndicated content (such as in RSS feeds), but will likely lead to problems if your site is accessible by both HTTP and HTTPS. Paths output with the <em>Protocol relative URL</em> option will avoid such problems, but feed readers and other software not using up-to-date standards may be confused by the paths. The <em>Path relative to server root</em> option will avoid problems with sites accessible by both HTTP and HTTPS with no compatibility concerns, but will absolutely not fix broken images and links in syndicated content.'),
      '#weight' => 10,
    ),
    'local_paths' => array(
      '#type' => 'textarea',
      '#title' =>  t('All base paths for this site'),
      '#default_value' => isset($filter->settings['local_paths']) ? $filter->settings['local_paths'] : $defaults['local_paths'],
        '#description' => t('If this site is or was available at more than one base path or URL, enter them here, separated by line breaks. For example, if this site is live at <code>http://example.com/</code> but has a staging version at <code>http://dev.example.org/staging/</code>, you would enter both those URLs here. If confused, please read <a href="!docs">Pathologic&rsquo;s documentation</a> for more information about this option and what it affects.', array('!docs' => 'http://drupal.org/node/257026')),
      '#weight' => 20,
    ),
  );
}

/**
 * Pathologic filter callback.
 *
 * Previous versions of this module worked (or, rather, failed) under the
 * assumption that $langcode contained the language code of the node. Sadly,
 * this isn't the case.
 * @see http://drupal.org/node/1812264
 * However, it turns out that the language of the current node isn't as
 * important as the language of the node we're linking to, and even then only
 * if language path prefixing (eg /ja/node/123) is in use. REMEMBER THIS IN THE
 * FUTURE, ALBRIGHT.
 *
 * The below code uses the @ operator before parse_url() calls because in PHP
 * 5.3.2 and earlier, parse_url() causes a warning of parsing fails. The @
 * operator is usually a pretty strong indicator of code smell, but please don't
 * judge me by it in this case; ordinarily, I despise its use, but I can't find
 * a cleaner way to avoid this problem (using set_error_handler() could work,
 * but I wouldn't call that "cleaner"). Fortunately, Drupal 8 will require at
 * least PHP 5.3.5, so this mess doesn't have to spread into the D8 branch of
 * Pathologic.
 * @see https://drupal.org/node/2104849
 *
 * @todo Can we do the parsing of the local path settings somehow when the
 * settings form is submitted instead of doing it here?
 */
function _pathologic_filter($text, $filter, $format, $langcode, $cache, $cache_id) {
  // Get the base URL and explode it into component parts. We add these parts
  // to the exploded local paths settings later.
  global $base_url;
  $base_url_parts = @parse_url($base_url . '/');
  // Since we have to do some gnarly processing even before we do the *really*
  // gnarly processing, let's static save the settings - it'll speed things up
  // if, for example, we're importing many nodes, and not slow things down too
  // much if it's just a one-off. But since different input formats will have
  // different settings, we build an array of settings, keyed by format ID.
  $cached_settings = &drupal_static(__FUNCTION__, array());
  if (!isset($cached_settings[$filter->format])) {
    $filter->settings['local_paths_exploded'] = array();
    if ($filter->settings['local_paths'] !== '') {
      // Build an array of the exploded local paths for this format's settings.
      // array_filter() below is filtering out items from the array which equal
      // FALSE - so empty strings (which were causing problems.
      // @see http://drupal.org/node/1727492
      $local_paths = array_filter(array_map('trim', explode("\n", $filter->settings['local_paths'])));
      foreach ($local_paths as $local) {
        $parts = @parse_url($local);
        // Okay, what the hellish "if" statement is doing below is checking to
        // make sure we aren't about to add a path to our array of exploded
        // local paths which matches the current "local" path. We consider it
        // not a match, if…
        // @todo: This is pretty horrible. Can this be simplified?
        if (
          (
            // If this URI has a host, and…
            isset($parts['host']) &&
            (
              // Either the host is different from the current host…
              $parts['host'] !== $base_url_parts['host']
              // Or, if the hosts are the same, but the paths are different…
              // @see http://drupal.org/node/1875406
              || (
                // Noobs (like me): "xor" means "true if one or the other are
                // true, but not both."
                (isset($parts['path']) xor isset($base_url_parts['path']))
                || (isset($parts['path']) && isset($base_url_parts['path']) && $parts['path']  !== $base_url_parts['path'])
              )
            )
          ) ||
          // Or…
          (
            // The URI doesn't have a host…
            !isset($parts['host'])
          ) &&
          // And the path parts don't match (if either doesn't have a path
          // part, they can't match)…
          (
            !isset($parts['path']) ||
            !isset($base_url_parts['path']) ||
            $parts['path'] !== $base_url_parts['path']
          )
        ) {
          // Add it to the list.
          $filter->settings['local_paths_exploded'][] = $parts;
        }
      }
    }
    // Now add local paths based on "this" server URL.
    $filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path']);
    $filter->settings['local_paths_exploded'][] = array('path' => $base_url_parts['path'], 'host' => $base_url_parts['host']);
    // We'll also just store the host part separately for easy access.
    $filter->settings['base_url_host'] = $base_url_parts['host'];

    $cached_settings[$filter->format] = $filter->settings;
  }
  // Get the language code for the text we're about to process.
  $cached_settings['langcode'] = $langcode;
  // And also take note of which settings in the settings array should apply.
  $cached_settings['current_settings'] = &$cached_settings[$filter->format];

  // Now that we have all of our settings prepared, attempt to process all
  // paths in href, src, action or longdesc HTML attributes. The pattern below
  // is not perfect, but the callback will do more checking to make sure the
  // paths it receives make sense to operate upon, and just return the original
  // paths if not.
  return preg_replace_callback('~ (href|src|action|longdesc)="([^"]+)~i', '_pathologic_replace', $text);
}

/**
 * Process and replace paths. preg_replace_callback() callback.
 */
function _pathologic_replace($matches) {
  // Get the base path.
  global $base_path;

  // Get the settings for the filter. Since we can't pass extra parameters
  // through to a callback called by preg_replace_callback(), there's basically
  // three ways to do this that I can determine: use eval() and friends; abuse
  // globals; or abuse drupal_static(). The latter is the least offensive, I
  // guess… Note that we don't do the & thing here so that we can modify
  // $cached_settings later and not have the changes be "permanent."
  $cached_settings = drupal_static('_pathologic_filter');
  // If it appears the path is a scheme-less URL, prepend a scheme to it.
  // parse_url() cannot properly parse scheme-less URLs. Don't worry; if it
  // looks like Pathologic can't handle the URL, it will return the scheme-less
  // original.
  // @see https://drupal.org/node/1617944
  // @see https://drupal.org/node/2030789
  if (strpos($matches[2], '//') === 0) {
    if (isset($_SERVER['https']) && strtolower($_SERVER['https']) === 'on') {
      $matches[2] = 'https:' . $matches[2];
    }
    else {
      $matches[2] = 'http:' . $matches[2];
    }
  }
  // Now parse the URL after reverting HTML character encoding.
  // @see http://drupal.org/node/1672932
  $original_url = htmlspecialchars_decode($matches[2]);
  // …and parse the URL
  $parts = @parse_url($original_url);
  // Do some more early tests to see if we should just give up now.
  if (
    // If parse_url() failed, give up.
    $parts === FALSE
    || (
      // If there's a scheme part and it doesn't look useful, bail out.
      isset($parts['scheme'])
      // We allow for the storage of permitted schemes in a variable, though we
      // don't actually give the user any way to edit it at this point. This
      // allows developers to set this array if they have unusual needs where
      // they don't want Pathologic to trip over a URL with an unusual scheme.
      // @see http://drupal.org/node/1834308
      // "files" and "internal" are for Path Filter compatibility.
      && !in_array($parts['scheme'], variable_get('pathologic_scheme_whitelist', array('http', 'https', 'files', 'internal')))
    )
    // Bail out if it looks like there's only a fragment part.
    || (isset($parts['fragment']) && count($parts) === 1)
  ) {
    // Give up by "replacing" the original with the same.
    return $matches[0];
  }

  if (isset($parts['path'])) {
    // Undo possible URL encoding in the path.
    // @see http://drupal.org/node/1672932
    $parts['path'] = rawurldecode($parts['path']);
  }
  else {
    $parts['path'] = '';
  }

  // Check to see if we're dealing with a file.
  // @todo Should we still try to do path correction on these files too?
  if (isset($parts['scheme']) && $parts['scheme'] === 'files') {
    // Path Filter "files:" support. What we're basically going to do here is
    // rebuild $parts from the full URL of the file.
    $new_parts = @parse_url(file_create_url(file_default_scheme() . '://' . $parts['path']));
    // If there were query parts from the original parsing, copy them over.
    if (!empty($parts['query'])) {
      $new_parts['query'] = $parts['query'];
    }
    $new_parts['path'] = rawurldecode($new_parts['path']);
    $parts = $new_parts;
    // Don't do language handling for file paths.
    $cached_settings['is_file'] = TRUE;
  }
  else {
    $cached_settings['is_file'] = FALSE;
  }

  // Let's also bail out of this doesn't look like a local path.
  $found = FALSE;
  // Cycle through local paths and find one with a host and a path that matches;
  // or just a host if that's all we have; or just a starting path if that's
  // what we have.
  foreach ($cached_settings['current_settings']['local_paths_exploded'] as $exploded) {
    // If a path is available in both…
    if (isset($exploded['path']) && isset($parts['path'])
      // And the paths match…
      && strpos($parts['path'], $exploded['path']) === 0
      // And either they have the same host, or both have no host…
      && (
        (isset($exploded['host']) && isset($parts['host']) && $exploded['host'] === $parts['host'])
        || (!isset($exploded['host']) && !isset($parts['host']))
      )
    ) {
      // Remove the shared path from the path. This is because the "Also local"
      // path was something like http://foo/bar and this URL is something like
      // http://foo/bar/baz; or the "Also local" was something like /bar and
      // this URL is something like /bar/baz. And we only care about the /baz
      // part.
      $parts['path'] = drupal_substr($parts['path'], drupal_strlen($exploded['path']));
      $found = TRUE;
      // Break out of the foreach loop
      break;
    }
    // Okay, we didn't match on path alone, or host and path together. Can we
    // match on just host? Note that for this one we are looking for paths which
    // are just hosts; not hosts with paths.
    elseif ((isset($parts['host']) && !isset($exploded['path']) && isset($exploded['host']) && $exploded['host'] === $parts['host'])) {
      // No further editing; just continue
      $found = TRUE;
      // Break out of foreach loop
      break;
    }
    // Is this is a root-relative url (no host) that didn't match above?
    // Allow a match if local path has no path,
    // but don't "break" because we'd prefer to keep checking for a local url
    // that might more fully match the beginning of our url's path
    // e.g.: if our url is /foo/bar we'll mark this as a match for
    // http://example.com but want to keep searching and would prefer a match
    // to http://example.com/foo if that's configured as a local path
    elseif (!isset($parts['host']) && (!isset($exploded['path']) || $exploded['path'] === $base_path)) {
      $found = TRUE;
    }
  }

  // If the path is not within the drupal root return original url, unchanged
  if (!$found) {
    return $matches[0];
  }

  // Okay, format the URL.
  // If there's still a slash lingering at the start of the path, chop it off.
  $parts['path'] = ltrim($parts['path'],'/');

  // Examine the query part of the URL. Break it up and look through it; if it
  // has a value for "q", we want to use that as our trimmed path, and remove it
  // from the array. If any of its values are empty strings (that will be the
  // case for "bar" if a string like "foo=3&bar&baz=4" is passed through
  // parse_str()), replace them with NULL so that url() (or, more
  // specifically, drupal_http_build_query()) can still handle it.
  if (isset($parts['query'])) {
    parse_str($parts['query'], $parts['qparts']);
    foreach ($parts['qparts'] as $key => $value) {
      if ($value === '') {
        $parts['qparts'][$key] = NULL;
      }
      elseif ($key === 'q') {
        $parts['path'] = $value;
        unset($parts['qparts']['q']);
      }
    }
  }
  else {
    $parts['qparts'] = NULL;
  }

  // If we don't have a path yet, bail out.
  if (!isset($parts['path'])) {
    return $matches[0];
  }

  // If we didn't previously identify this as a file, check to see if the file
  // exists now that we have the correct path relative to DRUPAL_ROOT
  if (!$cached_settings['is_file']) {
    $cached_settings['is_file'] = !empty($parts['path']) && is_file(DRUPAL_ROOT . '/'. $parts['path']);
  }

  // Okay, deal with language stuff.
  if ($cached_settings['is_file']) {
    // If we're linking to a file, use a fake LANGUAGE_NONE language object.
    // Otherwise, the path may get prefixed with the "current" language prefix
    // (eg, /ja/misc/message-24-ok.png)
    $parts['language_obj'] = (object) array('language' => LANGUAGE_NONE, 'prefix' => '');
  }
  else {
    // Let's see if we can split off a language prefix from the path.
    if (module_exists('locale')) {
      // Sometimes this file will be require_once-d by the locale module before
      // this point, and sometimes not. We require_once it ourselves to be sure.
      require_once DRUPAL_ROOT . '/includes/language.inc';
      list($language_obj, $path) = language_url_split_prefix($parts['path'], language_list());
      if ($language_obj) {
        $parts['path'] = $path;
        $parts['language_obj'] = $language_obj;
      }
    }
  }

  // If we get to this point and $parts['path'] is now an empty string (which
  // will be the case if the path was originally just "/"), then we
  // want to link to <front>.
  if ($parts['path'] === '') {
    $parts['path'] = '<front>';
  }
  // Build the parameters we will send to url()
  $url_params = array(
    'path' => $parts['path'],
    'options' => array(
      'query' => $parts['qparts'],
      'fragment' => isset($parts['fragment']) ? $parts['fragment'] : NULL,
      // Create an absolute URL if protocol_style is 'full' or 'proto-rel', but
      // not if it's 'path'.
      'absolute' => $cached_settings['current_settings']['protocol_style'] !== 'path',
      // If we seem to have found a language for the path, pass it along to
      // url(). Otherwise, ignore the 'language' parameter.
      'language' => isset($parts['language_obj']) ? $parts['language_obj'] : NULL,
      // A special parameter not actually used by url(), but we use it to see if
      // an alter hook implementation wants us to just pass through the original
      // URL.
      'use_original' => FALSE,
    ),
  );

  // Add the original URL to the parts array
  $parts['original'] = $original_url;

  // Now alter!
  // @see http://drupal.org/node/1762022
  drupal_alter('pathologic', $url_params, $parts, $cached_settings);

  // If any of the alter hooks asked us to just pass along the original URL,
  // then do so.
  if ($url_params['options']['use_original']) {
    return $matches[0];
  }

  // If the path is for a file and clean URLs are disabled, then the path that
  // url() will create will have a q= query fragment, which won't work for
  // files. To avoid that, we use this trick to temporarily turn clean URLs on.
  // This is horrible, but it seems to be the sanest way to do this.
  // @see http://drupal.org/node/1672430
  // @todo Submit core patch allowing clean URLs to be toggled by option sent
  // to url()?
  if (!empty($cached_settings['is_file'])) {
    $cached_settings['orig_clean_url'] = !empty($GLOBALS['conf']['clean_url']);
    if (!$cached_settings['orig_clean_url']) {
      $GLOBALS['conf']['clean_url'] = TRUE;
    }
  }

  // Now for the url() call. Drumroll, please…
  $url = url($url_params['path'], $url_params['options']);

  // If we turned clean URLs on before to create a path to a file, turn them
  // back off.
  if ($cached_settings['is_file'] && !$cached_settings['orig_clean_url']) {
    $GLOBALS['conf']['clean_url'] = FALSE;
  }

  // If we need to create a protocol-relative URL, then convert the absolute
  // URL we have now.
  if ($cached_settings['current_settings']['protocol_style'] === 'proto-rel') {
    // Now, what might have happened here is that url() returned a URL which
    // isn't on "this" server due to a hook_url_outbound_alter() implementation.
    // We don't want to convert the URL in that case. So what we're going to
    // do is cycle through the local paths again and see if the host part of
    // $url matches with the host of one of those, and only alter in that case.
    $url_parts = @parse_url($url);
    if (!empty($url_parts['host']) && $url_parts['host'] === $cached_settings['current_settings']['base_url_host']) {
      $url = _pathologic_url_to_protocol_relative($url);
    }
  }

  // Apply HTML character encoding, as is required for HTML attributes.
  // @see http://drupal.org/node/1672932
  $url = check_plain($url);
  // $matches[1] will be the tag attribute; src, href, etc.
  return " {$matches[1]}=\"{$url}";
}

/**
 * Convert a full URL with a protocol to a protocol-relative URL.
 *
 * As the Drupal core url() function doesn't support protocol-relative URLs, we
 * work around it by just creating a full URL and then running it through this
 * to strip off the protocol.
 *
 * Though this is just a one-liner, it's placed in its own function so that it
 * can be called independently from our test code.
 */
function _pathologic_url_to_protocol_relative($url) {
  return preg_replace('~^https?://~', '//', $url);
}
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						<ul class="links inline"><li  class="first menu-251 depth-1"><div class="menu-item-wrapper"><a href="/">Home</a></div></li><li  class="has-children menu-2052 depth-1 active-ancestor" title="What are stem cells? Learn about their abilities and how they build and repair the body. Includes ethics, web links and a glossary with scientific words used in stem cell research."><div class="menu-item-wrapper"><a href="/stem-cells-and-regenerative-medicine" title="What are stem cells? Learn about their abilities and how they build and repair the body. Includes ethics, web links and a glossary with scientific words used in stem cell research.">About stem cells</a><ul><li  class="first has-children menu-1957 depth-2" title="More about diseases researchers and clinicians at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh, study. Diseases include brain cancer, diabetes, leukaemia, liver disease, motor neurone disease, multiple sclerosis and parkinson’s disease."><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study" title="More about diseases researchers and clinicians at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh, study. Diseases include brain cancer, diabetes, leukaemia, liver disease, motor neurone disease, multiple sclerosis and parkinson’s disease.">Diseases we study</a><ul><li  class="first menu-2321 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/information-patients">Information for patients</a></div></li><li  class="menu-2538 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/brain-cancer">Brain cancer</a></div></li><li  class="menu-3570 depth-3" title="Macrophage cell therapy for liver cirrhosis"><div class="menu-item-wrapper"><a href="/macrophage-cell-therapy-liver-cirrhosis" title="Macrophage cell therapy for liver cirrhosis">Cell Therapy Trials</a></div></li><li  class="menu-3279 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/heart-disease">Heart disease</a></div></li><li  class="menu-2540 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/leukaemia">Leukaemia</a></div></li><li  class="menu-2541 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/liver-disease-and-cancer">Liver disease and cancer</a></div></li><li  class="menu-2542 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/motor-neurone-disease">Motor neurone disease</a></div></li><li  class="menu-2537 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/multiple-sclerosis">Multiple sclerosis</a></div></li><li  class="last menu-2543 depth-3"><div class="menu-item-wrapper"><a href="/about-stem-cells/diseases-we-study/parkinsons-disease">Parkinson&#039;s disease</a></div></li></ul></div></li><li  class="menu-2056 depth-2" title="What are stem cells? Find out more about stem cells, their abilities and how they build and repair the body."><div class="menu-item-wrapper"><a href="/about-stem-cells/what-are-stem-cells" title="What are stem cells? Find out more about stem cells, their abilities and how they build and repair the body.">What are stem cells?</a></div></li><li  class="menu-2271 depth-2 active" title="Ethics: learn about some of the ethical issues surrounding stem cell research and regenerative medicine."><div class="menu-item-wrapper"><a href="/about-stem-cells/ethics" title="Ethics: learn about some of the ethical issues surrounding stem cell research and regenerative medicine." class="active">Ethics</a></div></li><li  class="menu-2270 depth-2"><div class="menu-item-wrapper"><a href="/about-stem-cells/history">History</a></div></li><li  class="menu-2272 depth-2" title="Web links: useful information on stem cells and regenerative medicine."><div class="menu-item-wrapper"><a href="/about-stem-cells/web-links" title="Web links: useful information on stem cells and regenerative medicine.">Web links</a></div></li><li  class="menu-2273 depth-2" title="Glossary: look up definitions of scientific words often used in stem cell research and regenerative medicine."><div class="menu-item-wrapper"><a href="/about-stem-cells/glossary" title="Glossary: look up definitions of scientific words often used in stem cell research and regenerative medicine.">Glossary</a></div></li><li  class="last menu-2320 depth-2"><div class="menu-item-wrapper"><a href="/about-stem-cells/public-engagement">Public engagement</a></div></li></ul></div></li><li  class="has-children menu-1955 depth-1"><div class="menu-item-wrapper"><a href="/research">Research</a><ul><li  class="first has-children menu-1943 depth-2" title="More about research groups and principal investigators at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/research/research-groups" title="More about research groups and principal investigators at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">Research groups</a><ul><li  class="first menu-2869 depth-3"><div class="menu-item-wrapper"><a href="/research/group/chromatin-structure-and-cellular-identity">Abdenour Soufi</a></div></li><li  class="menu-1958 depth-3"><div class="menu-item-wrapper"><a href="/research/group/ontogeny-haematopoietic-stem-cells">Alexander Medvinsky</a></div></li><li  class="menu-2040 depth-3"><div class="menu-item-wrapper"><a href="/research/group/stem-cell-genome-engineering">Andrew Smith</a></div></li><li  class="menu-2041 depth-3"><div class="menu-item-wrapper"><a href="/research/group/remyelination-multiple-sclerosis">Anna Williams</a></div></li><li  class="menu-2042 depth-3"><div class="menu-item-wrapper"><a href="/research/group/adult-tissue-cell-plasticity-reprogramming-fate-change-and-regeneration">Anura Rambukkana</a></div></li><li  class="menu-2043 depth-3"><div class="menu-item-wrapper"><a href="/research/group/tissue-development-regeneration-and-repair">Bruno Péault</a></div></li><li  class="menu-2044 depth-3"><div class="menu-item-wrapper"><a 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class="menu-item-wrapper"><a href="/research/group/manipulating-stem-cell-niche-promote-regeneration" title="Mechanisms of regeneration with age">Elaine Emmerson</a></div></li><li  class="menu-3569 depth-3" title="Quantitative Biology of Pattern Formation"><div class="menu-item-wrapper"><a href="/research/group/quantitative-biology-pattern-formation" title="Quantitative Biology of Pattern Formation">Guillaume Blin</a></div></li><li  class="menu-1973 depth-3"><div class="menu-item-wrapper"><a href="/research/group/embryonic-stem-cell-biology">Ian Chambers</a></div></li><li  class="menu-2345 depth-3"><div class="menu-item-wrapper"><a href="/research/group/redirecting-cell-fate">Ian Wilmut</a></div></li><li  class="menu-2870 depth-3"><div class="menu-item-wrapper"><a href="/research/group/developmental-origins-blood-stem-cells-and-leukaemia">Katrin Ottersbach</a></div></li><li  class="menu-2347 depth-3"><div class="menu-item-wrapper"><a href="/research/group/biology-reprogramming">Keisuke Kaji</a></div></li><li  class="menu-2348 depth-3"><div class="menu-item-wrapper"><a href="/research/group/mesoderm-and-haematopoietic-differentiation">Lesley Forrester</a></div></li><li  class="menu-3465 depth-3" title="Computational biology of cell populations"><div class="menu-item-wrapper"><a href="/research/group/computational-biology-cell-populations" title="Computational biology of cell populations">Linus Schumacher</a></div></li><li  class="menu-3566 depth-3" title="Cell and tissue monitoring"><div class="menu-item-wrapper"><a href="/research/group/cell-and-tissue-monitoring" title="Cell and tissue monitoring">Pierre Bagnaninchi</a></div></li><li  class="menu-3567 depth-3" title="Epigenetics and Brain Development"><div class="menu-item-wrapper"><a href="/research/group/epigenetics-and-brain-development" title="Epigenetics and Brain Development">Robert Illingworth</a></div></li><li  class="menu-2349 depth-3"><div class="menu-item-wrapper"><a 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building and other facilities including GMP cell therapy, FACS, flow cytometry, cell sorting, imaging, transgenics, tissue culture, histology, and research tools of the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">Facilities</a><ul><li  class="first menu-3137 depth-2"><div class="menu-item-wrapper"><a href="/facilities/imaging">Imaging</a></div></li><li  class="menu-3139 depth-2"><div class="menu-item-wrapper"><a href="/facilities/flow-cytometry">Flow cytometry</a></div></li><li  class="menu-3138 depth-2"><div class="menu-item-wrapper"><a href="/facilities/gmp-cell-therapy">GMP cell therapy</a></div></li><li  class="menu-3145 depth-2"><div class="menu-item-wrapper"><a href="/facilities/ccbn">CCBN</a></div></li><li  class="menu-3141 depth-2"><div class="menu-item-wrapper"><a href="/facilities/transgenics">Transgenics</a></div></li><li  class="menu-3142 depth-2"><div class="menu-item-wrapper"><a href="/facilities/tissue-culture">Tissue culture</a></div></li><li  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menu-2033 depth-2"><div class="menu-item-wrapper"><a href="/join-us/phd-training">PhD training</a><ul><li  class="first menu-2305 depth-3" title="Stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/phd-structure" title="Stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">PhD structure</a></div></li><li  class="menu-2307 depth-3" title="Videos and testimonials from PhD student at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/what-our-phd-students-say" title="Videos and testimonials from PhD student at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">What our PhD students say</a></div></li><li  class="menu-2308 depth-3" title="Available stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/phd-opportunities" title="Available stem cell and regenerative medicine PhD student training opportunities at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">PhD opportunities</a></div></li><li  class="menu-2309 depth-3" title="Funding and finance opportunities for stem cell and regenerative medicine PhD studentships at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh."><div class="menu-item-wrapper"><a href="/join-us/phd-training/phd-funding-and-finance" title="Funding and finance opportunities for stem cell and regenerative medicine PhD studentships at the MRC Centre for Regenerative Medicine (CRM), University of Edinburgh.">PhD funding and finance</a></div></li><li  class="menu-2037 depth-3" title="How to apply 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										Ethics									</h1>
																							
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					<div class="field-item even"><p>All medical advancements come with ethical considerations; learn about some of the ethical issues surrounding stem cells in medicine.</p>
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<li><a href="#Regulation">Regulation of stem cell research</a></li>
<li><a href="#Embryonic">Embryonic stem cells</a></li>
<li><a href="#Induced">Induced pluripotent stem cells</a></li>
<li><a href="#Animal">Research on animals</a></li>
<li><a href="#Affording">Affording stem cell treatments</a></li>
<li><a href="#Responsibility">Responsibility of personal health</a></li>
</ul>
<h2><a name="Regulation" id="Regulation"></a>Regulation of stem cell research</h2>
<p>Ethical considerations and discussions have always been part of medicine and research. These discussions can greatly influence rules and regulations that impact the work of researchers and clinicians. A misconception about stem cell research is that scientists can isolate stem cells whenever they like, create stem cell lines, and use these cells in tests as they wish. In reality, the UK has put in place specific regulations for the creation and use of stem cells. These regulations require scientists to submit research proposals to government agencies (the <a href="https://www.hfea.gov.uk/">HFEA</a> and the <a href="https://www.hta.gov.uk/">HTA</a>) before creating or using human stem cells. Lawyers, clinicians, ethicists and other scientists evaluate the research proposals to make sure the use of stem cells is appropriate. If researchers want to carry out new experiments with stem cell lines they already made, a new proposal must be submitted for approval.</p>
<p>If approval is given to make new stem cells, UK regulations require that these cells are registered and stored in the <a href="https://nibsc.org/">UK Stem Cell Bank</a>. The stem cell bank acts as a resource for other researchers to obtain stem cells lines and as a way for the UK to oversee what stem cell lines researchers are making. Scientists can get approval to use cells stored in the stem cell bank rather than making new stem cells. Using existing stem cell lines saves researchers time, labour and guarantees the cells are of consistent quality. It also helps avoid some ethical issues surrounding making new cell lines like embryonic stem cells.</p>
<ul>
<li><a href="https://www.eurostemcell.org/regulation-stem-cell-research-europe">Overview</a> of stem cell regulation in EU countries on EuroStemCell.org.</li>
</ul>
<h2><a name="Embryonic" id="Embryonic"></a>Embryonic stem cells</h2>
<p><a href="https://www.eurostemcell.org/origins-ethics-and-embryos-sources-human-embryonic-stem-cells">Embryonic stem (ES) cells</a> can <span class="tooltip" title="The process of gaining specialised cellular functions by an immature cell. Fully differentiated cells (or terminally differentiated cells) cannot further alter their specialised functions.">differentiate</span> into any other <span class="tooltip" title="Cells that are fully differentiated and have specific roles within a tissue or organ. Examples include the ability of muscle cells to contract and stomach cells to produce acid for digestion. ">specialised cell</span> in the body. Studying ES cells allows researchers to learn how the human body <span class="tooltip" title="The biological process of a cell dividing, differentiating and growing to creating complex tissues, organs, and ultimately a whole organism. The developmental process is what allows a fertilized egg to grow and mature into an adult.">develops</span> under normal conditions. Additionally, understanding how these cells are derived and function is essential for developing regenerative medicine treatments.</p>
<p>Ethical discussions surrounding ES cells focus on how ES cells are created. ES are derived in the laboratory from cells collected from a very early <span class="tooltip" title="The stages of development during the first eight weeks of pregnancy; from the first cell division of the fertilised egg until becoming a foetus.">embryo</span>, called a <span class="tooltip" title="An early stage embryo that is formed approximately 5 days after fertilisation of a human egg and is made of roughly 150 cells.">blastocyst</span>. A blastocyst develops approximately 5 days after conception and has not yet implanted itself into the mother’s womb. Blastocysts are roughly 150 cells, which is very small, about the size of a pin head. Most blastocysts for scientific and medical research are donated by parents that have undergone an <span class="tooltip" title="A biological process or experiment that takes place under controlled laboratory conditions, outside of a living organism.">in vitro</span> fertilization (IVF) treatment. The process of collecting ES cells destroys the blastocyst, however, most unused blastocysts from IVF treatments are destroyed anyway. Still, some people ask whether it is justifiable to destroy early embryos at all, even if the research on ES cells might help treat people with diseases and injuries. This ethical discussion has resulted in strict regulations that monitor who can: supply the blastocysts to make ES cells, generate ES cells, and use ES cells once made (see the above section on regulations). The UK government’s regulations on ES cells have attempted to find a balance between different perspectives and values of the UK people in this ES cell <a href="https://www.eurostemcell.org/embryonic-stem-cell-research-ethical-dilemma">debate</a>. Likewise, government rules <a href="https://www.eurostemcell.org/regenerative-medicine-and-regulation-whats-gmp-got-do-it">vary from country to country</a> as the citizens and their governments come to different conclusions on stem cell research.</p>
<p>To a certain extent technologies, such as induced pluripotent stem (iPS) cells, provide a way to end the use of ES cells and avoid ethical issues. However, the reality is that some research will always require the use of ES cells to understand things such as human development and to examine/compare the ability of iPS cells (or any other new cell technology) to differentiate. Also, it is important to realise that iPS cells present some of their own ethical concerns, further discussed below.</p>
<ul>
<li><a href="https://www.eurostemcell.org/embryonic-stem-cell-research-ethical-dilemma">More information</a> about ethics of ES cells on EuroStemCell.org.</li>
</ul>
<h2><a name="Induced" id="Induced"></a>Induced pluripotent stem cells</h2>
<p>Technologies to create <span class="tooltip" title="Stem cells created from fully differentiated tissue cells that have been artificially stimulated to become pluripotent cells similar to embryonic stem cells.">induced pluripotent stem (iPS) cells</span>, or other <span class="tooltip" title="Stem cells with the ability to generate all the specialised cell types of an organism. Pluripotent cells can form the cells of an embryo, but lack the ability to create the supporting cells and tissues needed to permit the development of a whole organism.">pluripotent cells</span>, present researchers with exciting scientific possibilities as well as important <a href="https://www.eurostemcell.org/ethics-and-reprogramming-ethical-questions-after-discovery-ips-cells">ethical responsibilities that need to be well regulated</a>. Shinya Yamanaka, the scientist who led the discovery of iPS cells, emphasises the need for regulation. For example, <a href="https://www.nature.com/articles/500392a">researchers have demonstrated</a> they are able to make eggs and sperm from iPS cells. These reproductive cells were used to create mouse embryos that grew into live-born mice when hosted by a surrogate mother. Should iPS technologies be used to make human embryos from skin cells in a similar manner? Additionally, iPS cell technologies could permit men to make eggs from skin cells, and women to make sperm. This technology is not yet possible in humans, yet there is concern over how these procedures should be regulated.</p>
<p>Another ethical issue with iPS cells (and tissue stem cells) is deciding <a href="https://www.eurostemcell.org/media-and-resource-library?keywords=&amp;amp;amp;type[66]=66">who owns them</a>. Once iPS cells are created, are the cells the property of the creators, the donor, or both? Should iPS cells be provided to other patients with or without the consent of the original donor? These are just some ethical concerns still unanswered.</p>
<ul>
<li><a href="https://www.eurostemcell.org/ethics-and-reprogramming-ethical-questions-after-discovery-ips-cells">More information</a> about ethics of iPS cells on EuroStemCell.org.</li>
</ul>
<h2><a name="Animal" id="Animal"></a>Research on animals</h2>
<p>Research using animals has played and continues to play a key role in the advancement of medical, biological and veterinary science. It has made a vital contribution to the understanding, prevention, treatment and cure of a wide range of major health problems in both people and animals, including cancer, heart disease and diabetes. Presently, all new medical treatments in the UK, stem cell based or not, are required by law to be tested on animals to make sure they are safe before testing in people.</p>
<p>Medical research institutions have to follow very strict rules and regulations set and checked by the <a href="https://www.gov.uk/research-and-testing-using-animals">UK Government’s Home Office</a>. These regulations aim to maximise animal welfare and minimise the use of animals as much as possible in research. Researchers must, by law, show that their research could not be carried out using non-animal alternative methods before it can be approved. Additionally, licences to use animals in research are only granted where the potential benefits of the work are likely to outweigh the effects on the animals concerned.</p>
<p><strong>Replacement, Reduction and Refinement</strong><br />In the UK, the legal and ethical use of animals in research is guided by the ‘3 Rs’ – <a href="https://www.nc3rs.org.uk/">Replacement, Reduction and Refinement</a>. Researchers must replace animal studies with other research methods wherever possible; reduce the number of animals as far as possible while maintaining scientific rigor; and refine experimental and husbandry procedures to improve animal welfare and minimise potential distress. Scientists are developing new technologies to help them to achieve these aims. One such example is the development of technologies that use iPS cells to directly test drugs on a patient’s cells. However, new testing systems will never completely replace animal testing, as there are many biological systems too complex to be recreated in the laboratory. At present, testing the safety of treatments in animals is vital for rapid development of better and safer medicines.</p>
<ul>
<li><a href="https://mrc.ukri.org/research/research-policy-ethics/use-of-animals/?nav=sidebar&amp;amp;amp;nav=sidebar">More information</a> about the use of animals in medical research on the Medical Research Council website.</li>
<li><a href="https://www.ed.ac.uk/research-innovation/animal-research">More information</a> on the University of Edinburgh website.</li>
</ul>
<h2><a name="Affording" id="Affording"></a>Affording stem cell treatments</h2>
<p><span class="tooltip" title="Medical treatments that restore complete function to tissues and organs that are damaged by age, injury or disease. These treatments range from drugs that stimulate tissue regeneration to methods of cell and tissue replacement.">Regenerative medicines</span>, in theory, could be developed as <span class="tooltip" title="Medical treatments that are custom tailored to treat the complication and meet the immunological needs of a patient.">personalised medicine</span>, tailored to work specifically for each patient. As wonderful as personalised medicine sounds, this kind of medical treatment would be very costly. Stem cell technologies being created in today’s laboratories are time-consuming and very expensive. This raises questions of: Who will be able to afford these treatments? Will public healthcare include expensive regenerative medicines? Who will decide the balance between cost and a patient’s quality of life?</p>
<p>Ideas are needed to address the affordability and accessibility associated with regenerative medicines. One proposed idea is to <a href="https://www.eurostemcell.org/media-and-resource-library?keywords=&amp;amp;amp;type[66]=66">create a Global Stem Cell Bank</a>. One of the largest complications of transplanting organs, tissues and cells is immune system rejection of the transplant. The Global Stem Cell Bank could address this complication by carrying different types of stem cells that are matched to the <span class="tooltip" title="Biological processes, organs, tissues and cells that provide the body with resistance to infections. The immune system primarily works by destroying anything that is sees as foreign to the body.">immune system</span> requirements of groups of patients, much like blood banks carry different blood types (A, B, O &amp; Rh blood groups). Costs for making the stem cells could then be shared by everyone using the stem cell bank, making it much more affordable. Also, having stem cells already made, rather than taking weeks or months to make suitable stem cells in a lab, would allow treatments to be performed more quickly from the time of diagnosis.</p>
<h2><a name="Responsibility" id="Responsibility"></a>Responsibility for personal health</h2>
<p>Regenerative medicines may one day be able to cure injuries and treat many diseases and injuries. However, will this mean that people no longer need to worry about behaviour that leads to diseases and injuries? Will smokers be able to keep smoking, knowing they can just get fixed up? The same can be asked about other health issues, like heavy drinking, poor eating habits, drug abuse, and even injuries from extreme sports. Should costly regenerative medicine treatments be performed only if the patient is going to change his or her behaviour? Who should pay for treating these individuals if they will likely need to be re-treated in the future? Stem cell treatments may also allow individuals to live longer and longer. Questions about the costs associated with caring for an ageing population need to be asked as the average life span continues to rise.</p>
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